bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal Labor Markets and Worker Quits
Authors: FAIRRIS DAVID
Published: June 2004

This article uses establishment‐level data to explore the impact of internal labor markets on worker quits. Quits are lower where job ladders are long, pay growth from the bottom to the top of job ladders is high, and seniority is used as a criterion for promotion. Using a system of internal promotion without a commitment to seniority is associated with higher worker quits. These results hold true even when controlling for the specific human capital skills of workers, suggesting that personnel factors other than specific training are responsible both for the existence of internal labor markets and for the impact of internal labor markets on worker quits.
College Quality and Earnings in the Japanese Labor Market
Authors: ONO HIROSHI
Published: June 2004

The motivations underlying the pursuit of college prestige in Japan presumes a labor market that rewards workers according to the quality of the college that they attended. Yet studies that examine the relationship between college quality and earnings in Japan remain few and are riddled with shortcomings. This article examines the returns to college education among Japanese men using a 1995 cross‐sectional data set. I find that college quality significantly improves earnings. My findings confirm that college quality plays a crucial role in shaping incentives and earnings in the Japanese labor market.
Primary cutaneous CD30+ anaplastic large cell lymphoma with keratoacanthoma‐like pseudocarcinomatous hyperplasia and marked eosinophilia and neutrophilia
Authors: Lin Jeng‐Hsien , Lee J. Yu‐Yun
Published: June 2004

Background:  Pseudocarcinomatous hyperplasia (PCH) and marked tissue neutrophilia have been observed in cutaneous CD30+ anaplastic large cell lymphoma (ALCL) occasionally and may cause misdiagnosis.

Methods:  An unusual case of CD30+ ALCL of the skin resembling keratoacanthoma (KA) both clinically and pathologically was described. Histologic examination and immunostaining were performed.

Results:  A 55‐year‐old woman presented with a 3‐month history of an enlarging hyperkeratotic tumor on the forehead with a central keratinous plug. Microscopic examination showed epithelial hyperplasia resembling KA and a diffuse background infiltrate of large atypical lymphoid cells in the dermis. The atypical cells resembled epithelial cells and were obscured by a massive infiltrate of eosinophils and neutrophils. Immunostaining confirmed the presence of a diffuse infiltrate of CD30+ cells; these cells were negative for CD45RO, CD20, CD15, epithelial membrane antigen, anaplastic lymphoma kinase‐1, and cytokeratin. There was no evidence of extracutaneous involvement. The findings were consistent with primary cutaneous CD30+ ALCL of null cell phenotype with KA‐like epithelial hyperplasia and marked eosinophilia and neutrophilia.

Conclusions:  Our case illustrates that primary cutaneous ALCL may be associated with KA‐like PCH and concurrent marked tissue eosinophilia and neutrophilia. Diagnosis in such cases is challenging both clinically and histologically because the large atypical lymphoid cells may easily be obscured by the massive infiltrates of eosinophils and neutrophils or confused with invasive squamous cell carcinoma.
Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal
Authors: Saeed Sadia , Keehn Connie A. , Morgan Michael B.
Published: June 2004

Background:  Cutaneous tumor metastasis may be the first manifestation of cancer, but more often is a harbinger of advanced disease that portends an ominous prognosis. All skin accessions over the past 10 years from a large Veterans Administration (VA) hospital were reviewed.

Methods:  Archived histories, glass slides, and the immunohistochemical battery (IHC), were assessed to determine diagnostic accuracy.

Results:  Of the 100,453 cases reviewed, there were a total of 77 cases (75 males and 2 females) of cutaneous metastasis from the lungs (28.6%), metastatic melanoma (18.2%), gastrointestinal tract (14.2%), genitourinary tract (10.4%), head and neck (9.1%), hematologic (5.2%), breast (5.2%), and miscellaneous (<2%). Metastasis represented the first indication of an internal malignancy in 7.8% of cases. The cutaneous sites of involvement included the head and neck (28%), the trunk (40%), the extremities (18%), and multiple sites (14%). The age range was 38–83 years, with a mean of 62 years. The average time interval between diagnosis of internal malignancy and cutaneous presentation was 33 months (range: <1 month−22 years), and the average survival following diagnosis was 7.5 months (range: <1 month−8 years). In a cohort of subjects, a truncated immunohistochemical battery consisting of CK‐7, CK‐20, and S‐100 was consistent with the expected staining pattern of the primary source of cutaneous metastasis in 83.33% of the patients.

Conclusions:  Excluding the potential for age and gender bias in this study conducted in a VA setting, cutaneous metastases represent an uncommon, deadly, and late‐developing occurrence in many patients. Compared with previous studies, lung carcinoma remains the most common of the cutaneous metastases, with a relative rise in the incidence of metastatic melanoma. The immunohistochemical battery of CK‐7, CK‐20, and S‐100 is a helpful adjunct in narrowing the differential diagnosis of the primary site of a large proportion of cutaneous metastases, particularly tumors with an epithelioid appearance such as carcinomas and melanomas.
Perilesional vs. lesional skin changes in senile lentigo
Authors: Cario‐Andre Muriel , Lepreux Sebastien , Pain Catherine , Nizard Carine , Noblesse Emmanuelle , Taïeb Alain
Published: June 2004

Background:  Senile lentigo (SL) is a common component of photoaged skin. It is characterized by hyperpigmented macules which affect chronically irradiated skin mostly after 50 years of age. This study was undertaken to assess the basic morphology of SL on dorsum of hands.

Methods:  A systematic comparison between lesional vs. perilesional skin using immunohistochemistry and electron microscopy was done to detect precursor lesions of SL and to determine whether melanocytes or keratinocytes were first affected in the evolution of lesions.

Results:  In 12 cases studied, the main findings show that clusters of perilesional keratinocytes accumulate melanin in large melanosomial complexes, and that melanocytes counts are increased respective to total length of section in lesional skin, but the increment is probably due to the development of characteristic epidermal rete ridges. Melanocytes had overall a normal ultrastructure, with mostly quiescent features in perilesional skin and melanosomial transport seeming more active in lesional skin.

Conclusions:  Our data indicate that SL may represent a loss of epidermal melanin unit homeostasis due to chronic irradiation, where keratinocytic changes predominate over melanocytic changes. We hypothesize that abnormal pigment retention in keratinocytes is the primary defect in SL, which may partly explain the therapeutic effect of retinoids.
Human MHC class I chain related (MIC) genes: their biological function and relevance to disease and transplantation
Authors: Collins R. W. M.
Published: June 2004

Major histocompatibility complex (MHC) class I chain related (MIC) molecules show homology with classical human leukocyte antigen (HLA) molecules, but they do not combine with β2 microglobulin, do not bind peptide and are not expressed on normal circulating lymphocytes. In response to stress, MIC proteins are expressed on the cell surface of freshly isolated gastric epithelium, endothelial cells and fibroblasts and engage the activating natural killer cell receptor NKG2D, which is found on many cells within the immune system. Despite the highly polymorphic nature of MIC genes, only one polymorphic position has been identified that appears to affect the binding of NKG2D. Alleles with a methionine at codon 129 have a 10–50‐fold greater capacity to complex NKG2D than alleles with a valine at this position. Renal and pancreatic grafts with evidence of both acute and chronic rejection have been shown to express MIC proteins, and anti‐MIC antibodies have been identified in the serum of these patients. Some MIC molecules which are expressed by tumours appear to shed and solubilize in plasma. This soluble form of MIC engages cells expressing NKG2D, rendering them inactive, and impairs tumour cytolysis. Similarly, a protein encoded by human cytomegalovirus (CMV) prevents MICB surface expression and subsequent NKG2D interaction. Whereas the benefit of solid organ transplantation may be hindered by the expression of MIC molecules on grafts, tumours and viruses may take advantage of the expression of MIC molecules on transformed and virus‐infected cells in order to evade this recognition pathway.
Evaluating association and transmission of eight inflammatory genes with Viliuisk encephalomyelitis susceptibility
Authors: Oleksyk T. K. , Goldfarb L. G. , Sivtseva T. , Danilova A. P. , Osakovsky V. L. , Shrestha S. , O'Brien S. J. , Smith M. W.
Published: June 2004

Since the discovery of Viliuisk encephalomyelitis (VE) in 1887, scientists have tried to understand the natural history and aetiology of this endemic neurological disorder among the native Sakha population of Central Siberia. Familial aggregation and segregation analysis suggested a genetic influence on VE incidence. However, recent studies have implicated an unknown virus, possibly from the alpha herpesvirus family, as a possible cause for this disease. As VE is a neurological disease characterized by the inflammatory reactions systematically observed in the spinocerebellar fluid and in the brain tissue of deceased patients, we examined 17 single nucleotide polymorphisms (SNPs) across seven inflammation‐related candidate gene regions, including chemokine receptors type 2 and 5 (CCR2/CCR5), interferon‐γ (IFN‐γ), interleukin‐4 (IL‐4), IL‐6, IL‐10, stromal cell‐derived factor (SDF) and chemokine regulated upon activation, normal T‐cell expressed and presumably secreted (RANTES). Our main objective was to analyse the degree of genetic association between VE and candidate genes that have been previously implicated in other inflammatory diseases. Samples were collected from 83 affected families comprising 88 verified VE cases, 156 family members, and an additional 69 unrelated, unaffected inhabitants of the same geographical area. This collection included substantially all of the cases that are currently on the VE Registry. The experimental design included both case–control and transmission/disequilibrium test (TDT)‐based familial association analyses. None of 17 SNPs analysed was significantly associated with VE occurrence. Exclusion of these eight genes based on the lack of association has important implications for identifying the disease agent, as well as prescribing therapy and understanding Viliuisk encephalomyelitis.
Speciation in the Central American Seaway: the importance of taxon sampling in the identification of trans‐isthmian geminate pairs
Authors: Craig Matthew T. , Hastings Philip A. , Pondella Daniel J.
Published: June 2004

Aim To create a molecular phylogenetic hypothesis for the closely related serranid generaAlphestesBloch and Schneider andDermatolepisGill and assess the role of the Panamanian Isthmus in speciation within these reef fishes.

Location Tropical eastern Pacific, Caribbean, and Indian Oceans.

Methods Sequence data from one nuclear (TMO‐4C4) and three mitochondrial genes (16S, 12S, and cytochromeb) were used in maximum parsimony and maximum likelihood analyses.

Results Here we show that previously hypothesized trans‐isthmian geminate species are not each other's closest living relatives. Species ofAlphestesBloch and Schneider in the eastern Pacific are sister taxa indicating post‐closure speciation. WithinDermatolepisGill, we identify a sister group relationship between the Caribbean and western Indian Ocean species, a rarely reported biogeographic pattern. Based on sequence divergence, speciation among the three species ofDermatolepiswas, however, nearly simultaneous around the time of the isthmian closure event.

Main conclusions Our molecular phylogenetic analysis of two closely related genera of reef fishes, each with presumed trans‐isthmian geminates, cautions against the uncritical use of morphological similarity in identification of geminates, as well as the assumption that trans‐isthmian sister groups date to the isthmian closure event. These findings suggest that in some instances incomplete sampling of species within a clade including putative geminates may lead to improper conclusions regarding the pattern and timing of speciation, as well as incorrect estimation of the rate at which evolution has proceeded.
Representing species in reserves from patterns of assemblage diversity
Authors: Araújo M. B. , Densham P. J. , Williams P. H.
Published: June 2004

Aim  A positive relationship between assemblage diversity (AD) – equivalent to the biotic version of the environment diversity, ED, method – and species diversity has been reported. This being true, reserve networks with many different assemblages would be expected to represent more species than reserve networks including fewer and less different assemblages. This idea was tested using European species atlas distributions of terrestrial vertebrates and plants. It is asked whether: (1) maximizing AD within one group would represent species diversity of this group better than expected by chance; and (2) maximizing AD within one group would represent species diversity of other groups better than expected by chance.

Location  Europe.

Methods  Three ordination techniques (non‐metric multidimensional scaling, detrended correspondence analysis and correspondence analysis) are used to summarize patterns of compositional turnover within assemblages. p‐Median location‐allocation models are then calculated from ordination space to measure the degree of expected species representation within the group being sampled as well as the expected representation within other groups. Results are compared with near‐optimal solutions obtained with complementarity‐based algorithms and to a null model obtained by simulating selection of areas at random. Matrix correlation analysis was also performed to investigate broad patterns of covariation in compositional turnover of assemblages of species belonging to different taxonomic groups and these values were compared with correlation in species richness scores between groups.

Results  The AD model did not always represent more species of the group being sampled than expected by chance (P < 0.05). Results were independent of the method and taxonomic group considered. Effectiveness of AD within one group to represent species of other groups varied, but in most cases it was worse than using complementarity‐based algorithms as a surrogate strategy. Even when correlations indicated high coincidence between assemblages, taxonomic‐based surrogates did not always recover more species than expected by chance (P < 0.05).

Main conclusions  Results are discussed in the light of two possible explanations: (1) the AD model is based on unrealistic assumptions, namely that species have equal probability of having the centre of their distributions anywhere in ordination space and that species display unimodal, symmetrical, bell‐shaped response curves to gradients; (2) particular implementation of methods may be inadequate to summarize useful complementarity among assemblages, especially for restricted‐range species. We conclude that both arguments are likely to play a role in explaining results, but that opportunities exist to improve performance of existing surrogate strategies.
Regional biogeography of shallow reef fish and macro‐invertebrate communities in the Galapagos archipelago
Authors: Edgar G. J. , Banks S. , Fariña J. M. , Calvopiña M. , Martínez C.
Published: June 2004

Aim  To delineate biogeographical patterns in Galapagos shallow‐water reef fauna at regional scales.

Location  Galapagos Islands.

Methods  Fishes and macro‐invertebrates were quantitatively censused using underwater visual techniques along more than 500 transects at defined depth strata across the Galapagos archipelago. Data were analysed using multivariate techniques to define regional patterns and identify species typical of different regions.

Results  Subtidal communities of fishes and macro‐invertebrates on shallow reefs differed consistently in species composition across the Galapagos archipelago, with three major biogeographical groupings: (1) the ‘far‐northern area’ containing the islands of Darwin and Wolf, (2) the ‘central/south‐eastern area’, including the east coast of Isabela, and (3) the ‘western area’, encompassing Fernandina and western Isabela. In addition, the northern islands of Pinta, Marchena and Genovesa form a separate region in the central/south‐eastern area, and Bahia Elizabeth and Canal Bolivar separate from other parts of the western area. The far‐northern bioregion is characterized by high fish species richness overall, including a high proportion of species of Indo‐Pacific origin. However, very few endemic fishes or species with distributions extending south from Ecuador (‘Peruvian’ species) are present, and the bioregion also possesses relatively low species richness of mobile macro‐invertebrate taxa. By contrast, the ‘western’ bioregion possesses disproportionately high numbers of endemic fish taxa, high numbers of cool‐temperate Peruvian fish species, and high invertebrate species richness, but very few species of Indo‐Pacific origin. The Bahia Elizabeth/Canal Bolivar bioregion possesses more endemic species and fewer species with Peruvian affinities than coasts within the western bioregion. The northern bioregion of Pinta, Marchena and Genovesa represents an overlap zone with affinities to both the far‐northern and south‐eastern islands. The south‐eastern bioregion includes species from a variety of different sources, particularly ‘Panamic’ species with distributions extending north to Central America.

Main conclusions  On the basis of congruent divisions for reef fish and macro‐invertebrate communities, the Galapagos archipelago can be separated into three major biogeographical areas, two of which can be further subdivided into two regions. Each of these five bioregions possesses communities characterized by a distinctive mix of species derived from Indo‐Pacific, Panamic, Peruvian and endemic source areas. The conservation significance of different regions is not reflected in counts of total species richness. The regions with the lowest overall fish species richness possess a temperate rather than tropical climate and highest levels of endemism.
The distribution of divergent mitochondrial DNA lineages of threespine stickleback (Gasterosteus aculeatus) in the northeastern Pacific Basin: post‐glacial dispersal and lake accessibility
Authors: Johnson Lisa S. , Taylor Eric B.
Published: June 2004

Aim This study furthers the documentation of the geographical distribution of two divergent (c. 3%) mitochondrial DNA clades in the threespine stickleback (Gasterosteus aculeatus) and tests the hypotheses that the northeastern Pacific distribution has been influenced by post‐glacial colonization and lake elevation and that clade identity is associated with certain morphological attributes such as reduction in body armour.

Location Lakes and nearshore marine environments of the eastern Pacific Basin from southcentral Alaska to southeastern British Columbia, (BC) Canada.

Methods Restriction enzyme analysis of polymerase chain reaction‐amplified mitochondrial DNA fragments (cytochromeb) from a total of 45 new populations combined with existing data for a further 45 populations. Lake elevation data were collected for 78 localities and tested for an association with mtDNA clade by contingency table analyses. Morphological data were collected on sticklebacks from eight samples representing four lake‐stream systems and tested for differentiation among populations with different mtDNA clade identities using analyses of variance.

Results We extend the known distribution of the haplotypes diagnostic of the Trans‐North Pacific Clade (TNPC) southward to mid‐Vancouver Island and, for the first time, on mainland BC, in other island populations far from putative refugia, and in nearby anadromous populations. A morphological analysis indicated that the mainland population with the TNPC was not characterized by reduced spine or lateral plate (‘armour’) traits that characterize some putative relict populations on the Queen Charlotte Islands. We found a significant association between lake elevation and the presence of the TNPC; the TNPC was present more often in lakes located at or lower than 42 m than in higher elevation lakes.

Main conclusions Our data support the hypothesis that post‐glacial colonization by TNPC‐bearing marine sticklebacks and aspects of lake ‘accessibility’ were important in determining the distribution of mtDNA clades in the eastern Pacific Ocean basin. More generally, our study demonstrates how processes acting both across immense geographic scales (e.g. pan‐Pacific dispersal) and local scales (lake accessibility contingent on timing and extent of isostatic rebound) may interact to explain biogeographical patterns.
The biodiversity of Diptera in Old World rain forest surveys: a comparative faunistic analysis
Authors: Kitching R. L. , Bickel D. , Creagh A. C. , Hurley K. , Symonds C.
Published: June 2004

Aim  Identify the taxonomic patterns and the relative importance of particular families of Diptera sampled in comparative biodiversity surveys carried out at seven rain forest locations. We test and quantify the contention that different trapping methods routinely target different families. We identify the south–north (and upland/lowland) patterns and generate a set of hypotheses concerning mechanisms underlying these patterns.

Location  Australia and Papua New Guinea.

Methods  A total of 28,647 Diptera collected using canopy knockdown, yellow pan (water) traps and Malaise traps have been sorted to 56 families following these surveys. Comparative analyses across sites from Lamington National Park in south‐east Queensland, Australia to the Kau Wildlife area in Madang Province, Papua New Guinea, of the dipteran assemblages, and separately, of the 14 families which collectively made up 95.8% of the sample, are presented.

Results  Ordination by multi‐dimensional scaling and analyses of variances showed that the three methods complemented each other in terms of target families and, together, sampled a large proportion of the expected fauna of these sites. Ordinations on a method‐by‐method basis permitted the identification of groups of sites and analyses of variance indicated which taxa differed significantly across these groups.

Main conclusions  Recurrent patterns and associated hypotheses about their generation emerge from the data. These mirror floristic differences and reflect the biogeographic history of the sites since the Miocene. Clear linkages between the lowland faunas of Papua New Guinea and northern Australia are evident and are reflected in the abundances of the Dolichopodidae, Empididae, Muscidae and Tipulidae (other groupings underlined the essential difference of the New Guinean fauna which had characteristic proportions of Cecidomyiidae, Chironomidae, Dolichopodidae, Phoridae and Psychodidae). A subtropical grouping of families was evident comprising, inter alia, Chloropidae, Mycetophilidae, Drosophilidae and Phoridae which was frequently linked with the higher elevation tropical fauna at Robson's Creek, Atherton Tablelands. The long isolated, high elevation, rain‐forested massif at Eungella, central Queensland often emerged as a unique entity in the analyses, characterized by the high numbers of and proportions of Chironomidae, Psychodidae, Tipulidae and Empididae. This study supports the case for the wider use of Diptera in biodiversity analyses, complementing extensive earlier analyses which have used, predominantly, large coleopteran assemblages. The results indicate the potential power of family‐level analyses at large geographical scales and contribute to the ongoing debate on ‘taxonomic sufficiency’.
Systematic review of published multi‐practice audits from British general practice
Authors: Holden John D.
Published: June 2004

Background  Audit has been a major part of attempts to improve patient care in Britain, with substantial resources devoted to it since the 1990 National Health Service reforms. Systematic reviews have considered audit to be of variable, but often moderate, effectiveness. However, these have included few studies from British primary care, and as quality improvement activities may be context specific, it is hard to judge how effective audit has been here.

Results  A search for audits published in peer‐reviewed journals revealed 48 two‐stage projects carried out in British general practice, of which 27 principally concerned chronic disease management and nine prescribing. Most audits showed some improvements in performance, and those using controls showed 27/56 (48%) parameters had changed significantly (P < 0.05).

Conclusions  This review adds further evidence that audit can often be moderately effective. However, it is frequently used as one of a complex set of interventions making precise evaluation difficult. Those responsible for clinical governance will need to choose carefully the subjects they audit in order to use their limited resources to maximum effect. These projects are illustrative examples but once again do not identify any ‘magic bullets’ that would be highly likely to improve professional performance.
A practical approach to a multi‐level analysis with a sparse binary outcome within a large surgical trial
Authors: Fountain Jayne , Gallagher James , Brown Julia
Published: June 2004

Objectives  To assess the potential source of variation that surgeon may add to patient outcome in a clinical trial of surgical procedures.

Methods  Two large (n = 1380) parallel multicentre randomized surgical trials were undertaken to compare laparoscopically assisted hysterectomy with conventional methods of abdominal and vaginal hysterectomy; involving 43 surgeons. The primary end point of the trial was the occurrence of at least one major complication. Patients were nested within surgeons giving the data set a hierarchical structure. A total of 10% of patients had at least one major complication, that is, a sparse binary outcome variable. A linear mixed logistic regression model (with logit link function) was used to model the probability of a major complication, with surgeon fitted as a random effect. Models were fitted using the method of maximum likelihood in SAS®.

Results  There were many convergence problems. These were resolved using a variety of approaches including; treating all effects as fixed for the initial model building; modelling the variance of a parameter on a logarithmic scale and centring of continuous covariates. The initial model building process indicated no significant ‘type of operation’ across surgeon interaction effect in either trial, the ‘type of operation’ term was highly significant in the abdominal trial, and the ‘surgeon’ term was not significant in either trial.

Conclusions  The analysis did not find a surgeon effect but it is difficult to conclude that there was not a difference between surgeons. The statistical test may have lacked sufficient power, the variance estimates were small with large standard errors, indicating that the precision of the variance estimates may be questionable.
The view of evidence‐based medicine from the trenches: liberating or authoritarian?
Authors: Rosenfeld Jo Ann
Published: June 2004

Evidence‐based medicine at first promised to be a popularistic movement, bringing the fruits of research to all practising physicians. Instead it has created its own religion and dogma, further codifying daily practice.
Critique of (im)pure reason: evidence‐based medicine and common sense
Authors: Michelson James
Published: June 2004

While the goal of evidence‐based medicine (EBM) is certainly laudable, it is completely based on the proposition that ‘truth’ can be gleaned exclusively from statistical studies. In many instances, the complexity of human physiology and pathophysiology makes this a reasonable, if not necessary, assumption. However, there are two additional large classes of medical ‘events’ that are not well served by this paradigm: those that are based on physically required causality, and those that are so obvious (to the casual observer) that no self‐respecting study will ever be undertaken (let alone published). Frequently, cause‐and‐effect relationships are so evident that they fall into both categories, and are best dealt with by the judicious use of common sense. Unfortunately, the use of common sense is not encouraged in the EBM literature, as it is felt to be diametrically opposed to the very notion of EBM. As is more fully discussed in the manuscript, this active disregard for common sense leaves us at a great disadvantage in the practical practice of medicine.
Do physiotherapists’ attitudes towards evidence‐based practice change as a result of an evidence‐based educational programme?
Authors: Stevenson Kay , Lewis Martyn , Hay Elaine
Published: June 2004

Rationale  The concept of evidence‐based practice (EBP) encourages health care professionals to provide the most effective health care, and to be accountable for the interventions they provide. Little work has been undertaken to examine how practically allied health professionals’ encompass EBP and how they perceptive and understand the concept of EBP. The use of opinion leaders to disseminate new evidence into practice, and thereby encourage the behaviour of health care professionals has been proposed.

Aims  The aims of this study were to investigate physiotherapists’ attitudes towards EBP and to examine change in their attitudes following an education package,  which utilized local opinion leaders.

Method  Thirty musculoskeletal physiotherapists from a Community Trust in North Staffordshire were cluster randomized by location of work to two groups. The intervention group received an evidence‐based programme on aspects of EBP including literature searching and critical appraisal. The attention control group received a standard in‐service training package on the management of common knee pathologies. The physiotherapists’ attitudes towards EBP were measured at baseline (before randomization) and at 3 and 6 months follow‐up.

Results  Physiotherapists reported that they primarily relied on ‘courses’ and ‘in‐service training’ for informing their clinical practice. Most agreed that clinical practice should be based on the best available evidence and that they would change their clinical practice if evidence suggested they should do so. However, many of the physiotherapists reported difficulty in reading journals and could not identify opinion leaders in key areas. In terms of clinical practice, literature, journals and research were ascribed low priority throughout. Differences in attitudes between the intervention and control groups were observed in relation to management support for EBP at  3  and  6 months  follow‐up.

Conclusions  In this study, physiotherapists appeared to be in favour of the idea of EBP, yet they remained reluctant to change their practice. Opinion leaders were not easily identifiable by physiotherapists, suggesting that this method alone may not be an effective method of changing attitudes in clinical practice. The process of changing attitudes in the clinical environment is a complex issue worthy of further research.
Nursing based evidence: moving beyond evidence‐based practice in mental health nursing
Authors: Geanellos Rene
Published: June 2004

Various authors suggest mental health nursing is dominated by knowledge borrowed from psychiatry, pharmacology and the behavioural sciences. These disciplines favour knowledge developed using quantitative methodologies so they and evidence‐based practice (EBP) and evidence‐based nursing (EBN), increasingly called for in mental health nursing, fit seamlessly together. Nevertheless, as these movements dismiss qualitative approaches to knowledge (evidence) development, I argue against the move toward EBP/EBN in mental health nursing. This is because the specialty's primary interests – human experiences of illness/health care and human relationships, often do not lend themselves to being quantitatively researched. Using nursing examples, I demonstrate how qualitative research, wholly unacceptable in relation to EBP/EBN quality of evidence scales, is indispensable to mental health nursing. The need for evidence arising from qualitative research in no way precludes the need for quantitatively derived evidence. Indeed, the specialty's twofold interest – the work of nurses with clients and the explication of phenomena which inform practice, require diverse knowledge and thus, diverse research approaches. This twofold interest defines the area of mental health nursing practice, and knowledge informing it is referred to as nursing based evidence (NBE). Because it values multiple approaches to knowledge development, NBE provides a way to articulate the specialty's distinct contribution to the health care of people experiencing mental illness and advances mental health nursing.
A prospective study of the practical issues of local involvement in national audit of COPD
Authors: Roberts C. M. , Lowe D. , Barnes S. , Pearson M. G.
Published: June 2004

Rationale, aims and objectives  Variation in quality of local services is of great concern to the government and public. National audit is an important means of providing data of comparative performance but is hampered at local level by poor methodology including audit design, standard setting and data collection tools. A pilot audit of the hospital care of patients ad‐mitted with acute chronic obstructive pulmonary disease (COPD) was performed in preparation for a national audit programme and was designed and supported by experts. It was hoped to overcome these barriers. We report a prospective evaluation of the practical issues involved in local participation of hospital audit of COPD care within a national framework.

Methods  Hospitals were recruited to the study by random selection and voluntary participation. A clinical audit study was completed over an 8‐week period immediately followed by a survey of clinicians and audit staff to identify positive and negative issues of participation and the process  required  to  achieve  a successful outcome.

Results  Forty‐one hospitals were invited to participate, 26 (63%) accepted, and four others volunteered to meet the target of 30 enrolled centres. Reasons cited for non‐participation were of inadequate resources amongst either clinicians or audit departments or prior engagement in other national or local audit schemes. Following completion of the audit most (81%) participating units reported it was a useful exercise and were willing to be involved in future audits. Negative aspects of involvement included the lack of dedicated time and manpower for audit, poor information technology and inadequate systems for identifying patient diagnoses either at admission or at discharge and incomplete case note entries. Methodological issues such as study design and data collection tools were not cited as important barriers to participation. 

Conclusion  There is local willingness to be involved in national audit of hospital care of COPD and central provision of expert design of methods and tools may reduce some audit barriers. Nevertheless, priority must be given to improving resources identified to support audit and in improving methods and systems for data capture. These issues appear to be important in most units and represent a potentially serious barrier to achieving widespread local involvement in a national audit programme of COPD care and may also apply to other national audits designed to provide comparative assessment of National Health Service services.
Anucleate and titan cell phenotypes caused by insertional inactivation of the structural maintenance of chromosomes (smc) gene in the archaeon Methanococcus voltae
Authors: Long Steven W. , Faguy David M.
Published: June 2004

SMC (structural maintenance of chromosomes) proteins are highly conserved and present in eukaryotes, bacteria and archaea. They function in chromosome condensation and segregation and in DNA repair. Using an insertion vector containing the pac gene for resistance to puromycin, we have created an insertion in the smc gene of Methanococcus voltae. We used epifluorescence microscopy to examine the cell and nucleoid morphology, DNA content and metabolic activity. This insertion causes gross defects in chromosome segregation and cell morphology. Approximately 20% of mutant cells contain little or no DNA, and a subset of cells (≈ 2%) IS abnormally large (three to four times their normal diameter) titan cells. We believe that these titan cells indicate cell division arrest at a cell cycle checkpoint. The results confirm that SMC in archaea is an important player in chromosome dynamics (as it is in bacteria and eukaryotes).
The Mycobacterium tuberculosis protein serine/threonine kinase PknG is linked to cellular glutamate/glutamine levels and is important for growth in vivo
Authors: Cowley Siobhan , Ko Mary , Pick Neora , Chow Rayken , Downing Katrina J. , Gordhan Bhavna G. , Betts Joanna C. , Mizrahi Valerie , Smith Debbie A. , Stokes Richard W. , Av‐Gay Yossef
Published: June 2004

Summary The function of the Mycobacterium tuberculosis eukaryotic‐like protein serine/threonine kinase PknG was investigated by gene knock‐out and by expression and biochemical analysis. The pknG gene (Rv0410c), when cloned and expressed in Escherichia coli, encodes a functional kinase. An in vitro kinase assay of the recombinant protein demonstrated that PknG can autophosphorylate its kinase domain as well as its 30 kDa C‐terminal portion, which contains a tetratricopeptide (TPR) structural signalling motif. Western analysis revealed that PknG is located in the cytosol as well as in mycobacterial membrane. The pknG gene was inactivated by allelic exchange in M. tuberculosis. The resulting mutant strain causes delayed mortality in SCID mice and displays decreased viability both in vitro and upon infection of BALB/c mice. The reduced growth of the mutant was more pronounced in the stationary phase of the mycobacterial growth cycle and when grown in nutrient‐depleted media. The PknG‐deficient mutant accumulates glutamate and glutamine. The cellular levels of these two amino acids reached approximately threefold of their parental strain levels. Higher cellular levels of the amine sugar‐containing molecules, GlcN‐Ins and mycothiol, which are derived from glutamate, were detected in the ΔpknG mutant. De novo glutamine synthesis was shown to be reduced by 50%. This is consistent with current knowledge suggesting that glutamine synthesis is regulated by glutamate and glutamine levels. These data support our hypothesis that PknG mediates the transfer of signals sensing nutritional stress in M. tuberculosis and translates them into metabolic adaptation.
Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection
Authors: Centurion‐Lara Arturo , LaFond Rebecca E. , Hevner Karin , Godornes Charmie , Molini Barbara J. , Van Voorhis Wesley C. , Lukehart Sheila A.
Published: June 2004

The tprK gene sequence of Treponema pallidum subspecies pallidum (T. pallidum) is heterogeneous within and among isolates. Heterogeneity in the tprK open reading frame is localized in seven discrete variable (V) regions, and variability results from apparent base changes, insertions or deletions. The TprK V regions are the focus of anti‐TprK antibodies arising during infection. To test our hypothesis that V region sequences change during infection and passage, we developed a clonal isolate from the Chicago strain of T. pallidum and confirmed V region diversification during passage of this isolate. We describe the sequence anatomy of the seven V regions of tprK and the identification of putative donor sites for new V region sequences, and we propose a model for generation of new V regions by segmental gene conversion. These findings suggest that antigenic variation of TprK occurs in T. pallidum and may be important in immune evasion and persistence.
The Mycoplasma fermentans prophage φMFV1: genome organization, mobility and variable expression of an encoded surface protein
Authors: Röske K. , Calcutt M. J. , Wise K. S.
Published: June 2004

The ≈ 16 kb genome of the Mycoplasma fermentansφMFV1 prophage is described, and its mobility, replication and effect on the mycoplasma surface phenotype are demonstrated. In various M. fermentans strains, φMFV1 was either absent or integrated at diverse (and sometimes multiple) chromosomal sites, each marked by a conserved TTTTTA target sequence that is duplicated upon integration. Precise excision, replication of an extrachromosomal form and loss of φMFV1 from the mycoplasmal genome were documented in a series of clonal derivatives of M. fermentans propagated in culture. Of 18 open reading frames (ORFs) encoded by φMFV1, most can be ascribed functions related to phage biology, whereas one encodes a unique coiled‐coil membrane surface protein, Mem, that was confirmed to be expressed in propagating populations of M. fermentans. With the exception of Mem and other minor ORFs, the striking similarity between the deduced proteomes of φMFV1 and the recently described φMAV1 of arthritogenic strains of Mycoplasma arthritidis, along with the prominent gene synteny between these elements, provides the taxonomic basis for a new family of prophage. Their coding features are consistent with long‐term residence in mycoplasma genomes and the divergence of species within a phylogenetic clade of mycoplasmas. The unique Mem protein expressed from φMFV1 and the unique hypothetical surface lipoproteins encoded by φMAV1 and φMFV1 also suggest that prophage‐associated genes may provide specific, selectable phenotypic traits during co‐evolution of mycoplasma species with their respective mammalian hosts. Retention of these labile prophage elements in organisms with such drastically reduced genome sizes implies a significant role in adaptation and survival.
Visualization of DNA double‐strand break repair in live bacteria reveals dynamic recruitment of Bacillus subtilis RecF, RecO and RecN proteins to distinct sites on the nucleoids
Authors: Kidane Dawit , Sanchez Humberto , Alonso Juan C. , Graumann Peter L.
Published: June 2004

We have found that SMC‐like RecN protein, RecF and RecO proteins that are involved in DNA recombination play an important role in DNA double‐strand break (DSB) repair in Bacillus subtilis. Upon induction of DNA DSBs, RecN, RecO and RecF localized as a discrete focus on the nucleoids in a majority of cells, whereas two or three foci were rarely observed. RecN, RecO and RecF co‐localized to the induced foci, with RecN localizing first, while RecO localized later, followed by RecF. Thus, three repair proteins were differentially recruited to distinct sites on the nucleoids, potentially constituting active DSB repair centres (RCs). RecF did not form regular foci in the absence of RecN and failed to form any foci in recO cells, demonstrating a central role for RecN and RecO in initializing the formation of RCs. RecN/O/F foci were detected in recA, recG or recU mutant cells, indicating that the proteins act upstream of proteins involved in synapsis or post‐synapsis. In the absence of exogenous DNA damage, RCs were rare, but they accumulated in recA and recU cells, suggesting that DSBs occur frequently in the absence of RecA or RecU. The results suggest a model in which RecN that forms multimers in solution and high‐molecular‐weight complexes in cells containing DSBs initiates the formation of RCs that mediate DSB repair with the homologous sister chromosome, which presents a novel concept for DSB repair in prokaryotes.
A bispecific antibody against human IgE and human FcγRII that inhibits antigen‐induced histamine release by human mast cells and basophils
Authors: Tam S. W. , Demissie S. , Thomas D. , Daëron M.
Published: June 2004

Background:  FcγRIIB are low‐affinity immunoglobulin (Ig)G receptors that we previously demonstrated to negatively regulate IgE‐induced mast cell activation when coaggregated with FcɛRI. Here, we engineered and characterized a bispecific reagent capable of coaggregating FcγRIIB with FcɛRI on human mast cells and basophils.

Methods:  A bispecific antibody was constructed by chemically crosslinking one Fab’ fragment against human IgE and one Fab’ fragment against human FcγRII. This molecule was used to coaggregate FcɛRI with FcγRII on human mast cells and basophils sensitized with human IgE antibodies, and the effect of coaggregation was examined on mediator release upon challenge with specific antigen.

Results:  When used under these conditions, this bispecific antibody not only failed to trigger the release of histamine by IgE‐sensitized cells, but it also prevented specific antigen from triggering histamine release. Comparable inhibitions were observed with mast cells and basophils derived in vitro from cord blood cells and with peripheral blood basophils.

Conclusions:  The bispecific antibody described here is the prototype of similar molecules that could be used in new therapeutic approaches of allergic diseases based on the coaggregation of activating receptors, such as FcɛRI, with inhibitory receptors, such as FcγRIIB, that are constitutively expressed by mast cells and basophils.