The changing role of pre-admission work experience (clinical visits) in therapeutic radiography, diagnostic radiography and operating department practice: Academic perspectives (part 2).

INTRODUCTION: A clinical visit (work experience) provides an opportunity for prospective students, prior to registration, to visit a clinical department to observe health professionals in practice. The Covid-19 pandemic interrupted access to clinical visits; this article explores the value of clinical visits and the alternatives implemented as a response to Covid-19 restrictions from an academic perspective. METHODS: This article reports the quantitative phase of a three-phase mixed methods study. A survey was distributed to Higher Education Institution (HEI) education leaders for onward distribution to academics supporting recruitment for diagnostic radiography, therapeutic radiography and operating department practice programmes. Qualtrics online survey software was used to administer the survey which was launched in October 2020. Descriptive statistics summarised the data. RESULTS: Representing 37.7% (n = 18/49) of eligible universities, 34 responses from 18 HEIs across England and Wales were received Seventy-eight percent of respondents strongly agreed that they are vital in confirming career choices. Prior to the Covid-19 pandemic, 64% of respondents' programmes had a clinical visit requirement, yet with improvements in simulation and online learning alternatives, 48% agreed that in the longer-term clinical visits will become obsolete. CONCLUSION: Requirements for clinical visits vary between professions and HEIs; academics welcome an opportunity to standardise work experience. Regardless of prospective student background and selected profession/university, all should have equitable and easily available access to high quality resources to support career decision-making. IMPLICATIONS FOR PRACTICE: The enforced withdrawal of clinical visits may impact upon subsequent attrition associated with 'misinformed career choice'. Alternatives to clinical visits, while less onerous for students, admissions staff and clinical colleagues alike, need to be carefully evaluated to ensure they offer prospective students a realistic understanding of the profession.

The changing role of pre-admission work experience (clinical visits) in Therapeutic Radiography, Diagnostic Radiography and Operating Department Practice: Student perspectives (Part 1).

INTRODUCTION: Clinical visits (work experience opportunities) are a recommended part of admissions processes for many diagnostic and therapeutic radiography courses but not for operating department practice (ODP) where observational visits are challenging for applicants to obtain. The Covid-19 pandemic interrupted access to visits for all prospective students; this study presents a review of the value of clinical visits and alternatives. METHODS: This article reports the initial qualitative phase of a three-phase mixed methods study. Using a critical realist approach, focus groups explored first year student experiences of the 'ideal' pre-admission clinical visit and alternative resources. A structured review of Online Prospectus (OLP) entries was undertaken by two student researchers to ascertain the requirements for clinical visits for the three professions. RESULTS: Four focus groups included 25 first year students interviewed prior to their first clinical placement (14 therapeutic radiography, 5 diagnostic radiography and 6 ODP students). Three themes were constructed, namely: informing career choices, the clinical visit experience, and the value of clinical visits. Clinical visits affirmed rather than inspired career choices. The best timing for a visit was before admission interviews and optimal duration was a full day. Interacting with current students was the most valued aspect. Videos and simulations provided in-depth information about the professional role and allowed replay, but some participants found the videos uninspiring. OLP entries present a confusing picture for applicants who may be researching several Universities and professions. CONCLUSION: Clinical visits were deemed 'vital' to radiography student career choices, yet ODPs who could not access visits were comfortable with videos. Simulated visits are a safe option amidst the pandemic but must capture the dynamic and patient-centred nature of practice to accurately inform career choices.

A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation.

The biologic and pathologic features of B-cell malignancies bearing a translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 are still poorly described. Herein we report the results of a comprehensive cytogenetic, fluorescence in situ hybridization (FISH), molecular and histopathological survey of a large series of B-cell malignancies with t(14;19) or variant translocations. A total of 56 B-cell malignancies with a FISH-proven BCL3 involvement were identified with the translocation partners being IGH (n=51), IGL (n=2), IGK (n=2) and a non-IG locus (n=1). Hierarchical clustering of chromosomal changes associated with the t(14;19) indicated the presence of two different groups of IG/BCL3-positive lymphatic neoplasias. The first group included 26 B-cell malignancies of various histologic subtypes containing a relatively high number of chromosomal changes and mostly mutated IgVH genes. This cluster displayed three cytogenetic branches, one with rearrangements in 7q, another with deletions in 17p and a third one with rearrangements in 1q and deletions in 6q and 13q. The second group included 19 cases, mostly diagnosed as B-cell chronic lymphocytic leukemia (B-CLL), and characterized by few additional chromosomal changes (e.g. trisomy 12) and unmutated IgVH genes. In conclusion, our study indicates that BCL3 translocations are not restricted to B-CLL but present in a heterogeneous group of B-cell malignancies.

Neuroprostheses: method to evaluate the information content of stimulation strategies.

We propose a framework to evaluate the information content of different stimulation strategies used in neuroprosthetic implants. We analyze the responses of retinal ganglion cells to electrical stimulation using an information theory framework. This methodology allows us to calculate the information content by looking at the consistency of neural responses generated across multiple repetitions of the same stimulation protocol.

Differences between morphological and electrophysiological retinal ganglion cell classes.

Retinal prostheses work by delivering electrical pulses to the surviving retinal neurons. A pattern of electrical stimulation can generate a perception of vision in blind patients. To improve efficacy of retinal implants, it is important to understand how different classes of retinal neurons respond to electrical stimulation and if a classification can be made based on the electrophysiological properties of neurons. We use previously recorded patch clamp data from retinal ganglion cells classified into morphological classes (A,B,C, D) and functional types (ON, OFF, ON-OFF). We use a machine learning technique to separate data based on the recorded electrophysiological parameters. Results show that the clusters discovered using the machine learning technique do not correspond to the morphological or functional classes used by neuroscientists.

ZAP-70 by flow cytometry: a comparison of different antibodies, anticoagulants, and methods of analysis.

BACKGROUND: The clinical course of chronic lymphocytic leukaemia (CLL) is variable. ZAP-70 expression is believed to provide prognostic information. The flow cytometric detection of ZAP-70 is difficult because it is an intracellular antigen with weak expression in CLL. Consensus has not been reached as to the best method for measurement. METHODS: We analyzed 72 CLL patient samples for ZAP-70 expression and IgVH mutational status. Sensitivity and specificity of ZAP-70 expression against IgVH mutational status were assessed for two clones (2F3.2 and 1E7.2) and for four methods of analysis: percentage positivity (PP), comparing test to isotype control, ratio of geometric means of test and isotype control, and percentage and ratiometric methods comparing test and T/NK cell populations. The effects of anticoagulant, collection times, and time to analysis were also evaluated. RESULTS: Sensitivity and specificity were 85 and 88%, respectively, for Upstate PP; 70 and 88% for Caltag PP; 89 and 91% for Upstate ratio; 89 and 88% for Caltag ratio. Intraobserver variability was smaller when ZAP-70 expression was assessed using a ratiometric approach rather than the percentage method. By 48 h, we observed an average decrease of 13% in the Caltag ratio in the heparin preserved samples compared to an increase of 3% in those collected in EDTA. Within the first 24-h period, a greater percent variability was observed in those samples collected into EDTA compared with heparin. CONCLUSION: Our data support a rapid method for ZAP-70 measurement using commercially available fixation/permeabilization reagents, a conjugated antibody, and a ratiometric method of analysis that minimizes subjective interpretation of the results. This is a method of ZAP-70 assessment that could be included in a routine diagnostic CLL panel; however, the choice of anticoagulant and time of analysis after collection are critical factors in accurate assessment of ZAP-70 expression.

Views and experiences of using integrated care pathways (ICPs) for caring for people in the last days to hours of life: results from a cross-sectional survey of UK professionals.

OBJECTIVES: To determine the views and experiences of health and social care professionals on using integrated care pathways (ICPs)for caring for people in the last days to hours of life. METHODS: Online cross-sectional questionnaire survey of UK professionals working in UK primary and secondary care settings. RESULTS: 1331 professionals returned completed questionnaires. Ninety-three per cent (1138/1228) of respondents used the Liverpool Care Pathway (LCP) or local variant. Eighty-eight (1089/1234) felt ICPs enabled professionals to provide better care for individuals and their families/carers. ICPs were viewed as promoting patient-centred holistic care, improving pain and symptom control, providing guidance and standards and improving communication with patients/families. Sixty-two per cent (770/1234) had no concerns regarding the use of ICPs. Areas of concern included incorrect use and implementation of the ICP, poor communication with families, junior level staff making decisions and insufficient education and support. CONCLUSIONS: There was strong support for using ICPs for caring for people in the last days to hours of life. ICPs were viewed as supporting high-quality patient-centred holistic care. Given the recommendations of the More Care Less Pathway report, those that develop the guidance and support that replace the LCP need to incorporate the aspects of this that have resulted in the benefits seen by professionals within this survey, but also learn from the instances where ICPs have failed to prevent poor care, or worse, have contributed to it.

Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations.

The increased or inappropriate expression of genes with oncogenic properties through specific chromosome translocations is an important event in the pathogenesis of B-cell lymphoproliferative diseases. Recent studies have found deletions or translocations of chromosome 7q to be the most common cytogenetic abnormality observed in SLVL, a leukemic variant of SMZL, with the q21-q22 region being most frequently affected. In three patients with translocations between chromosomes 2 and 7, the cloning of the breakpoints at 7q21 revealed that each was located within a small region of DNA 3.6 kb upstream of the transcription start site of cyclin dependent kinase 6 (CDK6). In each case the translocation event was consistent with aberrant VJ recombination between the immunoglobulin light chain region (Ig kappa) on chromosome 2p12 and DNA sequences at 7q21, resembling the heptamer recombination site. The t(7;21) breakpoint in an additional patient with splenic marginal zone lymphoma (SMZL), resided 66 kb telomeric to the t(2;7) breakpoints juxtaposing CDK6 to an uncharacterized transcript. In two of the SLVL patient samples, the CDK6 protein was found to be markedly over expressed. These results suggest that dysregulation of CDK6 gene expression contributes to the pathogenesis of SLVL and SMZL.

Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia.

Previous studies have indicated the presence of a putative tumor suppressor gene on chromosome 13q14, commonly deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). We have previously defined a minimally deleted region of 130 kb centromeric to the marker D13S272, and constructed a PAC and cosmid contig encompassing this area. In the present study we have made a detailed restriction and transcriptional map of the region of interest. Using these tools we have screened a panel of 206 primary CLL clones and three cell lines. In five CLL cases we found limited deletions defining the region of interest to an area of no more than 10 kb. Two adjacent genes, termed Leu1 and Leu2 (leukemia-associated gene 1 and 2), were mapped to the minimally deleted region, with several patients showing deletion borders within these genes. The Leu1 and Leu2 genes show little homology to previously published genes at the nucleotide and expected translated amino acid sequence level. Mutational analysis of the Leu1 and 2 genes in 170 CLL samples revealed no small intragenic mutations or point mutations. However, in all cases of 13q14 loss examined, the first exon of both genes, which are only 300 bp apart, were deleted. We conclude that the Leu1 and Leu2 genes are strong candidates as tumor suppressor gene(s) involved in B-CLL leukemogenesis.

PCR analysis of polymorphisms at the D13S25 locus.

Evidence that the D13S25 locus lies close to a potential tumour suppressor gene implicated in the pathogenesis of B-CLL has been based on detection of LOH and bi-allelic loss using the pH2-42 probe. The SspI polymorphism detected by this probe has been identified by sequencing adjacent clones and a polymorphic (TA)n repeat has been found. Amplification of the region encompassing both polymorphic markers by PCR increases the informativity to 80%.

P2X7 polymorphism and chronic lymphocytic leukaemia: lack of correlation with incidence, survival and abnormalities of chromosome 12.

The P2X7 receptor, a plasma membrane ATP-gated ion channel that plays a role in lymphocyte apoptosis, has been suggested as an important contributory factor to the pathogenesis of chronic lymphocytic leukaemia (CLL). The P2X7 gene resides on chromosome 12 and is polymorphic in the population at large (1513A/C) with the A and C alleles encoding fully active and nonfunctional proteins, respectively. We have evaluated the significance of this polymorphism by genotyping 144 patients with CLL and 348 healthy controls using a tetraprimer ARMS assay. We found no significant difference in allele frequency between patients and controls. Although patients with the C allele (A/C heterozygotes or C/C homozygotes) had a marginally shorter survival than those who were homozygous for the A allele, this difference was not significant for either the patient group considered as a whole or for IgVH-mutated/unmutated subsets. Finally, no association was found between trisomy 12 and P2X7 genotype. We conclude that the influence, if any, of P2X7 genotype on susceptibility to CLL or clinical outcome is small.

A cosmid and cDNA fine physical map of a human chromosome 13q14 region frequently lost in B-cell chronic lymphocytic leukemia and identification of a new putative tumor suppressor gene, Leu5.

B-cell chronic lymphocytic leukemia (B-CLL) is a human hematological neoplastic disease often associated with the loss of a chromosome 13 region between RB1 gene and locus D13S25. A new tumor suppressor gene (TSG) may be located in the region. A cosmid contig has been constructed between the loci D13S1168 (WI9598) and D13S25 (H2-42), which corresponds to the minimal region shared by B-CLL associated deletions. The contig includes more than 200 LANL and ICRF cosmid clones covering 620 kb. Three cDNAs likely corresponding to three different genes have been found in the minimally deleted region, sequenced and mapped against the contigged cosmids. cDNA clone 10k4 as well as a chimeric clone 13g3, codes for a zinc-finger domain of the RING type and shares homology to some known genes involved in tumorigenesis (RET finger protein, BRCA1) and embryogenesis (MID1). We have termed the gene corresponding to 10k4/13g3 clones LEU5. This is the first gene with homology to known TSGs which has been found in the region of B-CLL rearrangements.

Sequence divergence and copy number of the middle- and long-wave photopigment genes in Old World monkeys.

We have studied the sequence and organization of the genes for the middle-wave (MW) and long-wave (LW) cone photopigment genes in six species of Old World monkeys. Previous studies have shown that the MW and LW pigments of all six species exhibit peak sensitivities near 535 nm and 565 nm, respectively, and thus resemble the equivalent human pigments. In the case of man, the protein components of the MW and LW photopigments differ by 15 amino acids, although only seven of these differences involve non-homologous substitutions and are therefore candidates for a role in spectral tuning. Regions corresponding to exons 4 and 5 of these genes, and including five such candidate sites, were sequenced in the Old World monkeys. In contrast to the equivalent human genes, substitutions were found at two of these sites, position 233 and 309 of the MW gene in all six species. The role of amino acid substitutions in the spectral tuning of these photopigments is discussed. A comparison of the nucleotide sequences of the MW and LW genes provides evidence for sequence homogenization within species; the role of gene conversion in the evolution of these genes is discussed. The close juxtaposition and homology of the MW and LW genes on the X chromosome is thought to underlie the high frequency of colour vision defects in man and the presence in many individuals of extra copies of the MW gene. A study of a group of talapoin (Ceropithecus talapoin) monkeys has revealed a similar numerical polymorphism for this gene to that present in man. In contrast to the situation in man, where the MW and LW genes may contain a shortened first intron, restriction digests of genomic DNA showed that the size of this intron does not differ across the six species of Old World monkeys examined.

The influence of paraproteinaemia on the technicon automated platelet counter.

In five patients whose serum contained a paraprotein it has been shown that platelet counts obtained using the Technicon AutoCounter are much too high. In two patients with IgG gammopathy the error is caused by some factor in the red cells lysed by the diluent solution 2M urea. In three patients with IgM gammopathy spurious platelet counts were produced by platelet-poor plasma when diluted with 2M urea. It is recommended that at the present time no patient known to have a paraprotein should have platelet counts performed on the AutoCounter.

Evaluation of the Honeywell ACS 1000 leucocyte differential counter.

The Honeywell ACS 1000 is a relatively inexpensive differential white cell counter, which is only partially automated. This instrument has been evaluated in a routine haematology laboratory.

Congenital dyserythropoietic anaemia with unusual cytoplasmic inclusions.

A case of congenital dyserythropoietic anaemia is described which appears to be at variance with the accepted classification. The morphological findings are of normoblastic hyperplasia with marked cytoplasmic vacuolation. Electron microscopy shows these to be myelin figures in all stages of erythroid differentiation.

Hospital blood bank laboratory data processing system.

A data processing system designed to improve the management and usage of blood and blood products has been developed as a pilot for general application throughout the West Midlands Regional Health Authority. The package provides for the routine clerical, patient record, and stock management aspects of a hospital blood bank laboratory. It can be tailored to the individual requirements of different laboratories and may be implemented in a variety of ways on a family of computer systems of differing power and capacity, thus accommodating widely varying workloads and archiving requirements. Bar code readers are included in the system design, and may be used for data input where standard Codabar labels are affixed to blood products by blood transfusion centres. The system has been installed in one hospital laboratory and preliminary results indicate a high degree of acceptability at all levels. Further refinement of the software to meet minor deficiencies and the requirements of the recent DHSS Health Circular BLD/2/13 are currently being specified.

Failure of orally administered hydroxychloroquine sulphate to prevent venous thromboembolism following elective hip operations.

In a double-blind, randomized trial of orally administered hydroxychloroquine sulphate in the prevention of venous thromboembolism after elective surgery on the hip, the drug or a placebo was given to fifty consecutive patients. Therapy was commenced on the day before the operation and continued for fourteen days. The diagnosis of deep venous thrombosis was made by daily thermographic scanning of the legs and confirmed by phlebography. The diagnosis of pulmonary embolism was made by perfusion lung scanning. No significant difference in the incidence of thromboembolism was found between treated and control groups. The results provide evidence that substances which reduce the incidence of thromboembolism in general surgery may not be effective in operations on the hip.

Developing and testing methods for deriving preference-based measures of health from condition-specific measures (and other patient-based measures of outcome).

OBJECTIVES: Generic preference-based measures such as EQ-5D are widely used to estimate quality-adjusted life-years but may not be available or, more importantly, appropriate in some medical conditions. Condition-specific preference-based measures (CSPBMs) provide an alternative to generic measures that may be more relevant in some conditions. This project conducted five studies to examine issues in the development and use of CSPBMS: (1) literature review of measures; (2) deriving health states values for classifications with highly correlated dimensions; (3) impact of condition labelling; (4) impact of add-on dimensions; and (5) comparative performance of measures. DESIGN: (1) Systematic search and literature review; (2) and (5) psychometric analyses on existing data; (2), (3) and (4) valuation surveys and survey analyses. SETTING: Valuation surveys conducted using face-to-face interviews in the respondents' homes. PARTICIPANTS: Valuation surveys conducted using representative samples of the UK general population. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The project developed a CSPBM CORE-6D and analyses AQL-5D, CORE-6D, EORTC-8D, EQ-5D, OAB-5D and SF-6D data. RESULTS: (1) There was substantial variability in methods used to develop CSPBMs. (2) A new method for generating states using Rasch analysis was undertaken, which successfully dealt with the problem of highly correlated domains. (3) Condition labels affected utility values but this was dependent on the condition and severity of the health state. (4) Adding on an extra dimension affected health-state values and preference weights for other dimensions. (5) The performance of CSPBMs was comparable with that of their parent instrument and of generic preference-based measures with better performance for discrimination between severity groups. CONCLUSIONS: CSPBMs have an important role for economic evaluation, for which generic measures are inappropriate. However, their use in economic evaluation may be compromised by naming the condition; the exclusion of side effects and comorbidities; and focusing effects. Whether a reduction in comparability should be accepted depends on the extent of any gain in validity and responsiveness. This will depend on the condition and measure in question. Research agenda: (1) The appropriateness of generic preference-based measures should be examined in more conditions (and compared with CSPBMs). (2) Further quantitative and qualitative work is requested into the impact of, and reasons for labelling effects. (3) Use of add-ons for condition-specific measures (for side effects and comorbidities) and as a solution to the limitation of generic measures should be explored. FUNDING: The National Institute for Health Research Health Technology Assessment programme.