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1.  ROCView: prototype software for data collection in jackknife alternative free-response receiver operating characteristic analysis 
The British Journal of Radiology  2012;85(1017):1320-1326.
ROCView has been developed as an image display and response capture (IDRC) solution to image display and consistent recording of reader responses in relation to the free-response receiver operating characteristic paradigm. A web-based solution to IDRC for observer response studies allows observations to be completed from any location, assuming that display performance and viewing conditions are consistent with the study being completed. The simplistic functionality of the software allows observations to be completed without supervision. ROCView can display images from multiple modalities, in a randomised order if required. Following registration, observers are prompted to begin their image evaluation. All data are recorded via mouse clicks, one to localise (mark) and one to score confidence (rate) using either an ordinal or continuous rating scale. Up to nine “mark-rating” pairs can be made per image. Unmarked images are given a default score of zero. Upon completion of the study, both true-positive and false-positive reports can be downloaded and adapted for analysis. ROCView has the potential to be a useful tool in the assessment of modality performance difference for a range of imaging methods.
PMCID: PMC3487065  PMID: 22573294
2.  Risk Factors for Group B Streptococcal Colonization: Potential for Different Transmission Systems by Capsular Type 
Annals of epidemiology  2007;17(11):854-862.
Group B Streptococcus (GBS) is a common inhabitant of the bowel and vaginal flora, with known transmission routes including sexual contact and vertical transmission from mother to infant. Foodborne transmission is also possible, as GBS is a known fish and bovine pathogen. We conducted a prospective cohort study in order to identify risk factors for acquisition.
We identified risk factors for GBS acquisition among college women (n=129) and men (n=128) followed at 3-week intervals for 3 months.
A doubling in sex acts significantly increased incidence of capsular type V by 80% (95% CI: 1.19, 2.58), and other non-Ia or Ib types combined by 40% (95% CI: 1.00, 2.06; incidence of capsular type Ia (OR=1.2; 95% CI: 0.71, 1.88 p=0.57) and Ib (OR=1.5, 95% CI: 0.75, 2.86, p=0.27) were elevated although not significantly. After adjustment for sexual activity and sexual history, gender, and eating venue, fish consumption increased risk of acquiring capsular types Ia and Ib combined 7.3 fold (95% CI: 2.34, 19.50), but not other capsular types. Beef and milk were not associated with GBS incidence.
Different GBS capsular types may have different transmission routes.
PMCID: PMC2099698  PMID: 17689259
Group B Streptococcus; Fish; Sexual Behavior; Epidemiology; Capsular Type; Transmission
4.  Social deprivation and admission for neonatal care 
Objective: To determine whether social deprivation is associated with neonatal unit admission.
Setting: English district general hospital.
Method: Retrospective review of neonatal unit admission records between 1990 and 2002.
Results: There was a linear increase in admission rates with increasing deprivation. The admission rate was 6.1% of live births for infants in the most affluent quartile compared with 11.1% for those in the most deprived quartile. Admission rates for all indications except jaundice and feeding problems increased with increasing deprivation.
Conclusion: Social deprivation correlates strongly with neonatal morbidity and the need for neonatal unit admission. This finding has implications for professionals in public health and primary and secondary care.
PMCID: PMC1721911  PMID: 16036892
6.  Social trends in singleton births and birth weight in Wirral residents, 1990–2001 
Objective: To examine social trends in the number of singleton births and birth weight in an English health district between 1990 and 2001, using an area based deprivation index.
Design: Analysis of routinely collected hospital data.
Setting: Wirral Health District in north west England.
Participants: All 48 452 live births to Wirral residents from 1990 to 2001.
Main outcome measures: Birth numbers, birth weight, and standard deviation score for birth weights for singleton births. Townsend material deprivation scores derived from postcodes.
Results: The number of singleton births fell by 28% over the 12 years. The fall in the least deprived Townsend quartile (45%) was more than triple that in the most deprived quartile (γ = 0.045; 95% confidence interval (CI) = 0.036 to 0.054; p < 0.001). Over the study period, the mean birth weight in the least deprived Townsend quartile was 141 g higher than in the most deprived quartile. There was a highly significant association between the standard deviation score for birth weight and Townsend quartile (τ-b = -0.062; 95% CI = -0.068 to -0.055; p < 0.001). Numbers of low birth weight babies in the least deprived quartile fell disproportionately compared with those from the most deprived quartile (γ = 0.17; 95% CI = 0.09 to 0.25; p < 0.001).
Conclusion: The reduction in birth rate in the Wirral was significantly less in the most deprived districts. This was accompanied by related differences in mean birth weight and the number of low birth weight babies, indicating increasing social inequality in birth trends. Previously described social inequity in birth weight and the number of low birth weight babies continues in the north west of England.
PMCID: PMC1721626  PMID: 12937049
7.  Sudden infant death syndrome: bed sharing with mothers who smoke 
Archives of Disease in Childhood  2003;88(2):112-113.
Aim: To examine the sleeping arrangements of sudden infant death syndrome (SIDS) cases on the Wirral. In particular to determine the prevalence of bed sharing with mothers who smoke, a known risk factor for SIDS.
Methods: Retrospective study of postmortem determined cases of SIDS from 1995 to 2000 on the Wirral peninsula (population 350 000, 3500 annual births). Ambulance crew reports, case notes, health visitor reports, postmortem reports, and case discussion records were studied for each case.
Results: There were 25 cases of SIDS in the postneonatal age group over the six year period. In nine cases the baby was bed sharing with the mother, of whom seven were smokers. Five of these mothers reported using alcohol or illicit drugs on the night of their infant's death. In two further cases the baby slept on a sofa with a parent.
Conclusions: Bed sharing and smoking remain important risk factors for SIDS. Mothers should be advised ante- and postnatally of this combination of risk factors. Such advice should also include a recommendation not to sleep with their baby if under the influence of alcohol or illicit drugs, and never to sleep on a sofa with their baby. All "Child Health Record" books given to parents on the Wirral now include this advice. "Reduce the Risk" advice leaflets given to parents pre- and postnatally also now carry the recommendation, and health visitors and midwives have been educated with respect to these additions.
PMCID: PMC1719436  PMID: 12538308
8.  Snapshots of five clinical ethics committees in the UK 
Journal of Medical Ethics  2001;27(Suppl 1):i9-i17.
Each of the following papers gives an account of a different UK clinical ethics committee. The committees vary in the length of time they have been established, and also in the main focus of their work. The accounts discuss the development of the committees and some of the ethical problems that have been brought to them. The issues raised will be relevant for other National Health Service (NHS) trusts in the UK that wish to set up such a committee.
Key Words: Ethics • committee • clinical • policy • ethicist
PMCID: PMC1765533  PMID: 11314616
9.  Presumed consent in emergency neonatal research 
Journal of Medical Ethics  2000;26(4):249-253.
Current methods of obtaining consent for emergency neonatal research are flawed. They risk aggravating the distress of parents of preterm and other sick neonates. This distress, and the inevitable time constraints, compromise understanding and voluntariness, essential components of adequately informed consent. Current practice may be unjust in over-representing babies of more vulnerable and deprived parents. The research findings may thus not be generalisable. Informing parents antenatally about the possible need for emergency neonatal research, with presumed consent and scope for opting out, would address these problems. It would spare parents of sick neonates, already terrified by their baby's illness, further distress. Experience with opting out suggests that recruitment might increase, thus generating earlier results, without compromising parental understanding of the nature and purpose of the research.
Key Words: consent • neonate • emergency research
PMCID: PMC1733262  PMID: 10951919
10.  Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome 
AIM—To compare patient triggered, with conventional fast rate, ventilation in a randomised controlled trial using the incidence of chronic lung disease as the primary outcome measure.
METHODS—Three hundred and eighty six preterm infants with birthweights from 1000 to 2000 g, and requiring ventilation for respiratory distress syndrome within 24 hours of birth, were randomised to receive either conventional or trigger ventilation with the SLE 2000ventilator.
RESULTS—There were no significant differences in the incidence of chronic lung disease (28 day and 36 week definitions), death, pneumothorax, intraventricular haemorrhage, number of ventilator days, or length of oxygen dependency between groups.
CONCLUSIONS—Patient triggered ventilation in preterm infants with respiratory distress syndrome is feasible. No significant differences, when compared with conventional fast rate ventilation in important medium and longer term outcome measures, were evident.

PMCID: PMC1721039  PMID: 10634835
11.  γδ T-Cell Function in Pathogenesis of Cerebral Malaria in Mice Infected with Plasmodium berghei ANKA 
Infection and Immunity  1999;67(1):446-448.
Mice depleted of γδ T cells by monoclonal antibody treatment and infected with Plasmodium berghei ANKA did not develop cerebral malaria (CM). In striking contrast, δ0/0 mice infected with P. berghei developed CM despite their γδ T-cell deficiency. γδ T cells appear to be essential for the pathogenesis of CM in mice having experienced normal ontogeny but not in mice genetically deprived of γδ T cells from the beginning of life.
PMCID: PMC96335  PMID: 9864254
12.  Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy. 
British Journal of Cancer  1998;77(10):1653-1656.
Northern hybridization analyses of the oestrogen-inducible mRNAs pLIV1 and pS2 were compared with oestrogen receptor (ER) immunocytochemistry assessments in 40 untreated primary or early recurrent breast tumours. Significant associations were observed between pLIV1/ER (P < 0.03), pS2/ER (P < 0.001) and pLIV1/pS2 (P < 0.04) status. After disease recurrence, patients were treated with assessable courses of endocrine therapies. Positive pLIV1, pS2 and ER statuses in primary disease were consequently found to be predictive of endocrine responsiveness in the secondary lesions (P < 0.03, P < 0.02, P < 0.005 respectively). However, despite these associations, a number of pLIV1- and/or pS2-positive tumours failed to respond to therapy.
PMCID: PMC2150074  PMID: 9635843
13.  Making the new deal for junior doctors happen. 
BMJ : British Medical Journal  1994;308(6943):1553-1555.
How can the new deal for juniors be implemented in today's overstretched health service? How do you get clinicians and management to work together? On the Wirral falling house officer morale and recruitment stimulated a new approach, action learning, which proved to be highly successful. Action learning is not a new approach in management terms, but it is rarely used in the health service. Guided by an experienced facilitator, a group of people learn management skills by exploring and resolving practical problems relevant to them. A group of general practitioners and consultants used action learning to teach themselves more about management and at the same time to make changes which addressed many of the junior doctors' difficulties and solved the hospital recruiting problem.
PMCID: PMC2540511  PMID: 8019316
14.  Expression of the major outer membrane protein of Chlamydia trachomatis in Escherichia coli. 
Infection and Immunity  1993;61(10):4093-4098.
The major outer membrane protein (MOMP) of Chlamydia trachomatis was expressed in Escherichia coli. To assess whether it assembled into a conformationally correct structure at the cell surface, we characterized the recombinant MOMP (rMOMP) by Western immunoblot analysis, indirect immunofluorescence, and immunoprecipitation with monoclonal antibodies (MAbs) that recognize contiguous and conformational MOMP epitopes. Western blot analysis showed that most of the rMOMP comigrated with authentic monomer MOMP, indicating that its signal peptide was recognized and cleaved by E. coli. The rMOMP could not be detected on the cell surface of viable or formalin-killed E. coli organisms by indirect immunofluorescence staining with a MAb specific for a MOMP contiguous epitope. In contrast, the same MAb readily stained rMOMP-expressing E. coli cells that had been permeabilized by methanol fixation. A MAb that recognizes a conformational MOMP epitope and reacted strongly with formalin- or methanol-fixed elementary bodies failed to stain formalin- or methanol-fixed E. coli expressing rMOMP. Moreover, this MAb did not immunoprecipitate rMOMP from expressing E. coli cells even though it precipitated the authentic protein from lysates of C. trachomatis elementary bodies. Therefore we concluded that rMOMP was not localized to the E. coli cell surface and was not recognizable by a conformation-dependent antibody. These results indicate that rMOMP expressed by E. coli is unlikely to serve as an accurate model of MOMP structure and function. They also question the utility of rMOMP as a source of immunogen for eliciting neutralizing antibodies against conformational antigenic sites of the protein.
PMCID: PMC281129  PMID: 8406797
15.  A poliovirus hybrid expressing a neutralization epitope from the major outer membrane protein of Chlamydia trachomatis is highly immunogenic. 
Infection and Immunity  1993;61(10):4406-4414.
Trachoma and sexually transmitted diseases caused by Chlamydia trachomatis are major health problems worldwide. Epitopes on the major outer membrane protein (MOMP) of C. trachomatis have been identified as important targets for the development of vaccines. In order to examine the immunogenicity of a recombinant vector expressing a chlamydial epitope, a poliovirus hybrid was constructed in which part of neutralization antigenic site I of poliovirus type 1 Mahoney (PV1-M) was replaced by a sequence from variable domain I of the MOMP of C. trachomatis serovar A. The chlamydial sequence included the neutralization epitope VAGLEK. This hybrid was viable, grew very well compared with PV1-M, and expressed both poliovirus and chlamydial antigenic determinants. When inoculated into rabbits, this hybrid was highly immunogenic, inducing a strong response against both PV1-M and C. trachomatis serovar A. Antichlamydia titers were 10- to 100-fold higher than the titers induced by equimolar amounts of either purified MOMP or a synthetic peptide expressing the VAGLEK epitope. Furthermore, rabbit antisera raised against this hybrid neutralized chlamydial infectivity both in vitro, for hamster kidney cells, and passively in vivo, for conjunctival epithelia of cynomolgus monkeys. Because poliovirus infection induces a strong mucosal immune response in primates and humans, these results indicate that poliovirus-chlamydia hybrids could become powerful tools for the study of mucosal immunity to chlamydial infection and for the development of recombinant chlamydial vaccines.
PMCID: PMC281173  PMID: 7691749
17.  Subcellular distribution of the alpha subunit(s) of Gi: visualization by immunofluorescent and immunogold labeling. 
Cell Regulation  1991;2(12):1097-1113.
The subcellular distribution of the alpha subunit(s) of Gi has an obvious bearing on the ability of this protein to interact with receptors and targets and on its potential to serve in still unexplored capacities. In this study, we have examined the distribution of Gi alpha by means of light and electron microscopy. The cells employed were mouse 3T3 fibroblasts, normal rat kidney fibroblasts, rat C6 glioma cells, human umbilical vein endothelial cells, and human 293 kidney fibroblasts. By indirect immunofluorescence, two patterns of Gi alpha were evident. The more prominent was that associated with phase-dense, cytoplasmic structures exhibiting a tubule-like morphology. A similar distribution was noted for mitochondria, indicating attachment to a subset of microtubules. The second pattern appeared as a diffuse, particulate fluorescence associated with the plasma membrane. By immunogold labeling and electron microscopy, two populations of Gi alpha were again evident. In this instance, labeling of the plasma membrane was the more prominent. Gold particles were most often evenly distributed along the plasma membrane and were concentrated along microspikes. The second, less abundant population of Gi alpha represented the subunit (or fragments) within lysosomes. Specificity in immunolabeling was confirmed in all instances by immunotransfer blotting, the use of antibodies differing in specificities for epitopes within Gi alpha, the absence of labeling with preimmune sera, and the decrease in labeling after preincubation of antisera with appropriate peptides. These results support the proposal that several populations of Gi alpha exist: those evident within the cytoplasm by immunofluorescence, those present at the plasma membrane, and those evident within lysosomes by immunogold labeling.
PMCID: PMC361908  PMID: 1801926
18.  Haem arginate in acute hereditary coproporphyria. 
Archives of Disease in Childhood  1991;66(6):730-731.
An 11 year old boy presented with severe acute hereditary coproporphyria. Despite supportive measures his condition deteriorated after admission. Haem arginate, started two days after presentation, produced appreciable inhibition of porphyrin precursor overproduction and clinical improvement.
PMCID: PMC1793153  PMID: 2053800
19.  Reproductive failure in mink and ferrets after intravenous or oral inoculation of Campylobacter jejuni. 
Four pregnant mink and seven pregnant ferrets, including five with previous exposure and specific antibody, were injected intravenously with 10(8)-10(10) colony-forming units of Campylobacter jejuni. All 11 pregnancies failed 1-16 days after infection, with results ranging from fetal resorption to expulsion of dead or premature living kits. In every case, uterine contents (placenta, uterine fluid and/or kits) were culture-positive for C. jejuni. Three pregnant mink and nine pregnant ferrets, including four with previous exposure and antibody, were fed 10(9)-10(11) C. jejuni. Two of the mink aborted; kits of all three were culture-positive, but those of one female survived. Seven of the nine ferrets aborted, with two having culture-positive uterine contents. None of 28 uninfected ferret control pregnancies ended in abortion. The most prominent histological feature observed was severe placentitis, which appears to be a more likely cause of Campylobacter-induced abortion than direct pathogenic effects on infected kits. These results suggest that infection of mink or ferrets with C. jejuni during pregnancy poses a serious risk of reproductive failure, even for previously exposed females.
PMCID: PMC1255689  PMID: 2249178
20.  Slip-shod or safely shod: the bighorn sheep as a natural model for research. 
Over a million injuries caused by slipping of footwear are believed to require treatment by doctors every year in the United Kingdom and many domestic animals are injured by slipping. Recent research has revealed that surface roughness of solings and floors is an important determinant of grip on lubricated surfaces and it is also known that soling friction is affected by hardness. The bighorn sheep (Ovis canadensis) an animal species which has adapted to a slippery environment, was studied to elucidate optimum roughness and hardness and other features which influence grip. Four adult ewes were examined in the London Zoo. The cloven hooves of this species are very mobile and the cranial tips of the hooves are the first parts to make contact with the ground. A very small contact area ensures penetration of a film of water. Mean roughness of the contact area was found to be 53 microns Rtm and the mean hardness 63 Shore A. These characteristics appear to facilitate an excellent grip on wet slippery rock but not on smooth ice. Further studies of the feet of wild species could contribute to an understanding of the factors which determine the safety of solings and floors.
PMCID: PMC1292912  PMID: 2250262
21.  Multiple tandem promoters of the major outer membrane protein gene (omp1) of Chlamydia psittaci. 
Infection and Immunity  1990;58(9):2850-2855.
The transcription of omp1, the gene encoding the major outer membrane protein, was studied for two strains of Chlamydia psittaci, guinea pig inclusion conjunctivitis (GPIC) and mouse pneumonitis (Mn). The transcriptional initiation sites for the omp1 of each strain were mapped by S1 nuclease and primer extension analyses. Three different sizes of omp1 transcripts were observed for GPIC and four were observed for Mn. The production of these transcripts appeared to be the consequence of multiple tandem promoters. The order in which the omp1 RNA transcripts appeared during the growth cycle of the C. psittaci strains was found to differ from that of C. trachomatis.
PMCID: PMC313577  PMID: 2387624
22.  A domestic ferret model of immunity to Campylobacter jejuni-induced enteric disease. 
Infection and Immunity  1990;58(6):1848-1852.
Oral or intravenous inoculation of previously unexposed juvenile and adult ferrets with Campylobacter jejuni uniformly resulted in intestinal colonization lasting 2 to 12 days. Disease varied from mild to moderate diarrhea, which resolved in 2 to 3 days. Orally infected animals developed agglutinin titers of 8 to 256 within 3 weeks, while those infected intravenously developed titers of 256 to 2,048. Ferrets which had recovered from campylobacteriosis all developed high titers of agglutinating and bacterial antibodies but were readily colonized by subsequent oral inoculation with the same strain of C. jejuni. Orally infected ferret kits 3 to 6 weeks of age exhibited the same general pattern of infection and disease as adults, but diarrhea was somewhat more severe. Kits resolved their diarrhea in 1 to 6 days and developed agglutinin titers in serum of 16 to 32 within 3 weeks. A series of five oral or rectal inoculations of kits during the 5- to 9-week age interval resulted in progressively shorter clearance times and eventual strain-specific resistance against infection, as well as disease. Gnotobiotic adults showed the same pattern of strain-specific accelerated clearance and resistance to disease. Kits born to immune dams with high levels of whey antibodies had passively acquired serum agglutinin titers of 256 to 2,048. These kits showed no resistance to colonization with the homologous strain of C. jejuni but were completely refractory to diarrhea. These observations suggest that (i) some form(s) of specific immunity, rather than factors relating solely to age or normal flora, is responsible for resistance to C. jejuni colonization and disease production and (ii) humoral immunity at a level that does not prevent colonization can protect against enteric disease caused by this organism.
PMCID: PMC258734  PMID: 2341180
25.  Non-convulsive status epilepticus. 
Status epilepticus can complicate any type of seizure activity. A group of 13 children with non-convulsive status has been studied. Five presented with chronic fluctuating neurological features, while eight had intermittent episodes of their atypical status, although each of these lasted for several days. The clinical features, treatment, and outcome for these groups of children are described. Most of the children in both groups are mentally retarded after regressing at the time of their status epilepticus. The recognition and aggressive treatment of atypical status is important in reducing the risk of subsequent mental handicap.
PMCID: PMC1778178  PMID: 3813634

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