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Objectives The optimal triage of screen-positive women is one of the most important considerations in the HPV cervical screening. Performing liquid based cytology (LBC) on HPV-positive (HPV+) women and/or limited genotyping has been recommended as a triage strategy. Additionally p16/ki-67 dual-stained cytology is a credible triage approach. We previously reported an evaluation of triage strategies in a cross sectional study. The aim of this study was to evaluate the cumulative incidence rate (CIR) of CIN2+ within 5 years of primary triage strategies of HPV+ women. Methods The study population comprised of 385 HPV+ women, who all had HPV 16/18 typing, LBC and p16/ki-67 dual-stained cytology at the first screening round. We used two rounds screening results to describe cumulative incidence rate (CIR) of CIN2+ within 5 years of primary HPV+ testing stratified by the various triage strategies with proportions reflected within 95% confidence intervals. Results The length of follow-up was up to 5.5 years. The HPV+ women with an LBC negative triage had 5-year CIR of CIN2+of 9.4%(6.5–13.3%) compared with 7.2% (4.6–11.1%) in women who were p16/ki-67 dual-stained cytology negative and 10.6% (7.5–15%) in women who were HVP 16/18 negative. Regarding combination approaches, HPV 16/18 negative/LBC negative women had 5-year CIR of CIN2+of 3.9% (2.0–7.6%). Women who were ‘‘‘‘‘triple’’’’’ triage negative had the lowest CIR of CIN2+ of 2.4% (0.9–6.0%). Conclusions Full analysis will be presented however; our initial data indicate that multistep triage options may offer the greatest longitudinal protection for concurrent and subsequent disease compare to individual approaches.

The management of cervical disease is changing worldwide as a result of HPV vaccination and the increasing use of HPV testing for cervical screening. However, the impact of vaccination on the performance of HPV based screening strategies is unknown. The SHEVa (Scottish HPV Prevalence in Vaccinated women) projects are designed to gain insight into the impact of vaccination on the performance of clinically validated HPV assays. Samples collated from women attending for first cervical smear who had been vaccinated as part of a national "catch-up" programme were tested with three clinically validated HPV assays (2 DNA and 1 RNA). Overall HR-HPV and type specific positivity was assessed in total population and according to underlying cytology and compared to a demographically equivalent group of unvaccinated women. HPV prevalence was significantly lower in vaccinated women and was influenced by assay-type, reducing by 23-25% for the DNA based assays and 32% for the RNA assay (p = 0.0008). All assays showed over 75% reduction of HPV16 and/or 18 (p < 0.0001) whereas the prevalence of non 16/18 HR-HPV was not significantly different in vaccinated vs unvaccinated women. In women with low grade abnormalities, the proportion associated with non 16/18 HR-HPV was significantly higher in vaccinated women (p < 0.0001). Clinically validated HPV assays are affected differentially when applied to vaccinated women, dependent on assay chemistry. The increased proportion of non HPV16/18 infections may have implications for clinical performance, consequently, longitudinal studies linking HPV status to disease outcomes in vaccinated women are warranted.

Background: To measure the uptake of first invitation to cervical screening by vaccine status in a population-based cohort offered HPV immunisation in a national catch-up campaign. Methods: A retrospective observational study of routinely collected data from the Scottish Cervical Screening Programme. Data were extracted and linked from the Scottish Cervical Call Recall System, the Scottish Population Register and the Scottish Index of Multiple Deprivation. Records from 201 023 women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. Attendance for screening was within 12 months of the first invitation at age 20 years. Results: There was a significant decline in overall attendance from the 1988 cohort to the 1993 cohort with the adjusted attendance ratio of the 1988 cohort being 1.49 times (95% CI 1.46–1.52) that of the 1993 cohort. Immunisation compensated for this decrease in uptake with unvaccinated individuals having a reduced ratio of attendance compared with those fully vaccinated (RR=0.65, 95% CI 0.64–0.65). Not taking up the opportunity for HPV immunisation was associated with an attendance for screening below the trend line for all women before the availability of HPV immunisation. Conclusions: HPV immunisation is not associated with the reduced attendance for screening that had been feared. Immunised women in the catch-up cohorts appear to be more motivated to attend than unimmunised women, but this may be a result of a greater awareness of health issues. These results, while reassuring, may not be reproduced in routinely immunised women. Continued monitoring of attendance for the first smear and subsequent routine smears is needed.

Objectives:This study aimed to investigate the prevalence and clinical significance of solitary thyroid nodules in patients who underwent thyroid surgery.Methods:A retrospective review was performed of the case notes of all adult patients who underwent thyroid surgery from January 2003 to December 2009. All patients with solitary thyroid nodules identified by ultrasonography were included.Results:In total, 225 patients underwent thyroid surgery. The prevalence of solitary thyroid nodules was 27.1 per cent (61 out of 225 patients). Seventy-two per cent of patients were women and the mean age at presentation was 52 ± 16 years. In all, 75.4 per cent of solitary nodules had neoplastic pathology and the malignancy rate was 34.4 per cent. The sensitivity and specificity of fine needle aspiration cytology for neoplasm detection were 73.9 per cent and 80.0 per cent, respectively. There was no association between the various ultrasonography parameters and malignancy risk (p > 0.05).Conclusion:Solitary thyroid nodules should be investigated thoroughly with a high index of suspicion because there is a high probability (34.0 per cent) of malignancy.

Background: In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established. Methods: We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20–21 in 2008–2012. Results: By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P

The Coinstone is a well known hiatus-concretion level in the Lower Lias (Lower Jurassic, Upper Sinemurian) of Dorset, southern England. It has long been recognized as a layer of bored and encrusted, early diagenetic, clay-hosted septarian concretions coincident with a biostratigraphic gap of three ammonite subzones. Several different types of concretion of variable complexity can be distinguished, of which two, probably derived from slightly different stratigraphic levels, have been juxtaposed by condensation at the erosion surface. Diagenetic and biological processes occurring before, during and after exhumation on the Jurassic sea-floor can be recognized. The relative timing of these events can be distinguished, suggesting that initial concretion consolidation, the first generation of septarian cracking, and the precipitation of the first generation of crack-lining calcite preceded exhumation. These, therefore, probably took place at an early stage, at shallow burial depths within the accumulating sediment pile. The early calcite is brown, UV-fluorescent and inclusion-rich, and is similar to the first calcite generations seen in many other clay-hosted septarian concretions. A generally early diagnetic origin of this material is thus inferred. Observations on crack textures and geometries and the interactions of the post-exhumation fauna of encrusters, borers and burrowers lend support to previous suggestions that initial cracking in some septarian concretions took place in a stiff rather than a fully rigid concretion body, possibly given coherence by initial growth of some organic substance that was only later replaced by the calcite cements seen in most such concretions today. The burrowing activities of a benthic fauna in muds cause resuspension of sediment and facilitate erosion, even in the absence of high energy physical processes. Regional stratigraphic gaps may be formed as a consequence of sea level rises or falls, or as a response to sediment supply reduction independent of sea level change. Such major episodes of biologically mediated erosion in mudstone sequences may be of more general importance than has hitherto been recognized.

T.J. Palmer, S.M. Nicoll, M.E. McKean, A.J. Park, D. Bishop, L. Baker and J.E.A. Imrie Prospective parallel randomized trial of the MultiCyte™ ThinPrep® imaging system: the Scottish experience Background: Computer-assisted screening of cervical liquid-based cytology (LBC) preparations using the ThinPrep® Imaging System (TIS) has shown improved qualitative and quantitative gains. The use of Multicyte™ has not been described in a well-established national screening programme with a low incidence of high-grade dyskaryosis. Objectives: To assess the impact of computer-assisted screening within the Scottish Cervical Screening Programme (SCSP). Methods: Two groups of three laboratories, each sharing a ThinPrep® Imager, screened 79 366 slides randomized to test and 90 551 to control arms by laboratory accession. Screeners were not blinded. Standard laboratory reporting profiles of the SCSP, sensitivity, specificity and false-negative rates of all grades of LBC abnormalities with respect to final cytology reports, predictive value for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on histology; and screening rates were compared for both arms. Results: Inadequate and negative reporting rates were significantly lower and low-grade reporting rates significantly higher in the imager arm. Imager-assisted screening showed significantly better specificity than manual screening with respect to the final cytology result. There was no evidence of a significant difference in the detection of CIN2 + or CIN3 + . Positive, abnormal and total predictive values (high-grade, low-grade and all abnormal cytology found to be CIN2 + , respectively) were similar in both arms. Productivity was significantly higher in the imager arm. Conclusion: Computer-assisted screening in a well established screening programme showed significantly improved productivity without loss of quality. These findings should inform future policy for cervical screening programmes.

The objective of this study is to identify a management or follow-up strategy for patients with laryngeal and oral dysplasia. A chart review of all patients with laryngeal and oral dysplasia over a 15-year period was performed. All patients were followed for a minimum period of 5 years from initial diagnosis of oropharyngeal or laryngeal dysplasia. If invasive carcinoma was demonstrated on subsequent biopsies, the exact time of this was recorded and Kaplan-Meier survival curves were plotted. In the laryngeal cohort, 45 patients were identified, 15 (33%) developed carcinoma, 7 of 30 patients (23%) with mild or moderate dysplasia, compared with 8 of 15 (53%) with severe dysplasia or CIS (P = 0.01). Thirteen of the carcinomas (87%) developed within 36 months of original biopsy. In the oral cohort, 32 patients were identified, 17 (53%) developed carcinoma, 1 of 9 patients (11%) with mild dysplasia, compared with 8 of 12 (67%) with severe dysplasia and 8 of 10 (80%) with CIS (P < 0.001). Fifteen of the 17 patients (88%) developed carcinoma within 36 months of original biopsy. In conclusion, although numbers are small, our results show that mild and moderate laryngeal dysplasia behaves differently to severe dysplasia and CIS. Mild oral dysplasia also behaves differently to severe dysplasia or CIS. In general, progress to malignancy happens within a 3-year period. Severe dysplasia or CIS should be managed aggressively.

Twenty-six benign oncocytic lesions of the salivary glands, excluding Warthin's tumours, have been reviewed and criteria for their classification as oncocy-toma, multifocal nodular oncocytic hyperplasia, diffuse oncocytosis, pleomorphic adenoma with oncocytic change or oncocytic monomorphic adenoma have been proposed. The histological and clinical features of this heterogeneous group of lesions are discussed. This analysis suggests that the majority of lesions initially categorized as oncocytomas were, in fact, either non-neoplastic or, alternatively, oncocytic change in other types of adenoma.

Background: To document the effect of bivalent HPV immunisation on cervical cytology as a screening test and assess the implications of any change, using a retrospective analysis of routinely collected data from the Scottish Cervical Screening Programme (SCSP). Methods: Data were extracted from the Scottish Cervical Call Recall System (SCCRS), the Scottish Population Register and the Scottish Index of Multiple Deprivation. A total of 95 876 cytology records with 2226 linked histology records from women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. The performance of cervical cytology as a screening test was evaluated using the key performance indicators used routinely in the English and Scottish Cervical Screening Programmes (NHSCSP and SCSP), and related to vaccination status. Results: Significant reductions in positive predictive value (16%) and abnormal predictive value (63%) for CIN2+ and the mean colposcopy score (18%) were observed. A significant increase (38%) in the number of women who had to be referred to colposcopy to detect one case of CIN2+ was shown. The negative predictive value of negative- or low-grade cytology for CIN2+ increased significantly (12%). Sensitivity and specificity, as used by the UK cervical screening programmes, were maintained. Conclusions: The lower incidence of disease in vaccinated women alters the key performance indicators of cervical cytology used to monitor the quality of the screening programme. These findings have implications for screening, colposcopy referral criteria, colposcopy practice and histology reporting.

Fine needle aspiration cytology (FNAC) is generally considered a safe, sensitive, and specific diagnostic tool and is widely used for various clinical indications. However, some authors have raised concerns regarding the possibility of tumor cell seeding along the needle track. We present to our knowledge the first case of tumor seeding after FNAC of a benign parotid tumor. This is followed by a review of the literature on tumor seeding after aspiration with fine needles of 20 gauge and smaller and the implications for clinical practice.

Sedimentological evidence suggests that sea-water chemistry has oscillated between ‘Aragonite’ and ‘Calcite’ seas during the course of Phanerozoic time. During ‘Calcite’ sea periods aragonite was soluble and dissolved on the sea-floor. Here we propose, using a survey of familial diversity, that during times of such corrosive seas bivalved molluscs which secreted their shells entirely of aragonite were at a selective disadvantage compared to those with calcitic outer shell layers. This is the first case in which it has been suggested that there was a dynamic link between sea-water chemistry and the evolution of a particular taxon throughout Phanerozoic time.

Computer-assisted screening of cervical liquid-based cytology (LBC) preparations using the ThinPrep® Imaging System (TIS) has shown improved qualitative and quantitative gains. The use of Multicyte™ has not been described in a well-established national screening programme with a low incidence of high-grade dyskaryosis.To assess the impact of computer-assisted screening within the Scottish Cervical Screening Programme (SCSP).Two groups of three laboratories, each sharing a ThinPrep® Imager, screened 79 366 slides randomized to test and 90 551 to control arms by laboratory accession. Screeners were not blinded. Standard laboratory reporting profiles of the SCSP, sensitivity, specificity and false-negative rates of all grades of LBC abnormalities with respect to final cytology reports, predictive value for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on histology; and screening rates were compared for both arms.Inadequate and negative reporting rates were significantly lower and low-grade reporting rates significantly higher in the imager arm. Imager-assisted screening showed significantly better specificity than manual screening with respect to the final cytology result. There was no evidence of a significant difference in the detection of CIN2+ or CIN3 +. Positive, abnormal and total predictive values (high-grade, low-grade and all abnormal cytology found to be CIN2+, respectively) were similar in both arms. Productivity was significantly higher in the imager arm. Computer-assisted screening in a well established screening programme showed significantly improved productivity without loss of quality. These findings should inform future policy for cervical screening programmes.

Small rosette borings, consisting of an excavated pit from which is subtended a system of branching galleries, are common in carbonate skeletal substrates in the Upper Jurassic Oxford Clay (Callovian-Oxfordian) and Kimmeridge Clay (Kimmeridgian) of southern England and northern France. The opening of the pit onto the substrate surface is surrounded by an agglutinated collar, which suggests that they may be the work of Foraminifera. The new genus and species, Globodendrina monile, are erected to accommodate them. Other examples of boring in the Foraminiferida are reviewed. It is proposed that other similar rosette boring ichnogenera may also be the work of foraminiferans.

Reef-forming lithistid sponges in the Middle Jurassic (Bathonian) of Normandy, France, were lithified on the sea floor by a peloidal cement, probably of an original low-Mg calcite composition precipitated under bacterial influence. This early lithification permitted early dissolution of the siliceous skeleton without the collapse or distortion of the resulting moulds. These moulds were encrusted and bored. This pathway for the fossilization of sponges is shown by other examples of Jurassic lithistids and is likely to be widely applicable throughout the fossil record, particularly at times during which calcite was the primary marine precipitate.

Negative pressure pulmonary edema (NPPE) continues to be reported as a complication of upper airway obstructions seen by anesthesia providers during induction or emergence. The majority of patients reported to have experienced NPPE have been healthy, without underlying pulmonary or cardiac disease. Factors associated with the formation of NPPE include young male patients and patients with long periods of airway obstruction. Overzealous intraoperative fluid administration and preexisting heart and lung disease also have been implicated as predisposing factors. Negative pressure pulmonary edema is the result of a marked decrease in intrathoracic pressure caused by ventilatory efforts against a closed glottis resulting in a disruption of the normal intravascular Starling mechanism, ultimately leading to the transudation of intravascular proteins and fluid into the pulmonary interstitium. The onset of NPPE is usually rapid, and without prompt recognition and intervention, the outcome can be fatal. A case of NPPE in a pediatric patient after an otherwise uncomplicated surgical procedure was observed in our institution and is described in this report.

Haemosuccus pancreaticus is a rare cause of gastrointestinal haemorrhage, and when it presents in otherwise healthy people, can prove difficult to diagnose. The cardinal features are episodic epigastric pain associated with a raised serum amylase and the passage of melaena. Failure to make the connection between recurrent gastrointestinal bleeding and apparently unrelated symptoms attributable to pancreatitis may lead to a significant delay in diagnosis.

Fine needle aspiration cytology (FNAC) was performed on 91 patients with lesions of salivary glands and cervical lymph nodes. The results were compared with histopathology in 58 patients who subsequently underwent surgery. Of a total of 105 aspirates, a definitive cytodiagnosis was possible in 88 (83.8%). An overall sensitivity of 77.7% and specificity of 93.3% were obtained when the cytological results were correlated with histopathology in 48 cases. The figures for salivary glands were 40.0 and 88.9%, and for cervical lymph nodes were 92.3 and 100.0% respectively. The incorrect diagnosis of some aspirates did not adversely affect the subsequent management of these cases. Fine needle aspiration cytology has a role in the diagnosis and management of a variety of head and neck lesions, although it should be used, along with other investigations, not as a substitute but as an adjunct to sound clinical judgement. The limitations of the procedure, including occasional errors of cytodiagnosis, should be borne in mind. The use of this technique by otolaryngologists has been limited, and we advocate that it becomes a more integral part of the diagnostic work-up in head and neck practice.

We present a case of plasmacytosis of the mucous membrane of the upper aerodigestive tract. This is a rare benign condition characterized by plasma cell infiltration of the mucosa, with only nine cases described previously (Ferreiro et al., 1994). The lesions, which have a cobblestone appearance, cause throat discomfort, dysphonia and mild dyspnoea. All the cases described previously failedto respond to antibiotics, systemic steroids, or to surgical resection. The present case has however responded favourably to intensive andprolonged treatment with beclamethasone oral spray and Corsodyl mouthwashes.

We report a case of vasculitis causing facial swelling and exophthalmos which on clinical and histological grounds is thought to be limited Churg-Strauss syndrome. An excellent response was achieved to high doses of systemic steroids and cyclophosphamide.

Summary Two cases of tumours arising in or near the pancreatic head are reported in patients previously treated with abdominal irradiation for testicular tumours. These are only the third and fourth such cases to be reported and they suggest that second cancers may develop as a result of abdominal irradiation for malignant disease.

The incidence of pancreatic cancer is increased in patients who have undergone gastric surgery. An animal model is described in which pancreatic hyperplasia and adenoma formation developed within 56 weeks. The effects of a simple gastrojejunostomy were compared with those after a split gastrojejunostomy, in which the jejunum was transected and the two limbs implanted separately into the greater curvature of the glandular stomach 1 cm apart. After 56 weeks no animals in the simple gastrojejunostomy group had pancreatic hyperplasia whereas all 10 animals in the split gastrojejunostomy group had generalised pancreatic hyperplasia with macroscopic nodules. Microscopy of the nodules showed that in nine animals hyperplastic nodules had developed, and four of these also had adenomatous nodules. The remaining animal had enlarged lymph nodes. Pancreatic hyperplasia was associated with jejunal hyperplasia. Jejunal morphometry showed that the villus height was doubled and the villus height:crypt depth ratio was higher in the split gastrojejunostomy group compared with those animals with a simple gastrojejunostomy. This finding represents a new model for the investigation of pancreatic neoplastic change.

On the foreshore east of Luc-sur-Mer, Normandy, an Upper Bathonian hard-ground which caps a sponge biostrome has been thrown into a series of troughs and ridges, the latter sometimes with very steep flanks. Faunal orientation and encrustation of extensive undercuts demonstrate that these structures are of a syn-sedimentary origin. They are interpreted as submarine pseudo-anticlines which have a composite origin. The following three factors are thought to have contributed to their formation: (a) a primary morphological differentiation of the underlying biostrome; (b) sediment expansion caused by force of crystallization during hardground formation; and (c) differential compaction, being greater where the hardground overlies mainly inter-reef mud as compared with the rigid sponge framework. The main episode of this compaction occurred at an early stage in the life of the hardground. Subsequent erosion, colonization by encrusters and borers, and burial beneath a fossiliferous clay were the final stages in the history of these pseudo-anticlines.

The histopathological appearance of proliferative squamous lesions removed from the skin of iatrogenically immunosuppressed patients differs subtly from that of classical malignant and premalignant epidermal lesions. The majority of cases show 'Bowenoid' changes with a marked degree of cellular atypia including characteristic multinucleate cells.

T. J. Palmer examines the institutional investor both as a large company with responsibilities to its own participants and as an important shareholder with supervisory responsibilities over other companies.

Transduction of resistance from a multiply antibiotic-resistant strain of Staphylococcus epidermidis sub-group II was studied using the typing phage 108. The effect of increasing doses of ultraviolet radiation on the transducing phage was used to indicate the chromosomal or plasmid nature of the genes. Tetracycline and chloramphenicol resistance behaved as plasmid genes and streptomycin resistance as a chromosomal marker. It was also possible to transduce penicillin resistance (Pc) due to penicillinase production (bla+) using a low level of benzylpenicillin (0.03 microgram ml-1) for recovery. Approximately 10(-5) transductant colonies per phage input were obtained and ultraviolet kinetics indicated that Pc was plasmid carried. Pc transductants fell into two categories. In one group PC was stable as in the donor strain and transductants had the same phage sensitivity as the recipient. In the other, Pc was unstable at 37 degrees C and the instability was enhanced by growth at approximately 43.5 degrees C; these transductants also gained genes for restriction and modification of certain phages. Transductants that subsequently lost bla+ also lost the restriction and modification characters.

A model for spontaneous tumour formation in the rat pancreas is described that requires neither cocarcinogens nor dietary manipulation. Short term hypercholecystokininaemia, when induced by raw soya flour feeding, induces benign and malignant tumours of the rat pancreas. Pancreaticobiliary diversion (PBD) results in hypercholecystokininaemia and in the short term, pancreatic hyperplasia. Longterm PBD was done to establish whether hypercholecystokininaemia thus produced would also lead to pancreatic neoplasia. After a period of 16-21 months hyperplastic and adenomatous nodules, one of the latter showing carcinoma in situ, were found in PBD rats but not in sham operated control rats.

HORNS, and other often elaborate forms of prothoracic and cephalic armature, are a well known feature of male and occasionally female beetles in the family Scarabaeidae (Coleoptera)1. Many of these, including rhinoceros beetles (Dynastinae) and dung beetles (Scarabaeinae, Geotrupinae), have been studied in detail, but the function of the horns is still the subject of dispute2. The idea that in certain circumstances it would be an advantage for male insects to fight for the possession of a female or a breeding site, and that horns and similar appendages have evolved as weapons, has recently been put forward by Hamilton3. The male of the geotrupine Typhoeus typhoeus (L.) is well armed in this way (Fig. 1), and the observations that I report here show for the first time in a burrowing beetle, not only that the horns are used for fighting between males, but that they are specifically designed for the purpose.

This book aims to fill a vacant niche in the literature of palaeoecology as a general text with a wide ranging review of the primary literature which has largely come out of Europe and North America in the past 20 years. Its intended audience (as stated in the preface) ranges from undergraduates to professional palaeontologists. Such an ambition inevitably lays a book open to charges that different topics are dealt with in different depths, because the requirements of the two groups are not the same. It is greatly to the credit of the two authors that they have produced such a consistent and useful book, the failings of which are greatly outweighed by its positive points.