Using Quantum Confinement to Uniquely Identify Devices.

Modern technology unintentionally provides resources that enable the trust of everyday interactions to be undermined. Some authentication schemes address this issue using devices that give a unique output in response to a challenge. These signatures are generated by hard-to-predict physical responses derived from structural characteristics, which lend themselves to two different architectures, known as unique objects (UNOs) and physically unclonable functions (PUFs). The classical design of UNOs and PUFs limits their size and, in some cases, their security. Here we show that quantum confinement lends itself to the provision of unique identities at the nanoscale, by using fluctuations in tunnelling measurements through quantum wells in resonant tunnelling diodes (RTDs). This provides an uncomplicated measurement of identity without conventional resource limitations whilst providing robust security. The confined energy levels are highly sensitive to the specific nanostructure within each RTD, resulting in a distinct tunnelling spectrum for every device, as they contain a unique and unpredictable structure that is presently impossible to clone. This new class of authentication device operates with minimal resources in simple electronic structures above room temperature.

Regeneration of cervix after excisional treatment for cervical intraepithelial neoplasia: a study of collagen distribution.

OBJECTIVE: To study the distribution of collagen in the regenerated cervical tissue after excisional treatment for cervical intraepithelial neoplasia (CIN). DESIGN: Cohort study. SETTING: A large tertiary teaching hospital in London. POPULATION: Women who underwent repeat excisional treatment for treatment failure or persistent CIN. METHODS: Eligible women who underwent a repeat excisional treatment for treatment failure, including hysterectomy, between January 2002 and December 2007 in our colposcopy unit were identified by the Infoflex(®) database and SNOMED encoded histopathology database. Collagen expression was assessed using picro-Sirius red stain and the intensity of staining was compared in paired specimens from the first and second treatments. MAIN OUTCOME MEASURE: Differences in collagen expression were examined in the paired excisional treatment specimens. RESULTS: A total of 17 women were included. Increased collagen expression in the regenerated cervical tissue of the second cone compared with the first cone was noted in six women, decreased expression was noted in five women, and the pattern of collagen distribution was equivocal in six women. CONCLUSION: There is no overall change in collagen distribution during regeneration following excisional treatment for CIN.

Secondary excision for cervical intraepithelial neoplasia: an evaluation of two treatment methods.

A small proportion of women require repeat treatments for cervical intraepithelial neoplasia (CIN). This study aimed to compare the effectiveness of two cervical excisional techniques offered within a London teaching hospital (large loop excision of the transformation zone (LLETZ) and laser cone biopsy) when carried out as secondary procedures. A significantly larger volume of tissue was excised following laser cone biopsy, however the depth of the specimen did not differ significantly. A trend for a larger percentage of secondary specimens, resulting in complete endo-cervical margins and a larger proportion of women achieving cytology negative for CIN post-treatment was shown within the laser cone biopsy group.

The volume perspective: a comparison of two excisional treatments for cervical intraepithelial neoplasia (laser versus LLETZ).

OBJECTIVE: To compare two excisional treatments, laser cone biopsy and large loop excision of the transformation zone (LLETZ), in terms of the volume of tissue removed, and to determine the relation between the height and the total volume of the cone specimen. DESIGN: Retrospective cross-sectional study. SETTING: Large teaching hospital in London. POPULATION: A total of 1136 eligible excisional treatments (laser cone or large loop excision of the transformation zone, LLETZ). METHODS: Eligible excisional treatments (laser cone or LLETZ) performed between 1 January 2002 and 31 December 2007 in our colposcopy unit were identified using the Infoflex(R) database. The total volume of the cone biopsy was calculated mathematically using the data provided in the histopathology reports. MAIN OUTCOME MEASURES: The volume of the cone biopsy was compared with the technique of excision and the histology grades. RESULTS: Three hundred and thirty-nine laser cone biopsies were performed, whereas 797 LLETZ biopsies were recorded, during the study period. There was no difference in the mean age in the two groups. However, there is a proportional increase in the volume of the cone as the height of the cone increases, and a significant number of the values are skewed, suggesting that the diameter of the base of the cone contributes significantly to the total volume. Laser cone biopsies (median volume 1.84 cm(3), 95% CI 1.98-2.54 cm(3)) account for a larger volume of tissue excised compared with LLETZ (median volume 0.78 cm(3), 95% CI 0.91-1.02 cm(3)) (P < 0.0001). This relationship is not altered when the two procedures are stratified for grade of lesion, i.e. excision for low-grade cervical intraepithelial neoplasia (CIN) (laser median volume 1.55 cm(3), 95% CI 1.46-2.06; LLETZ median volume 0.62 cm(3), 95% CI 0.73-0.88 cm(3)) (P < 0.0001) or high-grade CIN (laser median volume 1.84 cm(3), 95% CI 2.11-2.53 cm(3); LLETZ median volume 0.82 cm(3), 95% CI 0.94-1.07 cm(3)) (P < 0.0001). CONCLUSIONS: The volume of cervical tissue removed during laser conisation is significantly more than that removed with LLETZ. The indication of the cone biopsy does influence the volume of tissue removed.

Challenges and constraints to vaccination in developing countries.

The challenges and constraints to vaccinating poultry in areas where adequate infrastructure and human resources are lacking are addressed in both a technical and a socioeconomic framework. The key issues discussed are: (1) selection of an appropriate vaccine and vaccination technique, including the advantages and disadvantages of a combined vaccine against highly pathogenic avian influenza (HPAI) and Newcastle disease and addressing the differences between endemic disease and emergency disease control; (2) vaccine conservation and distribution; (3) evaluation of the flocks to be vaccinated in terms of their disease status, immunocompetence and production systems; (4) design of effective information, education and communication materials and methods with and for veterinary and extension staff as well as commercial and smallholder producers and community vaccinators in rural areas; (5) evaluation and monitoring systems for technical and socioeconomic factors that affect vaccination; (6) support and coordination of and by relevant public and private agencies; (7) the role of simultaneous implementation of other control activities in addition to vaccination; (8) the importance of assessing the costs and cost-effectiveness of various approaches to the control of HPAI, including the prevention of other endemic killer diseases and options for cost-sharing; (9) evaluation of the incentives for poultry-holders, vaccinators and vaccine producers to contribute to and participate in effective vaccination campaigns; and (10) policy development and the organizational framework for short- and long-term implementation and communication to decision-makers.

Primary visual cortex neurons that contribute to resolve the aperture problem.

It is traditional to believe that neurons in primary visual cortex are sensitive only or principally to stimulation within a spatially restricted receptive field (classical receptive field). It follows from this that they should only be capable of encoding the direction of stimulus movement orthogonal to the local contour, since this is the only information available in their classical receptive field "aperture." This direction is not necessarily the same as the motion of the entire object, as the direction cue within an aperture is ambiguous to the global direction of motion, which can only be derived by integrating with unambiguous components of the object. Recent results, however, show that primary visual cortex neurons can integrate spatially and temporally distributed cues outside the classical receptive field, and so we reexamined whether primary visual cortex neurons suffer the "aperture problem." With the stimulation of an optimally oriented bar drifting across the classical receptive field in different global directions, here we show that a subpopulation of primary visual cortex neurons (25/81) recorded from anesthetized and paralyzed marmosets is capable of integrating informative unambiguous direction cues presented by the bar ends, well outside their classical receptive fields, to encode global motion direction. Although the stimuli within the classical receptive field were identical, their directional responses were significantly modulated according to the global direction of stimulus movement. Hence, some primary visual cortex neurons are not local motion energy filters, but may encode signals that contribute directly to global motion processing.

Data-robust tight lower bounds to the information carried by spike times of a neuronal population.

We develop new data-robust lower-bound methods to quantify the information carried by the timing of spikes emitted by neuronal populations. These methods have better sampling properties and are tighter than previous bounds based on neglecting correlation in the noise entropy. Our new lower bounds are precise also in the presence of strongly correlated firing. They are not precise only if correlations are strongly stimulus modulated over a long time range. Under conditions typical of many neurophysiological experiments, these techniques permit precise information estimates to be made even with data samples that are three orders of magnitude smaller than the size of the response space.

Comparison of particle penetration with non-spherical polyvinyl alcohol versus trisacryl gelatin microspheres in women undergoing premyomectomy uterine artery embolization.

AIM: The purpose of this study was to compare the depth of vascular penetration of non-spherical polyvinyl alcohol (PVA) versus trisacryl gelatin microspheres (MS) in women undergoing uterine artery embolization (UAE) immediately before transabdominal myomectomy. MATERIALS AND METHODS: A total of 17 patients who had been referred for embolization before myomectomy underwent bilateral uterine artery embolization using either 355-500 microm PVA (group A) or 700-900 microm MS (group B). The depth of penetration of the particles was assessed by identifying their presence and location in the resected specimen. RESULTS: Of the 17 women enrolled in this study, 10 were in group A and 6 in group B. One woman underwent embolization using both types of particle and was excluded from the analysis. Embolic particles were significantly (p = 0.048) more frequently located within the fibroid (4/6, 67%) in Group B than Group A (1/10, 10%). Particles were also identified in the perifibroid tissues in 4/6 (67%) in Group B and 4/10 (40%) in Group A, with no statistical difference. There were no procedural complications. CONCLUSION: MS particles (700-900 microm) penetrate significantly deeper into leiomyomata compared with non-spherical PVA (355-500 microm). MS may therefore confer advantages in UAE, as they may more specifically target the fibroid, allowing an earlier end-point to embolization and minimizing ischaemic damage to normal myometrium and ovaries.

Effect of deproteination on bone mineral morphology: implications for biomaterials and aging.

Bone mineral morphology is altered by processing and this is rarely considered when preparing bone as a bioimplant material. To examine the degree of transformation, a commercial, coarsely particulate bone mineral biomaterial produced by prolonged deproteination, defatting, dehydration, and heating (donor material) was compared with similar particles of human bone (recipient material) prepared optimally by low-temperature milling. The two powders were freeze-substituted and embedded without thawing in Lowicryl K4M before sectioning for transmission electron microscopy (TEM) (other aliquots were processed by traditional TEM methods). To maximize resolution, electron micrographs were image-enhanced by digitization and printed as negatives using a Polaroid Sprint Scan 45. In addition to their morphology, the particles were examined for antigenicity (specific by reference to fluorescein isothiocyanate [FITC]-conjugated fibronectin, and nonspecific by reference to general FITC-conjugated immunoglobulins). Results showed that the optimally prepared human bone fragments stained discretely for fibronectin with negligible background autofluorescence. In contrast, the bioimplant fragments stained extensively with this and any other FITC-conjugated antibody and, unlike fresh bone, it also autofluoresced a uniform yellow. This difference was also expressed structurally and, although the bioimplant mineral consisted of rhomboidal plates up to 200 nm across and 10 nm thick, the optimally prepared bone mineral was composed of numerous clusters of 5-nm-wide sinuous calcified filaments of variable density and indeterminate length (which became straight needles 50 nm long and 5 nm thick following traditional chemical TEM fixation/staining). It was concluded that the inorganic phase of bone is both morphologically and immunologically transmutable and that, in biomaterials, the transformation is apparently so great that a broad indigenous antigenicity is unmasked, increasing the likelihood of resorption or rejection. This marked change may also provide preliminary insight into a more modest natural aging phenomenon with the localized lateral fusion of calcified filaments into less flexible, more immunologically reactive fenestrated plates.

Anterior prostate cancer: is it more difficult to diagnose?

UNLABELLED: OBJECTIVE; To determine whether anterior prostatic tumours are adequately sampled using the Stamey sextant protocol, as a fifth of prostate cancers are anterior in distribution at radical prostatectomy. MATERIALS AND METHODS: All tumours (62) with an anterior distribution (>or=75% of the tumour anterior to the urethra) on radical prostatectomy whole-mounts, and in which the number and results of the sextant biopsies were available, were extracted from a prostate cancer database. Sixty-one posterior tumours (>or=75% of the malignant tissue posterior to the urethra) and their corresponding sextant biopsies were also retrieved for comparison. The number of biopsy sessions, the number of cores involved and the summated tumour length were recorded, together with the prostate gland weight, the tumour volume and the site of >or=75% of tumour in the superior-inferior axis. RESULTS: Anterior tumours required significantly more biopsy sessions to diagnose prostate cancer than posterior neoplasms (anterior, one set 47; > one set 15; posterior, one set 57; > one set, four, P=0.007). Anterior tumours had fewer cores with tumour involvement and less summated tumour length than had posterior cancers. The mean (sd) number of positive cores was; anterior 1.8 (1.01), posterior 2.50 (1.30) (P=0.001); the summated tumour length was; anterior 5.05 (4.10) mm, posterior 9.25 (7.80) mm (P<0.001). There was no significant difference in gland weight (mean anterior 43.8 g; posterior 48.3 g, P=0.3) or tumour volume (mean anterior 1.85 mL; posterior 1.49 mL, P=0.11) between the groups. There was no significant difference between the incidence of anterior and posterior neoplasms with respect to their position in the superior-inferior axis (P=0.96). CONCLUSIONS: Anterior prostate tumours account for 21% of all prostate cancers. They more often require multiple sets of sextant biopsies for diagnosis, and yield smaller areas of cancer on core biopsies than do posterior tumours in glands of similar weight and tumour volume. If prostate cancer is suspected clinically but biopsies are negative, targeting the anterior gland at subsequent prostatic biopsy should be considered.

Good occlusal practice in the provision of implant borne prostheses.

The increased use of endosseous dental implants means that many dentists will encounter patients with dental implants in their everyday practice. Dental practitioners might be actively involved in the provision of implant borne prostheses at both the surgical and restorative phases, or only at the restorative stage. This section is written for all dentists and aims to examine the subject of occlusion within implantology. It aims to provide guidelines of good occlusal practice to be used in the design of the prosthesis that is supported or retained by one or more implants. As implantology is a 'new' discipline of dentistry, there are fewer standard texts and this section, therefore, is much more extensively referenced than the subjects that have been considered to date.

Advanced database methodology for the Collation of Connectivity data on the Macaque brain (CoCoMac).

The need to integrate massively increasing amounts of data on the mammalian brain has driven several ambitious neuroscientific database projects that were started during the last decade. Databasing the brain's anatomical connectivity as delivered by tracing studies is of particular importance as these data characterize fundamental structural constraints of the complex and poorly understood functional interactions between the components of real neural systems. Previous connectivity databases have been crucial for analysing anatomical brain circuitry in various species and have opened exciting new ways to interpret functional data, both from electrophysiological and from functional imaging studies. The eventual impact and success of connectivity databases, however, will require the resolution of several methodological problems that currently limit their use. These problems comprise four main points: (i) objective representation of coordinate-free, parcellation-based data, (ii) assessment of the reliability and precision of individual data, especially in the presence of contradictory reports, (iii) data mining and integration of large sets of partially redundant and contradictory data, and (iv) automatic and reproducible transformation of data between incongruent brain maps. Here, we present the specific implementation of the 'collation of connectivity data on the macaque brain' (CoCoMac) database (http://www.cocomac.org). The design of this database addresses the methodological challenges listed above, and focuses on experimental and computational neuroscientists' needs to flexibly analyse and process the large amount of published experimental data from tracing studies. In this article, we explain step-by-step the conceptual rationale and methodology of CoCoMac and demonstrate its practical use by an analysis of connectivity in the prefrontal cortex.

Simultaneity of responses in a hierarchical visual network.

The pattern of anatomical connections between areas of the primate visual system is organized hierarchically. However, onset latencies in parietal and occipital stations are often simultaneous, and this seems to contradict hierarchical organization in its simplest interpretation, as serial organization. To understand the reasons for this contradiction, we simulated the cortical network for which there is onset data, including the network's hierarchical structure. The network's dynamics reproduced the simultaneous onset latencies reported in several dorsal areas. These results show that a strictly hierarchical visual system is compatible with much more complex dynamics than serial processing, and that hodological and biophysical properties, are more closely related to onset dynamics than is hierarchical organisation.

A survey of clinical members of the association of dental implantology in the United Kingdom. Part II. The use of augmentation materials in dental implant surgery.

The following were the objectives of Part II of the survey: (1) to determine which augmentation materials were used by respondents, (2) to elicit which factors influenced the choice of augmentation materials, (3) to establish the perceived levels of evidence that support augmentation materials, and (4) to ascertain the clinical applications of particulate augmentation materials (autografts, allografts, and alloplasts). Autogenous bone and demineralized freeze-dried bone are used most frequently. The majority of respondents involved in bone augmentation indicated that alloplasts and allografts should be used to correct small defects or as volume expanders in conjunction with autogenous bone. Research publications and personal clinical observation mainly determine the choice of an augmentation material. Of the clinicians who preferred to use autogenous bone, 26.3% thought that there was at least one randomized controlled trial with histological evidence supporting its use in oral implantology. In comparison, 30% of demineralized freeze-dried bone users thought that there was at least one randomized controlled trial with histological evidence supporting its use. Collected bone debris is currently used for the correction of bone dehiscences and fenestrations around endosseous dental implants in the simultaneous implant-placement augmentation technique. There is a pressing requirement for the two most commonly used augmentation materials (autogenous bone and demineralized freeze-dried bone) to be evaluated by accepted scientific protocols. Although regard for autogenous bone as an augmentation material is high, its use in the form of collected bone debris seems to be limited at present.

Survey of clinical members of the association of dental implantology in the United Kingdom: Part I. Levels of activity and experience in oral implantology.

The aims of this survey were to 1) determine recruitment rates of active oral implantologists, 2) establish the proportion of participants who carry out the surgical aspects of implantology, 3) quantify levels of surgical activity, 4) determine the type of qualifications held by this sample, and 5) identify the location of implant activity of clinical members of the Association of Dental Implantology (UK). Questionnaires were mailed to the 408 members of the ADI registered as clinical members of the ADI; data were collected between July 1998 and May 1999. A response rate of 66.9% was achieved. Active members increased markedly from 1985 to 1995. Surgical activity and clinical experience varied widely: 32.9% had placed 100 to 499 implants, 29.8% had inserted 1 to 49 implants, and 4.3% had inserted > or = 2,000 implants. The total number of implants inserted by this sample could only be estimated (between 51,000 and 90,000). The majority of this sample possessed postgraduate qualifications, although only 2.6% possessed a degree in oral implantology. The data from this sample indicated that the recruitment rate to the ADI (UK) increased markedly between 1985 to 1995, after which it seems to have slowed down. Most of the respondents were involved in the surgical aspects of implantology, although the level of surgical involvement varied widely. The low incidence of postgraduate degrees in implantology might reflect the relatively limited opportunities currently available for such training in the UK.

Microbial analysis of bone collected during implant surgery: a clinical and laboratory study.

Dental implant surgery produces bone debris which can be used to correct bone defects in the "simultaneous-augmentation" technique. However, this debris is potentially contaminated with oral bacteria. Therefore, this study examined bone debris collected during dental implant surgery in order 1) to identify the microbial contaminants and 2) to compare the effects of two different aspiration protocols on the levels of microbial contamination. Twenty-four partially dentate patients were randomly allocated into two equal groups and underwent bone collection using the Frios Bone Collector during surgery to insert two endosseous dental implants. In group S (using a stringent aspiration protocol), bone collection occurred within the surgical site only. In group NS (utilizing a non-stringent aspiration protocol), bone collection and tissue fluid control was achieved using the same suction tip. Bone samples were immediately transported for microbial analysis. Colonial and microscopic morphology, gaseous requirements and identification kits were utilized for identification of the isolated microbes. Twenty-eight species were identified including a number associated with disease, in particular, Enterococcus faecalis and Staphylococcus epidermidis as well as the anaerobes Actinomyces odontolyticus, Eubacterium sp., Prevotella intermedia, Propionibacterium propionicum and Peptostreptococcus asaccharolyticus. In group S (stringent aspiration protocol), significantly fewer organisms were found than in group NS, the non-stringent aspiration protocol (P=0.001). Gram-positive cocci dominated the isolates from both groups. It is concluded that if bone debris is collected for implantation around dental implants, it should be collected with a stringent aspiration protocol (within the surgical site only) to minimize bacterial contaminants.

A survey of clinical members of the Association of Dental Implantology in the United Kingdom. Part III. The use of augmentation techniques in dental implant surgery.

The aims of the survey were to: (1) determine the use of the staged and simultaneous augmentation techniques; (2) determine trends in the use of barrier membranes; (3) establish the perceived reliability of techniques used to monitor implants that have undergone simultaneous augmentation; and (4) assess the use of biopsy techniques to confirm the histologic outcome of bone augmentation. One hundred seventy-two respondents replied to this section of the survey and indicated that the "staged" and "simultaneous" augmentation techniques were used in roughly equal numbers during 1997, and a wide range of complications was reported with the latter. The majority used barrier membranes to correct defects of between 5 and 10 mm3, and resorbable membranes were preferred. With regard to clinical techniques used to monitor augmented implants, these were mainly considered to be "adequate" or "poor." Tissue biopsy was recognized as an important tool for determining the outcome of augmentation procedures but was rarely used. The use of resorbable membranes is likely to increase. The diagnostic tools currently used to monitor augmented implants are considered to have limited reliability, and they should be evaluated by prospective, comparative studies. More widespread use of biopsy techniques might help establish an evidence base for the histologic outcome of augmentation materials and techniques.

Molecular markers for predicting prostate cancer stage and survival.

OBJECTIVE: To assess several molecular markers (detected by immunohistochemistry, IHC) to determine whether they can be used to improve the prognostic value of histological grade alone in predicting the behaviour of prostate cancer. PATIENTS AND METHODS: Tumour tissue was retrieved from 156 men in whom tumour grade, stage and survival were known. The outcome measures were: (i) local stage (T-stage, organ-confined vs extraprostatic); (ii) metastatic status (M-stage, bone metastasis vs no bone metastasis); and (iii) survival. The IHC markers used were chosen to provide a broad representation of various aspects of tumour biology, i.e. the androgen receptor (AR) and oestrogen receptor (ER), adhesion molecules (E-cadherin), proliferation markers (MIB-1), tumour-suppressor genes (TP53 and the retinoblastoma gene product, Rb) and other novel cancer-related proteins (cyclin D1 and the breast cancer susceptibility gene product, BRCA2). All factors were assessed using logistic regression and Cox proportional-hazards survival models for predictive value, after adjusting for effects. RESULTS: MIB-1, ER, cyclin D1 and E-cadherin all showed close statistically significant univariate associations with histological grade. Univariate analysis also identified close statistically significant associations between T-stage and both MIB-1 and E-cadherin. Likewise, there were close univariate associations for both M-stage and survival, and MIB-1, cyclin D1 and ER. Logistic regression modelling identified MIB-1, cyclin D1 and ER as statistically significant predictors of M-stage and, once MIB-1 was entered into the model, the effects of grade no longer made a significant contribution. MIB-1 was a significant predictor for T-stage, but the effects of grade remained significant in this model. Cox proportional-hazards modelling identified MIB-1, cyclin D1 and ER as being statistically significant predictors of survival, after adjusting for grade. After adjusting for both grade and MIB-1, the effects of cyclin D1 and ER were no longer statistically significant. Excess MIB-1, cyclin D1 or ER expression tended to be present within the most poorly differentiated and advanced-stage lesions; this provides an inherent instability to the models described. TP53, Rb, AR and BRCA2 were of limited prognostic value. CONCLUSIONS: MIB-1, ER and cyclin D1 provide prognostic information that is clearly independent of grade. However, their true clinical value is probably limited because they are expressed mainly in the most advanced lesions. Nevertheless, MIB-1 expression is of sufficient value to warrant inclusion in future prognostic models. Furthermore, the expression of cyclin D1 and ER may reflect aspects of tumour biology that individually are worthy of further investigation. However, none of the IHC markers used in this study can be recommended for use in routine histological preparations.

Human first trimester fetal ovaries express oncofetal antigens and steroid receptors.

OBJECTIVE: To document the expression of oncofetal antigens and steroid receptors in first trimester human fetal ovaries and to determine the effect of advancing gestation on expression patterns. METHODS: Fetal gonads were collected from surgical terminations of pregnancy, and fetal sex was determined by fluorescence in situ hybridization. Immunocytochemical analysis was performed on paraffin sections of microdissected fetal ovaries using antibodies to carcinoembryonic antigen (CEA), placental alkaline phosphatase (PLAP), hCG, alpha fetoprotein (AFP), CA 125, estrogen receptor (ER) and progesterone receptor (PR) in 12 first trimester human fetal ovaries. Expression was quantified objectively by measuring percentage area of immunoreactivity (PAI) on whole sections of the ovary using an interactive image analysis system. Two pathologists, blinded to the antibodies used, independently viewed and scored all sections. RESULTS: PLAP, PR, ER and CEA were expressed in all 12 ovaries (31%, 28%, 21%, and 16% mean PAI, respectively). A diffuse staining pattern was observed at 8 weeks' gestation, which was more focal and confined to the cortical regions of the gonad by 12 weeks' gestation. Putative primordial germ cells were positive for PLAP, PR and ER but rarely for CEA. The expression (PAI) of PLAP and PR was unchanged during the first trimester, whereas that of ER decreased from 28% to 12%. The expression of CEA and hCG decreased from 8 to 11 weeks and then increased markedly by 13 weeks. AFP had a medullary distribution and was expressed in nine of 12 ovaries (mean PAI 18%). CA 125 expression was minimal or undetected. CONCLUSION: PLAP, ER and PR were the most extensively expressed protein antigens, particularly in fetal ovarian cortex. These variable patterns of expression suggest levels of differentiation in the immature first trimester human fetal ovary.