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.

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.

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.

Sparse population coding of faces in the inferotemporal cortex.

How does the brain represent objects in the world? A proportion of cells in the temporal cortex of monkeys responds specifically to objects, such as faces, but the type of coding used by these cells is not known. Population analysis of two sets of such cells showed that information is carried at the level of the population and that this information relates, in the anterior inferotemporal cortex, to the physical properties of face stimuli and, in the superior temporal polysensory area, to other aspects of the faces, such as their familiarity. There was often sufficient information in small populations of neurons to identify particular faces. These results suggest that representations of complex stimuli in the higher visual areas may take the form of a sparse population code.

Visual attention. Turn on, tune in and drop out.

The effects of attention are not equally distributed in the visual cortex, do not bear a straightforward relationship to cells' stimulus preferences and act on a surprisingly restricted representation of any visual scene.

The connectional organization of neural systems in the cat cerebral cortex.

BACKGROUND: The mammalian brain consists of the cerebral cortical sheet, which is composed of many distinct areas, the cerebellar cortex, and many non-cortical nuclei. Powerful neuroanatomical techniques have revealed a large number of connections between these structures. The large number of brain structures and the very many connections between them form a strikingly complex network. The complexity of this network has made it difficult to understand how the central nervous system is organized. Recently, however, optimization analysis of an important subset of central nervous connections that occur between the different areas of the cerebral cortex has produced understandable and quantitative representations of the organization of cortical systems of the primate brain. RESULTS: Here we briefly report the extension of this approach to the cortical systems of the cat. There were four connectional clusters of cortical areas in the cat. These clusters of areas corresponded to the visual, auditory, and somato-motor systems, and to the frontal and limbic areas, which we call the fronto-limbic complex. All the major sensory systems were hierarchically organized, and their 'higher' stations were more closely associated with the fronto-limbic complex than were their 'lower' stations. CONCLUSIONS: Features of the organization of the cat brain, together with earlier primate results, suggest that there may be a common cortical plan in mammals. We suggest that this common plan may involve relatively discrete, hierarchically organized, cortical sensory systems and a topologically central fronto-limbic complex. Specific variations on this wiring plan may relate to evolutionary history and selection for particular ecological niches.

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.

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.

Analysis of connectivity: neural systems in the cerebral cortex.

The mammalian cerebral cortex is composed of many distinct areas, which are very richly interconnected. The very large number of connections between cortical areas require analysis to be undertaken before reliable conclusions about the organization of neural systems in the cortex can be drawn. We review the methodology and results of two means of analysing central nervous connectivity, hierarchical analysis and optimization analysis. We conclude that these methods are reliable methods for analysing neural connectivity data, and that their results concur. The analyses indicate that all major cortical sensory systems are organized hierarchically, some central sensory systems are divided structurally into several "streams" of processing, the cortical motor system is embedded in the cortical somatosensory system, the frontal and limbic structures are connectionally associated, and that these frontal and limbic areas are invariably associated with the least peripheral sensory processing regions, and are therefore connectionally central. Finally, we discuss the differences on this common plan between the organizations of the cat and primate that these analyses reveal.

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.

An epidemiological assessment of blood pressure determinants in an adolescent population of Nigerians.

An epidemiological assessment of blood pressure determinants in a random sample of 254 Nigerian adolescents aged 6-17 years in Benin City, Nigeria, was conducted. None of the adolescents reported cigarette smoking. Only 2.6% of the males and 0% of the females were alcohol users. Socio-economic status of the children according to parental education revealed that approximately 23% of the mothers and 9.8% of the fathers received less than a secondary (high school) education. At the other end of the education spectrum, a college education was received by 64.1% and 30.8% of the fathers and mothers, respectively. Two percent of the females and 1.3% of the males either had systolic blood pressures of greater than or equal to 140 mmHg or diastolic blood pressures of greater than or equal to 90 mmHg. No significant blood pressure differences existed between the two sexes. Among the males, it was demonstrated that age, body mass index, and heart rate were significant independent predictors of systolic blood pressure, explaining 49% of the variance. Forty-seven per cent of systolic blood pressure variance was explained by age and heart rate, for females. It was interesting to note that age was the only independent predictor of diastolic blood pressure for both males and females after control for heart rate and body mass index.

The organization of neural systems in the primate cerebral cortex.

The primate cerebral cortex is a sheet composed of many distinct areas. Each of these areas receives a large number of afferent inputs from other cortical areas (and elsewhere) and in return issues a large number of output projections. The cortex is thus innervated by a very large number of cortico-cortical connections, so that the areas and their interconnections form a network of startling complexity. The complexity of this network presents a formidable topological problem that hinders understanding of its organization. Recently, however, an optimization analysis has been applied to the connections between visual cortical areas. This optimization analysis derived a structure for the cortical visual system, a system whose organization has been extensively explored, that is consistent with known organizational features. This paper concerns an application of the same approach to the cortico-cortical connections of other major sensory systems in the primate brain, and to the connections of the entire cerebral cortex, whose organizations have not been extensively explored. The latter analysis suggests the gross topological organization of the cortical information processing system of this animal, and shows the 'place' of individual areas within this organization. The results may be suggestive for further theory and experiment.

Neuronal population activity and functional imaging.

Human functional brain imaging detects blood flow changes that are thought to reflect the activity of neuronal populations and, thus, the responses of neurons that carry behaviourally relevant information. Since this relationship is poorly understood, we explored the link between the activity of single neurons and their neuronal population. The functional imaging results were in good agreement with levels of population activation predicted from the known effects of sensory stimulation, learning and attention on single cortical neurons. However, the nature of the relationship between population activation and single neuron firing was very surprising. Population activation was strongly influenced by those neurons firing at low rates and so was very sensitive to the baseline or 'spontaneous' firing rate. When neural representations were sparse and neurons were tuned to several stimulus dimensions, population activation was hardly influenced by the few neurons whose firing was most strongly modulated by the task or stimulus. Measures of population activation could miss changes in information processing given simultaneous changes in neurons' baseline firing, response modulation or tuning width. Factors that can modulate baseline firing, such as attention, may have a particularly large influence on population activation. The results have implications for the interpretation of functional imaging signals and for cross-calibration between different methods for measuring neuronal activity.

Metabolic integrity of the isolated perfused lobule of human placenta.

Tissue levels of lactate, pyruvate and the adenine nucleotides were measured in samples of human placenta obtained (1) immediately on delivery, (2) after perfusion on the maternal side for one hour, and (3) after a corresponding period of warm ischaemia. Metabolic activity in the isolated perfused placental lobule was assessed in terms of these tissue metabolites and by measuring protein synthetic rate by means of determining the incorporation of a labelled amino acid. Perfusion was found to lower significantly the lactate level whereas ATP was maintained at comparable levels with those in the placenta just after delivery. Perfused placental ATP levels are lower than in vivo levels seen in other tissues with high metabolic rates such as rat liver, kidney and also in guinea-pig placenta. Protein synthetic rate was found to be lower than that observed in other fetal tissues.

Ki-67 expression in early prostate cancer and associated pathological lesions.

AIM: To assess cell proliferation in early prostate cancer and associated pathological lesions. METHODS: Using the Ki-67 antibody, the cell proliferation index was measured in early stage prostatic carcinoma in 37 incidental tumours diagnosed at transurethral prostatectomy (TURP) and in 20 low volume cancers treated by radical prostatectomy. Proliferation indexes have also been measured in areas of normal peripheral zone, transition zone hyperplasia, atrophic appearing lobules, and high grade prostatic intraepithelial neoplasia in the radical prostatectomy cases. RESULTS: In the TURP series the proliferation index correlated with grade and stage. Logistic regression analysis, however, showed that Gleason grade was the most reliable predictor of biopsy proven residual disease and clinical progression. In the radical series transition zone carcinoma the proliferation index was half that of peripheral zone carcinoma. The atrophic lobules also showed a high proliferation index of the same order as seen in the peripheral zone carcinoma. Normal peripheral zone showed the lowest proliferation index and in hyperplastic transition zone it was also less than the other areas. CONCLUSIONS: There is only limited support for the correlation of proliferation index with grade in early stage prostatic carcinoma. The findings do not suggest that proliferation index adds to the prognostic information given by grade and stage in pT1 disease. The significant difference in proliferation index in transition zone and peripheral zone carcinomas supports the morphological distinction of these tumour types and is consistent with differences in biological behaviour. The high proliferation index in lobules considered morphologically atrophic is reminiscent of previous observations in which carcinoma was spatially associated with atrophy.

Accuracy and cost of intraoperative lymph node frozen sections at radical prostatectomy.

AIM: To assess the value of intraoperative diagnostic examination of frozen sections of lymph nodes removed during radical prostatectomy. METHODS: Pelvic lymph nodes from patients with prostatic carcinoma were obtained (1) as frozen sections during radical prostatectomy, to exclude patients from non-curative surgery, and (2) as paraffin sections postoperatively from lymphadenectomy performed at radical prostatectomy, to stage the tumour and assess need for adjuvant treatment. Findings from the two approaches were used to assess the accuracy and cost of frozen section diagnosis, and to judge the results of omitting intraoperative diagnosis. RESULTS: In 82 patients frozen section revealed metastasis in six (7.3%), and metastases were found in a further four (4.9%) on paraffin sections (false negatives). Of the 195 patients undergoing staging lymphadenectomy (without frozen section), metastatic cancer was seen in nine cases (4.6%). The frozen section cost of metastatic cancer detection per patient was calculated as 7516 Pounds (550 Pounds x 82/6), with an associated false negative rate of 33%. CONCLUSIONS: Frozen section diagnosis of metastatic carcinoma in pelvic lymph nodes before radical prostatectomy has a high false negative rate and is costly. It may not be justified with the observed low incidence of lymph node metastasis.

Blomstrand osteochondrodysplasia: three novel cases and histological evidence for heterogeneity.

Blomstrand osteochondrodysplasia (BOCD) is a rare, autosomal recessive, lethal skeletal dysplasia characterized by generalized osteosclerosis and advanced skeletal maturation. The histopathological characteristics of three novel cases (two isolated cases and a sib-pair) of BOCD are presented and correlated with the clinical and radiographical findings, and the relevant literature is reviewed. The results of our study confirm the existence of two separate types of BOCD, which we propose naming type I: the severe, 'classical' form, and type II: a less severe form.

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.