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Study question Does gender-affirming testosterone therapy alter the composition of the extra-cellular matrix (ECM) within the ovarian stroma and subsequently affect follicle activation in vivo Summary answer Ovarian stroma of trans men is more collagenous and less elastic, indicating fibrotic change. This may affect in vivo follicle growth activation What is known already Changes in the ovarian stroma have been demonstrated in the ovaries of transgender men taking testosterone, including thickening of the tunica albuginea, stromal cell hyperplasia and stromal cell luteinisation. Ovaries of trans men also have increased cortical stiffness. These changes are similar to those seen in female patients with PCOS and in physiological ovarian aging, which has been attributed to accumulation of collagen in the ECM. Increasing stiffness of the supportive follicular microenvironment has been shown to reduce follicle growth activation in vitro Study design, size, duration Whole ovaries were obtained from transgender men (mean age 27.6 ± 1.7 years, n = 8) with informed consent at oophorectomy. All patients had received 1000mg testosterone undecanoate intramuscularly at 12-16 week intervals for a minimum of 18 months pre-operatively (range 18 months-10 years). Cortical tissue was dissected into small fragments (≈1x1x0.5mm) and fixed for histological and immunohistochemical analysis. Testosterone-treated ovaries were compared to cortical biopsies from age-matched healthy women obtained at caesarean section (mean age 31.8±1.5, n = 8). Participants/materials, setting, methods Follicle number, classification of developmental stage, non-growing follicle density (NGFD) and stromal cell density were evaluated by histological analysis of ovarian cortical tissue. Sections were stained with Picrosirius red (PSR) to analyse total collagen content using brightfield microscopy. Polarised light was also used to analyse the collagen birefringence, which allows quantification of collagen fibre thickness into thick, medium or thin. Total elastin content was evaluated using immunofluorescence. Main results and the role of chance 4526 follicles were analysed. Transgender ovary showed a higher proportion of non-growing follicles found compared to control (93.9±1.2% vs 84.6±1.5% p < 0.05): the proportions of primary (4.7±0.9% vs 10.6±1.5%, p = 0.2) and secondary (1.4±0.4% vs 4.6±0.7%, p = 0.1) follicles tended to be lower. Stromal cell density was significantly higher in transgender ovarian cortex than control (2.5±0.1 x106cells/mm3 vs 1.7±0.1 x106cells/mm3), indicating stromal cell hyperplasia. Combined data from control and transgender groups showed a positive correlation between NGFD and stromal density (r = 0.64, p = 0.01). Transgender ovary had a higher total collagen content (77.2±1.2%) compared to control (31.3±3.3%, p Limitations, reasons for caution The impact of these findings on in vivo follicle growth are unclear. The effect of duration of testosterone treatment has not investigated. Wider implications of the findings More collagenous, less elastic ovarian stroma in trans men indicates fibrotic change; these findings are similar to women with PCOS and with reproductive ageing. These stromal changes may alter follicle growth activation and may contribute value to our understanding of the regulation of follicle function in a range of conditions. Trial registration number nil

Study question Does high-dose testosterone therapy affect the stage distribution, morphological health and DNA damage repair capacity of human ovarian follicles and their survival in vitro? Summary answer Testosterone exposure is associated with reduced follicle growth activation, reduced follicle health and increased DNA damage: these further deteriorate after six days of culture. What is known already Androgens have diverse actions within the ovary, however, there is a lack of information regarding the long-term effects of high-dose testosterone on ovarian function and reproductive potential. Cumulus-oocyte complexes recovered from transgender men have been successfully matured in-vitro but little is known regarding the impact of this gender affirming endocrine therapy on the primordial follicle pool Study design, size, duration Whole ovaries were obtained from four transgender men aged 25-36 years with informed consent at oophorectomy. All patients had received 1000mg testosterone undecanoate intramuscularly at 12-16 week intervals for a minimum of 4 years pre-operatively. Cortical tissues were dissected into small pieces (≈1x1x0.5mm) and either immediately fixed for histological analysis or cultured for 6 days. Testosterone-treated ovaries were compared to cortical biopsies from age-matched healthy women obtained at caesarean section (n = 4, age 26-36). Participants/materials, setting, methods Follicle number, classification of developmental stage and morphology were evaluated by histological analysis of ovarian cortical tissue from day 0 and 6 days post culture. Immunohistochemical analysis included γH2AX as a marker of DNA damage, and meiotic recombination 11 (MRE11), ataxia telangiectasia mutated (ATM) and Rad51 as DNA repair proteins. A total of 3802 follicles from testosterone exposed and 878 from control ovaries were analysed. Main results and the role of chance At day 0 (D0), transgender tissue had a higher proportion of non-growing follicles (92.7±1.7%) compared to control (85.4±6.2%, p DNA damage was assessed by expression of γH2AX. At D0, the proportion of oocytes showing DNA damage was significantly higher in transgender non-growing follicles (48.1±12.5%, vs 12.3±0.25%, p At D0, there was no difference in expression of DNA repair enzymes ATM and RAD51 between transgender and control oocytes, and increased expression of MRE11 in control non-growing follicles (p Limitations, reasons for caution A large number of follicles have been analysed, but only from a small number of ovaries. DNA damage at D0 and after 6 days of culture may not reflect DNA damage and repair capacity at later stages of follicle growth. The effect of duration of testosterone treatment was not investigated. Wider implications of the findings These data indicate that high circulating concentrations of testosterone have previously unrecognised effects on the primordial and small-growing follicles of the ovary. These results may have implications for transgender men receiving gender-affirming therapy prior to considering pregnancy or fertility preservation measures. Trial registration number n/a

Testicular trauma is common, usually trivial and rarely requires hospital attendance, but if it does, then imaging becomes essential as scrotal assessment may be difficult due to pain and/or scrotal disruption. Ultrasound (US) assumes a crucial role as other cross-sectional modalities have a limited use in the acute presentation. Despite the acceptable accuracy of conventional US techniques, there are limitations which hinder a thorough evaluation, critically the assessment of tissue viability, crucial for clinical management and prognosis. Contrast-enhanced ultrasound (CEUS) has been shown to offer improved flow visualisation and tissue perfusion compared with conventional Doppler techniques. CEUS can accurately and confidently demonstrate the viability of testicular parenchyma, delineate fracture lines and haematomas and guide treatment for testis-sparing surgery or orchidectomy. The purpose of this review is to present the literature, familiarise physicians with the principles of CEUS and findings of scrotal trauma and illustrate the main abnormalities through characteristic and educative cases.

As commercial and naval ships push to reduce manning requirements, the complexity of the platform management and control systems is increasing. The current route to compliance relies heavily on audits of the detailed design during the design/commissioning of the ship. Having it so late in the lifecycle adds risk of rework to the Shipbuilder and system supplier. As the complexity of control increases both the probability that changes will be required in response to identified safety issues, and the cost of making these changes will rise significantly. For systems that have safety significance, and will be expected to comply with IEC 61508, this poses even more of a challenge as the level of evidence needed to support the functional safety argument will be almost impenetrable if viewed in the form of a single audit. This paper proposes a staged approach to compliance, which will build confidence in the control and management system during the development lifecycle. It incorporates practices from other industries, such as aerospace, where complex control and safety systems have been in use for some time. Using a gated approach, loosely based on a tailored ARP 4754A model, Shipbuilders can mitigate much of the risk, and prevent cost overruns. This systematic approach to progressively accumulating and signing off evidence increases auditor involvement, and keeps them much more informed throughout the design. This will allow the auditor to have more confidence in the suitability of complex control and protection systems, and being assured of the safe running of the ship. This model has been common practice in aerospace for a number of years, and has supported advances in automation beyond the accepted norms of the marine industry. This paper provides an overview of the risks presented by the current Certification mechanisms, and discusses possible solutions presented by ARP 4754A.

Objective To describe ultrasound (US) and pathologic findings in 11 patients with multiple, synchronous lesions of different histology within the same testis. Materials and methods We reviewed US and pathologic findings in 11 patients with multiple, synchronous lesions of different histology within the same testis. Lesions were classified as separate or adjacent one to another and attempt was made to predict tumor type on their US textures. Pathologic review assessed presence of normal tissue between adjacent lesions and of Germ Cell Neoplasia In Situ in surrounding parenchyma. Nine cases were from files specifically dedicated to testicular tumors and estimated prevalence was calculated. Results Two nodules were seen in nine patients and 3 in remaining two. Nine had tumors of different histology; two had one malignancy and one focal benign lesion. Germ Cell Neoplasia In Situ was seen in 7/11 cases. In dedicated archives, these lesions had 1.83% prevalence. Conclusion Multiple focal lesions identified at imaging within the testis are not always of the same histology. This can be suspected in some cases basing on US texture. Recognition that lesions are multiple and an indication of their locations within the testis is the most important role of imaging and may help pathologists correctly sample the specimen to establish nature of each of them. Presence of multiple lesions is regarded as a contraindication to testicular sparing surgery. In two of our patients, one lesion was benign. Then, when the procedure is indicated all lesions have to be sampled and assessed by pathologists before deciding between conservative or radical technique.

The treatment of chronic osteomyelitis requires both appropriate surgical and antibiotic management. Prolonged intravenous antibiotic therapy followed by oral therapy is widely utilised. Despite this, the long-term recurrence rate can be up to 30%. A cohort of 50 patients from a 7-year period, 2003 to 2010, with chronic osteomyelitis was identified. This cohort was treated by surgical marginal resection in combination with local application of antibiotics (Collatamp G - gentamicin in a collagen fleece), a short course of systemic antibiotics post-operatively and conversion to oral antibiotics on discharge. Information was retrieved from case notes and computerized records. Outcomes from this cohort were compared with a historical cohort treated with marginal resection followed by 6 weeks of systemic antibiotics and 6 weeks of oral antibiotics. The mean follow-up duration was 3.2 years (SD 1.8). The average length of admission was 9.8 days (SD 11.4). 6 patients (12%) suffered recurrence of infection requiring further treatment. We used the Cierny and Mader classification to stratify the patients. 'A' hosts had a shorter duration of admission (7.1 days) than 'B' hosts (12.3 days). There was no significant difference between recurrence rates of 'A' and 'B' hosts. Where available, we found pre-operative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels had no correlation with disease recurrence. Disease-free probability for this cohort compared favourably with the historical cohort. We believe local administration of gentamicin in a collagen fleece is a useful component in the management of chronic osteomyelitis.

Tracks and trackways of the vertebrate ichnotaxon Ichniotherium sphaerodactylum and a trace of the invertebrate ichnotaxon Striatichnium bromackerense are described for the first time in association outside of Europe. The tracks are identified as I. sphaerodactylum based on their characteristic rounded digit ends, the ovoid sole-pad of the pedal imprint and the increase in digit lengths from digits I–IV, and the invertebrate trace is identifiable as S. bromackerense based on the band-like systems of distally bifurcated striae. The tracks of I. sphaerodactylum are the largest known to date and represent rare evidence of large-bodied terrestrial vertebrates in the Kildare Capes Formation of Prince Edward Island, Canada. Morphometric differences between ichnospecies of Ichniotherium and other ichnospecies previously collected from Prince Edward Island are examined in a multivariate analysis, and results suggest that the distance between the manus and pes of the same imprint pair, the width of pace and the length of certain digits is useful for species identification. The association between I. sphaerodactylum and S. bromackerense was previously known only from the Bromacker quarry, Tambach Formation, Germany, which is interpreted as a seasonally dry, semi-arid upland environment. The co-occurrence of these traces suggests that the Eldon locality of Prince Edward Island is similar in depositional environment to the Bromacker quarry in Germany, and allows for comparison of these two localities for the first time. As diadectids are thought to be the trackmakers of Ichniotherium, the Eldon locality of the Kildare Capes Formation may, with further work, be considered as another example of the rare, herbivore-dominated palaeoenvironment, which is generally uncharacteristic of the Early Permian of North America.

Arctium minus (Hill) Bernh., common burdock, and A. lappa L., great burdock, are introduced weeds of abandoned fields, roadsides, pastures and streambanks. The species are naturalized throughout much of southern Canada, especially in the eastern provinces, and the U.S.A. A summary of the biology of these two ruderal species is presented as part of a series of the biology of Canadian weeds.

This summary of biological information of Plantago major L. (broad-leaved plantain) and P. rugelii Decne. (Rugel’s plantain) is part of a series on the biology of Canadian weeds. P. major is a weed of disturbed habitats throughout Canada whereas P. rugelii is restricted to similar habitats in eastern Canada.

We have most of us been surprised when, after reading the history of the late Republic, we first discovered that in the year 50 a motion was proposed in the Senate that Pompey and Caesar should both lay down their commands, that it was passed by 370 votes to 22, and that it was disregarded in the interests of the optimate leaders. Who were these 370 men, and why do we not hear more of them? We have read, of course, that the Senate consisted of this or that number at this or that time; and then we read all about the Claudii and Metelli, with scarcely a word about the massed ranks behind them. Yet there they are, and the picture is incomplete without them. It is likely that we shall never complete it satisfactorily—there are so many of them we do not know, and the few we do know are quite likely to be exceptional in some way—but we can at least make a start by considering the numbers involved and the likely divergence as well as the unity of their interests.

Demographic information about plant populations has accumulated over the last few years, and some generalizations are now possible from these data. Sarukhan & Harper (1973) used published information on the survivorship of several herbs and grasses from different geographic regions, and from their own studies on buttercups, to show that established plants of perennials, including Plantago lanceolatat (Sagar 1959), suffer approximately constant annual mortality, though the mortality rate varies between species. Mortality rates appear to be affected by environmental conditions in the year of germination and during subsequent years (Williams 1970; Antonovics 1972). This information has been used to prepare preliminary models of the regulation of plant populations (Harper & White 1971). The complete life cycle has rarely been assembled in a life table (Sharitz & McCormick 1973), and then may be useful for annual species only. Sarukhan & Harper (1973) recognized that mortality rates of perennials need not be constant. Although most survivorship curves for plant populations approximate to the Type II described by Deevey (1947), those for range grasses studied by Canfield (1957) were negatively skewed (Deevey type I) while those of grasses studied by Williams (1970) were slightly positively skewed (Deevey type III). The few studies available on the survivorship of populations of seedlings show that the mortality rate declines with age (Sharitz & McCormick 1973; Sarukhan & Harper 1973), eventually attaining a constant loss rate (Harper 1967; Hett & Loucks 1971; Hett 1971; Antonovics 1972; Thomas 1972). Mortality rates in populations of dormant seeds, like those for established plants, are usually fairly constant (Roberts 1962; Sarukhan 1974). Only two studies are known to us where differences in longevity, mortality, natality, and density were examined in closely related species under natural conditions. Sarukhan & Harper (1973) investigated the demography of Ranunculus repens, R. bulbosus and R. acris, and Thomas (1972) investigated the dynamics of Hieracium florentinum, H. floribundum, and H. pratense. Such taxonomically related species can live in the same area if the factors regulating the size of their populations, at any stage of the life cycle, are different (Harper et al. 1961). For example, Sagar (1959) showed that Plantago major, P. media and P. lanceolata could cohabit, in part, because seeds of each species had different requirements for germination.