Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice

<b>Background</b>: Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM) has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM.<BR/> <b>Methods</b>: This was an observational study of the testicular phenotype of different mouse models. The mouse models were: cryptorchid mice, mice lacking androgen receptors (ARs) on the Sertoli cells (SCARKO), mice with a ubiquitous loss of androgen ARs (ARKO), hypogonadal (hpg) mice which lack circulating gonadotrophins, and hpg mice crossed with SCARKO (hpg.SCARKO) and ARKO (hpg.ARKO) mice.<BR/> <b>Results</b>: Microscopic TM was seen in 94% of hpg.ARKO mice (n=16) and the mean number of microliths per testis was 81 +/- 54. Occasional small microliths were seen in 36% (n=11) of hpg testes (mean 2 +/- 0.5 per testis) and 30% (n=10) of hpg.SCARKO testes (mean 8 +/- 6 per testis). No microliths were seen in cryptorchid, ARKO or SCARKO mice. There was no significant effect of FSH or androgen on TM in hpg.ARKO mice.<BR/> <b>Conclusions</b>: We have identified a mouse model of TM and show that lack of endocrine stimulation is a cause of TM. Importantly, this model will provide a means with which to identify the mechanisms of TM development and the underlying changes in protein and gene expression

Plasticity and rectangularity in survival curves

Living systems inevitably undergo a progressive deterioration of physiological function with age and an increase of vulnerability to disease and death. To maintain health and survival, living systems should optimize survival strategies with adaptive interactions among molecules, cells, organs, individuals, and environments, which arises plasticity in survival curves of living systems. In general, survival dynamics in a population is mathematically depicted by a survival rate, which monotonically changes from 1 to 0 with age. It would be then useful to find an adequate function to describe complicated survival dynamics. Here we describe a flexible survival function, derived from the stretched exponential function by adopting an age-dependent shaping exponent. We note that the exponent is associated with the fractal-like scaling in cumulative mortality rate. The survival function well depicts general features in survival curves; healthy populations exhibit plasticity and evolve towards rectangular-like survival curves, as examples in humans or laboratory animals

Informed consent in veterinary medicine: ethical implications for the profession and the animal 'patient'

Informed consent processes are a vital component of both human and veterinary medicine. Current practice encourages veterinarians to learn from insights in the human medical field about how best to achieve valid consent. However, drawing on published literature in veterinary and medical ethics, this paper identifies considerable differences between the purposes of veterinary and human medical consent. Crucially, it is argued that the legal status of animal patients as ‘property’ has implications for the ethical role of veterinary informed consent and the protection of the animal ‘patient’. It is suggested that veterinary informed consent should be viewed as an ethical pivot point where the multiple responsibilities of a veterinary professional converge. In practice, balancing these responsibilities creates considerable ethical challenges. As an example, the paper discusses the renewed call for UK veterinarians to make animal welfare their first priority; we predict that this imperative may increasingly cause veterinary informed consent to become an ethical pressure point due to tensions caused by the often conflicting interests of animals, owners and the veterinary profession. In conclusion, the paper argues that whilst gaining informed consent can often be presented as a robust ethical justification in human medicine, the same cannot be said in veterinary medicine. If the veterinary profession wish to prioritise animal welfare, there is an urgent need to re-evaluate the nature of authority gained through owner informed consent and to consider whether animal patients might need to be better protected outside the consent process in certain circumstances

Space- and time-resolved investigation on diffusion kinetics of human skin following macromolecule delivery by microneedle arrays

Microscale medical devices are being developed for targeted skin delivery of vaccines and the extraction of biomarkers, with the potential to revolutionise healthcare in both developing and developed countries. The effective clinical development of these devices is dependent on understanding the macro-molecular diffusion properties of skin. We hypothesised that diffusion varied according to specific skin layers. Using three different molecular weights of rhodamine dextran (RD) (MW of 70, 500 and 2000 kDa) relevant to the vaccine and therapeutic scales, we deposited molecules to a range of depths (0–300 µm) in ex vivo human skin using the Nanopatch device. We observed significant dissipation of RD as diffusion with 70 and 500 kDa within the 30 min timeframe, which varied with MW and skin layer. Using multiphoton microscopy, image analysis and a Fick’s law analysis with 2D cartesian and axisymmetric cylindrical coordinates, we reported experimental trends of epidermal and dermal diffusivity values ranging from 1–8 µm2 s-1 to 1–20 µm2 s-1 respectively, with a significant decrease in the dermal-epidermal junction of 0.7–3 µm2 s-1. In breaching the stratum corneum (SC) and dermal-epidermal junction barriers, we have demonstrated practical application, delivery and targeting of macromolecules to both epidermal and dermal antigen presenting cells, providing a sound knowledge base for future development of skin-targeting clinical technologies in humans

Feasibility and acceptability of point of care HIV testing in community outreach and GUM drop-in services in the North West of England: A programmatic evaluation

Background: In Liverpool, injecting drug users (IDUs), men-who-have-sex-with-men (MSM) and UK Africans experience a disproportionate burden of HIV, yet services do not reach out to these groups and late presentations continue. We set out to: increase testing uptake in targeted marginalized groups through a community and genitourinary medicine (GUM)-based point of care testing (POCT) programme; and conduct a process evaluation to examine service provider inputs and document service user perceptions of the programme. Methods: Mixed quantitative, qualitative and process evaluation methods were used. Service providers were trained to use fourth generation rapid antibody/antigen HIV tests. Existing outreach services incorporated POCT into routine practice. Clients completed a semi-structured questionnaire and focus group discussions (FGDs) were held with service providers. Results: Between September 2009 and June 2010, 953 individuals underwent POCT (GUM: 556 [59%]; communitybased sites: 397 [42%]). Participants in the community were more likely to be male (p = 0.028), older (p < 0.001), of UK African origin (p < 0.001) and IDUs (p < 0.001) than participants from the GUM clinic. Seventeen new HIV diagnoses were confirmed (prevalence = 1.8%), 16 of whom were in risk exposure categories (prevalence: 16/517, 3.1%). Questionnaires and FGDs showed that clients and service providers were supportive of POCT, highlighting benefits of reaching out to marginalised communities and incorporating HIV prevention messages. Conclusions: Community and GUM clinic-based POCT for HIV was feasible and acceptable to clients and service providers in a low prevalence setting. It successfully reached target groups, many of whom would not have otherwise tested. We recommend POCT be considered among strategies to increase the uptake of HIV testing among groups who are currently underserved

Nuclear β-catenin expression is closely related to ulcerative growth of colorectal carcinoma

Although most colorectal cancer develops based on the adenoma–adenocarcinoma sequence, morphologically, colorectal cancer is not a homogeneous disease entity. Generally, there are two distinct morphological types: polypoid and ulcerative colorectal tumours. Previous studies have demonstrated that K-ras codon 12 mutations are preferentially associated with polypoid growth of colorectal cancer; however, little is known about the molecular mechanism that determines ulcerative growth of colorectal cancer. β-catenin complex plays a critical role both in tumorigenesis and morphogenesis. We examined the differential expression of β-catenin and its related factors among different types of colorectal cancer in order to determine any relationship with gross tumour morphology. Immunohistochemical staining of β-catenin, E-cadherin and MMP-7 was performed on 51 tumours, including 26 polypoid tumours and 25 ulcerative tumours. Protein truncation tests and single-strand conformational polymorphism for mutation of the adenomatous polyposis coli tumour suppressor gene, as well as single-strand conformational polymorphism for the mutation of β-catenin exon 3 were also done. Nuclear expression of β-catenin was observed in 18 out of 25 (72%) cases of ulcerative colorectal cancer and seven out of 26 (26.9%) cases of polypoid colorectal cancer. A significant relationship of nuclear β-catenin expression with ulcerative colorectal cancer was found (P<0.001). However, this finding was independent of adenomatous polyposis coli tumour suppressor gene mutation and E-cadherin expression. Together with previous data, we propose that different combinations of genetic alterations may underlie different morphological types of colorectal cancer. These findings should be taken into consideration whenever developing a new genetic diagnosis or therapy for colorectal cancer

First International External Quality Assessment Study on Molecular and Serological Methods for Yellow Fever Diagnosis

Objective: We describe an external quality assurance (EQA) study designed to assess the efficiency and accurateness of molecular and serological methods used by expert laboratories performing YF diagnosis. Study Design: For molecular diagnosis evaluation, a panel was prepared of 14 human plasma samples containing specific RNA of different YFV strains (YFV-17D, YFV South American strain [Brazil], YFV IvoryC1999 strain), and specificity samples containing other flaviviruses and negative controls. For the serological panel, 13 human plasma samples with anti-YFVspecific antibodies against different strains of YFV (YFV-17D strain, YFV IvoryC1999 strain, and YFV Brazilian strain), as well as specificity and negative controls, were included. Results: Thirty-six laboratories from Europe, the Americas, Middle East, and Africa participated in these EQA activities. Only 16% of the analyses reported met all evaluation criteria with optimal performance. Serial dilutions of YFV-17D showed that in general the methodologies reported provided a suitable sensitivity. Failures were mainly due to the inability to detect wild-type strains or the presence of false positives. Performance in the serological diagnosis varied, mainly depending on the methodology used. Anti-YFV IgM detection was not performed in 16% of the reports using IIF or ELISA techniques, although it is preferable for the diagnosis of YFV acute infections. A good sensitivity profile was achieved in general; however, in the detection of IgM antibodies a lack of sensitivity of anti-YFV antibodies against the vaccine strain 17D was observed, and of the anti-YFV IgG antibodies against a West African strain. Neutralization assays showed a very good performance; however, the unexpected presence of false positives underlined the need of improving the running protocols. Conclusion: This EQA provides information on each laboratory’s efficacy of RT-PCR and serological YFV diagnosis techniques. The results indicate the need for improving serological and molecular diagnosis techniques and provide a follow-up of the diagnostic profiles

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN