The sand goby (Pomatoschistus spp.) is a small estuarine fish. Its abundance, life history, and sedentary nature lead to its adoption as a key species in the U.K. Endocrine Disruption in the Marine Environment (EDMAR) Program. This study investigated the presence of classic markers of estrogenic exposure by determining vitellogenin (VTG) and zona radiata protein (ZRP) mRNA levels and ovotestis in estuarine-caught male gobies and investigated morphological changes in the urogenital papilla (UGP). Laboratory exposures to estrogens were also conducted to ascertain the responses of these markers. Wild-caught male fish showed no evidence of ovotestis, VTG, or ZRP mRNA induction. Laboratory exposures suggested that sensitivity of the goby to VTG/ ZRP mRNA induction was similar to flounder. The UGP inspection of wild-caught specimens revealed evidence of feminization of male papillae, a condition denoted as morphologically intermediate papilla syndrome (MIPS). Morphologically intermediate papilla syndrome was more prevalent at estrogenically contaminated sites. Juvenile goby experimentally exposed to 17beta-estradiol for 11 to 32 weeks exhibited signs of the MIPS condition, showing that it was inducible by estrogenic exposure and could therefore be a form of estrogenic endocrine disruption. The estuaries where the MIPS condition was most prevalent (>50% at certain sites) were the Tees, Mersey, and Clyde. The potential of the MIPS condition to significantly interfere with reproductive performance is discussed as well as its use as a monitoring tool for endocrine disruption in the estuarine environment.

The Sandia Fracture Challenges provide the mechanics community a forum for assessing its ability to predict ductile fracture through a blind, round-robin format where mechanicians are challenged to predict the deformation and failure of an arbitrary geometry given experimental calibration data. The Third Challenge, issued in 2017, required participants to predict fracture in an additively manufactured 316L stainless steel tensile-bar configuration containing through holes and internal cavities that could not have been conventionally machined. The volunteer participants were provided extensive materials data, from tensile tests of specimens printed on the same build tray to electron backscatter diffraction maps of the microstructure and micro-computed tomography scans of the Challenge geometry. The teams were asked to predict a number of quantities of interest in the response, including predictions of variability in the resulting fracture response, as the basis for assessment of the predictive capabilities of the modeling and simulation strategies. This paper describes the Third Challenge, compares the experimental results to the predictions, and identifies successes and gaps in capabilities in both the experimental procedures and the computational analyses to inform future investigations.

Ductile failure of structural metals is relevant to a wide range of engineering scenarios. Computational methods are employed to anticipate the critical conditions of failure, yet they sometimes provide inaccurate and misleading predictions. Challenge scenarios, such as the one presented in the current work, provide an opportunity to assess the blind, quantitative predictive ability of simulation methods against a previously unseen failure problem. Rather than evaluate the predictions of a single simulation approach, the Sandia Fracture Challenge relies on numerous volunteer teams with expertise in computational mechanics to apply a broad range of computational methods, numerical algorithms, and constitutive models to the challenge. This exercise is intended to evaluate the state of health of technologies available for failure prediction. In the first Sandia Fracture Challenge, a wide range of issues were raised in ductile failure modeling, including a lack of consistency in failure models, the importance of shear calibration data, and difficulties in quantifying the uncertainty of prediction [see Boyce et al. (Int J Fract 186:5-68, 2014) for details of these observations]. This second Sandia Fracture Challenge investigated the ductile rupture of a Ti-6Al-4V sheet under both quasi-static and modest-rate dynamic loading (failure in ∼0.1 s). Like the previous challenge, the sheet had an unusual arrangement of notches and holes that added geometric complexity and fostered a competition between tensile-and shear-dominated failure modes. The teams were asked to predict the fracture path and quantitative far-field failure metrics such as the peak force and displacement to cause crack initiation. Fourteen teams contributed blind predictions, and the experimental outcomes were quantified in three independent test labs. Additional shortcomings were revealed in this second challenge such as inconsistency in the application of appropriate boundary conditions, need for a thermomechanical treatment of the heat generation in the dynamic loading condition, and further difficulties in model calibration based on limited realworld engineering data. As with the prior challenge, this work not only documents the 'state-of-the-art' in computational failure prediction of ductile tearing scenarios, but also provides a detailed dataset for non-blind assessment of alternative methods.

Active chronic iridocyclitis is a suspected autoimmune disease, although specific autoantibodies to uveal or lens tissue are not demonstrable. The condition may respond to corticosteroid drugs, but these seldom effect a "cure" (Duke-Elder and Perkins, I966). Hence we decided to assess whether the immunosuppressive drug, azathioprine, would induce remissions of active chronic iridocyclitis, and if so, whether such remissions would be permanent. This to our knowledge has been the first fully controlled double-blind assessment using objective criteria of any form of immunosuppressive therapy in man. Methods PatientsAdult patients with diagnoses of active iritis or iridocyclitis were admitted to the trial from the Department of Ophthalmology. The patients were told that they were to be subjects of a research study and that they might receive a new drug or a "dummy" tablet for 3 months. All agreed to participate. The hospital pharmacist arranged for the patients to be allocated randomly, in approximately equal numbers, to a "treatment" group or a "control" group. Patients in the "treatment" group were given ioo mg. azathioprine twice daily for 3 months and patients in the "control" group received identical inert tablets. At monthly intervals blood examinations were made and the patients were seen in both the Ophthalmology Clihic and in the Medical Clinic. The patient, the ophthalmologists (J.B. and B.C.), and the supervising physician (I.M.) were unaware of which preparation was supplied. Systemic or local corticosteroid preparations and other standard treatments were maintained (or added) as necessary for uveitis, or for complicating systemic disease or glaucoma. Assessment of responseThe effect of the treatment, azathioprine or placebo, was assessed by the patient's subjective impressions and by a semi-quantitative recording of the following indices: visual acuity, intraocular pressure, and, by slit-lamp, "flare" and cells in the anterior chamber. Although disease was unilateral in some patients, both eyes were assessed at each examination. The scoring system shown in Table I was arranged so that an increase in score indicated an improvement in the particular index, i.e. better visual acuity, decreased intraocular pressure, or decreased flare or cells in the anterior chamber.

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