Localisation of an occult thyrotropinoma with 11^{11}C-methionine PET-CT before and after somatostatin analogue therapy

A 75-year-old woman presented to her local endocrine service with tiredness, palpitations, and enlargement of a longstanding goitre. Unexpectedly, her thyrotropin (thyroid-stimulating hormone [TSH]) concentration was not suppressed (6·3 mU/L; reference range 0·35–5·5) despite raised concentrations of thyroid hormones (free thyroxine [T$_{4}$] 89·1 pmol/L [reference range 10–19·8]; free triiodothyronine [T$_{3}$] 11·7 pmol/L [3·0–6·5]). After exclusion of laboratory assay interference, a thyrotropin-releasing hormone test showed an attenuated response (TSH at 0 min was 6·1 mU/L, at 20 min was 6·8 mU/L, and at 60 min was 8·5 mU/L), raising suspicion of a thyrotropinoma (also known as TSHoma). However, pituitary MRI was normal. The patient was referred to our centre for further assessment. On repeat MRI, the pituitary gland showed mild asymmetry (right larger than left; figure A). Functional imaging with 11C-methionine ($^{11}$C-Met) PET-CT revealed intense tracer uptake (denoting active peptide synthesis) on the right side of the sella (red hot spot in figure A). Treatment with a depot somatostatin analogue (SSA) led to resolution of symptoms and normalisation of thyroid function (TSH 0·6 mU/L, free T$_{4}$ 12·5 pmol/L, and free T$_{3}$ 3·8 pmol/L). Repeat $^{11}$C-Met PET-CT showed absence of the right-sided focal hot spot (figure B). 14 months into treatment, the patient had several hypoglycaemic episodes, which resolved after discontinuation of SSA. However, thyrotoxicosis recurred (TSH 4·3 mU/L, free T$_{4}$ 38·1 pmol/L, free T$_{3}$ 11·6 pmol/L), and repeat $^{11}$C-Met PET-CT revealed the reappearance of the right-sided hot spot (figure C). During pituitary surgery, a microthyrotropinoma was resected from the right side of the gland (figure D). The patient remains in clinical and biochemical remission more than 12 months after surgery and has normal pituitary function

Learning HCI Across Institutions, Disciplines and Countries: A Field Study of Cognitive Styles in Analytical and Creative Tasks

Human-computer interaction (HCI) is increasingly becoming a subject taught in universities around the world. However, little is known of the interactions of the HCI curriculum with students in different types of institutions and disciplines internationally. In order to explore these interactions, we studied the performance of HCI students in design, technology and business faculties in universities in UK, India, Namibia, Mexico and China who participated in a common set of design and evaluation tasks. We obtained participants’ cognitive style profiles based on Allinson and Hayes scale in order to gain further insights into their learning styles and explore any relation between these and performance. We found participants’ cognitive style preferences to be predominantly in the adaptive range, i.e. with combined analytical and intuitive traits, compared to normative data for software engineering, psychology and design professionals. We further identified significant relations between students’ cognitive styles and performance in analytical and creative tasks of a HCI professional individual. We discuss the findings in the context of the distinct backgrounds of the students and universities that participated in this study and the value of research that explores and promotes diversity in HCI education

Deafening silence? Marxism, international historical sociology and the spectre of Eurocentrism

Approaching the centenary of its establishment as a formal discipline, International Relations today challenges the ahistorical and aspatial frameworks advanced by the theories of earlier luminaries. Yet, despite a burgeoning body of literature built on the transdisciplinary efforts bridging International Relations and its long-separated nomothetic relatives, the new and emerging conceptual frameworks have not been able to effectively overcome the challenge posed by the ‘non-West’. The recent wave of international historical sociology has highlighted possible trajectories to problematise the myopic and unipolar conceptions of the international system; however, the question of Eurocentrism still lingers in the developing research programmes. This article interjects into the ongoing historical materialist debate in international historical sociology by: (1) conceptually and empirically challenging the rigid boundaries of the extant approaches; and (2) critically assessing the postulations of recent theorising on ‘the international’, capitalist states-system/geopolitics and uneven and combined development. While the significance of the present contributions in international historical sociology should not be understated, it is argued that the ‘Eurocentric cage’ still occupies a dominant ontological position which essentially silences ‘connected histories’ and conceals the role of inter-societal relations in the making of the modern states-system and capitalist geopolitics

Therapeutic opportunities within the DNA damage response

The DNA damage response (DDR) is essential for maintaining the genomic integrity of the cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have been exploited therapeutically in the treatment of cancer with radiation therapies or genotoxic chemotherapies. More recently, protein components of the DDR systems have been identified as promising avenues for targeted cancer therapeutics. Here, we present an in-depth analysis of the function, role in cancer and therapeutic potential of 450 expert-curated human DDR genes. We discuss the DDR drugs that have been approved by the US Food and Drug Administration (FDA) or that are under clinical investigation. We examine large-scale genomic and expression data for 15 cancers to identify deregulated components of the DDR, and we apply systematic computational analysis to identify DDR proteins that are amenable to modulation by small molecules, highlighting potential novel therapeutic targets

Evaluation of a novel wafer-scale CMOS APS X-ray detector for use in mammography

The most important factors that affect the image quality are contrast, spatial resolution and noise. These factors and their relationship are quantitatively described by the Contrast-to-Noise Ratio (CNR), Signal-to-Noise Ratio (SNR), Modulation Transfer Function (MTF), Noise Power Spectrum (NPS) and Detective Quantum Efficiency (DQE) parameters. The combination of SNR, MTF and NPS determines the DQE, which represents the ability to visualize object details of a certain size and contrast at a given dose. In this study the performance of a novel large area Complementary Metal-Oxide-Semiconductor (CMOS) Active Pixel Sensor (APS) X-ray detector, called DynAMITe (Dynamic range Adjustable for Medical Imaging Technology), was investigated and compared to other three digital mammography systems (namely a) Large Area Sensor (LAS), b) Hamamatsu C9732DK, and c) Anrad SMAM), in terms of physical characteristics and evaluation of the image quality. DynAMITe detector consists of two geometrically superimposed grids: a) 2560 × 2624 pixels at 50 μm pitch, named Sub-Pixels (SP camera) and b) 1280 × 1312 pixels at 100 μm pitch, named Pixels (P camera). The X-ray performance evaluation of DynAMITe SP detector demonstrated high DQE results (0.58 to 0.64 at 0.5 lp/mm). Image simulation based on the X-ray performance of the detectors was used to predict and compare the mammographic image quality using ideal software phantoms: a) one representing two three dimensional (3-D) breasts of various thickness and glandularity to estimate the CNR between simulated microcalcifications and the background, and b) the CDMAM 3.4 test tool for a contrast-detail analysis of small thickness and low contrast objects. The results show that DynAMITe SP detector results in high CNR and contrast-detail performance. © 2012 IEEE

Observations on the Estrogenic Activity and Concentration of 17b-Estradiol in the Discharges of 12 Wastewater Treatment Plants in Southern Australia

Abstract There is very little information on the overall level of estrogenic activity, or concentrations of specific hormonal compounds in wastewater treatment plant (WWTP) discharges in Australia, compared with Europe, Japan, and North America. To partly address this, in 2004, water samples were collected as ‘‘grab’’ or ‘‘spot’’ samples from 12 WWTP facilities across southern Victoria at the point at which effluent enters the environment, either as recycled water or direct discharge to the receiving water. The WWTPs were of a variety of treatment types and served a diverse range of rural and regional municipalities. For instance, of the 12 WWTPs, 3 served municipalities with populations greater than 100,000, 4 with populations between 20,000 and 100,000, and 5 with populations less than 5,000. The principal treatment process in six was an activated sludge system, and three were trickle-filter-based systems. The remaining plants fall into a ‘‘miscellaneous’’ category, each plant having a mixture of treatment processes within the overall systems. The estrogenic activity and 17b-estradiol concentrations of the samples were assessed using a yeast-based, in vitro reporter gene assay and enzyme-linked immunosorbant assays, respectively. Most of the effluents showed estrogenic activity in the assays (hER, no response: 7.9 ng/L EEQ; mER, no response: 44.5 ng/L EEQ). There was no correlation between estrogenic response and the results of a concurrent toxicity assay, suggesting that a lack of bioassay response was related to lack of estrogenic compounds, rather than the direct toxic effect of the sample. Estradiol concentrations were for the most part in the range 2–5 ng/L, with one sample at 18 ng/L. Despite the assurance our results might provide (of minimal impact in most cases if there is significant dilution), there is still a need for further extensive on-ground reassurance research to provide data for higherlevel risk assessment by industry and government agencies. In particular, more research is warranted to verify the estrogenic activity and to expand the range of specific hormone/metabolites reported in these studies. Moreover, studies are required to determine if the estrogenic activity reported in this and other recent Australian studies is sufficient to induce a physiological effect in exposed aquatic organisms, especially Australian native fish