Disorders of Sex Development: Lessons to be Learned from Studies of Spina Bifida and Craniofacial Conditions

The purpose of this review is to discuss research methods and clinical management strategies employed with other conditions (i. e., spina bifida and craniofacial conditions) and how these methods and strategies could be applied to youth with disorders of sex development (DSD). The review focuses specifically on the potential overlap between DSD and these other conditions across the following 3 areas: (1) developmentally- oriented theories that underlie the research base for chronic physical conditions; (2) research designs and methodological features that have proved fruitful in these areas; and (3) the potential applicability to DSD of clinical management practices for youth with craniofacial conditions

Amortised resource analysis with separation logic

Type-based amortised resource analysis following Hofmann and Jost—where resources are associated with individual elements of data structures and doled out to the programmer under a linear typing discipline—have been successful in providing concrete resource bounds for functional programs, with good support for inference. In this work we translate the idea of amortised resource analysis to imperative languages by embedding a logic of resources, based on Bunched Implications, within Separation Logic. The Separation Logic component allows us to assert the presence and shape of mutable data structures on the heap, while the resource component allows us to state the resources associated with each member of the structure. We present the logic on a small imperative language with procedures and mutable heap, based on Java bytecode. We have formalised the logic within the Coq proof assistant and extracted a certified verification condition generator. We demonstrate the logic on some examples, including proving termination of in-place list reversal on lists with cyclic tails

Memory usage verification using Hip/Sleek.

Embedded systems often come with constrained memory footprints. It is therefore essential to ensure that software running on such platforms fulfils memory usage specifications at compile-time, to prevent memory-related software failure after deployment. Previous proposals on memory usage verification are not satisfactory as they usually can only handle restricted subsets of programs, especially when shared mutable data structures are involved. In this paper, we propose a simple but novel solution. We instrument programs with explicit memory operations so that memory usage verification can be done along with the verification of other properties, using an automated verification system Hip/Sleek developed recently by Chin et al.[10,19]. The instrumentation can be done automatically and is proven sound with respect to an underlying semantics. One immediate benefit is that we do not need to develop from scratch a specific system for memory usage verification. Another benefit is that we can verify more programs, especially those involving shared mutable data structures, which previous systems failed to handle, as evidenced by our experimental results

MATRIX Reference Reports

The Multi-HAzard and MulTi-RIsK Assessment MethodS for Europe or MATRIX project (01.10.2010 to 31.12.2013), coordinated by the GFZ, set out to tackle some of the issues associated with multi-hazard and risk assessment. Disaster risk reduction (DDR) activities generally treat different natural hazards and their associated risks separately within what may be termed a "single-type" approach. However, this ignores the spatial and temporal interactions that often arise along the disaster risk chain. For instance, one hazardous event may trigger others, e.g., earthquakes causing tsunamis, or several different types may occur concurrently, e.g., severe weather and earthquakes. Considering vulnerability, an initial event would leave a community more susceptible to future, possibly different, hazards, e.g., an earthquake weakening buildings which are damaged further by windstorms. The temporal dimension may include changes in exposure, e.g., increased urbanisation, altering the total risk to an area, while repeated events lessen a community's resilience. Meanwhile, although losses are estimated by usually only considering direct economic losses or casualties, this ignores less tangible losses such as reduced business activity or the loss of cultural heritage. In short, the total risk estimated when incorporating interactions between multiple hazards and risks is likely to be greater than the sum of the individual parts. Hence, for a more comprehensive risk assessment paradigm, these, and other, interactions need to be considered. Therefore, MATRIX set out to develop concepts, methods, frameworks and tools for dealing with risk assessment within a multi-hazard and risk environment. The focus was on the hazards that most affect Europe, namely earthquakes, landslides, volcanos, tsunamis, wild fires, storms and fluvial and coastal flooding. Interactions at all the different levels were considered, such as cascading events and time dependency in vulnerability. The resulting products were applied at three test cases: Naples, Italy, the French West Indies, and Cologne, Germany. Considerable interaction with end-users was also undertaken, including identifying biases at the individual and institutional level which may hinder employing a multi-type framework for risk governance. This Scientific Technical Report presents two so-called "Reference reports" produced during the MATRIX project. These reports were provided to the European Commission as deliverables, namely D8.4 "MATRIX Results I and Reference Report" and D8.5 "MATRIX Results II and Reference Report". D8.4 presented a series of specific reports outlining the results of the project, written in a manner accessible not only to the specialist but with a broader audience in mind. D8.5 deals with the risk governance within a multi-hazard and risk context and has since been published. We therefore divide with document in two, where part 1 represented the outcomes presented in D8.4 while D8.5 forms part 2. We believe the MATRIX project was a very important step towards the goal of establishing the multi-hazard and risk environment as the norm within a European context, and we hope that the reader will benefit from the results presented here

Expression of the androgen receptor and an androgen-responsive protein, apolipoprotein D, in human breast cancer.

Little is known regarding the activity and function of the androgen receptor (AR) in human breast cancer. In the present study AR was evaluated in untreated primary breast cancers using antisera to the amino- and carboxy-termini of the receptor and quantitated using colour video image analysis. A strong correlation between tissue concentration and percentage AR-positive cells was observed for each antiserum. However, comparison of percentage positive cells using the amino- and carboxy-terminal AR antisera in individual breast cancer specimens revealed a subset of tumours with discordantly increased staining for the carboxy terminus. These findings suggest the presence of amino-terminal-truncated AR in a proportion of breast cancer cells or presence of AR mutations or associated protein alterations that affect binding of the amino-terminal AR antiserum. Immunohistochemical expression of the androgen-regulated glycoprotein, apolipoprotein D (apo-D), was also evaluated in the breast cancer specimens. Focal positivity of apo-D staining, which did not always co-localise with AR-positive cells, was observed within breast tumours. Furthermore, no correlation was evident between percentage positive cells stained for AR and apo-D in breast cancer specimens. These findings indicate that, although apo-D expression is androgen regulated in human breast cancer cell lines in vitro, its expression in primary breast cancers may be regulated by other factors. The expression of AR in primary breast cancers also suggests that the receptor may be involved in tumour responsiveness or in abnormal responses to endocrine therapies

Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

Sustainability and the financial system – Review of Literature

open access articleMuch actuarial work is underpinned by the use of economic models derived from mainstream academic theories of finance and economics which treat money as being a neutral medium of exchange. The sustainability of a financial system whose understanding is based on a limited view of the role of money has increasingly been subject to criticism. In order to identify needed research programmes to address such criticisms and improve these disciplines, we sought to understand the current state of knowledge in economics and finance concerning the link between monetary and financial factors and sustainability. We have approached this through a search for relevant literature published in the highest-rated academic journals in economics, finance and the social sciences for titles and abstracts containing both references to the financial system on the one hand, and sustainability and environmental factors on the other. The systematic search of a universe of 125 journals and 355,000 articles yielded the finding that surprisingly few research papers jointly address these concepts. Nevertheless, we find that current research shares a broad consensus that the implications of the growth-oriented economic model results in an increasingly interconnected and fragile financial system whose participants are not incentivised to fully recognise the natural environment and resource constraints. We further observe that the prescriptions offered are relatively limited and small-scale in their outlook and that there is a vital need for further research, particularly for actuaries who are required to take a longer-term outlook. The Resource and Environment Board has supported this work with two key objectives: first, to identify research that may have direct application to actuarial work and, second, to identify gaps in academic research that would help drive the Institute and Faculty of Actuaries’ own research agenda. With this in mind there are three further areas of potential actuarial research. These are the policy aim of pursuing growth without limit within a finite ecosystem; discount factors as the primary means of capital allocation and investment decisions; and the use of gross domestic product as the key metric of economic activity and success. We also conclude that further academic research is urgently needed to understand the sustainability of the banking and monetary system