Bayesian photon counting with electron-multiplying charge coupled devices (EMCCDs)

The EMCCD is a CCD type that delivers fast readout and negligible detector noise, making it an ideal detector for high frame rate applications. Because of the very low detector noise, this detector can potentially count single photons. Considering that an EMCCD has a limited dynamical range and negligible detector noise, one would typically apply an EMCCD in such a way that multiple images of the same object are available, for instance, in so called lucky imaging. The problem of counting photons can then conveniently be viewed as statistical inference of flux or photon rates, based on a stack of images. A simple probabilistic model for the output of an EMCCD is developed. Based on this model and the prior knowledge that photons are Poisson distributed, we derive two methods for estimating the most probable flux per pixel, one based on thresholding, and another based on full Bayesian inference. We find that it is indeed possible to derive such expressions, and tests of these methods show that estimating fluxes with only shot noise is possible, up to fluxes of about one photon per pixel per readout.Comment: Fixed a few typos compared to the published versio

Methamphetamine Induces Striatal Cell Death Followed by the Generation of New Cells and a Second Round of Cell Death in Mice

Our laboratory has been investigating the impact of a neurotoxic exposure to methamphetamine (METH) on cellular components of the striatum post-synaptic to the dopaminergic terminals. A systemic bolus injection of METH (30 mg/kg, ip) induces the production of new cells in the striatum during a period lasting from 24-48 hours after METH. The newly generated cells arise from dormant striatal progenitors and not from the subventricular zone. The newly generated cells display glial phenotypes and begin to die 24 hours after birth, or 2.5 days post-METH. The protracted phase of cell death lasts for at least three months post-METH at which time the bulk of the newly generated cells have disappeared. The METH-induced production of new cells is associated with enlarged striatal volume (up to 50% larger than controls in some animals). As the newly generated cells die over a period of three months, the enlarged striatal volume normalizes. In conclusion, a neurotoxic dose of METH induces the generation of new cells in the striatum associated with enlarged striatal volume. The new cells die over three months post-METH and the enlarged striatal volume returns to control levels. This observation is significant because studies involving METH users show striatal enlargement and the normalization of striatal volume in METH users who have been abstinent for up to 20 months

Factoring attitudes towards conflict risk into selection of protected areas for conservation

The high incidence of armed conflicts in biodiverse regions poses significant challenges in achieving international conservation targets. Because attitudes towards risk vary, we assessed different strategies for protected area planning that reflected alternative attitudes towards the risk of armed conflicts. We find that ignoring conflict risk will deliver the lowest return on investment. Opting to completely avoid conflict-prone areas offers limited improvements and could lead to species receiving no protection. Accounting for conflict by protecting additional areas to offset the impacts of armed conflicts would not only increase the return on investment (an effect that is enhanced when high-risk areas are excluded) but also increase upfront conservation costs. Our results also demonstrate that fine-scale estimations of conflict risk could enhance the cost-effectiveness of investments. We conclude that achieving biodiversity targets in volatile regions will require greater initial investment and benefit from fine-resolution estimates of conflict risk

Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development

Stranded research? Leading finance journals are silent on climate change

Finance research has shaped the modern financial system, influencing investors and market participants directly through research findings and indirectly through teaching and training programmes. Climate change presents major risks to the global financial system as well as new opportunities for investors. Is climate finance an important topic in finance research? We systematically analyse the content of 20,725 articles published in the leading 21 finance journals between January 1998 and June 2015. We find that only 12 articles (0.06%) are related in some way to climate finance. The three elite finance journals (Journal of Finance, Journal of Financial Economics and Review of Financial Studies) did not publish a single article related to climate finance over the 17.5-year period. We repeat our analysis across a sample of 29 elite business journals spanning accounting, economics, management, marketing and operations research, as well as finance. We find a similar dearth of published climate finance research. We consider four possible explanations for this failure of top finance and business journals to engage with climate finance as a research topic. These include methodological constraints and editorial policies. We conclude by arguing why it is critical for climate-related research to be given greater attention and prominence in finance journals

Determinants of impact : towards a better understanding of encounters with the arts

The article argues that current methods for assessing the impact of the arts are largely based on a fragmented and incomplete understanding of the cognitive, psychological and socio-cultural dynamics that govern the aesthetic experience. It postulates that a better grasp of the interaction between the individual and the work of art is the necessary foundation for a genuine understanding of how the arts can affect people. Through a critique of philosophical and empirical attempts to capture the main features of the aesthetic encounter, the article draws attention to the gaps in our current understanding of the responses to art. It proposes a classification and exploration of the factors—social, cultural and psychological—that contribute to shaping the aesthetic experience, thus determining the possibility of impact. The ‘determinants of impact’ identified are distinguished into three groups: those that are inherent to the individual who interacts with the artwork; those that are inherent to the artwork; and ‘environmental factors’, which are extrinsic to both the individual and the artwork. The article concludes that any meaningful attempt to assess the impact of the arts would need to take these ‘determinants of impact’ into account, in order to capture the multidimensional and subjective nature of the aesthetic experience

Bladder cancer diagnosis and identification of clinically significant disease by combined urinary detection of Mcm5 and nuclear matrix protein 22.

Urinary biomarkers for bladder cancer detection are constrained by inadequate sensitivity or specificity. Here we evaluate the diagnostic accuracy of Mcm5, a novel cell cycle biomarker of aberrant growth, alone and in combination with NMP22

Mapping policies and programmes: the use of GIS to communicate spatial relationships in England

It has long been acknowledged that there is a gap between the advancement of GIS in the research field and its application in planning practice. This paper demonstrates the potential for employing simple GIS mapping overlays as a way of communicating complex planning issues in a ‘language’ that is easily understandable and effective at stimulating policy debate, critical thinking and learning. The analysis focuses on capturing the synergies and conflicts in two key planning challenges in England, progrowth and housing delivery agendas. In a political context where spatial evidencebased policymaking has been eroded in recent years, the analysis demonstrates the need for policymakers to ‘think spatially, act spatially’ when developing different policies and programmes. The paper concludes that only by making spatial relationships of policies and programmes explicit in a manner that is easily understood by a range of actors, can different spatial scenarios and metaphors of future opportunities and challenges be developed to inform long-range development and planning

The exceptional value of intact forest ecosystems

As the terrestrial human footprint continues to expand, the amount of native forest that is free from significant damaging human activities is in precipitous decline. There is emerging evidence that the remaining intact forest supports an exceptional confluence of globally significant environmental values relative to degraded forests, including imperilled biodiversity, carbon sequestration and storage, water provision, indigenous culture and the maintenance of human health. Here we argue that maintaining and, where possible, restoring the integrity of dwindling intact forests is an urgent priority for current global efforts to halt the ongoing biodiversity crisis, slow rapid climate change and achieve sustainability goals. Retaining the integrity of intact forest ecosystems should be a central component of proactive global and national environmental strategies, alongside current efforts aimed at halting deforestation and promoting reforestation

Orthodontic treatment needs in the western region of Saudi Arabia: a research report

BACKGROUND: Evaluation of self perceived and actual need for orthodontic treatment helps in planning orthodontic services and estimating the required resources and man power. In the present study, the perceptive need as evaluated by patients and the actual need to orthodontic treatment, as assessed by orthodontists, were evaluated at two types of dental practices in the city of Jeddah using the Index of Orthodontic Treatment Need (IOTN). METHODS: A consecutive sample of 743 adults seeking orthodontic treatment at two different types of dental practices in Jeddah; King Abdulaziz University, Faculty of Dentistry (KAAU) (Free treatment) and two private dental polyclinics (PDP) (Paid treatment), was examined for orthodontic treatment need using the dental health component (DHC) of the IOTN. The self-perceived need for orthodontic treatment was also determined using the aesthetic component (AC) of the IOTN. The IOTN score and the incidence of each variable were calculated statistically. AC and DHC categories were compared using the Chi-Square and a correlation between them was assessed using Spearman's correlation test. AC and DHC were also compared between the two types of dental practices using the Chi-Square. RESULTS: The results revealed that among the 743 patients studied, 60.6% expressed no or slight need for treatment, 23.3% expressed moderate to borderline need and only16.1% thought they needed orthodontic treatment. Comparing these estimates to professional judgments, only 15.2% conformed to little or no need for treatment, 13.2% were assessed as in borderline need and 71.6% were assessed as in need for treatment (p < 0.001). Spearman's correlation test proved no correlation (r = -.045) between the two components. Comparing the AC and the DHC between the KAAU group and PDP group showed significant differences between the two groups (p < 0.001). CONCLUSION: Patient's perception to orthodontic treatment does not always correlate with professional assessment. The IOTN is a valid screening tool that should be used in orthodontic clinics for better services especially, in health centers that provide free treatment