Storm surge frequency reduction in Venice under climate change

Increased tidal levels and storm surges related to climate change are projected to result in extremely adverse effects on coastal regions. Predictions of such extreme and small-scale events, however, are exceedingly challenging, even for relatively short time horizons. Here we use data from observations, ERA-40 reanalysis, climate scenario simulations, and a simple feature model to find that the frequency of extreme storm surge events affecting Venice is projected to decrease by about 30% by the end of the twenty-first century. In addition, through a trend assessment based on tidal observations we found a reduction in extreme tidal levels. Extrapolating the current +17 cm/century sea level trend, our results suggest that the frequency of extreme tides in Venice might largely remain unaltered under the projected twenty-first century climate simulations.

Application of the BRAFO-tiered approach for benefit-risk assessment to case studies on natural foods

There is evidence that consumption of fish, especially oily fish, has substantial beneficial effects on health. In particular an inverse relationship of oily fish intake to coronary heart disease incidence has been established. These beneficial effects are ascribed to fish oil components including long chain ω-3 polyunsaturated fatty acids. On the other hand it should be noted that oily fish also contains hazardous substances such as dioxins, PCBs and methylmercury. Soy consumption has been associated with potential beneficial and adverse effects. The claimed benefits include reduced risk of cardiovascular disease; osteoporosis, breast and prostate cancer whereas potential adverse effects include impaired thyroid function, disruption of sex hormone levels, changes in reproductive function and increased breast cancer risk The two cases of natural foods highlight the need to consider both risks and benefits in order to establish the net health impact associated to the consumption of specific food products. Within the Sixth Framework programme of the European Commission, the BRAFO project was funded to develop a framework that allows for the quantitative comparison of human health risks and benefits in relation to foods and food compounds. This paper describes the application of the developed framework to two natural foods, farmed salmon and soy protein. We conclude that the BRAFO methodology is highly applicable to natural foods. It will help the benefit-risk managers in selecting the appropriate dietary recommendations for the population.

Soy products in the management of breast cancer

Purpose of review: Meta-analyses of epidemiological studies of soy consumption and breast cancer risk have demonstrated modest protective effects, usually attributed to isoflavones. Concern has been expressed, however, that the estrogenic activity of isoflavones may have adverse effects on breast cancer recurrence. Recent findings: The review covers epidemiological studies that have investigated the impact of soy consumption in breast cancer patients on recurrence and mortality. There are preliminary data to suggest that soy has differential effects on recurrence in human epidermal growth factor receptor-2 positive and human epidermal growth factor receptor-2 negative tumours. Recent studies on mechanisms of action of soy in breast cancer provide insights into epigenetic effects and the interaction of isoflavones with IGF-1 and with a number of polymorphisms of genes associated with breast cancer risk such as MDM2 and CYP1B1. Summary: Overall, these studies indicate that soy foods consumed at levels comparable to those in Asian populations have no detrimental effects on risk of breast cancer recurrence and in some cases significantly reduce the risk. Importantly, soy does not appear to interfere with tamoxifen or anastrozole therapy. Recent research suggests that women who are at increased risk of breast cancer due to polymorphisms in genes associated with the disease may especially benefit from high soy isoflavone intake.

Legal outlier, again? U.S. felon suffrage: comparative and international human rights perspectives

The judiciousness of American felon suffrage policies has long been the subject of scholarly debate, not least due to the large number of affected Americans: an estimated 5.3 million citizens are ineligible to vote as a result of a criminal conviction. This article offers comparative law and international human rights perspectives and aims to make two main contributions to the American and global discourse. After an introduction in Part I, Part II offers comparative law perspectives on challenges to disenfranchisement legislation, juxtaposing U.S. case law against recent judgments rendered by courts in Canada, South Africa, Australia, and by the European Court of Human Rights. The article submits that owing to its unique constitutional stipulations, as well as to a general reluctance to engage foreign legal sources, U.S. jurisprudence lags behind an emerging global jurisprudential trend that increasingly views convicts’ disenfranchisement as a suspect practice and subjects it to judicial review. This transnational judicial discourse follows a democratic paradigm and adopts a “residual liberty” approach to criminal justice that considers convicts to be rights-holders. The discourse rejects regulatory justifications for convicts’ disenfranchisement, and instead sees disenfranchisement as a penal measure. In order to determine its suitability as a punishment, the adverse effects of disenfranchisement are weighed against its purported social benefits, using balancing or proportionality review. Part III analyzes the international human rights treaty regime. It assesses, in particular, Article 25 of the International Covenant on Civil and Political Rights (“ICCPR”), which proclaims that “every citizen” has a right to vote without “unreasonable restrictions.” The analysis concludes that the phrase “unreasonable restrictions” is generally interpreted in a manner which tolerates certain forms of disenfranchisement, whereas other forms (such as life disenfranchisement) may be incompatible with treaty obligations. This article submits that disenfranchisement is a normatively flawed punishment. It fails to treat convicts as politically-equal community members, degrades them, and causes them grave harms both as individuals and as members of social groups. These adverse effects outweigh the purported social benefits of disenfranchisement. Furthermore, as a core component of the right to vote, voter eligibility should cease to be subjected to balancing or proportionality review. The presumed facilitative nature of the right to vote makes suffrage less susceptible to deference-based objections regarding the judicial review of legislation, as well as to cultural relativity objections to further the international standardization of human rights obligations. In view of this, this article proposes the adoption of a new optional protocol to the ICCPR proscribing convicts’ disenfranchisement. The article draws analogies between the proposed protocol and the ICCPR’s “Optional Protocol Aiming at the Abolition of the Death Penalty.” If adopted, the proposed protocol would strengthen the current trajectory towards expanding convicts’ suffrage that emanates from the invigorated transnational judicial discourse.

Polyphenols in the diet: friend or foe?

Polyphenols are suggested to have human health benefits, yet debate still exists over their value in the diet. This review examines their efficacy and the effect of structural diversity on their reactivity and any implications this may have with respect to possible unfavourable adverse effects. We propose that polyphenols are of benefit to humans through dietary consumption, yet care should be taken over excessive consumption, particularly in some subgroups of the population, e.g. those on certain medications because of complex nutrient–drug interactions. Pharmaceutical application should be avoided until there is greater understanding of absorption and behaviour of polyphenols within the body.

Pungent general anesthetics activate transient receptor potential-A1 to produce hyperalgesia and neurogenic bronchoconstriction

BACKGROUND: Volatile anesthetics such as isoflurane and halothane have been in clinical use for many years and represent the group of drugs most commonly used to maintain general anesthesia. However, despite their widespread use, the molecular mechanisms by which these drugs exert their effects are not completely understood. Recently, a seemingly paradoxical effect of general anesthetics has been identified: the activation of peripheral nociceptors by irritant anesthetics. This mechanism may explain the hyperalgesic actions of inhaled anesthetics and their adverse effects in the airways. METHODS: To test the hypothesis that irritant inhaled anesthetics activate the excitatory ion-channel transient receptor potential (TRP)-A1 and thereby contribute to hyperalgesia and irritant airway effects, we used the measurement of intracellular calcium concentration in isolated cells in culture. For our functional experiments, we used models of isolated guinea pig bronchi to measure bronchoconstriction and withdrawal threshold to mechanical stimulation with von Frey filaments in mice. RESULTS: Irritant inhaled anesthetics activate TRPA1 expressed in human embryonic kidney cells and in nociceptive neurons. Isoflurane induces mechanical hyperalgesia in mice by a TRPA1-dependent mechanism. Isoflurane also induces TRPA1-dependent constriction of isolated bronchi. Nonirritant anesthetics do not activate TRPA1 and fail to produce hyperalgesia and bronchial constriction. CONCLUSIONS: General anesthetics induce a reversible loss of consciousness and render the patient unresponsive to painful stimuli. However, they also produce excitatory effects such as airway irritation and they contribute to postoperative pain. Activation of TRPA1 may contribute to these adverse effects, a hypothesis that remains to be tested in the clinical setting.

Evaluation of negative photo-patternable PDMS for the encapsulation of neural electrodes

This communication examines the suitability of a photo-patternable polydimethylsiloxane (PP-PDMS) elastomer as an insulating material for implantable microelectrodes. PP-PDMS is produced by mixing a photoinitiator (2-hydroxy-2-methylpropiophenone) with the PDMS base and curing agent. Subsequent exposure to UV radiation and development of the elastomeric “photo-resist” allows for the definition of well-defined openings within the PP-PDMS film. The dielectric constants of PP-PDMS and PDMS are similar (ε ≈ 2.6, f <;1MHz). Gold film microelectrodes patterned on glass or a PDMS substrate are encapsulated with PP-PDMS, while recording sites as small as 104 μm2 can be obtained in the PP-PDMS layer. The cytotoxicity of the PP-PDMS was preliminary tested in vitro by culturing 3T3 fibroblasts in PP-PDMS extracts. No adverse effects were observed in cultures exposed to PP-PDMS films initially leached in isopropanol solvent for 48h.

Essays on labour market dualisation in Western Europe: active labour market policies, temporary work regulation and inequality

European labour markets are increasingly divided between insiders in full-time permanent employment and outsiders in precarious work or unemployment. Using quantitative as well as qualitative methods, this thesis investigates the determinants and consequences of labour market policies that target these outsiders in three separate papers. The first paper looks at Active Labour Market Policies (ALMPs) that target the unemployed. It shows that left and right-wing parties choose different types of ALMPs depending on the policy and the welfare regime in which the party is located. These findings reconcile the conflicting theoretical expectations from the Power Resource approach and the insider-outsider theory. The second paper considers the regulation and protection of the temporary work sector. It solves the puzzle of temporary re-regulation in France, which contrasts with most other European countries that have deregulated temporary work. Permanent workers are adversely affected by the expansion of temporary work in France because of general skills and low wage coordination. The interests of temporary and permanent workers for re-regulation therefore overlap in France and left governments have an incentive to re-regulate the sector. The third paper then investigates what determines inequality between median and bottom income workers. It shows that non-inclusive economic coordination increases inequality in the absence of compensating institutions such as minimum wage regulation. The deregulation of temporary work as well as spending on employment incentives and rehabilitation also has adverse effects on inequality. Thus, policies that target outsiders have important economic effects on the rest of the workforce. Three broader contributions can be identified. First, welfare state policies may not always be in the interests of labour, so left parties may not always promote them. Second, the interests of insiders and outsiders are not necessarily at odds. Third, economic coordination may not be conducive to egalitarianism where it is not inclusive.

Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1.

Prostaglandins (PG) are known to induce pain perception indirectly by sensitizing nociceptors. Accordingly, the analgesic action of nonsteroidal anti-inflammatory drugs (NSAIDs) results from inhibition of cyclooxygenases and blockade of PG biosynthesis. Cyclopentenone PGs, 15-d-PGJ(2), PGA(2), and PGA(1), formed by dehydration of their respective parent PGs, PGD(2), PGE(2), and PGE(1), possess a highly reactive alpha,beta-unsaturated carbonyl group that has been proposed to gate the irritant transient receptor potential A1 (TRPA1) channel. Here, by using TRPA1 wild-type (TRPA1(+/+)) or deficient (TRPA1(-/-)) mice, we show that cyclopentenone PGs produce pain by direct stimulation of nociceptors via TRPA1 activation. Cyclopentenone PGs caused a robust calcium response in dorsal root ganglion (DRG) neurons of TRPA1(+/+), but not of TRPA1(-/-) mice, and a calcium-dependent release of sensory neuropeptides from the rat dorsal spinal cord. Intraplantar injection of cyclopentenone PGs stimulated c-fos expression in spinal neurons of the dorsal horn and evoked an instantaneous, robust, and transient nociceptive response in TRPA1(+/+) but not in TRPA1(-/-) mice. The classical proalgesic PG, PGE(2), caused a slight calcium response in DRG neurons, increased c-fos expression in spinal neurons, and induced a delayed and sustained nociceptive response in both TRPA1(+/+) and TRPA1(-/-) mice. These results expand the mechanism of NSAID analgesia from blockade of indirect nociceptor sensitization by classical PGs to inhibition of direct TRPA1-dependent nociceptor activation by cyclopentenone PGs. Thus, TRPA1 antagonism may contribute to suppress pain evoked by PG metabolites without the adverse effects of inhibiting cyclooxygenases.

Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers

Reduced subjective experience of reward (anhedonia) is a key symptom of major depression. The anti-obesity drug and cannabinoid type 1 receptor (CB(1)) antagonist, rimonabant, is associated with significant rates of depression and anxiety in clinical use and was recently withdrawn from the market because of these adverse effects. Using a functional magnetic resonance imaging (fMRI) model of reward we hypothesized that rimonabant would impair reward processing. Twenty-two healthy participants were randomly allocated to receive rimonabant (20 mg), or placebo, for 7 d in a double-blind, parallel group design. We used fMRI to measure the neural response to rewarding (sight and/or flavour of chocolate) and aversive (sight of mouldy strawberries and/or an unpleasant strawberry taste) stimuli on the final day of drug treatment. Rimonabant reduced the neural response to chocolate stimuli in key reward areas such as the ventral striatum and the orbitofrontal cortex. Rimonabant also decreased neural responses to the aversive stimulus condition in the caudate nucleus and ventral striatum, but increased lateral orbitofrontal activations to the aversive sight and taste of strawberry condition. Our findings are the first to show that the anti-obesity drug rimonabant inhibits the neural processing of rewarding food stimuli in humans. This plausibly underlies its ability to promote weight loss, but may also indicate a mechanism for inducing anhedonia which could lead to the increased risk of depressive symptomatology seen in clinical use. fMRI may be a useful method of screening novel agents for unwanted effects on reward and associated clinical adverse reactions.

MODIS-based vegetation index has sufficient sensitivity to indicate stand-level intra-seasonal climatic stress in oak and beech forests

Context: Variation in photosynthetic activity of trees induced by climatic stress can be effectively evaluated using remote sensing data. Although adverse effects of climate on temperate forests have been subjected to increased scrutiny, the suitability of remote sensing imagery for identification of drought stress in such forests has not been explored fully. Aim: To evaluate the sensitivity of MODIS-based vegetation index to heat and drought stress in temperate forests, and explore the differences in stress response of oaks and beech. Methods: We identified 8 oak and 13 beech pure and mature stands, each covering between 4 and 13 MODIS pixels. For each pixel, we extracted a time series of MODIS NDVI from 2000 to 2010. We identified all sequences of continuous unseasonal NDVI decline to be used as the response variable indicative of environmental stress. Neural Networks-based regression modelling was then applied to identify the climatic variables that best explain observed NDVI declines. Results: Tested variables explained 84–97% of the variation in NDVI, whilst air temperature-related climate extremes were found to be the most influential. Beech showed a linear response to the most influential climatic predictors, while oak responded in a unimodal pattern suggesting a better coping mechanism. Conclusions: MODIS NDVI has proved sufficiently sensitive as a stand-level indicator of climatic stress acting upon temperate broadleaf forests, leading to its potential use in predicting drought stress from meteorological observations and improving parameterisation of forest stress indices.

Single-carrier frequency domain equalisation for hammerstein communication systems using complex-valued neural networks

Single-carrier (SC) block transmission with frequency-domain equalisation (FDE) offers a viable transmission technology for combating the adverse effects of long dispersive channels encountered in high-rate broadband wireless communication systems. However, for high bandwidthefficiency and high power-efficiency systems, the channel can generally be modelled by the Hammerstein system that includes the nonlinear distortion effects of the high power amplifier (HPA) at transmitter. For such nonlinear Hammerstein channels, the standard SC-FDE scheme no longer works. This paper advocates a complex-valued (CV) B-spline neural network based nonlinear SC-FDE scheme for Hammerstein channels. Specifically, We model the nonlinear HPA, which represents the CV static nonlinearity of the Hammerstein channel, by a CV B-spline neural network, and we develop two efficient alternating least squares schemes for estimating the parameters of the Hammerstein channel, including both the channel impulse response coefficients and the parameters of the CV B-spline model. We also use another CV B-spline neural network to model the inversion of the nonlinear HPA, and the parameters of this inverting B-spline model can easily be estimated using the standard least squares algorithm based on the pseudo training data obtained as a natural byproduct of the Hammerstein channel identification. Equalisation of the SC Hammerstein channel can then be accomplished by the usual one-tap linear equalisation in frequency domain as well as the inverse B-spline neural network model obtained in time domain. Extensive simulation results are included to demonstrate the effectiveness of our nonlinear SC-FDE scheme for Hammerstein channels.

Attribution of extreme weather events in Africa: A preliminary exploration of the science and policy implications

At the most recent session of the Conference of the Parties (COP19) in Warsaw (November 2013) the Warsaw international mechanism for loss and damage associated with climate change impacts was established under the United Nations Framework Convention on Climate Change (UNFCCC). The mechanism aims at promoting the implementation of approaches to address loss and damage associated with the adverse effects of climate change. Specifically, it aims to enhance understanding of risk management approaches to address loss and damage. Understanding risks associated with impacts due to highly predictable (slow onset) events like sea-level rise is relatively straightforward whereas assessing the effects of climate change on extreme weather events and their impacts is much more difficult. However, extreme weather events are a significant cause of loss of life and livelihoods, particularly in vulnerable countries and communities in Africa. The emerging science of probabilistic event attribution is relevant as it provides scientific evidence on the contribution of anthropogenic climate change to changes in risk of extreme events. It thus provides the opportunity to explore scientifically-backed assessments of the human influence on such events. However, different ways of framing attribution questions can lead to very different assessments of change in risk. Here we explain the methods of, and implications of different approaches to attributing extreme weather events with a focus on Africa. Crucially, it demonstrates that defining the most appropriate attribution question to ask is not a science decision but needs to be made in dialogue with those stakeholders who will use the answers.

Methods to assess the effectiveness of naturally ventilated classrooms in Gauteng, South Africa

There is a tendency to reduce ventilation rates and natural or hybrid ventilation systems to ensure the conservation of energy in school buildings. However, high indoor pollutant concentration, due to natural or hybrid ventilation systems may have a significant adverse impact on the health and academic performance of pupils and students. Reviewed evidence shows that this can be detrimental to health and wellbeing in schools because of the learner density within a small area, eventually indicating that CO2 concentrations can rise to very high levels (about 4000 ppm) in classrooms during occupancy periods. In South Africa’s naturally ventilated classrooms, it is not clear whether the environmental conditions are conducive for learning. In addition, natural ventilation will be minimized given the fact that in cold, wet or windy weather, doors and windows will commonly remain closed. Evidence from literature based studies indicates that the significance of ventilation techniques is not understood satisfactorily and additional information concerning naturally ventilated schools has to be provided for better design and policy formulation. To develop a thorough understanding of the environments in classrooms, many other parameters have to be considered as well, such as outdoor air quality, CO2 concentrations, temperature and relative humidity and safety issues that may be important drawbacks for naturally ventilated schools. The aim of this paper is to develop a conceptual understanding of methods that can be implemented to assess the effectiveness of naturally ventilated classrooms in Gauteng, South Africa. A theoretical concept with an embedded practical methodology have been proposed for the research programme to investigate the relationship between ventilation rates and learning in schools in Gauteng , a province in South Africa. It is important that existing and future school buildings must include adequate outdoor ventilation, control of moisture, and avoidance of indoor exposures to microbiologic and chemical substances considered likely to have adverse effects in South Africa. Adequate ventilation in classrooms is necessary to reduce and/or eradicate the transmission of indoor pollutants.

Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea

Rationale: Anticipatory nausea (AN) is a poorly controlled side-effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, significant sedative effects, and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation. Objectives: To assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours. Methods: Male Lister hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-supressed feeding (NSF) tests. Results: CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box. Conclusions: CBDA is very well tolerated and devoid of the sedative side-effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.