Advancing the defensive explanation for anxiety disorders: lorazepam effects on human defense are systematically modulated by personality and threat-type

Clinically effective drugs against human anxiety and fear systematically alter the innate defensive behavior of rodents, suggesting that in humans these emotions reflect defensive adaptations. Compelling experimental human evidence for this theory is yet to be obtained. We report the clearest test to date by investigating the effects of 1 and 2mg of the anti-anxiety drug lorazepam on the intensity of threat-avoidance behavior in 40 healthy adult volunteers (20 females). We found lorazepam modulated the intensity of participants’ threat-avoidance behavior in a dose-dependent manner. However, the pattern of effects depended upon two factors: type of threat-avoidance behavior and theoretically relevant measures of personality. In the case of flight behavior (one-way active avoidance), lorazepam increased intensity in low scorers on the Fear Survey Schedule tissuedamage fear but reduced it in high scorers. Conversely, in the case of risk-assessment behavior (two-way active avoidance), lorazepam reduced intensity in low scorers on the Spielberger trait anxiety but increased it in high scorers. Anti-anxiety drugs do not systematically affect rodent flight behavior; therefore, we interpret this new finding as suggesting that lorazepam has a broader effect on defense in humans than in rodents, perhaps by modulating general perceptions of threat intensity. The different patterning of lorazepam effects on the two behaviors implies that human perceptions of threat intensity are nevertheless distributed across two different neural streams, which influence effects observed on one-way or two-way active avoidance demanded by the situation

Seasonal Arctic sea ice forecasting with probabilistic deep learning

Anthropogenic warming has led to an unprecedented year-round reduction in Arctic sea ice extent. This has far-reaching consequences for indigenous and local communities, polar ecosystems, and global climate, motivating the need for accurate seasonal sea ice forecasts. While physics-based dynamical models can successfully forecast sea ice concentration several weeks ahead, they struggle to outperform simple statistical benchmarks at longer lead times. We present a probabilistic, deep learning sea ice forecasting system, IceNet. The system has been trained on climate simulations and observational data to forecast the next 6 months of monthly-averaged sea ice concentration maps. We show that IceNet advances the range of accurate sea ice forecasts, outperforming a state-of-the-art dynamical model in seasonal forecasts of summer sea ice, particularly for extreme sea ice events. This step-change in sea ice forecasting ability brings us closer to conservation tools that mitigate risks associated with rapid sea ice loss

Predicting consumer biomass, size-structure, production, catch potential, responses to fishing and associated uncertainties in the world's marine ecosystems

Existing estimates of fish and consumer biomass in the world’s oceans are disparate. This creates uncertainty about the roles of fish and other consumers in biogeochemical cycles and ecosystem processes, the extent of human and environmental impacts and fishery potential. We develop and use a size-based macroecological model to assess the effects of parameter uncertainty on predicted consumer biomass, production and distribution. Resulting uncertainty is large (e.g. median global biomass 4.9 billion tonnes for consumers weighing 1 g to 1000 kg; 50% uncertainty intervals of 2 to 10.4 billion tonnes; 90% uncertainty intervals of 0.3 to 26.1 billion tonnes) and driven primarily by uncertainty in trophic transfer efficiency and its relationship with predator-prey body mass ratios. Even the upper uncertainty intervals for global predictions of consumer biomass demonstrate the remarkable scarcity of marine consumers, with less than one part in 30 million by volume of the global oceans comprising tissue of macroscopic animals. Thus the apparently high densities of marine life seen in surface and coastal waters and frequently visited abundance hotspots will likely give many in society a false impression of the abundance of marine animals. Unexploited baseline biomass predictions from the simple macroecological model were used to calibrate a more complex size- and trait-based model to estimate fisheries yield and impacts. Yields are highly dependent on baseline biomass and fisheries selectivity. Predicted global sustainable fisheries yield increases ≈4 fold when smaller individuals (< 20 cm from species of maximum mass < 1kg) are targeted in all oceans, but the predicted yields would rarely be accessible in practice and this fishing strategy leads to the collapse of larger species if fishing mortality rates on different size classes cannot be decoupled. Our analyses show that models with minimal parameter demands that are based on a few established ecological principles can support equitable analysis and comparison of diverse ecosystems. The analyses provide insights into the effects of parameter uncertainty on global biomass and production estimates, which have yet to be achieved with complex models, and will therefore help to highlight priorities for future research and data collection. However, the focus on simple model structures and global processes means that non-phytoplankton primary production and several groups, structures and processes of ecological and conservation interest are not represented. Consequently, our simple models become increasingly less useful than more complex alternatives when addressing questions about food web structure and function, biodiversity, resilience and human impacts at smaller scales and for areas closer to coasts

Location of the CD8 T Cell Epitope within the Antigenic Precursor Determines Immunogenicity and Protection against the Toxoplasma gondii Parasite

CD8 T cells protect the host from disease caused by intracellular pathogens, such as the Toxoplasma gondii (T. gondii) protozoan parasite. Despite the complexity of the T. gondii proteome, CD8 T cell responses are restricted to only a small number of peptide epitopes derived from a limited set of antigenic precursors. This phenomenon is known as immunodominance and is key to effective vaccine design. However, the mechanisms that determine the immunogenicity and immunodominance hierarchy of parasite antigens are not well understood.Here, using genetically modified parasites, we show that parasite burden is controlled by the immunodominant GRA6-specific CD8 T cell response but not by responses to the subdominant GRA4- and ROP7-derived epitopes. Remarkably, optimal processing and immunodominance were determined by the location of the peptide epitope at the C-terminus of the GRA6 antigenic precursor. In contrast, immunodominance could not be explained by the peptide affinity for the MHC I molecule or the frequency of T cell precursors in the naive animals. Our results reveal the molecular requirements for optimal presentation of an intracellular parasite antigen and for eliciting protective CD8 T cells. © 2013 Feliu et al

Unemployment by Gender: Evidence from EU Countries

This paper applies panel unit-root tests that allow for structural breaks and cross-sectional dependence to examine the validity of hysteresis in gender unemployment rates and gender unemployment gap for a panel of 15 European countries. Addressing breaks, there is evidence to reject the null hypothesis of hysteresis for the unemployment rates and unemployment gap series. Allowing for both cross-sectional dependence and heterogeneous structural breaks this result is reverted and we fail to reject the null hypothesis of unit root

Brazilian obstetrician-gynecologists and abortion: a survey of knowledge, opinions and practices

BACKGROUND: Abortion laws are extremely restrictive in Brazil. The knowledge, opinions of abortion laws, and abortion practices of obstetrician-gynecologists can have a significant impact on women's access to safe abortion. METHODS: We conducted a mail-in survey with a 10% random sample of obstetrician-gynecologists affiliated with the Brazilian Federation of Obstetricians and Gynecologists. We documented participants' experiences performing abortion under a range of legal and illegal circumstances, and asked about which abortion techniques they had experience with. We used chi-square tests and crude logistic regression models to determine which sociodemographic, knowledge-related, or practice-related variables were associated with physician opinion. RESULTS: Of the 1,500 questionnaires that we mailed out, we received responses from 572 (38%). Less than half (48%) of the respondents reported accurate knowledge about abortion law and 77% thought that the law should be more liberal. One-third of respondents reported having previous experience performing an abortion, and very few of these physicians reported having experience with manual vacuum aspiration (MVA) or with misoprostol with either mifepristone or methotrexate. Physicians that favored liberalization of the law were more likely to have correct knowledge about abortion law, and to be in favor of public funding for abortion services. CONCLUSION: Brazilian obstetrician-gynecologists need more information on abortion laws and on safe, effective abortion procedures

In-training assessment using direct observation of single-patient encounters: a literature review

We reviewed the literature on instruments for work-based assessment in single clinical encounters, such as the mini-clinical evaluation exercise (mini-CEX), and examined differences between these instruments in characteristics and feasibility, reliability, validity and educational effect. A PubMed search of the literature published before 8 January 2009 yielded 39 articles dealing with 18 different assessment instruments. One researcher extracted data on the characteristics of the instruments and two researchers extracted data on feasibility, reliability, validity and educational effect. Instruments are predominantly formative. Feasibility is generally deemed good and assessor training occurs sparsely but is considered crucial for successful implementation. Acceptable reliability can be achieved with 10 encounters. The validity of many instruments is not investigated, but the validity of the mini-CEX and the ‘clinical evaluation exercise’ is supported by strong and significant correlations with other valid assessment instruments. The evidence from the few studies on educational effects is not very convincing. The reports on clinical assessment instruments for single work-based encounters are generally positive, but supporting evidence is sparse. Feasibility of instruments seems to be good and reliability requires a minimum of 10 encounters, but no clear conclusions emerge on other aspects. Studies on assessor and learner training and studies examining effects beyond ‘happiness data’ are badly needed