Choosing the lesser of two evils, the better of two goods: Specifying the roles of ventromedial prefrontal cortex and dorsal anterior cingulate in object choice

The ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortices (ACd) are considered important for reward-based decision making. However, work distinguishing their individual functional contributions has only begun. One aspect of decision making that has received little attention is that making the right choice often translates to making the better choice. Thus, response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or crème caramel cheesecake from a menu) or, alternatively, in situations where both options are undesirable. Moreover, response choice is easier when the reinforcements associated with the objects are far apart, rather than close together, in value. We used functional magnetic resonance imaging to delineate the functional roles of the vmPFC and ACd by investigating these two aspects of decision making: (1) decision form (i.e., choosing between two objects to gain the greater reward or the lesser punishment), and (2) between-object reinforcement distance (i.e., the difference in reinforcements associated with the two objects). Blood oxygen level-dependent (BOLD) responses within the ACd and vmPFC were both related to decision form but differentially. Whereas ACd showed greater responses when deciding between objects to gain the lesser punishment, vmPFC showed greater responses when deciding between objects to gain the greater reward. Moreover, vmPFC was sensitive to reinforcement expectations associated with both the chosen and the forgone choice. In contrast, BOLD responses within ACd, but not vmPFC, related to between-object reinforcement distance, increasing as the distance between the reinforcements of the two objects decreased. These data are interpreted with reference to models of ACd and vmPFC functioning

Hygrothermal performance of vernacular stone in a desert climate

Remote desert communities are often the most vulnerable to temperature extremes, as lack of access to reliable electricity prevents the use of active cooling or heating. Hence, there is a need to investigate how the building envelope itself can be used to passively regulate indoor environments. Readily available vernacular building materials in such areas are thought to aid in not only attenuating temperature swings but also moisture regulation, which improves comfort in a dry climate. Thus, the aim of this research is to investigate the hygrothermalproperties of three different stone types commonly used as building materials in the Western Desertof Egypt: sandstone, limestone and, uniquely,Karshif, a rock rich insodium chloride. The materials’ thermal conductivity, moisture sorption and buffering, water vapour resistance, porosity distribution and phase composition are experimentally investigated. Our results show that the local perception of limestone buildings having poor indoor comfort, despite the material’s superior thermal conductivity and specific heat capacity is only explainable through the relative superiority of sandstone and Karshif in moisture buffering. Vernacular materials need to be tested in environmental conditions representative of their local climate, rather than standardised conditions, as the latter may paint an incorrect picture of performance which, in the case of Karshif, led to partial dissolution under relative humidity of greater than 80%. However, testing under typical desert conditions demonstrates that both Karshif and sandstone are viable building materials that exhibit excellent moisture regulation behaviour. Since building materials in desert conditions may have to withstand atypical weather extremes, including rain, local materials need to be utilised within carefully designed wall assemblies or treated wall sections and, in the case of Karshif, not used in areas where relative humidity regularly reaches 80%. These findings are an important contribution in validating the performance of vernacular stone, and more widely, in demonstrating the importance of selecting appropriate testing conditions

Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity

Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))

The effect of sampling effort and methodology on range size estimates of poorly-recorded species for IUCN Red List assessments

Geographic range size is the most commonly implemented criterion of species’ extinction risk used in IUCN Red List assessments, especially for poorly-recorded species. IUCN applies two contrasting range size measures to capture different facets of a species’ distribution: Extent of Occurrence (EOO; Criterion B1) is the area bounding all known occurrences and is a proxy for the spatial autocorrelation of risk, while the Area of Occupancy (AOO; Criterion B2) is the area occupied within this boundary and is related to population size at finer grains. Various methods have been proposed to measure both EOO and AOO. We evaluate the impact of applying four methods for each of Criterion B1 and of B2, as well as key parameter choices, on the Red List status of 227 poorly-recorded neotropical pteridophyte species. Between 2 and 100% of species would be considered threatened depending on methodology. The minimum convex polygon method of estimating EOO was relatively robust to sampling effort for all but the least-recorded species. The IUCN-recommended method for estimating AOO of summing occupied 2 × 2 km grid cells was very strongly correlated with the total number of records. It is likely that only a small fraction of species can be adequately assessed using this method, and we recommend caution applying the method to poorly-recorded species in particular, where models predicting occupancy in unsampled areas (e.g. species distribution models) may provide more accurate assessments. It is vital that methodological information is retained with assessments, and comparisons should only be made between assessments utilising equivalent methods

Cancer pharmacogenetics

The large number of active combination chemotherapy regimens for most cancers has led to the need for better information to guide the \u27standard\u27 treatment for each patient. In an attempt to individualise therapy, pharmacogenetics and pharmacogenomics (a polygenic approach to pharmacogenetic studies) encompass the search for answers to the hereditary basis for interindividual differences in drug response. This review will focus on the results of studies assessing the effects of polymorphisms in drug-metabolising enzymes and drug targets on the toxicity and response to commonly used chemotherapy drugs. In addition, the need for polygenic pharmacogenomic strategies to identify patients at risk for adverse drug reactions will be highlighted

Astronomical Spectroscopy

Spectroscopy is one of the most important tools that an astronomer has for studying the universe. This chapter begins by discussing the basics, including the different types of optical spectrographs, with extension to the ultraviolet and the near-infrared. Emphasis is given to the fundamentals of how spectrographs are used, and the trade-offs involved in designing an observational experiment. It then covers observing and reduction techniques, noting that some of the standard practices of flat-fielding often actually degrade the quality of the data rather than improve it. Although the focus is on point sources, spatially resolved spectroscopy of extended sources is also briefly discussed. Discussion of differential extinction, the impact of crowding, multi-object techniques, optimal extractions, flat-fielding considerations, and determining radial velocities and velocity dispersions provide the spectroscopist with the fundamentals needed to obtain the best data. Finally the chapter combines the previous material by providing some examples of real-life observing experiences with several typical instruments.Comment: An abridged version of a chapter to appear in Planets, Stars and Stellar Systems, to be published in 2011 by Springer. Slightly revise

Geotemporal analysis of Neisseria meningitidis clones in the United States: 2000-2005

Background: The detection of meningococcal outbreaks relies on serogrouping and epidemiologic definitions. Advances in molecular epidemiology have improved the ability to distinguish unique Neisseria meningitidis strains, enabling the classification of isolates into clones. Around 98% of meningococcal cases in the United States are believed to be sporadic. Methods: Meningococcal isolates from 9 Active Bacterial Core surveillance sites throughout the United States from 2000 through 2005 were classified according to serogroup, multilocus sequence typing, and outer membrane protein (porA, porB, and fetA ) genotyping. Clones were defined as isolates that were indistinguishable according to this characterization. Case data were aggregated to the census tract level and all non-singleton clones were assessed for non-random spatial and temporal clustering using retrospective space-time analyses with a discrete Poisson probability model. Results: Among 1,062 geocoded cases with available isolates, 438 unique clones were identified, 78 of which had ≥2 isolates. 702 cases were attributable to non-singleton clones, accounting for 66.0% of all geocoded cases. 32 statistically significant clusters comprised of 107 cases (10.1% of all geocoded cases) were identified. Clusters had the following attributes: included 2 to 11 cases; 1 day to 33 months duration; radius of 0 to 61.7 km; and attack rate of 0.7 to 57.8 cases per 100,000 population. Serogroups represented among the clusters were: B (n = 12 clusters, 45 cases), C (n = 11 clusters, 27 cases), and Y (n = 9 clusters, 35 cases); 20 clusters (62.5%) were caused by serogroups represented in meningococcal vaccines that are commercially available in the United States. Conclusions: Around 10% of meningococcal disease cases in the U.S. could be assigned to a geotemporal cluster. Molecular characterization of isolates, combined with geotemporal analysis, is a useful tool for understanding the spread of virulent meningococcal clones and patterns of transmission in populations

Stakeholder involvement in Multi-Criteria Decision Analysis

This brief perspective highlights the importance of decision maker buy-in and ownership through stakeholder engagement in the co-construction of the multi-criteria decision analysis (MCDA) model. A brief historical overview of MCDA is presented before outlining the importance of bridging the gap (and to gain trust) between the tool developers and users. The issues with the current MCDA tool development and testing efforts are highlighted, and the ownership and routine adoption of the MCDA process is discussed

Diagnostic and prognostic utility of an inexpensive rapid on site malaria diagnostic test (ParaHIT f) among ethnic tribal population in areas of high, low and no transmission in central India

BACKGROUND: Malaria presents a diagnostic challenge in most tropical countries. Rapid detection of the malaria parasite and early treatment of infection still remain the most important goals of disease management. Therefore, performance characteristics of the new indigenous ParaHIT f test (Span diagnostic Ltd, Surat, India) was determined among ethnic tribal population in four districts of different transmission potential in central India to assess whether this rapid diagnostic test (RDT) could be widely applied as a diagnostic tool to control malaria. Beyond diagnosis, the logical utilization of RDTs is to monitor treatment outcome. METHODS: A finger prick blood sample was collected from each clinically suspected case of malaria to prepare blood smear and for testing with the RDT after taking informed consent. The blood smears were read by an experienced technician blinded to the RDT results and clinical status of the subjects. The figures for specificity, sensitivity, accuracy and predictive values were calculated using microscopy as gold standard. RESULTS: The prevalence of malaria infection estimated by RDT in parallel with microscopy provide evidence of the type of high, low or no transmission in the study area. Analysis revealed (pooled data of all four epidemiological settings) that overall sensitivity, specificity and accuracy of the RDT were >90% in areas of different endemicity. While, RDT is useful to confirm the diagnosis of new symptomatic cases of suspected P. falciparum infection, the persistence of parasite antigen leading to false positives even after clearance of asexual parasitaemia has limited its utility as a prognostic tool. CONCLUSION: The study showed that the ParaHIT f test was easy to use, reliable and cheap. Thus this RDT is an appropriate test for the use in the field by paramedical staff when laboratory facilities are not available and thus likely to contribute greatly to an effective control of malaria in resource poor countries

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression