Proteomic analysis of the rare Uracoan rattlesnake Crotalus vegrandis venom: evidence of a broad arsenal of toxins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Planning “Discrete” Movements Using a Continuous System: Insights from a Dynamic Field Theory of Movement Preparation

The timed-initiation paradigm developed by Ghez and colleagues (1997) has revealed two modes of motor planning: continuous and discrete. Continuous responding occurs when targets are separated by less than 60° of spatial angle, and discrete responding occurs when targets are separated by greater than 60°. Although these two modes are thought to reflect the operation of separable strategic planning systems, a new theory of movement preparation, the Dynamic Field Theory, suggests that two modes emerge flexibly from the same system. Experiment 1 replicated continuous and discrete performance using a task modified to allow for a critical test of the single system view. In Experiment 2, participants were allowed to correct their movements following movement initiation (the standard task does not allow corrections). Results showed continuous planning performance at large and small target separations. These results are consistent with the proposal that the two modes reflect the time-dependent “preshaping” of a single planning system.

Generalizing the dynamic field theory of spatial cognition across real and developmental time scales

Within cognitive neuroscience, computational models are designed to provide insights into the organization of behavior while adhering to neural principles. These models should provide sufficient specificity to generate novel predictions while maintaining the generality needed to capture behavior across tasks and/or time scales. This paper presents one such model, the Dynamic Field Theory (DFT) of spatial cognition, showing new simulations that provide a demonstration proof that the theory generalizes across developmental changes in performance in four tasks—the Piagetian A-not-B task, a sandbox version of the A-not-B task, a canonical spatial recall task, and a position discrimination task. Model simulations demonstrate that the DFT can accomplish both specificity—generating novel, testable predictions—and generality—spanning multiple tasks across development with a relatively simple developmental hypothesis. Critically, the DFT achieves generality across tasks and time scales with no modification to its basic structure and with a strong commitment to neural principles. The only change necessary to capture development in the model was an increase in the precision of the tuning of receptive fields as well as an increase in the precision of local excitatory interactions among neurons in the model. These small quantitative changes were sufficient to move the model through a set of quantitative and qualitative behavioral changes that span the age range from 8 months to 6 years and into adulthood. We conclude by considering how the DFT is positioned in the literature, the challenges on the horizon for our framework, and how a dynamic field approach can yield new insights into development from a computational cognitive neuroscience perspective.

Tests of the Dynamic Field Theory and the Spatial Precision Hypothesis: Capturing a Qualitative Developmental Transition in Spatial Working Memory

This study tested a dynamic field theory (DFT) of spatial working memory and an associated spatial precision hypothesis (SPH). Between 3 and 6 years of age, there is a qualitative shift in how children use reference axes to remember locations: 3-year-olds’ spatial recall responses are biased toward reference axes after short memory delays, whereas 6-year-olds’ responses are biased away from reference axes. According to the DFT and the SPH, quantitative improvements over development in the precision of excitatory and inhibitory working memory processes lead to this qualitative shift. Simulations of the DFT in Experiment 1 predict that improvements in precision should cause the spatial range of targets attracted toward a reference axis to narrow gradually over development, with repulsion emerging and gradually increasing until responses to most targets show biases away from the axis. Results from Experiment 2 with 3- to 5-year-olds support these predictions. Simulations of the DFT in Experiment 3 quantitatively fit the empirical results and offer insights into the neural processes underlying this developmental change.

EFFECTS OF IMPLEMENTING EPA'S ENDANGERED SPECIES PROTECTION PROGRAM ON NATIONAL FOREST SYSTEM LANDS

In 1986, the U.S. Environmental Protection Agency (EPA) initiated an effort to comply more fully with the Endangered Species Act. This effort became their "Endangered Species Protection Program." The possibility of such a program was forecast in 1982 when Donald A. Spencer gave a presentation to the Tenth Vertebrate Pest Conference on "Vertebrate Pest Management and Changing Times." This paper focuses on current plans for implementing the EPA's Endangered Species Protection Program as it relates to the USDA Forest Service. It analyzes the potential effects this program will have on the agency, using the pocket gopher (Thomomys spp.), strychnine, and the grizzly bear (Ursus arctos horribilis) as examples of an affected pest, pesticide, and predator.

THE ROLE OF INDUSTRY IN DEVELOPING NEW MATERIALS FOR VERTEBRATE PEST CONTROL

In the first paper presented to you today by Dr. Spencer, an expert in the Animal Biology field and an official authority at the same time, you heard about the requirements imposed on a chemical in order to pass the different official hurdles before it ever will be accepted as a proven tool in wildlife management. Many characteristics have to be known and highly sophisticated tests have to be run. In many instances the governmental agency maintains its own screening, testing or analytical programs according to standard procedures. It would be impossible, however, for economic and time reasons to work out all the data necessary for themselves. They, therefore, depend largely on the information furnished by the individual industry which naturally has to be established as conscientiously as possible. This, among other things, Dr. Spencer has made very clear; and this is also what makes quite a few headaches for the individual industry, but I am certainly not speaking only for myself in saying that Industry fully realizes this important role in developing materials for vertebrate control and the responsibilities lying in this. This type of work - better to say cooperative work with the official institutions - is, however, only one part and for the most of it, the smallest part of work which Industry pays to the development of compounds for pest control. It actually refers only to those very few compounds which are known to be effective. But how to get to know about their properties in the first place? How does Industry make the selection from the many thousands of compounds synthesized each year? This, by far, creates the biggest problems, at least from the scientific and technical standpoint. Let us rest here for a short while and think about the possible ways of screening and selecting effective compounds. Basically there are two different ways. One is the empirical way of screening as big a number of compounds as possible under the supposition that with the number of incidences the chances for a "hit" increase, too. You can also call this type of approach the statistical or the analytical one, the mass screening of new, mostly unknown candidate materials. This type of testing can only be performed by a producer of many new materials,that means by big industries. It requires a tremendous investment in personnel, time and equipment and is based on highly simplified but indicative test methods, the results of which would have to be reliable and representative for practical purposes. The other extreme is the intellectual way of theorizing effective chemical configurations. Defenders of this method claim to now or later be able to predict biological effectiveness on the basis of the chemical structure or certain groups in it. Certain pre-experience should be necessary, that means knowledge of the importance of certain molecular requirements, then the detection of new and effective complete molecules is a matter of coordination to be performed by smart people or computers. You can also call this method the synthetical or coordinative method.

Unifying Representations and Responses: Perseverative Biases Arise From a Single Behavioral System

A dominant account of perseverative errors in early development contends that such errors reflect a failure to inhibit a prepotent response. This study investigated whether perseveration might also arise from a failure to inhibit a prepotent representation. Children watched as a toy was hidden at an A location, waited during a delay, and then watched the experimenter find the toy. After six observation-only A trials, the toy was hidden at a B location, and children were allowed to search for the toy. Two- and 4-year-olds’ responses on the B trials were significantly biased toward A even though they had never overtly responded to this location. Thus, perseverative biases in early development can arise as a result of prepotent representations, demonstrating that the prepotent-response account is incomplete. We discuss three alternative interpretations of these results, including the possibility that representational and response-based biases reflect the operation of a single, integrated behavioral system.

Somatic Mosaic Activating Mutations in PIK3CA Cause CLOVES Syndrome

Congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies (CLOVES) is a sporadically occurring, nonhereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. We hypothesized that CLOVES syndrome would be caused by a somatic mutation arising during early embryonic development. Therefore, we employed massively parallel sequencing to search for somatic mosaic mutations in fresh, frozen, or fixed archival tissue from six affected individuals. We identified mutations in PIK3CA in all six individuals, and mutant allele frequencies ranged from 3% to 30% in affected tissue from multiple embryonic lineages. Interestingly, these same mutations have been identified in cancer cells, in which they increase phosphoinositide-3-kinase activity. We conclude that CLOVES is caused by postzygotic activating mutations in PIK3CA. The application of similar sequencing strategies will probably identify additional genetic causes for sporadically occurring, nonheritable malformations.

The identity of Sertularia reptans Linnaeus, 1758 (Bryozoa, Candidae)

This paper includes a reassessment of Scrupocellaria reptans (Linnaeus, 1758) (basionym Sertularia reptans), the lectotype of which is selected and figured from among herbarium-sheet specimens held at the Linnean Society of London. Material previously assigned to S. reptans was examined, providing morphological characteristics to distinguish Scrupocellaria ellisi n. sp. Scrupocellaria reptans has a geographically limited distribution in the United Kingdom, while S. ellisi is more widespread in the North Sea, Northeast Atlantic, Adriatic and Tasmania.

Duodenal stenting for malignant gastric outlet obstruction: Prospective study

AIM: To evaluate the results of duodenal stenting for palliation of gastroduodenal malignant obstruction by using a gastric outlet obstruction score (GOOS). METHODS: A prospective, non-randomized study was performed at a tertiary center between August 2005 and April 2010. Patients were eligible if they had malignant gastric outlet obstruction (GOO) and were not candidates for surgical treatment. Medical history and patient demographics were collected at baseline. Scheduled interviews were made on the day of the procedure and 15, 30, 90 and 180 d later or unscheduled as necessary. RESULTS: Fifteen patients (6 male, 9 female; median age 61 years) with GOO who had undergone duodenal stenting were evaluated. Ten patients had metastasis at baseline (66.6%) and 14 were unable to accept oral intake (93.33%), including 7 patients who were using a feeding tube. Laboratory data showed biliary obstruction in eight cases (53.33%); all were submitted to biliary drainage. Two patients developed obstructive symptoms due to tumor ingrowth after 30 d and another due to tumor overgrowth after 180 d. Two cases of stent migration occurred. A good response to treatment was observed, with a mean time of approximately 1 d (19 h) until toleration of a liquid diet and slightly more than 2 d for both soft solids (51 h) and a solid food/normal diet (55 h). The mean time to first failure to maintain liquid intake (GODS >= 1) was 93 d. During follow-up, the mean time to first failure to maintain the previously achieved GODS of 2-3 (solid/semi-solid food), considered technical failure, was 71 d. On the basis of oral intake a GODS is defined: 0 for no oral intake; 1 for liquids only; 2 for soft solids only; 3 for low-residue or full diet. CONCLUSION: Enteral stenting to alleviate gastroduodenal malignant obstruction improves quality of life in patients with limited life expectancy, which can be evaluated by using a GOO scoring system. (C) 2012 Baishideng. All rights reserved.

Optimized Duration of Clopidogrel Therapy Following Treatment with the Endeavor Zotarolimus-Eluting Stent in Real-World Clinical Practice (OPTIMIZE) Trial: Rationale and design of a large-scale, randomized, multicenter study

Background Current recommendations for antithrombotic therapy after drug-eluting stent (DES) implantation include prolonged dual antiplatelet therapy (DAPT) with aspirin and clopidogrel >= 12 months. However, the impact of such a regimen for all patients receiving any DES system remains unclear based on scientific evidence available to date. Also, several other shortcomings have been identified with prolonged DAPT, including bleeding complications, compliance, and cost. The second-generation Endeavor zotarolimus-eluting stent (E-ZES) has demonstrated efficacy and safety, despite short duration DAPT (3 months) in the majority of studies. Still, the safety and clinical impact of short-term DAPT with E-ZES in the real world is yet to be determined. Methods The OPTIMIZE trial is a large, prospective, multicenter, randomized (1: 1) non-inferiority clinical evaluation of short-term (3 months) vs long-term (12-months) DAPT in patients undergoing E-ZES implantation in daily clinical practice. Overall, 3,120 patients were enrolled at 33 clinical sites in Brazil. The primary composite endpoint is death (any cause), myocardial infarction, cerebral vascular accident, and major bleeding at 12-month clinical follow-up post-index procedure. Conclusions The OPTIMIZE clinical trial will determine the clinical implications of DAPT duration with the second generation E-ZES in real-world patients undergoing percutaneous coronary intervention. (Am Heart J 2012;164:810-816.e3.)

Treatment of malignant gastroduodenal obstruction with a nitinol self-expanding metal stent: An international prospective multicentre registry

Background: Duodenal stenting has become a broadly accepted first line of treatment for patients with advanced malignant gastroduodenal obstruction as these patients are difficult to treat and are poor surgical candidates. Aims: To document duodenal stent performance for palliative management of malignant gastroduodenal obstruction. Methods: Multicentre, single arm, prospective registry documenting peroral endoscopic duodenal stenting procedures in 202 patients. Results: Technical success achieved in 98% (CI. 95%, 99%) of stent placements. Increase of Gastric Outlet Obstruction Score by at least 1 point compared to baseline was achieved in 91% (CI, 86%, 95%) of patients persisting for a median of 184 days (CI, 109, 266). By day 5 (CI, 4,6) after stent placement, 50% of patients experienced a score increase of at least 1 point. Improvement from 14% of patients at baseline tolerating soft solids or low residue/normal diet to 84% at 15 days, 86% at 30 days, 81% at 90 days, 79% at 180 days, and 70% at 270 days. Complications included stent ingrowth and/or overgrowth (12.4%), transient periprocedural symptoms (3%), bleeding (3%), stent migration (1.5%), and perforation (0.5%). Conclusions: Safety and effectiveness of duodenal stenting for palliation of malignant gastroduodenal obstruction was confirmed in the largest international prospective series to date. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Determinants of discordance in patients' and physicians' rating of rheumatoid arthritis disease activity

Objective To assess the determinants of patients' (PTGL) and physicians' (MDGL) global assessment of rheumatoid arthritis (RA) activity and factors associated with discordance among them. Methods. A total of 7,028 patients in the Quantitative Standard Monitoring of Patients with RA study had PTGL and MDGL assessed at the same clinic visit on a 0-10-cm visual analog scale (VAS). Three patient groups were defined: concordant rating group (PTGL and MDGL within >= 2 cm), higher patient rating group (PTGL exceeding MDGL by > 2 cm), and lower patient rating group (PTGL less than MDGL by > 2 cm). Multivariable regression analysis was used to identify determinants of PTGL and MDGL and their discordance. Results. The mean +/- SD VAS scores for PTGL and MDGL were 4.01 +/- 2.70 and 2.91 +/- 2.37, respectively. Pain was overwhelmingly the single most important determinant of PTGL, followed by fatigue. In contrast, MDGL was most influenced by swollen joint count (SJC), followed by erythrocyte sedimentation rate (ESR) and tender joint count (TJC). A total of 4,454 (63.4%), 2,106 (30%), and 468 (6.6%) patients were in the concordant, higher, and lower patient rating groups, respectively. Odds of higher patient rating increased with higher pain, fatigue, psychological distress, age, and morning stiffness, and decreased with higher SJC, TJC, and ESR. Lower patient rating odds increased with higher SJC, TJC, and ESR, and decreased with lower fatigue levels. Conclusion. Nearly 36% of patients had discordance in RA activity assessment from their physicians. Sensitivity to the "disease experience" of patients, particularly pain and fatigue, is warranted for effective care of RA.

Strategies for Multivessel Revascularization in Patients with Diabetes

BACKGROUND In some randomized trials comparing revascularization strategies for patients with diabetes, coronary-artery bypass grafting (CABG) has had a better outcome than percutaneous coronary intervention (PCI). We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease. METHODS In this randomized trial, we assigned patients with diabetes and multivessel coronary artery disease to undergo either PCI with drug-eluting stents or CABG. The patients were followed for a minimum of 2 years (median among survivors, 3.8 years). All patients were prescribed currently recommended medical therapies for the control of low-density lipoprotein cholesterol, systolic blood pressure, and glycated hemoglobin. The primary outcome measure was a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke. RESULTS From 2005 through 2010, we enrolled 1900 patients at 140 international centers. The patients' mean age was 63.1 +/- 9.1 years, 29% were women, and 83% had three-vessel disease. The primary outcome occurred more frequently in the PCI group (P=0.005), with 5-year rates of 26.6% in the PCI group and 18.7% in the CABG group. The benefit of CABG was driven by differences in rates of both myocardial infarction (P<0.001) and death from any cause (P=0.049). Stroke was more frequent in the CABG group, with 5-year rates of 2.4% in the PCI group and 5.2% in the CABG group (P=0.03). CONCLUSIONS For patients with diabetes and advanced coronary artery disease, CABG was superior to PCI in that it significantly reduced rates of death and myocardial infarction, with a higher rate of stroke. (Funded by the National Heart, Lung, and Blood Institute and others; FREEDOM ClinicalTrials.gov number, NCT00086450.)

Cradoscrupocellaria, a new bryozoan genus for Scrupocellaria bertholletii (Audouin) and related species (Cheilostomata, Candidae): taxonomy, biodiversity and distribution

A new genus, Cradoscrupocellaria n. gen., is erected for Scrupocellaria bertholletii Audouin, 1826), reported as widespread in tropical and subtropical waters. Here we select a neotype of this species in order to establish its identity and distinguish it from morphologically similar species. We include redescriptions and figures of additional species now assigned to this new genus: Cradoscrupocellaria curacaoensis (Fransen, 1986) n. comb., Cradoscrupocellaria hirsuta (Jullien & Calvet, 1903) n. comb., and Cradoscrupocellaria macrorhyncha (Gautier, 1962) n. comb. Five additional species are assigned to the genus: Cradoscrupocellaria ellisi (Vieira & Spencer Jones, 2012) n. comb., Cradoscrupocellaria nanshaensis (Liu, 1991) n. comb., Cradoscrupocellaria reptans (Linnaeus, 1758) n. comb., Cradoscrupocellaria serrata (Waters, 1909) n. comb., and Cradoscrupocellaria tenuirostris (Osburn, 1950) n. comb. Eighteen new species are described: Cradoscrupocellaria aegyptiana n. sp., Cradoscrupocellaria arisaigensis n. sp., Cradoscrupocellaria atlantica n. sp., Cradoscrupocellaria calypso n. sp., Cradoscrupocellaria floridana n. sp., Cradoscrupocellaria galapagensis n. sp., Cradoscrupocellaria gautieri n. sp., Cradoscrupocellaria gorgonensis n. sp., Cradoscrupocellaria hastingsae n. sp., Cradoscrupocellaria insularis n. sp., Cradoscrupocellaria jamaicensis n. sp., Cradoscrupocellaria lagaaiji n. sp., Cradoscrupocellaria macrorhynchoides n. sp., Cradoscrupocellaria makua n. sp., Cradoscrupocellaria marcusorum n. sp., Cradoscrupocellaria normani n. sp., Cradoscrupocellaria odonoghuei n. sp., and Cradoscrupocellaria osburni n. sp.