Toddlers infer unobserved causes for spontaneous events

Previous research suggests that children infer the presence of unobserved causes when objects appear to move spontaneously. Are such inferences limited to motion events or do children assume that unexplained physical events have causes more generally? Here we introduce an apparently spontaneous event and ask whether, even in the absence of spatiotemporal and co-variation cues linking the events, toddlers treat a plausible variable as a cause of the event. Toddlers (24 months) saw a toy that appeared to light up either spontaneously or after an experimenter’s action. Toddlers were also introduced to a button but were not shown any predictive relation between the button and the light. Across three different dependent measures of exploration, predictive looking (Study 1), prompted intervention (Study 2), and spontaneous exploration (Study 3), toddlers were more likely to represent the button as a cause of the light when the event appeared to occur spontaneously. In Study 4, we found that even in the absence of a plausible candidate cause, toddlers engaged in selective exploration when the light appeared to activate spontaneously. These results suggest that toddlers’ exploration is guided by the causal explanatory power of events.National Science Foundation (U.S.). Faculty Early Career Development ProgramTempleton FoundationJames S. McDonnell Foundation (Collaborative Interdisciplinary Grant on Causal Reasoning

Giving the Giggles: Prediction, Intervention, and Young Children's Representation of Psychological Events

Adults recognize that if event A predicts event B, intervening on A might generate B. Research suggests that young children have difficulty making this inference unless the events are initiated by goal-directed actions. The current study tested the domain-generality and development of this phenomenon. Replicating previous work, when the events involved a physical outcome, toddlers (mean: 24 months) failed to generalize the outcome of spontaneously occurring predictive events to their own interventions; toddlers did generalize from prediction to intervention when the events involved a psychological outcome. We discuss these findings as they bear on the development of causal concepts.Templeton Foundation (Grant 12667)James S. McDonnell FoundationNational Science Foundation (U.S.). (CAREER Award 0744213

Effect of antimicrobial stewardship on antimicrobial prescriptions for selected diseases of dogs in Switzerland.

BACKGROUND Antimicrobial stewardship programs (ASPs) are important tools to foster prudent antimicrobial use. OBJECTIVE To evaluate antimicrobial prescriptions by Swiss veterinarians before and after introduction of the online ASP AntibioticScout.ch in December 2016. ANIMALS Dogs presented to 2 university hospitals and 14 private practices in 2016 or 2018 for acute diarrhea (AD; n = 779), urinary tract infection (UTI; n = 505), respiratory tract infection (RTI; n = 580), or wound infection (WI; n = 341). METHODS Retrospective study. Prescriptions of antimicrobials in 2016 and 2018 were compared and their appropriateness assessed by a justification score. RESULTS The proportion of dogs prescribed antimicrobials decreased significantly between 2016 and 2018 (74% vs 59%; P < .001). The proportion of prescriptions in complete agreement with guidelines increased significantly (48% vs 60%; P < .001) and those in complete disagreement significantly decreased (38% vs 24%; P < .001) during this time. Antimicrobial prescriptions for dogs with AD were significantly correlated with the presence of hemorrhagic diarrhea in both years, but a significantly lower proportion of dogs with hemorrhagic diarrhea were unnecessarily prescribed antimicrobials in 2018 (65% vs 36%; P < .001). In private practices, in 2018 a bacterial etiology of UTI was confirmed in 16% of dogs. Prescriptions for fluoroquinolones significantly decreased (29% vs 14%; P = .002). Prescriptions for antimicrobials decreased significantly in private practices for RTI (54% vs 31%; P < .001). CONCLUSION Antimicrobials were used more prudently for the examined indications in 2018 compared to 2016. The study highlights the continued need for ASPs in veterinary medicine

Synthesis of trinorbornane

Herein we report the synthesis and characterisation of the until recently unreported chiral C-11 skeleton of tetracyclo[5.2.2.01,6.04,9]undecane ("trinorbornane'') which could be obtained in 7% overall yield in 9 steps. This new rigid structural type was found to be present in the computer generated Chemical Universe Data-base (GDB) and has until now no real-world counterpart

Mind the Gap: Investigating Toddlers’ Sensitivity to Contact Relations in Predictive Events

Toddlers readily learn predictive relations between events (e.g., that event A predicts event B). However, they intervene on A to try to cause B only in a few contexts: When a dispositional agent initiates the event or when the event is described with causal language. The current studies look at whether toddlers’ failures are due merely to the difficulty of initiating interventions or to more general constraints on the kinds of events they represent as causal. Toddlers saw a block slide towards a base, but an occluder prevented them from seeing whether the block contacted the base; after the block disappeared behind the occluder, a toy connected to the base did or did not activate. We hypothesized that if toddlers construed the events as causal, they would be sensitive to the contact relations between the participants in the predictive event. In Experiment 1, the block either moved spontaneously (no dispositional agent) or emerged already in motion (a dispositional agent was potentially present). Toddlers were sensitive to the contact relations only when a dispositional agent was potentially present. Experiment 2 confirmed that toddlers inferred a hidden agent was present when the block emerged in motion. In Experiment 3, the block moved spontaneously, but the events were described either with non-causal (“here’s my block”) or causal (“the block can make it go”) language. Toddlers were sensitive to the contact relations only when given causal language. These findings suggest that dispositional agency and causal language facilitate toddlers’ ability to represent causal relationships.John Templeton Foundation (#12667)James S. McDonnell Foundation (Causal Learning Collaborative Initiative)National Science Foundation (U.S.) (Career Award (# 0744213

Localization of ligands within human carbonic anhydrase II using F-19 pseudocontact shift analysis

Unraveling the native structure of protein-ligand complexes in solution enables rational drug design. We report here the use of 19F pseudocontact shift (PCS) NMR as a method to determine fluorine positions of high affinity ligands bound within the drug target human carbonic anhydrase II with high accuracy. Three different ligands were localized within the protein by analysis of the obtained PCS from simple onedimensional 19F spectra with an accuracy of up to 0.8 degrees A. In order to validate the PCS, four to five independent magnetic susceptibility tensors induced by lanthanide chelating tags bound site-specifically to single cysteine mutants were refined. Least-squares minimization and a Monte-Carlo approach allowed the assessment of experimental errors on the intersection of the corresponding four to five PCS isosurfaces. By defining an angle score that reflects the relative isosurface orientation for different tensor combinations, it was established that the ligand can be localized accurately using only three tensors, if the isosurfaces are close to orthogonal. For two out of three ligands, the determined position closely matched the X-ray coordinates. Our results for the third ligand suggest, in accordance with previously reported ab initio calculations, a rotated position for the difluorophenyl substituent, enabling a favorable interaction with Phe-131. The lanthanide-fluorine distance varied between 22 and 38 degrees A and induced 19F PCS ranged from 0.078 to 0.409 ppm, averaging to 0.213 ppm. Accordingly, even longer metal-fluorine distances will lead to meaningful PCS, rendering the investigation of protein-ligand complexes significantly larger than 30 kDa feasible

Chemoprophylaxis and Malaria Death Rates

Malaria chemoprophylaxis increases the survival of nonimmune travelers

Comparison of different methods for delayed post-mortem diagnosis of falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Between 10,000 and 12,000 cases of imported malaria are notified in the European Union each year. Despite an excellent health care system, fatalities do occur. In case of advanced autolysis, the post-mortem diagnostic is impaired. Quicker diagnosis could be achieved by using rapid diagnostic malaria tests.</p> <p>Methods</p> <p>In order to evaluate different methods for the post-mortem diagnosis of <it>Plasmodium falciparum </it>malaria in non-immunes, a study was performed on the basis of forensic autopsies of corpses examined at variable intervals after death in five cases of fatal malaria (with an interval of four hours to five days), and in 20 cases of deaths unrelated to malaria. Detection of parasite DNA by PCR and an immunochromatographic test (ICT) based upon the detection of <it>P. falciparum </it>histidine-rich protein 2 (PfHRP2) were compared with the results of microscopic examination of smears from cadaveric blood, histopathological findings, and autopsy results.</p> <p>Results</p> <p>In all cases of fatal malaria, post-mortem findings were unsuspicious for the final diagnosis, and autoptic investigations, including histopathology, were only performed because of additional information by police officers and neighbours. Macroscopic findings during autopsy were unspecific. Histopathology confirmed sequestration of erythrocytes and pigment in macrophages in most organs in four patients (not evaluable in one patient due to autolysis). Microscopy of cadaveric blood smears revealed remnants of intraerythrocytic parasites, and was compromised or impossible due to autolysis in two cases. PCR and ICT performed with cadaveric blood were positive in all malaria patients and negative in all controls.</p> <p>Conclusion</p> <p>In non-immune fatalities with unclear anamnesis, ICT can be recommended as a sensitive and specific tool for post-mortem malaria diagnosis, which is easier and faster than microscopy, and also applicable when microscopic examination is impossible due to autolysis. PCR is more expensive and time-consuming, but may be used as confirmatory test. In highly endemic areas where asymptomatic parasitaemia is common, confirmation of the diagnosis of malaria as the cause of death has to rely on histopathological findings.</p

Imported Malaria in Children in Industrialized Countries, 1992–2002

Children account for a considerable proportion of cases imported to the United States and Europe