Chimpanzee APOBEC3 proteins deter SIVs from any monkey business

Cross-species transmissions of viruses from animals to humans are at the origin of major human pathogenic viruses. While the role of ecological and epidemiological factors in the emergence of new pathogens is well documented, the importance of host factors is often unknown. Chimpanzees are the closest relatives of humans and the animal reservoir at the origin of the human AIDS pandemic. However, despite being regularly exposed to monkey lentiviruses through hunting, chimpanzees are naturally infected by only a single simian immunodeficiency virus, SIVcpz. Here, we asked why chimpanzees appear to be protected against the successful emergence of other SIVs. In particular, we investigated the role of the chimpanzee APOBEC3 genes in providing a barrier to infection by most monkey lentiviruses. We found that most SIV Vifs, including Vif from SIVwrc infecting western-red colobus, the chimpanzee's main monkey prey in West Africa, could not antagonize chimpanzee APOBEC3G. Moreover, chimpanzee APOBEC3D, as well as APOBEC3F and APOBEC3H, provided additional protection against SIV Vif antagonism. Consequently, lentiviral replication in primary chimpanzee CD4(+) T cells was dependent on the presence of a lentiviral vif gene that could antagonize chimpanzee APOBEC3s. Finally, by identifying and functionally characterizing several APOBEC3 gene polymorphisms in both common chimpanzees and bonobos, we found that these ape populations encode APOBEC3 proteins that are uniformly resistant to antagonism by monkey lentiviruses

Factors underlying suboptimal diagnostic performance in physicians under time pressure

diagnostic performance of doctors and in increases in diagnostic errors. However, the reasons underlying these effects are not clear. The aim of this study was to investigate the influence of time pressure on physicians’ diagnostic accuracy and to explore the mediating effects of perceived stress (emotional pathway) and number of plausible diagnostic hypotheses (cognitive pathway) on the proposed relationship. Methods: We conducted a randomised controlled experiment. A total of 75 senior internal medicine residents completed eight written clinical cases under conditions with (n = 40) or without (n = 35) time pressure. They were then asked to: (i) rate the overall stress experienced, and (ii) write down any alternative hypotheses they had thought of when diagnosing the cases. In a post hoc analysis, a mediation path analysis was performed to test the causal relationships between time pressure, perceived stress and number of alternative diagnoses. Results: Participants who were under time pressure spent less time diagnosing the cases (85.54 seconds versus 181.81 seconds; p< 0.001) and had a lower mean diagnostic accuracy score (0.44 versus 0.53; p = 0.01). In addition, they reported more stress (5.80 versus 4.69; p = 0.01) and generated fewer plausible tentative hypotheses (0.37 versus 0.51; p = 0.01). Two path coefficients were found to be statistically significant; the first path coefficient referred to the relationship between time pressure and perceived stress (standardised ? = 0.25, p = 0.029), and the second negative path coefficient referred to the relationship between time pressure and number of plausible alternative hypotheses (standardised ? = ?0.32, p< 0.01). Conclusions: Time pressure adversely influences physicians’ diagnostic accuracy by increasing their stress response and reducing the number of plausible hypotheses as mediators

Inducing System-1-type diagnostic reasoning in second-year medical students within 15 minutes

Purpose: Diagnostic reasoning literature debates the significance of“dual-process theory”and the importance of its con- stituent types of thinking: System-1and System-2. This experimental study aimed to determine whether novice medical stu- dents could be trained to utilize System-1 thinking when making diagnoses based on chest X-rays. Method: Second-year medical students were recruited and presented with a series of eight online chest X-rays cases. Participants were shown half of the cases repeatedly during a training phase and the other half only twice. During the final test phase, they were shown all eight cases, providing a diagnosis as a free text answer. Dependent variables were diagnos- tic accuracy and response time. Results: Thirty-two students participated. During the test phase, students responses were significantly more accurate and faster for cases which had been seen repeatedly during the training phase (mean score¼3.56/4, mean time¼2.34 s) com- pared with cases which had been seen only twice (mean score¼1.59/4, mean time¼7.50 s). Conclusion: This study demonstrates that it is possible to induce in novice students the speed-to-diagnosis and diagnostic accuracy typical of System-1-type reasoning. The full experimental design and the chest X-rays used may provide new opportunities to explore some of the issues surrounding dual-process theory

Teaching clinical reasoning through hypothetico-deduction is (slightly) better than self-explanation in tutorial groups: An experimental study

Background Self-explanation while individually diagnosing clinical cases has proved to be an effective instructional approach for teaching clinical reasoning. The present study compared the effects on diagnostic performance of self-explanation in small groups with the more commonly used hypothetico-deductive approach. Methods Second-year students from a six-year medical school in Saudi Arabia (39 males; 49 females) worked in small groups on seven clinical vignettes (four criterion cases representing cardiovascular diseases and three ‘fillers’, i.e. cases of other unrelated diagnoses). The students followed diffe