The Dreyfus model of clinical problem-solving skills acquisition: a critical perspective

Context: The Dreyfus model describes how individuals progress through various levels in their acquisition of skills and subsumes ideas with regard to how individuals learn. Such a model is being accepted almost without debate from physicians to explain the ‘acquisition’ of clinical skills. Objectives: This paper reviews such a model, discusses several controversial points, clarifies what kind of knowledge the model is about, and examines its coherence in terms of problem-solving skills. Dreyfus’ main idea that intuition is a major aspect of expertise is also discussed in some detail. Relevant scientific evidence from cognitive science, psychology, and neuroscience is reviewed to accomplish these aims. Conclusions: Although the Dreyfus model may partially explain the ‘acquisition’ of some skills, it is debatable if it can explain the acquisition of clinical skills. The complex nature of clinical problem-solving skills and the rich interplay between the implicit and explicit forms of knowledge must be taken into consideration when we want to explain ‘acquisition’ of clinical skills. The idea that experts work from intuition, not from reason, should be evaluated carefully

Bragg reflection waveguides as integrated sources of entangled photon pairs

We explore the potential of versatile and efficient entangled photon pair generation by spontaneous parametric downconversion in Bragg reflection waveguides. By employing a quantum treatment of modes in channel waveguides, and by accounting for group velocity dispersion in the modes, the quantum state of the generated biphotons is realistically calculated. The pair production rate is predicted to reach 4 x 10⁸ pairs /s/nm/mW of pump light in a 2mm-long structure, on parwith or exceeding the performance of previously reported designs. This is attributable to an enhanced nonlinear interaction through tight mode confinement in the waveguide. Strategies for device performance optimization and phase matching wavelength tunability are outlined and numerically demonstrated. The proposed design platformis versatile and allows photon pair generation with controllable flux, bandwidth, Schmidt number, and degree of polarization entanglement. The possibility of monolithic integration with a diode laser pump offers a way to design an electrically pumped entangled photon source.8 page(s

AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury.

Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterized. Combining axoplasmic proteomics from peripheral sciatic or central projecting dorsal root ganglion (DRG) axons with cell body RNA-seq, we uncover injury-dependent signalling pathways that are uniquely represented in peripheral versus central projecting sciatic DRG axons. We identify AMPK as a crucial regulator of axonal regenerative signalling that is specifically downregulated in injured peripheral, but not central, axons. We find that AMPK in DRG interacts with the 26S proteasome and its CaMKIIα-dependent regulatory subunit PSMC5 to promote AMPKα proteasomal degradation following sciatic axotomy. Conditional deletion of AMPKα1 promotes multiple regenerative signalling pathways after central axonal injury and stimulates robust axonal growth across the spinal cord injury site, suggesting inhibition of AMPK as a therapeutic strategy to enhance regeneration following spinal cord injury

Epigenomic signatures underpin the axonal regenerative ability of dorsal root ganglia sensory neurons

Axonal injury results in regenerative success or failure, depending on whether the axon lies in the peripheral or the CNS, respectively. The present study addresses whether epigenetic signatures in dorsal root ganglia discriminate between regenerative and non-regenerative axonal injury. Chromatin immunoprecipitation for the histone 3 (H3) post-translational modifications H3K9ac, H3K27ac and H3K27me3; an assay for transposase-accessible chromatin; and RNA sequencing were performed in dorsal root ganglia after sciatic nerve or dorsal column axotomy. Distinct histone acetylation and chromatin accessibility signatures correlated with gene expression after peripheral, but not central, axonal injury. DNA-footprinting analyses revealed new transcriptional regulators associated with regenerative ability. Machine-learning algorithms inferred the direction of most of the gene expression changes. Neuronal conditional deletion of the chromatin remodeler CCCTC-binding factor impaired nerve regeneration, implicating chromatin organization in the regenerative competence. Altogether, the present study offers the first epigenomic map providing insight into the transcriptional response to injury and the differential regenerative ability of sensory neurons

HIV alters neuronal mitochondrial fission/fusion in the brain during HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorders (HAND) still occur in approximately 50% of HIV patients, and therapies to combat HAND progression are urgently needed. HIV proteins are released from infected cells and cause neuronal damage, possibly through mitochondrial abnormalities. Altered mitochondrial fission and fusion is implicated in several neurodegenerative disorders. Here, we hypothesized that mitochondrial fission/fusion may be dysregulated in neurons during HAND. We have identified decreased mitochondrial fission protein (dynamin 1-like; DNM1L) in frontal cortex tissues of HAND donors, along with enlarged and elongated mitochondria localized to the soma of damaged neurons. Similar pathology was observed in the brains of GFAP-gp120 tg mice. In vitro, recombinant gp120 decreased total and active DNM1L levels, reduced the level of Mitotracker staining, and increased extracellular acidification rate (ECAR) in primary neurons. DNM1L knockdown enhanced the effects of gp120 as measured by reduced Mitotracker signal in the treated cells. Interestingly, overexpression of DNM1L increased the level of Mitotracker staining in primary rat neurons and reduced neuroinflammation and neurodegeneration in the GFAP-gp120-tg mice. These data suggest that mitochondrial biogenesis dynamics are shifted towards mitochondrial fusion in brains of HAND patients and this may be due to gp120-induced reduction in DNM1L activity. Promoting mitochondrial fission during HIV infection of the CNS may restore mitochondrial biogenesis and prevent neurodegeneration

Why Are Some Nations More Successful Than Others in Research Impact? A Comparison Between Denmark and Sweden

Bibliometric impact analyses show that Swedish research has less international visibility than Danish research. When taking a global view on all subject fields and selecting publications cited higher than the 90th percentile, i.e., the Top 10 %—publications, the Swedish Research Council shows that although Sweden ranks 15 % above world average, Denmark, the Netherlands and Switzerland rank 35–40 % above. To explain these different performances, The Royal Swedish Academy of Sciences asked us to compare the national research systems on three levels: priority setting at national level, governance of universities and direction and funding of research. There are of course many similarities between the Danish and Swedish research systems but there are still subtle differences that have developed over time, which may explain the different international visibility. First of all, it does not depend on different levels of public spending on research and development. However, the core funding of universities relative external funding is higher in Denmark than in Sweden. The academic leadership of Danish universities in terms of board, vice-chancellor, faculty dean and department chair is also more coherent and focused on priority setting, recruitment, organization and deployment of resources to establish research environments that operate at the forefront of international research. On all these points we see a weaker leadership in Sweden. Furthermore, over the last 20 years, public funding of research in Sweden has become more and more unpredictable and program oriented with many new actors, while the Danish funding system, although it also has developed over time, shows more consistency with strong actors to fund individuals with novel ideas. The research policy in Sweden has also developed multiple, sometimes even conflicting goals, which have undermined conditions for high-impact research, while in Denmark a policy to support excellence in research has been more coherent