The many faces of COPD in real life: a longitudinal analysis of the NOVELTY cohort.

Background: The diagnosis of COPD requires the demonstration of non-fully reversible airflow limitation by spirometry in the appropriate clinical context. Yet, there are patients with symptoms and relevant exposures suggestive of COPD with either normal spirometry (pre-COPD) or preserved ratio but impaired spirometry (PRISm). Their prevalence, clinical characteristics and associated outcomes in a real-life setting are unclear. Methods: To investigate them, we studied 3183 patients diagnosed with COPD by their attending physician included in the NOVELTY study (clinicaltrials.gov identifier NCT02760329), a global, 3-year, observational, real-life cohort that included patients recruited from both primary and specialist care clinics in 18 countries. Results: We found that 1) approximately a quarter of patients diagnosed with (and treated for) COPD in real life did not fulfil the spirometric diagnostic criteria recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), and could be instead categorised as pre-COPD (13%) or PRISm (14%); 2) disease burden (symptoms and exacerbations) was highest in GOLD 3-4 patients (exacerbations per person-year (PPY) 0.82) and lower but similar in those in GOLD 1-2, pre-COPD and PRISm (exacerbations range 0.27-0.43 PPY); 3) lung function decline was highest in pre-COPD and GOLD 1-2, and much less pronounced in PRISm and GOLD 3-4; 4) PRISm and pre-COPD were not stable diagnostic categories and change substantially over time; and 5) all-cause mortality was highest in GOLD 3-4, lowest in pre-COPD, and intermediate and similar in GOLD 1-2 and PRISm. Conclusions: Patients diagnosed COPD in a real-life clinical setting present great diversity in symptom burden, progression and survival, warranting medical attention.

Retracted: Exploring resident reflections to understand burnout.

Retraction: Winkel, A. F., Jakalow, H., Benton, L., Moss, H., Mitchell, L. and Feldman, N. (2016), Exploring resident reflections to understand burnout. The Clinical Teacher. doi: 10.1111/tct.12513 The above article, published online on 5th April 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Co-Editors, and John Wiley & Sons Ltd. The retraction has been agreed due to a change in the status of the research project's Institutional Review Board approval, leading to permission to use some of the data in this article being revoked.

Emotion recognition in animated compared to human stimuli in adolescents with autism spectrum disorder.

There is equivocal evidence as to whether there is a deficit in recognising emotional expressions in Autism spectrum disorder (ASD). This study compared emotion recognition in ASD in three types of emotion expression media (still image, dynamic image, auditory) across human stimuli (e.g. photo of a human face) and animated stimuli (e.g. cartoon face). Participants were 37 adolescents (age 11-16) with a diagnosis of ASD (33 male, 4 female). 42 males and 39 females served as typically developing, age-matched controls. Overall there was significant advantage for control groups over the ASD group for emotion recognition in human stimuli but not animated stimuli, across modalities. For static animated images specifically, those with ASD significantly outperformed controls. The findings are consistent with the ASD group using atypical explicit strategies.

Unexpected effects of macromolecular crowding on protein stability.

Most theories about macromolecular crowding focus on two ideas: the macromolecular nature of the crowder and entropy. For proteins, the volume excluded by the crowder favors compact native states over expanded denatured states, enhancing protein stability by decreasing the entropy of unfolding. We tested these ideas with the widely used crowding agent Ficoll-70 and its monomer, sucrose. Contrary to expectations, Ficoll and sucrose have approximately the same stabilizing effect on chymotrypsin inhibitor 2. Furthermore, the stabilization is driven by enthalpy, not entropy. These results point to the need for carefully controlled studies and more sophisticated theories for understanding crowding effects.

Disordered Protein Diffusion under Crowded Conditions.

Intrinsically disordered proteins are important in signaling, regulation, and translocation. Understanding their diffusion under physiologically relevant conditions will yield insight into their functions. We used NMR to quantify the translational diffusion of a globular and a disordered protein in dilute solution and under crowded conditions. In dilute solution, the globular protein chymotrypsin inhibitor 2 (CI2, 7.4 kDa) diffuses faster than the disordered protein α-synuclein (14 kDa). Surprisingly, the opposite occurs under crowded conditions; α-synuclein diffuses faster than CI2, even though α-synuclein is larger than CI2. These data show that shape is a key parameter determining protein diffusion under crowded conditions, adding to the properties known to be affected by macromolecular crowding. The results also offer a clue about why many signaling proteins are disordered.