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Class IA PI3Ks have many roles in health and disease. The rules that govern intersubunit and receptor associations, however, remain unclear. We engineered mouse lines in which individual endogenous class IA PI3K subunits were C-terminally tagged with 17aa that could be biotinylated in vivo. Using these tools we quantified PI3K subunits in streptavidin or PDGFR pull-downs and cell lysates. This revealed that p85α and β bound equivalently to p110α or p110β but p85α bound preferentially to p110δ. p85s were found in molar-excess over p110s in a number of contexts including MEFs (p85β, 20%) and liver (p85α, 30%). In serum-starved MEFs, p110-free-p85s were preferentially, compared with heterodimeric p85s, bound to PDGFRs, consistent with in vitro assays that demonstrated they bound PDGFR-based tyrosine-phosphorylated peptides with higher affinity and cooperativity; suggesting they may act to tune a PI3K activation threshold. p110α-heterodimers were recruited 5–6× more efficiently than p110β-heterodimers to activated PDGFRs in MEFs or to PDGFR-based tyrosine-phosphorylated peptides in MEF-lysates. This suggests that PI3Kα has a higher affinity for relevant tyrosine-phosphorylated motifs than PI3Kβ. Nevertheless, PI3Kβ contributes substantially to acute PDGF-stimulation of PIP₃ and PKB in MEFs because it is synergistically, and possibly sequentially, activated by receptor-recruitment and small GTPases (Rac/CDC42) via its RBD, whereas parallel activation of PI3Kα is independent of its RBD. These results begin to provide molecular clarity to the rules of engagement between class IA PI3K subunits in vivo and past work describing “excess p85,” p85α as a tumor suppressor, and differential receptor activation of PI3Kα and PI3Kβ.

Despite its established benefits, breastfeeding is no longer a norm in many communities. Multifactorial determinants of breastfeeding need supportive measures at many levels, from legal and policy directives to social attitudes and values, women's work and employment conditions, and health-care services to enable women to breastfeed. When relevant interventions are delivered adequately, breastfeeding practices are responsive and can improve rapidly. The best outcomes are achieved when interventions are implemented concurrently through several channels. The marketing of breastmilk substitutes negatively affects breastfeeding: global sales in 2014 of US$44·8 billion show the industry's large, competitive claim on infant feeding. Not breastfeeding is associated with lower intelligence and economic losses of about $302 billion annually or 0·49% of world gross national income. Breastfeeding provides short-term and long-term health and economic and environmental advantages to children, women, and society. To realise these gains, political support and financial investment are needed to protect, promote, and support breastfeeding.

Production systems, traditionally analyzed as almost independent national systems, are increasingly connected on a global scale. Only recently becoming available, the World Input-Output Database (WIOD) is one of the first efforts to construct the global multi-regional input-output (GMRIO) tables. By viewing the world input-output system as an interdependent network where the nodes are the individual industries in different economies and the edges are the monetary goods flows between industries, we analyze respectively the global, regional, and local network properties of the so-called world input-output network (WION) and document its evolution over time. At global level, we find that the industries are highly but asymmetrically connected, which implies that micro shocks can lead to macro fluctuations. At regional level, we find that the world production is still operated nationally or at most regionally as the communities detected are either individual economies or geographically well defined regions. Finally, at local level, for each industry we compare the network-based measures with the traditional methods of backward linkages. We find that the network-based measures such as PageRank centrality and community coreness measure can give valuable insights into identifying the key industries.

The objective of this study was to investigate the relationship between temperature–humidity index (THI) and rumination time (RT) in order to possibly exploit it as a useful tool for animal welfare improvement. During summer 2015 (1 June to 31 August), data from an Italian Holstein dairy farm located in the North of Italy were collected along with environmental data (i.e. ambient temperature and relative humidity) recorded with a weather station installed inside the barn. Rumination data were collected through the Heatime® HR system (SCR Engineers Ltd., Hadarim, Netanya, Israel), an automatic system composed of a neck collar with a Tag that records the RT and activity of each cow. A significant negative correlation was observed between RT and THI. Mixed linear models were fitted, including animal and test day as random effects, and parity, milk production level and date of last calving as fixed effects. A statistically significant effect of THI on RT was identified, with RT decreasing as THI increased.

Evaluating capacities of quantum channels is the first purpose of quantum Shannon theory, but in most cases the task proves to be very hard. Here, we introduce the set of Multi-level Amplitude Damping quantum channels as a generalization of the standard qubit Amplitude Damping Channel to quantum systems of finite dimension d . In the special case of d  = 3, by exploiting degradability, data-processing inequalities, and channel isomorphism, we compute the associated quantum and private classical capacities for a rather wide class of maps, extending the set of models whose capacity can be computed known so far. We proceed then to the evaluation of the entanglement assisted quantum and classical capacities. Estimating the capacity of quantum channels is relevant to understand at which rate quantum information can be exchanged. Here, the authors introduce multi-level amplitude damping channels that generalize the qubit amplitude damping noise model, analyse their quantum and private capacities, and exactly derive the capacities of quantum channels that are not anti-degradable.

Strategies to tackle stunting, obesity, and micronutrient deficiencies must take into account the inequities in which these diseases are rooted, argue Rafael Perez-Escamilla and colleagues

Cybersickness is one of the major roadblocks in the widespread adoption of mixed reality devices. Prolonged exposure to these devices, especially virtual reality devices, can cause users to feel discomfort and nausea, spoiling the immersive experience. Incorporating spatial blur in stereoscopic 3D stimuli has shown to reduce cybersickness. In this paper, we develop a technique to incorporate spatial blur in VR systems inspired by the human physiological system. The technique makes use of concepts from foveated imaging and depth-of-field. The developed technique can be applied to any eye tracker equipped VR system as a post-processing step to provide an artifact-free scene. We verify the usefulness of the proposed system by conducting a user study on cybersickness evaluation. We used a custom-built rollercoaster VR environment developed in Unity and an HTC Vive Pro Eye headset to interact with the user. A Simulator Sickness Questionnaire was used to measure the induced sickness while gaze and heart rate data were recorded for quantitative analysis. The experimental analysis highlighted the aptness of our foveated depth-of-field effect in reducing cybersickness in virtual environments by reducing the sickness scores by approximately 66%.

We propose and theoretically analyze a measure to encourage greater voluntary contributions to public goods. Our measure is a simple intervention that restricts individuals’ strategy sets by imposing a minimum individual contribution level while still allowing for full free riding for those who do not want to contribute. We show that for a well-chosen value of the minimum individual contribution level, this measure does not incentivize any additional free riding while strictly increasing the total contributions relative to the situation without the minimum contribution level. Our measure is appealing because it is nonintrusive and in line with the principle of “freedom of choice.” It is easily implementable for many different public goods settings where more intrusive measures are less accepted. This approach has been implemented in practice in some applications, such as charities.

A systematic review and meta-analysis were conducted, according to the PRISMA methodology, to summarize current evidence on the prevalence and predictors of long-term glucocorticoid (GC) treatment and disease relapses in the real-life management of polymyalgia rheumatica (PMR). Out of 5442 retrieved studies, 21 were eligible for meta-analysis and 24 for qualitative analysis. The pooled proportions of patients still taking GCs at 1, 2, and 5 years were respectively 77% (95%CI 71–83%), 51% (95%CI 41–61%), and 25% (95CI% 15–36%). No significant difference was recorded by distinguishing study cohorts recruited before and after the issue of the international recommendations in 2010. The pooled proportion of patients experiencing at least one relapse at 1 year from treatment initiation was 43% (95%CI 29–56%). Female gender, acute-phase reactants levels, peripheral arthritis, starting GCs dosage, and tapering speed were the most frequently investigated potential predictors of prolonged GC treatment and relapse, but with inconsistent results. Only a few studies and with conflicting results evaluated the potential role of early treatment with methotrexate in reducing the GC exposure and the risk of relapse in PMR. This study showed that a high rate of prolonged GC treatment is still recorded in the management of PMR. The relapse rate, even remarkable, can only partially explain the long-term GC treatment, suggesting that other and not yet identified factors may be involved. Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies. Key Points: • High rate of long-term glucocorticoid (GC) treatment is recorded in polymyalgia rheumatica (PMR), being 77%, 51%, and 25% of patients still on GCs after respectively 1, 2, and 5 years. • A pooled relapse rate of 43% at 1 year, even remarkable, can only partially explain the long-term GC treatment in PMR. • Several studies have attempted to identify potential predictors of prolonged treatment with GCs and relapse, but with inconsistent results. • Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies.