Revealing the Archetype: The Journey of a Trecento Madonna and Child at the National Museum of Scotland

The National Museums Scotland Madonna and Child project sought to uncover and document the history of a fine polychrome wood carving attributed to The Master of the Gualino St Catherine and to prepare it for display. A new body of knowledge has been assembled by the interdisciplinary team. The conservation treatment was informed by this work and led to further discoveries: the removal of overpaint exposing a previously hidden underdrawing. The ethics of the treatment decisions, including the removal of the Christ Child’s 1960s’ fingers required team dialogue and was opened up for the public to respond to in a series of blogs. The discovery of a rich polychromy including gold and glazed tin has led to further plans to produce a 3-D colour reconstruction. The collaborations developed during this project will facilitate future joint ventures for polychrome sculpture in Scottish collections

Interstate Variation in the Burden of Fragility Fractures

Demographic differences may produce interstate variation in the burden of osteoporosis. We estimated the burden of fragility fractures by race/ethnicity, age, sex, and service site across five diverse and populous states. State inpatient databases for 2000 were used to describe hospital fracture admissions, and a Markov decision model was used to estimate annual fracture incidence and cost for populations ≥50 yr of age for 2005–2025 in Arizona (AZ), California (CA), Florida (FL), Massachusetts (MA), and New York (NY). In 2000, mean hospital charges for incident fractures varied 1.7-fold across states. For hip fracture, mean charges ranged from $16,700 (MA) to$29,500 (CA), length of stay from 5.3 (AZ) to 8.9 days (NY), and discharge rate to long-term care from 43% (NY) to 71% (CA). In 2005, projected fracture incidence rates ranged from 199 (CA) to 266 (MA) per 10,000. Total cost ranged from $270 million (AZ) to$1,434 million (CA). Men accounted for 26–30% of costs. Across states, hip fractures constituted on average 77% of costs; “other” fractures (e.g., leg, arm), 10%; pelvic, 6%; vertebral, 5%; and wrist, 2%. By 2025, Hispanics are projected to represent 20% of fractures in AZ and CA and Asian/Other populations to represent 27% of fractures in NY. In conclusion, state initiatives to prevent fractures should include nonwhite populations and men, as well as white women, and should address fractures at all skeletal sites. Interstate variation in service utilization merits further evaluation to determine efficient and effective disease management strategies

Reciprocal regulation of PKA and rac signaling

Activated G protein-coupled receptors (GPCRs) and receptor tyrosine kinases relay extracellular signals through spatial and temporal controlled kinase and GTPase entities. These enzymes are coordinated by multifunctional scaffolding proteins for precise intracellular signal processing. The cAMP-dependent protein kinase A (PKA) is the prime example for compartmentalized signal transmission downstream of distinct GPCRs. A-kinase anchoring proteins tether PKA to specific intracellular sites to ensure precision and directionality of PKA phosphorylation events. Here, we show that the Rho-GTPase Rac contains A-kinase anchoring protein properties and forms a dynamic cellular protein complex with PKA. The formation of this transient core complex depends on binary interactions with PKA subunits, cAMP levels and cellular GTP-loading accounting for bidirectional consequences on PKA and Rac downstream signaling. We show that GTP-Rac stabilizes the inactive PKA holoenzyme. However, β-adrenergic receptor-mediated activation of GTP-Rac–bound PKA routes signals to the Raf-Mek-Erk cascade, which is critically implicated in cell proliferation. We describe a further mechanism of how cAMP enhances nuclear Erk1/2 signaling: It emanates from transphosphorylation of p21-activated kinases in their evolutionary conserved kinase-activation loop through GTP-Rac compartmentalized PKA activities. Sole transphosphorylation of p21-activated kinases is not sufficient to activate Erk1/2. It requires complex formation of both kinases with GTP-Rac1 to unleash cAMP-PKA–boosted activation of Raf-Mek-Erk. Consequently GTP-Rac functions as a dual kinase-tuning scaffold that favors the PKA holoenzyme and contributes to potentiate Erk1/2 signaling. Our findings offer additional mechanistic insights how β-adrenergic receptor-controlled PKA activities enhance GTP-Rac–mediated activation of nuclear Erk1/2 signaling

A Longitudinal Study of the Relation between Childhood Activities and Psychosocial Adjustment in Early Adolescence

Background: Although an increasing body of research shows that excessive screen time could impair brain development, whereas non-screen recreational activities can promote the development of adaptive emotion regulation and social skills, there is a lack of comparative research on this topic. Hence, this study examined whether and to what extent the frequency of early-life activities predicted later externalizing and internalizing problems. Methods: In 2012/13, we recruited Kindergarten 3 (K3) students from randomly selected kindergartens in two districts of Hong Kong and collected parent-report data on children’s screen activities and parent–child activities. In 2018/19, we re-surveyed the parents of 323 students (aged 11 to 13 years) with question items regarding their children’s externalizing and internalizing symptoms in early adolescence. Linear regression analyses were conducted to examine the associations between childhood activities and psychosocial problems in early adolescence. Results: Early-life parent–child activities (β = −0.14, p = 0.012) and child-alone screen use duration (β = 0.15, p = 0.007) independently predicted externalizing problems in early adolescence. Their associations with video game exposure (β = 0.19, p = 0.004) and non-screen recreational parent–child activities (β = −0.14, p = 0.004) were particularly strong. Conclusions: Parent–child play time is important for healthy psychosocial development. More efforts should be directed to urge parents and caregivers to replace child-alone screen time with parent–child play time

Structure and bonding of [(SIPr)AgX] (X = Cl, Br, i and OTf)

© 2015 The Royal Society of Chemistry.A series of iso-structural complexes [(SIPr)AgX] (X = Cl, Br, I, OTf; SIPr = 1,3-bis(2,6-diisopropylphenyl)imidazolidene) were synthesised, including the first example of a N-heterocyclic carbene silver(i) complex containing an O-bound triflate. Bond Energy Dissociation and Natural Orbitals for Chemical Valence bond analyses (BEDA & ETS-NOCV) revealing a significant NHC → M σ-back-donation, which influences the stability and sigma-donicity of these complexes.Link_to_subscribed_fulltex

Experimental evidence for 56Ni-core breaking from the low-spin structure of the N=Z nucleus 58Cu

Low-spin states in the odd-odd N=Z nucleus 58Cu were investigated with the 58Ni(p,n gamma)58Cu fusion evaporation reaction at the FN-tandem accelerator in Cologne. Seventeen low spin states below 3.6 MeV and 17 new transitions were observed. Ten multipole mixing ratios and 17 gamma-branching ratios were determined for the first time. New detailed spectroscopic information on the 2+,2 state, the Isobaric Analogue State (IAS) of the 2+,1,T=1 state of 58Ni, makes 58Cu the heaviest odd-odd N=Z nucleus with known B(E2;2+,T=1 --> 0+,T=1) value. The 4^+ state at 2.751 MeV, observed here for the first time, is identified as the IAS of the 4+,1,T=1 state in 58Ni. The new data are compared to full pf-shell model calculations with the novel GXPF1 residual interaction and to calculations within a pf5/2 configurational space with a residual surface delta interaction. The role of the 56Ni core excitations for the low-spin structure in 58Cu is discussed.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Alterations in Retinal Microvascular Geometry in Young Type 1 Diabetes

OBJECTIVE - To describe retinal microvascular geometric parameters in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Patients with type 1 diabetes (aged 12-20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed. RESULTS - Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P ≤ 0.001) and increased arteriolar optimality deviation (P = 0.018), higher A1C was associated with increased arteriolar tortuosity (>8.5 vs. ≤8.5%, P = 0.008), higher SBP was associated with decreased arteriolar LDR (P = 0.002), and higher total cholesterol levels were associated with increased arteriolar LDR (P = 0.044) and decreased venular optimality deviation (P = 0.044). These associations remained after controlling for A1C, retinal vessel caliber, and retinopathy status and were seen in subjects without retinopathy. CONCLUSIONS - Key diabetes-related factors affect retinal microvascular geometry in young type 1 diabetes, even in those without evidence of retinopathy. These early retinal alterations may be markers of diabetes microvascular complications. © 2010 by the American Diabetes Association.link_to_OA_fulltex