Mice lacking C1q or C3 show accelerated rejection of minor H disparate skin grafts and resistance to induction of tolerance

Complement activation is known to have deleterious effects on organ transplantation. On the other hand, the complement system is also known to have an important role in regulating immune responses. The balance between these two opposing effects is critical in the context of transplantation. Here, we report that female mice deficient in C1q (C1qa(−/−)) or C3 (C3(−/−)) reject male syngeneic grafts (HY incompatible) at an accelerated rate compared with WT mice. Intranasal HY peptide administration, which induces tolerance to syngeneic male grafts in WT mice, fails to induce tolerance in C1qa(−/−) or C3(−/−) mice. The rejection of the male grafts correlated with the presence of HY D(b)Uty-specific CD8(+) T cells. Consistent with this, peptide-treated C1qa(−/−) and C3(−/−) female mice rejecting male grafts exhibited more antigen-specific CD8(+)IFN-γ(+) and CD8(+)IL-10(+) cells compared with WT females. This suggests that accumulation of IFN-γ- and IL-10-producing T cells may play a key role in mediating the ongoing inflammatory process and graft rejection. Interestingly, within the tolerized male skin grafts of peptide-treated WT mice, IFN-γ, C1q and C3 mRNA levels were higher compared to control female grafts. These results suggest that C1q and C3 facilitate the induction of intranasal tolerance

Nonlinear cascades of surface oceanic geostrophic kinetic energy in the frequency domain

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111877/1/jpo_frequencycascades_2012.pd

Thermodynamic insights and assessment of the ‘circular economy’

This study analyses the effect on energy use of applying a wide range of circular economy approaches. By collating evidence on specific quantifiable approaches and then calculating and analyzing their combined full supply chain impacts through input-output analysis, it provides a more complete assessment of the overall potential scope for energy savings that these approaches might deliver than provided elsewhere. Assessment is conducted globally, across the EU-27 and in the UK. Overall, the identified opportunities have the potential to save 6%–11% of energy used to support economic activity, worldwide and in the EU, and 5%–8% in the UK. Their potential is equivalent to the total scope for other industrial energy efficiency savings. The potential savings are further divided into those due to sets of approaches relating to food waste, steel production, other materials production, product refurbishment, vehicle provision, construction and other equipment manufacture. Each of these sets of approaches can make a key contribution to the total savings that are possible. Complementary use of energy and exergy metrics illustrates the way in which energy use might change and for the first time provides indication that in most cases other energy efficiency measures are unlikely to be adversely affected by the circular economy approaches. Potential for savings in the energy embodied in each key product input to each major sector is assessed, enabling prioritization of the areas in which the circular economy approaches have the greatest scope for impact and identification of supply chains for which they are underrepresented

Thermodynamic insights and assessment of the ‘circular economy’

This study analyses the effect on energy use of applying a wide range of circular economy approaches. By collating evidence on specific quantifiable approaches and then calculating and analyzing their combined full supply chain impacts through input-output analysis, it provides a more complete assessment of the overall potential scope for energy savings that these approaches might deliver than provided elsewhere. Assessment is conducted globally, across the EU-27 and in the UK. Overall, the identified opportunities have the potential to save 6%–11% of energy used to support economic activity, worldwide and in the EU, and 5%–8% in the UK. Their potential is equivalent to the total scope for other industrial energy efficiency savings. The potential savings are further divided into those due to sets of approaches relating to food waste, steel production, other materials production, product refurbishment, vehicle provision, construction and other equipment manufacture. Each of these sets of approaches can make a key contribution to the total savings that are possible. Complementary use of energy and exergy metrics illustrates the way in which energy use might change and for the first time provides indication that in most cases other energy efficiency measures are unlikely to be adversely affected by the circular economy approaches. Potential for savings in the energy embodied in each key product input to each major sector is assessed, enabling prioritization of the areas in which the circular economy approaches have the greatest scope for impact and identification of supply chains for which they are underrepresented

Does lateral lift-off occur in static and dynamic activity in a medially spherical total knee arthroplasty? A pulsed-fluoroscopic investigation.

Objectives: The medially spherical GMK Sphere (Medacta International AG, Castel San Pietro, Switzerland) total knee arthroplasty (TKA) was previously shown to accommodate lateral rollback while pivoting around a stable medial compartment, aiming to replicate native knee kinematics in which some coronal laxity, especially laterally, is also present. We assess coronal plane kinematics of the GMK Sphere and explore the occurrence and pattern of articular separation during static and dynamic activities. Methods: Using pulsed fluoroscopy and image matching, the coronal kinematics and articular surface separation of 16 well-functioning TKAs were studied during weight-bearing and non-weight-bearing, static, and dynamic activities. The closest distances between the modelled articular surfaces were examined with respect to knee position, and proportions of joint poses exhibiting separation were computed. Results: Overall, 1717 joint poses were analyzed. At a 1.0 mm detection threshold, 37 instances of surface separation were observed in the lateral compartment and four medially (p < 0.001). Separation was activity-dependent, both laterally and medially (p < 0.001), occurring more commonly during static deep flexion in the lateral compartment, and during static rotation in the medial compartment. Lateral separation occurred more frequently than medial during kneeling (7/14 lateral vs 1/14 medial; p = 0.031) and stepping (20/1022 lateral vs 0/1022 medial; p < 0.001). Separation varied significantly between individuals during dynamic activities. Conclusion: No consistent association between closest distances of the articular surfaces and knee position was found during any activity. Lift-off was infrequent and depended on the activity performed and the individual knee. Lateral separation was consistent with the design rationale. Medial lift-off was rare and mostly in non-weight-bearing activities.Cite this article: S. Key, G. Scott, J.G. Stammers, M. A. R. Freeman†, V. Pinskerova, R. E. Field, J. Skinner, S. A. Banks. Does lateral lift-off occur in static and dynamic activity in a medially spherical total knee arthroplasty? A pulsed-fluoroscopic investigation. Bone Joint Res 2019;8:207-215. DOI: 10.1302/2046-3758.85.BJR-2018-0237.R1

The Kennack Gneiss of the Lizard Peninsula, Cornwall, SW England: Commingling and mixing of mafic and felsic magmas accompanying Givetian continental incorporation of the Lizard ophiolite

The Kennack Gneiss comprises a suite of interlayered mafic and felsic igneous rocks that intruded the 397 Ma Lizard Ophiolite Complex, Cornwall, at 376.4 ± 1.7 Ma (U-Pb single-zircon date) and were shortly thereafter (c. 370 Ma) metamorphosed to the amphibolite facies. Weakly deformed examples at the type-locality of Kennack Sands reveal net-veining of the mafic by the felsic component, dispersed enclaves of the former in the latter and flame-like interfingering of the two, features indicative of magmatic commingling and mixing. The silicic components of the Kennack Gneiss range from granodiorite to syenogranite and from metaluminous to peraluminous, the least silicic rocks being the most peraluminous. They were generated through anatexis of a predominantly metasedimentary crustal source having trace element and isotopic compositions comparable to those of the Devonian Gramscatho Group of South Cornwall. The mafic component of the gneiss includes members (group 1) which are weakly enriched in light REE, have minor negative Ta, Nb, P and Ti anomalies in extended trace element plots, and display primitive, time-corrected 143Nd/ 144Nd and 87Sr/ 86Sr values, and others (group 2) which are more strongly enriched in all incompatible trace elements, exhibit more prominent negative Ta, Nb, P and Ti anomalies, and have isotopic ratios intermediate between group 1 mafic components and the associated felsic gneiss. Group 2 represents mixtures of group 1 and granitic melts, whereas group 1 rocks are comparable to EMORB and were probably generated through partial melting of a weakly enriched mantle source. Emplacement of two commingled magmas into the base of the Lizard ophiolite, one representing the products of crustal anatexis, implies that the ophiolite was removed from its oceanic setting and was in the process of obduction in the Givetian.published_or_final_versio

Two-dimensional Dirac fermions in a topological insulator: transport in the quantum limit

Pulsed magnetic fields of up to 55T are used to investigate the transport properties of the topological insulator Bi_2Se_3 in the extreme quantum limit. For samples with a bulk carrier density of n = 2.9\times10^16cm^-3, the lowest Landau level of the bulk 3D Fermi surface is reached by a field of 4T. For fields well beyond this limit, Shubnikov-de Haas oscillations arising from quantization of the 2D surface state are observed, with the \nu =1 Landau level attained by a field of 35T. These measurements reveal the presence of additional oscillations which occur at fields corresponding to simple rational fractions of the integer Landau indices.Comment: 5 pages, 4 figure

Attention deficit hyperactivity and oppositional defiant disorder symptoms in adolescence and risk of substance use disorders - a general population-based birth cohort study

BACKGROUND: Externalizing symptoms are associated with risk of future substance use disorder (SUD). Few longitudinal studies exist using general population-based samples which assess the spectrum of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms. AIMS/OBJECTIVES: We aimed to study the associations between adolescent ADHD symptoms and subsequent SUD and additionally examine whether the risk of SUD is influenced by comorbid oppositional defiant disorder (ODD) symptoms. METHODS: The Northern Finland Birth Cohort 1986 was linked to nationwide health care register data for incident SUD diagnoses until age 33 years (n = 6278, 49.5% male). ADHD/ODD-case status at age 16 years was defined using parent-rated ADHD indicated by Strengths and Weaknesses of ADHD symptoms and Normal Behaviors (SWAN) questionnaire with 95% percentile cut-off. To assess the impact of ODD comorbidity on SUD risk, participants were categorized into four groups based on their ADHD/ODD case status. Cox-regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to study associations between adolescent ADHD/ODD case statuses and subsequent SUD. RESULTS: In all, 552 participants (8.8%) presented with ADHD case status at the age of 16 years, and 154/6278 (2.5%) were diagnosed with SUD during the follow-up. ADHD case status was associated with SUD during the follow-up (HR = 3.84, 95% CI 2.69-5.50). After adjustments for sex, family structure, and parental psychiatric disorder and early substance use the association with ADHD case status and SUD remained statistically significant (HR = 2.60, 95% CI 1.70-3.98). The risk of SUD remained elevated in individuals with ADHD case status irrespective of ODD symptoms. CONCLUSIONS: ADHD in adolescence was associated with incident SUD in those with and without symptoms of ODD. The association of ADHD and SUD persisted even after adjustment for a wide range of potential confounds. This emphasizes the need to identify preventative strategies for adolescents with ADHD so as to improve health outcomes

Bistability in Apoptosis by Receptor Clustering

Apoptosis is a highly regulated cell death mechanism involved in many physiological processes. A key component of extrinsically activated apoptosis is the death receptor Fas, which, on binding to its cognate ligand FasL, oligomerize to form the death-inducing signaling complex. Motivated by recent experimental data, we propose a mathematical model of death ligand-receptor dynamics where FasL acts as a clustering agent for Fas, which form locally stable signaling platforms through proximity-induced receptor interactions. Significantly, the model exhibits hysteresis, providing an upstream mechanism for bistability and robustness. At low receptor concentrations, the bistability is contingent on the trimerism of FasL. Moreover, irreversible bistability, representing a committed cell death decision, emerges at high concentrations, which may be achieved through receptor pre-association or localization onto membrane lipid rafts. Thus, our model provides a novel theory for these observed biological phenomena within the unified context of bistability. Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our model also suggests a mechanism by which cells may function as bistable life/death switches independently of any such dynamics in their downstream components. Our results highlight the role of death receptors in deciding cell fate and add to the signal processing capabilities attributed to receptor clustering.Comment: Accepted by PLoS Comput Bio

Branch facial nerve trauma after superficial temporal artery biopsy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Giant cell arteritis is an emergency requiring prompt diagnosis and treatment. Superficial temporal artery biopsy is the gold diagnostic standard. Complications are few and infrequent; however, facial nerve injury has been reported, leaving an untoward cosmetic outcome. This case report is to the best of our knowledge only the fourth one presented in the available literature so far regarding facial nerve injury from superficial temporal artery biopsy.</p> <p>Case presentation</p> <p>A 73-year-old Caucasian woman presented for neurological evaluation regarding eyebrow and facial asymmetry after a superficial temporal artery biopsy for presumptive giant cell arteritis-induced cephalalgia.</p> <p>Conclusion</p> <p>Damage to branches of the facial nerve may occur after superficial temporal artery biopsy, resulting in eyebrow droop. Although an uncommon and sparsely reported complication, all clinicians of various specialties involved in the care of these patients should be aware of this given the gravity of giant cell arteritis and the widespread use of temporal artery biopsy.</p