Metamorphism-facilitated faulting in deforming orthopyroxene: Implications for global intermediate-depth seismicity.

SignificanceThe exothermic metamorphic reaction in orthopyroxene (Opx), a major component of oceanic lithospheric mantle, is shown to trigger brittle failure in laboratory deformation experiments under conditions where garnet exsolution takes place. The reaction product is an extremely fine-grained material, forming narrow reaction zones that are mechanically weak, thereby facilitating macroscopic faulting. Oceanic subduction zones are characterized by two separate bands of seismicity, known as the double seismic zone. The upper band of seismicity, located in the oceanic crust, is well explained by dehydration-induced mechanical instability. Our newly discovered metamorphism-induced mechanical instability provides an alternative physical mechanism for earthquakes in the lower band of seismicity (located in the oceanic lithospheric mantle), with no requirement of hydration/dehydration processes.

Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-κB pathways.

The NF-κB protein RelB controls dendritic cell (DC) maturation and may be targeted therapeutically to manipulate T cell responses in disease. Here we report that RelB promoted DC activation not as the expected RelB-p52 effector of the noncanonical NF-κB pathway, but as a RelB-p50 dimer regulated by canonical IκBs, IκBα and IκBɛ. IκB control of RelB minimized spontaneous maturation but enabled rapid pathogen-responsive maturation. Computational modeling of the NF-κB signaling module identified control points of this unexpected cell type-specific regulation. Fibroblasts that we engineered accordingly showed DC-like RelB control. Canonical pathway control of RelB regulated pathogen-responsive gene expression programs. This work illustrates the potential utility of systems analyses in guiding the development of combination therapeutics for modulating DC-dependent T cell responses.

Self-Limiting Sub-5 nm Nanodiamonds by Geochemistry-Inspired Synthesis.

Controlling diamond structures with nanometer precision is fundamentally challenging owing to their extreme and far-from-equilibrium synthetic conditions. State-of-the-art techniques, including detonation, chemical vapor deposition, mechanical grinding, and high-pressure-high-temperature synthesis, yield nanodiamond particles with a broad distribution of sizes. Despite many efforts, the direct synthesis of nanodiamonds with precisely controlled diameters remains elusive. Here the geochemistry-inspired synthesis of sub-5 nm nanodiamonds with sub-nanometer size deviation is described. High-pressure-high-temperature treatment of uniform iron carbide nanoparticles embedded in iron oxide matrices yields nanodiamonds with tunable diameters down to 2.13 and 0.22 nm standard deviation. A self-limiting, redox-driven, and diffusion-controlled solid-state reaction mechanism is proposed and supported by in situ X-ray diffraction, ex situ characterizations, and computational modeling. This work provides a unique mechanism for the precise control of nanostructured diamonds under extreme conditions and paves the road for the full realization of their potential in emerging technologies.

High-pressure elastic properties of dolomite melt supporting carbonate-induced melting in deep upper mantle.

Deeply subducted carbonates likely cause low-degree melting of the upper mantle and thus play an important role in the deep carbon cycle. However, direct seismic detection of carbonate-induced partial melts in the Earth's interior is hindered by our poor knowledge on the elastic properties of carbonate melts. Here we report the first experimentally determined sound velocity and density data on dolomite melt up to 5.9 GPa and 2046 K by in-situ ultrasonic and sink-float techniques, respectively, as well as first-principles molecular dynamics simulations of dolomite melt up to 16 GPa and 3000 K. Using our new elasticity data, the calculated VP/VS ratio of the deep upper mantle (∼180-330 km) with a small amount of carbonate-rich melt provides a natural explanation for the elevated VP/VS ratio of the upper mantle from global seismic observations, supporting the pervasive presence of a low-degree carbonate-rich partial melt (∼0.05%) that is consistent with the volatile-induced or redox-regulated initial melting in the upper mantle as argued by petrologic studies. This carbonate-rich partial melt region implies a global average carbon (C) concentration of 80-140 ppm. by weight in the deep upper mantle source region, consistent with the mantle carbon content determined from geochemical studies.

Synthesis of the Candidate Topological Compound Ni3Pb2.

Spin-orbit coupling enables the realization of topologically nontrivial ground states. As spin-orbit coupling increases with increasing atomic number, compounds featuring heavy elements, such as lead, offer a pathway toward creating new topologically nontrivial materials. By employing a high-pressure flux synthesis method, we synthesized single crystals of Ni3Pb2, the first structurally characterized bulk binary phase in the Ni-Pb system. Combining experimental and theoretical techniques, we examined structure and bonding in Ni3Pb2, revealing the impact of chemical substitutions on electronic structure features of importance for controlling topological behavior. From these results, we determined that Ni3Pb2 completes a series of structurally related transition-metal-heavy main group intermetallic materials that exhibit diverse electronic structures, opening a platform for synthetically tunable topologically nontrivial materials.

Structure-Property Relationships for 3D printed PEEK Intervertebral Lumbar Cages Produced using Fused Filament Fabrication.

Recent advances in additive manufacturing technology now enable fused filament fabrication (FFF) of Polyetheretherketone (PEEK). A standardized lumbar fusion cage design was 3D printed with different speeds of the print head nozzle to investigate whether 3D printed PEEK cages exhibit sufficient material properties for lumbar fusion applications. It was observed that the compressive and shear strength of the 3D printed cages were 63-71% of the machined cages, whereas the torsion strength was 92%. Printing speed is an important printing parameter for 3D printed PEEK, which resulted in up to 20% porosity at the highest speed of 3000 mm/min, leading to reduced cage strength. Printing speeds below 1500 mm/min can be chosen as the optimal printing speed for this printer to reduce the printing time while maintaining strength. The crystallinity of printed PEEK did not differ significantly from as-machined PEEK cages from extruded rods, indicating that the processing provides similar microstructure.

Discovery of a Superconducting Cu-Bi Intermetallic Compound by High-Pressure Synthesis.

A new intermetallic compound, the first to be structurally identified in the Cu-Bi binary system, is reported. This compound is accessed by high-pressure reaction of the elements. Its detailed characterization, physical property measurements, and ab initio calculations are described. The commensurate crystal structure of Cu11 Bi7 is a unique variation of the NiAs structure type. Temperature-dependent electrical resistivity and heat capacity measurements reveal a bulk superconducting transition at Tc =1.36 K. Density functional theory calculations further demonstrate that Cu11 Bi7 can be stabilized (relative to decomposition into the elements) at high pressure and temperature. These results highlight the ability of high-pressure syntheses to allow for inroads into heretofore-undiscovered intermetallic systems for which no thermodynamically stable binaries are known.

Ionic high-pressure form of elemental boron.

Boron is an element of fascinating chemical complexity. Controversies have shrouded this element since its discovery was announced in 1808: the new 'element' turned out to be a compound containing less than 60-70% of boron, and it was not until 1909 that 99% pure boron was obtained. And although we now know of at least 16 polymorphs, the stable phase of boron is not yet experimentally established even at ambient conditions. Boron's complexities arise from frustration: situated between metals and insulators in the periodic table, boron has only three valence electrons, which would favour metallicity, but they are sufficiently localized that insulating states emerge. However, this subtle balance between metallic and insulating states is easily shifted by pressure, temperature and impurities. Here we report the results of high-pressure experiments and ab initio evolutionary crystal structure predictions that explore the structural stability of boron under pressure and, strikingly, reveal a partially ionic high-pressure boron phase. This new phase is stable between 19 and 89 GPa, can be quenched to ambient conditions, and has a hitherto unknown structure (space group Pnnm, 28 atoms in the unit cell) consisting of icosahedral B(12) clusters and B(2) pairs in a NaCl-type arrangement. We find that the ionicity of the phase affects its electronic bandgap, infrared adsorption and dielectric constants, and that it arises from the different electronic properties of the B(2) pairs and B(12) clusters and the resultant charge transfer between them.

Immunotherapy-Responsive Neuropathic Pain and Allodynia in a Patient With Glycine Receptor Autoantibodies: A Case Report.

OBJECTIVES: Neuropathic pain is common and distressing. Improved mechanistic understanding and pharmacotherapies are urgently needed. Molecularly specific pain syndromes may provide insights with translational relevance. Glycine receptors are known to play a key role in inhibitory neurotransmission in the spinal dorsal horn and have therefore been considered as targets for analgesic development. While autoantibodies directed against glycine receptors may rarely arise spontaneously in humans, a detailed phenotype of neuropathic pain and allodynia in association with these autoantibodies has not been described. METHODS: We describe the case of a previously well adult presenting with severe neuropathic pain and allodynia as part of an autoimmune brainstem and spinal syndrome with glycine receptor autoantibodies. RESULTS: Our patient experienced a severe illness, including marked neuropathic pain and allodynia, hypoventilation, tetraparesis, and ophthalmoplegia. A diagnosis of progressive encephalomyelitis with rigidity and myoclonus was made. Neuropathic pain was characterized with validated instruments and responded promptly to cause-directed immunotherapy. DISCUSSION: A detailed longitudinal phenotyping, using validated pain measurement instruments, of severe neuropathic pain and allodynia associated with likely pathogenic glycine receptor autoantibodies is reported. This case may have relevance for translational development of analgesics targeting glycinergic neurotransmission.

Fracture toughness of fibrin gels as a function of protein volume fraction: Mechanical origins.

The mechanical stability of blood clots necessary for their functions is provided by fibrin, a fibrous gel. Rupture of clots leads to life-threatening thrombotic embolization, which is little understood. Here, we combine experiments and simulations to determine the toughness of plasma clots as a function of fibrin content and correlate toughness with fibrin network structure characterized by confocal and scanning electron microscopy. We develop fibrin constitutive laws that scale with fibrin concentration and capture the force-stretch response of cracked clot specimens using only a few material parameters. Toughness is calculated from the path-independent J* integral that includes dissipative effects due to fluid flow and uses only the constitutive model and overall stretch at crack propagation as input. We show that internal fluid motion, which is not directly measurable, contributes significantly to clot toughness, with its effect increasing as fibrin content increases, because the reduced gel porosity at higher density results in greater expense of energy in fluid motion. Increasing fibrin content (1→10mg/mL) results in a significant increase in clot toughness (3→15 N/m) in accordance with a power law relation reminiscent of cellular solids and elastomeric gels. These results provide a basis for understanding and predicting the tendency for thrombotic embolization. STATEMENT OF SIGNIFICANCE: Fibrin, a naturally occurring biomaterial, is the major determinant of the structural and mechanical integrity of blood clots. We determined that increasing the fibrin content in clots, as in some thrombi and fibrin-based anti-bleeding sealants, results in an increase in clot toughness. Toughness corresponds to the ability to resist rupturing in the presence of a defect. We couple bulk mechanical testing, microstructural measurements, and finite element modeling to capture the force-stretch response of fibrin clots and compute toughness. We show that increased fibrin content in clots reduces porosity and limits fluid motion and that fluid motion drastically alters the clot toughness. These results provide a fundamental understanding of blood clot rupture and could help in rational design of fibrin-containing biomaterials.

Fog deposition and accumulation on smooth and textured hydrophobic surfaces.

We investigated the deposition and accumulation of droplets on both smooth substrates and substrates textured with square pillars, which were tens of micrometers in size. After being coated with a hydrophobic monolayer, substrates were placed in an air flow with a sedimenting suspension of micrometer-sized water droplets (i.e., fog). We imaged the accumulation of water and measured the evolution of the mean drop size. On smooth substrates, the deposition process was qualitatively similar to condensation, but differences in length scale revealed a transient regime not reported in condensation experiments. Based on previous simulation results, we defined a time-scale characterizing the transition to steady-state behavior. On textured substrates, square pillars promoted spatial ordering of accumulated drops. Furthermore, texture regulated drop growth: first enhancing coalescence when the mean drop size was smaller than the pillar, and then inhibiting coalescence when drops were comparable to the pillar size. This inhibition led to a monodisperse drop regime, in which drop sizes varied by less than 5%. When these monodisperse drops grew sufficiently large, they coalesced and could either remain suspended on pillars (i.e., Cassie-Baxter state) or wet the substrate (i.e., Wenzel state).

Insight on the Role of Poly(acrylic acid) for Directing Calcium Phosphate Mineralization of Synthetic Polymer Bone Scaffolds.

Bone is a complex tissue with robust mechanical and biological properties originating from its nanoscale composite structure. Although much research has been conducted on designing bioinspired artificial bone, the role of biological macromolecules such as noncollagenous proteins (NCPs) in influencing the formation of biominerals is not fully understood. In this work, we have designed nanofiber shish-kebab (NFSK) structures that can template mineral location by recruiting calcium cations from an ion-rich mineralization solution. Poly(acrylic acid) (PAA) is used as the NCP analogue to understand the role of polyelectrolytes in scaffold mineralization. We demonstrate that the addition of PAA in the mineralization solution suppresses the development of extrafibrillar minerals as well as slows down the accumulation and development of mineral phases within NFSKs. We probe the mechanism behind this effect by monitoring the free calcium ion concentration, investigating the PAA molecular weight effect, and conducting mineralization in membrane-partitioned solutions. Our results suggest the 2-fold effect of PAA as a solution stabilizer and physical barrier on the NFSK surface. This work could shed light on the understanding of the NCP effect in biomineralization.

Mixed Metal Allergy Ancillary to Surgical Staples.

Metal allergies to surgical clips are atypical and often neglected as a differential. It becomes even more unexpected when there is a lack of relevant medical history of the patient reacting poorly to known metals. This study entails the unique finding of newly discovered hypersensitivity to nickel and zirconium, metals commonly found in surgical clips, in a 28-year-old female who underwent laparoscopic cholecystectomy with a cholangiogram.

MC3T3 E1 cell response to mineralized nanofiber shish kebab structures.

Block copolymers (BCPs) are of growing interest because of their extensive utility in tissue engineering, particularly in biomimetic approaches where multifunctionality is critical. We synthesized polycaprolactone-polyacrylic acid (PCL-b-PAA) BCP and crystallized it onto PCL nanofibers, making BCP nanofiber shish kebab (BCP NFSK) structures. When mineralized in 2× simulated body fluid, BCP NFSK mimic the structure of mineralized collagen fibrils. We hypothesized that the addition of a calcium phosphate layer of graded roughness on the nano-structure of the nanofiber shish kebabs would enhance preosteoblast alkaline phosphatase (ALP) activity, which has been shown to be a critical component in bone matrix formation. The objectives in the study were to investigate the effect of mineralization on cell proliferation and ALP activity, and to also investigate the effect of BCP NFSK periodicity, a structural feature describing the distance between PCL-b-PAA crystals on the nanofiber core, on cell proliferation, and ALP activity. ALP activity of cells cultured on the mineralized BCP NFSK template was significantly higher than the nonmineralized BCP NFSK templates. Interestingly, no statistical difference was observed in ALP activity when the periodic varied, indicating that surface chemistry seemed to play a larger role than the surface roughness.

Plastic Deformation and Strengthening Mechanisms of Nanopolycrystalline Diamond.

Bulk nanopolycrystalline diamond (NPD) samples were deformed plastically within the diamond stability field up to 14 GPa and above 1473 K. Macroscopic differential stress Δσ was determined on the basis of the distortion of the 111 Debye ring using synchrotron X-ray diffraction. Up to ∼5(2)% strain, Debye ring distortion can be satisfactorily described by lattice strain theories as an ellipse. Beyond ∼5(2)% strain, lattice spacing d111 along the Δσ direction becomes saturated and remains constant with further deformation. Transmission electron microscopy on as-synthesized NPD shows well-bonded grain boundaries with no free dislocations within the grains. Deformed samples also contain very few free dislocations, while density of {111} twins increases with plastic strain. Individual grains display complex contrast, exhibiting increasing misorientation with deformation according electron diffraction. Thus, NPD does not deform by dislocation slip, which is the dominated mechanism in conventional polycrystalline diamond composites (PCDCs, grain size >1 µm). The nonelliptical Debye ring distortion is modeled by nucleating 12⟨110⟩ dislocations or their dissociated 16⟨112⟩ partials gliding in the {111} planes to produce deformation twinning. With increasing strain up to ∼5(2)%, strength increases rapidly to ∼20(1) GPa, where d111 reaches saturation. Strength beyond the saturation shows a weak dependence on strain, reaching ∼22(1) GPa at >10% strain. Overall, the strength is ∼2-3 times that of conventional PCDCs. Combined with molecular dynamics simulations and lattice rotation theory, we conclude that the rapid rise of strength with strain is due to defect-source strengthening, whereas further deformation is dominated by nanotwinning and lattice rotation.

Serum galectins as potential biomarkers of inflammatory bowel diseases.

The inflammatory bowel diseases (IBD), which include mainly Crohn's disease (CD) and ulcerative colitis (UC), are common chronic inflammatory conditions of the digestive system. The diagnosis of IBD relies on the use of a combination of factors including symptoms, endoscopy and levels of serum proteins such as C-reactive protein (CRP) or faecal calprotectin. Currently there is no single reliable biomarker to determine IBD. Galectins are a family of galactoside-binding proteins that are commonly altered in the circulation of disease conditions such as cancer and inflammation. This study investigated serum galectin levels as possible biomarkers in determining IBD and IBD disease activity. Levels of galectins-1, -2, -3, -4, -7 and -8 were analysed in 208 samples from ambulant IBD patients (97 CD, 71 UC) patients and 40 from healthy people. Disease activity was assessed using Harvey-Bradshaw Index for CD and simple clinical colitis activity index for UC. The relationship of each galectin in determining IBD and IBD disease activity were analysed and compared with current IBD biomarker CRP. It was found that serum level of galectin-1 and -3, but not galectins-2, -4, -7 and -8, were significantly higher in IBD patients than in healthy people. At cut-off of 4.1ng/ml, galectin-1 differentiated IBD from healthy controls with 71% sensitivity and 87% specificity. At cut-off of 38.5ng/ml, galectin-3 separated IBD from healthy controls with 53% sensitivity and 87% specificity. None of the galectins however were able to distinguish active disease from remission in UC or CD. Thus, levels of galectins-1 and -3 are significantly elevated in both UC and CD patients compared to healthy people. Although the increased galectin levels are not able to separate active and inactive UC and CD, they may have the potential to be developed as useful biomarkers for IBD diagnosis either alone or in combination with other biomarkers.

Does annealing improve the interlayer adhesion and structural integrity of FFF 3D printed PEEK lumbar spinal cages?

Polyaryletheretherketone (PEEK) has been commonly used for interbody fusion devices because of its biocompatibility, radiolucency, durability, and strength. Although the technology of PEEK Additive Manufacturing (AM) is rapidly developing, post-processing techniques of 3D printed PEEK remain poorly understood. AM of PEEK has been challenging because of its high melt temperature (over 340 °C) and requires specialized equipment which was not commercially available until recently. A lumbar fusion cage design, used in ASTM interlaboratory studies, was 3D printed with a medical grade PEEK filament via Fused Filament Fabrication (FFF) under two different print speeds. PEEK cages were then annealed above the PEEK's glass transition temperature, at 200 °C or 300 °C. AM cages were CT scanned to determine the porosity before and after annealing. Mechanical tests were conducted on cages according to ASTM F2077 (ASTM F2077, 2014). SEM images helped to evaluate the cages' surface morphology before and after heat treatment. It was observed that annealing did not produce markedly better mechanical properties at either temperature, however, it had an effect on the cages' mechanical properties at lower printing speed under all loading conditions. Although the structure of the pores changed after annealing, annealing conditions examined here as a post-processing method were not able to decrease the undesired porosity formed during the 3D printing process or change the failure mechanism, which is due interlayer debonding.

Documentation-based clinical decision support to improve antibiotic prescribing for acute respiratory infections in primary care: a cluster randomised controlled trial.

BACKGROUND AND OBJECTIVE: Clinical guidelines discourage antibiotic prescribing for many acute respiratory infections (ARIs), especially for non-antibiotic appropriate diagnoses. Electronic health record (EHR)-based clinical decision support has the potential to improve antibiotic prescribing for ARIs. METHODS: We randomly assigned 27 primary care clinics to receive an EHR-integrated, documentation-based clinical decision support system for the care of patients with ARIs - the ARI Smart Form - or to offer usual care. The primary outcome was the antibiotic prescribing rate for ARIs in an intent-to-intervene analysis based on administrative diagnoses. RESULTS: During the intervention period, patients made 21 961 ARI visits to study clinics. Intervention clinicians used the ARI Smart Form in 6% of 11 954 ARI visits. The antibiotic prescribing rate in the intervention clinics was 39% versus 43% in the control clinics (odds ratio (OR), 0.8; 95% confidence interval (CI), 0.6-1.2, adjusted for clustering by clinic). For antibiotic appropriate ARI diagnoses, the antibiotic prescribing rate was 54% in the intervention clinics and 59% in the control clinics (OR, 0.8; 95% CI, 0.5-1.3). For non-antibiotic appropriate diagnoses, the antibiotic prescribing rate was 32% in the intervention clinics and 34% in the control clinics (OR, 0.9; 95% CI, 0.6-1.4). When the ARI Smart Form was used, based on diagnoses entered on the form, the antibiotic prescribing rate was 49% overall, 88% for antibiotic appropriate diagnoses and 27% for non-antibiotic appropriate diagnoses. In an as-used analysis, the ARI Smart Form was associated with a lower antibiotic prescribing rate for acute bronchitis (OR, 0.5; 95% CI, 0.3-0.8). CONCLUSIONS: The ARI Smart Form neither reduced overall antibiotic prescribing nor significantly improved the appropriateness of antibiotic prescribing for ARIs, but it was not widely used. When used, the ARI Smart Form may improve diagnostic accuracy compared to administrative diagnoses and may reduce antibiotic prescribing for certain diagnoses.

Risks of complications by attending physicians after performing nighttime procedures.

CONTEXT: Few data exist on the relationships between experienced physicians' work hours and sleep, and patient safety. OBJECTIVE: To determine if sleep opportunities for attending surgeons and obstetricians/gynecologists are associated with the risk of complications. DESIGN, SETTING, AND PATIENTS: Matched retrospective cohort study of procedures performed from January 1999 through June 2008 by attending physicians (86 surgeons and 134 obstetricians/gynecologists) who had been in the hospital performing another procedure involving adult patients for at least part of the preceding night (12 am-6 am, postnighttime procedures). Sleep opportunity was calculated as the time between end of the overnight procedure and start of the first procedure the following day. Matched control procedures included as many as 5 procedures of the same type performed by the same physician on days without preceding overnight procedures. Complications were identified and classified by a blinded 3-step process that included administrative screening, medical record reviews, and clinician ratings. MAIN OUTCOME MEASURES: Rates of complications in postnighttime procedures as compared with controls; rates of complications in postnighttime procedures among physicians with more than 6-hour sleep opportunities vs those with sleep opportunities of 6 hours or less. RESULTS: A total of 919 surgical and 957 obstetrical postnighttime procedures were matched with 3552 and 3945 control procedures, respectively. Complications occurred in 101 postnighttime procedures (5.4%) and 365 control procedures (4.9%) (odds ratio, 1.09; 95% confidence interval [CI], 0.84-1.41). Complications occurred in 82 of 1317 postnighttime procedures with sleep opportunities of 6 hours or less (6.2%) vs 19 of 559 postnighttime procedures with sleep opportunities of more than 6 hours (3.4%) (odds ratio, 1.72; 95% CI, 1.02-2.89). Postnighttime procedures completed after working more than 12 hours (n = 958) compared with 12 hours or less (n = 918) had nonsignificantly higher complication rates (6.5% vs 4.3%; odds ratio, 1.47; 95% CI, 0.96-2.27). CONCLUSION: Overall, procedures performed the day after attending physicians worked overnight were not associated with significantly increased complication rates, although there was an increased rate of complications among postnighttime surgical procedures performed by physicians with sleep opportunities of less than 6 hours.