Coseismic fault lubrication by viscous deformation

Despite the hazard posed by earthquakes, we still lack fundamental understanding of the processes that control fault lubrication behind a propagating rupture front and enhance ground acceleration. Laboratory experiments show that fault materials dramatically weaken when sheared at seismic velocities (>0.1 m s−1). Several mechanisms, triggered by shear heating, have been proposed to explain the coseismic weakening of faults, but none of these mechanisms can account for experimental and seismological evidence of weakening. Here we show that, in laboratory experiments, weakening correlates with local temperatures attained during seismic slip in simulated faults for diverse rock-forming minerals. The fault strength evolves according to a simple, material-dependent Arrhenius-type law. Microstructures support this observation by showing the development of a principal slip zone with textures typical of sub-solidus viscous flow. We show evidence that viscous deformation (at either sub- or super-solidus temperatures) is an important, widespread and quantifiable coseismic lubrication process. The operation of these highly effective fault lubrication processes means that more energy is then available for rupture propagation and the radiation of hazardous seismic waves

Biomechanical evaluation of fixation of comminuted olecranon fractures: one-third tubular versus locking compression plating

New concepts in plate fixation have led to an evolution in plate design for olecranon fractures. The purpose of this study was to compare the stiffness and strength of locking compression plate (LCP) fixation to one-third tubular plate fixation in a cadaveric comminuted olecranon fracture model with a standardised osteotomy. Five matched pairs of cadaveric elbows were randomly assigned for fixation by either a contoured LCP combined with an intramedullary screw and unicortical locking screws or a one-third tubular plate combined with bicortical screws. Construct stiffness was measured by subjecting the specimens to cyclic loading while measuring gapping at the osteotomy site. Construct strength was measured by subjecting specimens to ramp load until failure. There was no significant difference in fixation stiffness and strength between the two fixation methods. All failures consisted of failure of the bone and not of the hardware. Contoured LCP and intramedullary screw fixation can be used as an alternative treatment method for comminuted olecranon fractures as its stiffness and strength were not significantly different from a conventional plating techniqu

Treatment of diaphyseal non-unions of the ulna and radius

Non-unions of the forearm often cause severe dysfunction of the forearm as they affect the interosseus membrane, elbow and wrist. Treatment of these non-unions can be challenging due to poor bone stock, broken hardware, scarring and stiffness due to long-term immobilisation. We retrospectively reviewed a large cohort of forearm non-unions treated by using a uniform surgical approach during a period of 33 years (1975-2008) in a single trauma centre. All non-unions were managed following the AO-principles of compression plate fixation and autologous bone grafting if needed. The study cohort consisted of 47 patients with 51 non-unions of the radius and/or ulna. The initial injury was a fracture of the diaphyseal radius and ulna in 22 patients, an isolated fracture of the diaphyseal ulna in 13, an isolated fracture of the diaphyseal radius in 5, a Monteggia fracture in 5, and a Galeazzi fracture-dislocation of the forearm in 2 patients. Index surgery for non-union consisted of open reduction and plate fixation in combination with a graft in 30 cases (59%), open reduction and plate fixation alone in 14 cases (27%), and only a graft in 7 cases (14%). The functional result was assessed in accordance to the system used by Anderson and colleagues. Average follow-up time was 75 months (range 12-315 months). All non-unions healed within a median of 7 months. According to the system of Anderson and colleagues, 29 patients (62%) had an excellent result, 8 (17%) had a satisfactory result, and 10 (21%) had an unsatisfactory result. Complications were seen in six patients (13%). Our results show that treatment of diaphyseal forearm non-unions using classic techniques of compression plating osteosynthesis and autologous bone grafting if needed will lead to a high union rate (100% in our series). Despite clinical and radiographic bone healing, however, a substantial subset of patients will have a less than optimal functional outcom

Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) protocol : a pragmatic multi-centre randomised controlled trial of cast treatment versus surgical fixation for the treatment of bi-cortical, minimally displaced fractures of the scaphoid waist in adults

BACKGROUND: A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. METHODS/DESIGN: We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. DISCUSSION: Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013

Cast immobilization with and without immobilization of the thumb for nondisplaced and minimally displaced scaphoid waist fractures: a multicenter, randomized, controlled trial

The aim of this prospective randomized trial was to test the null hypothesis that there was no difference in the percentage of the fracture line of scaphoid waist fractures that demonstrated bridging bone on computed tomography (CT) 10 weeks after injury between patients treated in a below-elbow cast including or excluding the thumb. A total of 62 patients with a CT or magnetic resonance image-confirmed nondisplaced or minimally displaced fracture of the scaphoid were enrolled in a prospective, multicenter, randomized trial comparing treatment in a below-elbow cast including or excluding the thumb. There were 55 waist and 7 distal fractures (owing to a miscommunication at 3 of the centers). We adhered to intention-to-treat principles. The primary outcome was the extent of union on CT performed after 10 weeks of cast treatment, expressed as a percentage of the fracture line that had bridging bone, determined by musculoskeletal radiologists blinded to treatment. Secondary study outcomes included wrist motion; grip strength; the Mayo Modified Wrist Score; the Disabilities of the Arm, Shoulder and Hand score; a visual analog scale for pain; and radiographic union at 6 months after injury. There was a significant difference in the average extent of union on CT at 10 weeks (85% vs 70%) favoring treatment with a cast excluding the thumb. The overall union rate was 98%. The 1 exception was a patient in the thumb immobilization group who elected operative treatment 1 week after enrollment, used crutches, and failed to heal. There were no significant differences between groups for wrist motion; grip strength; Mayo Modified Wrist Score; Disabilities of the Arm, Shoulder, and Hand score; or pain intensity. Immobilization of the thumb appears unnecessary for CT or magnetic resonance image-confirmed nondisplaced or minimally displaced fractures of the waist of the scaphoid. Therapeutic

Interobserver reliability of computed tomography to diagnose scaphoid waist fracture union

To determine the interobserver agreement and diagnostic performance characteristics of computed tomography (CT) for determining union of scaphoid waist fractures. A total of 59 orthopedic and trauma surgeons rated for union a set of 30 sagittal CT scans of 30 scaphoid waist fractures. Of these fractures, 20 were treated nonoperatively, were imaged between 6 and 10 weeks after injury, and were known to have eventually achieved union. Ten were operatively confirmed to be ununited. We rated each scan as united or ununited using a Web-based rating application. We assessed interobserver reliability using Siegel's multirater Kappa. We calculated diagnostic performance characteristics using Bayesian formulas. The interobserver agreement among 59 raters was substantial. The average sensitivity, specificity, and accuracy of diagnosing union of scaphoid waist fractures on sagittal CT scans were 78%, 96%, and 84%, respectively. Assuming a 90% prevalence of fracture union of the scaphoid, the positive predictive value of a diagnosis of union on sagittal CT scan was 0.99 and the negative predictive value was 0.41. Our results suggest that CT scans are accurate and reliable for diagnosis of union but inadequate for ruling out nonunion of scaphoid waist fractures between 6 and 10 weeks after injury. Diagnostic II

Pain experience and functional outcome of inpatient versus outpatient anterior cruciate ligament reconstruction, an equivalence randomized controlled trial with 12 months follow-up

Arthroscopic reconstruction of the anterior cruciate ligament (ACL) has traditionally been performed in an inpatient setting. Outpatient treatment may offer the advantages of cost reduction and higher patient satisfaction. We investigated whether ACL reconstruction in an outpatient setting is equally safe as in an inpatient setting and whether comparable functional outcomes can be achieved. We hypothesized that the outcomes of outpatient ACL reconstruction result in similar outcomes as inpatient ACL reconstruction. A prospective randomized controlled trial was conducted at one centre. Forty-six patients were randomized to outpatient treatment or a 2-day admission after ACL reconstruction. The functional outcome was evaluated with the Lysholm, Tegner and International Knee Documentation Committee scores. Safety of the procedures was judged according to pain experience and readmission rate. The duration of follow-up was 1 year after ACL reconstruction. The patients were provided with a simple postoperative analgesic protocol. The linear mixed effect model for repeated measures was used for testing the differences between the study groups. No significant differences were found between the study groups in all the outcome measures. No readmissions were recorded related to pain. One complication was recorded in the outpatient group versus three in the inpatient group. This study indicates that outpatient care after ACL reconstruction yields comparable functional results and postoperative pain experience as inpatient care and is a safe option. A simple analgesic protocol provides adequate pain relief during the postoperative phase.

The E3 ubiquitin ligase NEDD4 enhances killing of membrane-perturbing intracellular bacteria by promoting autophagy

The E3 ubiquitin ligase NEDD4 has been intensively studied in processes involved in viral infections, such as virus budding. However, little is known about its functions in bacterial infections. Our investigations into the role of NEDD4 in intracellular bacterial infections demonstrate that Mycobacterium tuberculosis and Listeria monocytogenes, but not Mycobacterium bovis BCG, replicate more efficiently in NEDD4 knockdown macrophages. In parallel, NEDD4 knockdown or knockout impaired basal macroautophagy/autophagy, as well as infection-induced autophagy. Conversely, NEDD4 expression promoted autophagy in an E3 catalytic activity-dependent manner, thereby restricting intracellular Listeria replication. Mechanistic studies uncovered that endogenous NEDD4 interacted with BECN1/Beclin 1 and this interaction increased during Listeria infection. Deficiency of NEDD4 resulted in elevated K48-linkage ubiquitination of endogenous BECN1. Further, NEDD4 mediated K6- and K27- linkage ubiquitination of BECN1, leading to elevated stability of BECN1 and increased autophagy. Thus, NEDD4 participates in killing of intracellular bacterial pathogens via autophagy by sustaining the stability of BECN1

The E3 ubiquitin ligase NEDD4 enhances killing of membrane-perturbing intracellular bacteria by promoting autophagy

The E3 ubiquitin ligase NEDD4 has been intensively studied in processes involved in viral infections, such as virus budding. However, little is known about its functions in bacterial infections. Our investigations into the role of NEDD4 in intracellular bacterial infections demonstrate that Mycobacterium tuberculosis and Listeria monocytogenes, but not Mycobacterium bovis BCG, replicate more efficiently in NEDD4 knockdown macrophages. In parallel, NEDD4 knockdown or knockout impaired basal macroautophagy/autophagy, as well as infection-induced autophagy. Conversely, NEDD4 expression promoted autophagy in an E3 catalytic activity-dependent manner, thereby restricting intracellular Listeria replication. Mechanistic studies uncovered that endogenous NEDD4 interacted with BECN1/Beclin 1 and this interaction increased during Listeria infection. Deficiency of NEDD4 resulted in elevated K48-linkage ubiquitination of endogenous BECN1. Further, NEDD4 mediated K6- and K27- linkage ubiquitination of BECN1, leading to elevated stability of BECN1 and increased autophagy. Thus, NEDD4 participates in killing of intracellular bacterial pathogens via autophagy by sustaining the stability of BECN1