Hot off the presses! May 17 J Biomech

The May 17 issue of the J Biomech is now up on Pubget (About J Biomech): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Editorial Board and Publication Information
  - J Biomech 44(8):IFC (2011)
  
• Virtual anthropology meets biomechanics
  - J Biomech 44(8):1429-1432 (2011)
  A meeting in Vienna in October 2010 brought together researchers using Virtual Anthropology (VA) and Finite Element Analysis (FEA) in order to explore the benefits and problems facing a collaboration between the two fields. FEA is used to test mechanical hypotheses in functional anatomy and VA complements and augments this process by virtue of its tools for acquiring data, for segmenting and preparing virtual specimens, and for generating reconstructions and artificial forms. This represents a critical methodological advance because geometry is one of the crucial inputs of FEA and is often the variable of interest in functional anatomy. However, we currently lack tools that quantitatively relate differences in geometry to differences in stress and strain, or that evaluate the impact on FEA of variation within and between biological samples. Thus, when comparing models of different geometry, we do not currently obtain sufficiently informative answers to questions such a! s "How different are these models, and in what manner are they different? Are they different in some anatomical regions but not others?" New methodologies must be developed in order to maximize the potential of FEA to address questions in comparative and evolutionary biology. In this paper we review these and other important issues that were raised during our Vienna meeting.
• Actuation means for the mechanical stimulation of living cells via microelectromechanical systems: A critical review
  - J Biomech 44(8):1433-1446 (2011)
  Within a living body, cells are constantly exposed to various mechanical constraints. As a matter of fact, these mechanical factors play a vital role in the regulation of the cell state. It is widely recognized that cells can sense, react and adapt themselves to mechanical stimulation. However, investigations aimed at studying cell mechanics directly in vivo remain elusive. An alternative solution is to study cell mechanics via in vitro experiments. Nevertheless, this requires implementing means to mimic the stresses that cells naturally undergo in their physiological environment. In this paper, we survey various microelectromechanical systems (MEMS) dedicated to the mechanical stimulation of living cells. In particular, we focus on their actuation means as well as their inherent capabilities to stimulate a given amount of cells. Thereby, we report actuation means dependent upon the fact they can provide stimulation to a single cell, target a maximum of a hundred cells! , or deal with thousands of cells. Intrinsic performances, strengths and limitations are summarized for each type of actuator. We also discuss recent achievements as well as future challenges of cell mechanostimulation.
• Phalanx force magnitude and trajectory deviation increased during power grip with an increased coefficient of friction at the hand–object interface
  - J Biomech 44(8):1447-1453 (2011)
  This study examined the effect of friction between the hand and grip surface on a person's grip strategy and force generation capacity. Twelve young healthy adults performed power grip exertions on an instrumented vertical cylinder with the maximum and 50% of maximum efforts (far above the grip force required to hold the cylinder), while normal and shear forces at each phalanx of all five fingers in the direction orthogonal to the gravity were recorded. The cylinder surface was varied for high-friction rubber and low-friction paper coverings. An increase in surface friction by replacing the paper covering with the rubber covering resulted in 4% greater mean phalanx normal force (perpendicular to the cylinder surface) and 22% greater mean phalanx shear force in either the proximal or distal direction of the digits (p<0.05; for both 50% and maximum grip efforts). Consequently, increased friction with the rubber surface compared to the paper surface was associated with a ! 20% increase in the angular deviation of the phalanx force from the direction normal to the cylinder surface (p<0.05). This study demonstrates that people significantly changed the magnitude and direction of phalanx forces depending on the surface they gripped. Such change in the grip strategy appears to help increase grip force generation capacity. This finding suggests that a seemingly simple power grip exertion involves sensory feedback-based motor control, and that people's power grip capacity may be reduced in cases of numbness, glove use, or injuries resulting in reduced sensation.
• Reduction in wire tension caused by dynamic loading. An experimental Ilizarov frame study
  - J Biomech 44(8):1454-1458 (2011)
  Small diameter transosseous wires are main parts of the Ilizarov frame concept. Wire tensioning is essential to gain the necessary transversal stiffness, and the wire fixators are therefore important, coupling the wire to the ring. The ability of three different wire fixator designs to maintain wire tension under dynamic loading is described. The three fixator designs were combinations of two types of bolts and one washer. In a simplified frame set-up consisting of one ring and one wire, sixty wires were dynamically loaded in sequence with 200 N for 450 times and wire tension was repeatedly measured. The tension loss employing the different fixator types at two wire pretension levels (883 N, 1275 N) was measured. Wire slippage in the fixators and the midpoint deflection angle of the wires were measured. Large differences in fixation ability were observed. Wire fixators holding a larger and rougher contact surface had significant smaller tension loss compared to fixators with a smaller and smother contact surface. Both plastic wire deformation and slippage causes tension loss with slippage as the main contributor. Wire fixators' design can be improved in order to maintain wire tension. Such improvement could be of clinical interest enhancing the mechanical stability of the fixator.
• Regional analysis of dynamic deformation characteristics of native aortic valve leaflets
  - J Biomech 44(8):1459-1465 (2011)
  Background The mechanical environment of the aortic valve (AV) has a significant impact on valve cellular biology and disease progression, but the regional variation in stretch across the AV leaflet is not well understood. This study, therefore, sought to quantify the regional variation in dynamic deformation characteristics of AV leaflets in the native mechanical environment in order to link leaflet stretch variation to reported AV calcification patterns. Methods Whole porcine AVs (n=6) were sutured into a physiological left heart simulator and subjected to pulsatile and physiologically normal hemodynamic conditions. A grid of ink dots was marked on the entire ventricular surface of the AV leaflet. Dual camera stereo photogrammetry was used to determine the stretch magnitudes across the entire ventricular surface over the entire diastolic duration. Results Elevated stretch magnitudes were observed along the leaflet base and coaptation line consistent with previously reported calcification patterns suggesting the higher mechanical stretch experienced by the leaflets in these regions may contribute to increased disease propensity. Transient stretch overloads were observed during diastolic closing, predominantly along the leaflet base, indicating the presence of a dynamic fluid hammer effect resulting from retrograde blood flow impacting the leaflet. We speculate the function of the leaflet base to act in cooperation with the sinuses of Valsalva to dampen the fluid hammer effect and reduce stress levels imparted on the rest of the leaflet.
• Frontal plane standing balance with an ambulation aid:Upper limb biomechanics
  - J Biomech 44(8):1466-1470 (2011)
  Despite widespread acceptance of clinical benefits, empirical evidence to evaluate the advantages and limitations of ambulation aids for balance control is limited. The current study investigates the upper limb biomechanical contributions to the control of frontal plane stability while using a 4-wheeled walker in quiet standing. We hypothesized that: (1) upper limb stabilizing moments would be significant, and (2) would increase under conditions of increased stability demand. Factors influencing upper limb moment generation were also examined. Specifically, the contributions of upper limb center-of-pressure (COPhands), vertical and horizontal loads applied to the assistive device were assessed. The results support a significant mechanical role for the upper limbs, generating 27.1% and 58.8% of overall stabilizing moments under baseline and challenged stability demand conditions, respectively. The increased moment was achieved primarily through the preferential use of p! hasic upper limb control, reflected by increased COPhands (baseline vs. challenged conditions: 0.29 vs. 0.72 cm). Vertical, but not horizontal, was the primary force direction contributing to stabilizing moments in quiet standing. The key finding that the upper limbs play an important role in effecting frontal plane balance control has important implications for ambulation aid users (e.g., elderly, stroke, and traumatic brain injury).
• The mathematical description of the body centre of mass 3D path in human and animal locomotion
  - J Biomech 44(8):1471-1477 (2011)
  Although the 3D trajectory of the body centre of mass during ambulation constitutes the 'locomotor signature' at different gaits and speeds for humans and other legged species, no quantitative method for its description has been proposed in the literature so far. By combining the mathematical discoveries of Jean Baptiste Joseph Fourier (1768–1830, analysis of periodic events) and of Jules Antoine Lissajous (1822–1880, parametric equation for closed loops) we designed a method simultaneously capturing the spatial and dynamical features of that 3D trajectory. The motion analysis of walking and running humans, and the re-processing of previously published data on trotting and galloping horses, as moving on a treadmill, allowed to obtain closed loops for the body centre of mass showing general and individual locomotor characteristics. The mechanical dynamics due to the different energy exchange, the asymmetry along each 3D axis, and the sagittal and lateral energy ! recovery, among other parameters, were evaluated for each gait according to the present methodology. The proposed mathematical description of the 3D trajectory of the body centre of mass could be used to better understand the physiology and biomechanics of normal locomotion, from monopods to octopods, and to evaluate individual deviations with respect to average values as resulting from gait pathologies and the restoration of a normal pattern after pharmacological, physiotherapeutic and surgical treatments.
• The feasibility of modal testing for measurement of the dynamic characteristics of goat vertebral motion segments
  - J Biomech 44(8):1478-1483 (2011)
  Structural vibration testing might be a promising method to study the mechanical properties of spinal motion segments as an alternative to imaging and spinal manipulation techniques. Structural vibration testing is a non-destructive measurement technique that measures the response of a system to an applied vibration as a function of frequency, and allows determination of modal parameters such as resonance frequencies (ratio between stiffness and mass), vibration modes (pattern of motion) and damping. The objective of this study was to determine if structural vibration testing can reveal the resonance frequencies that correspond to the mode shapes flexion–extension, lateroflexion and axial rotation of lumbar motion segments, and to establish whether resonance frequencies can discriminate specific structural alterations of the motion segment. Therefore, a shaker was used to vibrate the upper vertebra of 16 goat lumbar motion segments, while the response was obtained fr! om accelerometers on the transverse and spinous processes and the anterior side of the upper vertebra. Measurements were performed in three conditions: intact, after dissection of the ligaments and after puncturing the annulus fibrosus. The results showed clear resonance peaks for flexion–extension, lateral bending and axial rotation for all segments. Dissection of the ligaments did not affect the resonance frequencies, but puncturing the annulus reduced the resonance frequency of axial rotation. These results indicate that vibration testing can be utilised to assess the modal parameters of lumbar motion segments, and might eventually be used to study the mechanical properties of spinal motion segments in vivo.
• Bone cell elasticity and morphology changes during the cell cycle
  - J Biomech 44(8):1484-1490 (2011)
  The mechanical properties of cells are reported to be regulated by a range of factors including interactions with the extracellular environment and other cells, differentiation status, the onset of pathological states, as well as the intracellular factors, for example, the cytoskeleton. The cell cycle is considered to be a well-ordered sequence of biochemical events. A number of processes reported to occur during its progression are inherently mechanical and, as such, require mechanical regulation. In spite of this, few attempts have been made to investigate the putative regulatory role of the cell cycle in mechanobiology. In the present study, Atomic Force Microscopy (AFM) was employed to investigate the elastic modulus of synchronised osteoblasts. The data obtained confirm that osteoblast elasticity is regulated by cell cycle phase; specifically, cells in S phase were found to have a modulus approximately 1.7 times that of G1 phase cells. Confocal microscopy studies ! revealed that aspects of osteoblast morphology, namely F-actin expression, were also modulated by the cell cycle, and tended to increase with phase progression from G0 onwards. The data obtained in this study are likely to have implications for the fields of tissue- and bio-engineering, where prior knowledge of cell mechanobiology is essential for the effective replacement and repair of tissue. Furthermore, studies focused on biomechanics and the biophysical properties of cells are important in the understanding of the onset and progression of disease states, for example cancer at the cellular level. Our study demonstrates the importance of the combined use of traditional and relatively novel microscopy techniques in understanding mechanical regulation by crucial cellular processes, such as the cell cycle.
• Designing polyHEMA substrates that mimic the viscoelastic response of soft tissue
  - J Biomech 44(8):1491-1498 (2011)
  Matching the mechanical properties of a biomaterial to soft tissue is often overlooked despite the fact that it is well known that cells respond to and are capable of changing their mechanical environment. In this paper, we used NaCl and alginate beads as porogens to make a series of micro- and macro-porous pHEMA substrates (poly(2-hydroxyethly methacrylate)) and quantified their mechanical behavior under low-magnitude shear loads over physiologically relevant frequencies. Using a stress-controlled rheometer, we performed isothermal (37 °C) frequency response experiments between 0.628 and 75.4 rad/s (0.01–12 Hz) at 0.1% strain. Both micro- and macro-porous pHEMA substrates were predominately elastic in nature with a narrow range of G′ and G″ values that mimicked the response of human skin. The magnitude of the G′ and G″ values of the macro-porous substrates were designed to closely match human skin. To determine how cell growth might alter their mechanical p! roperties, pHEMA substrates were functionalized and human skin fibroblasts grown on them for fourteen days. As a result of cell growth, the magnitude of G′ and G″ increased at low frequencies while also altering the degree of high frequency dependence, indicating that cellular interactions with the micro-pore infrastructure has a profound effect on the viscoelastic behavior of the substrates. These data could be fit to a mathematical model describing a soft-solid. A quantitative understanding of the mechanical behavior of biomaterials in regimes that are physiologically relevant and how these mechanics may change after implantation may aid in the design of new materials.
• Bayesian sensitivity analysis of a model of the aortic valve
  - J Biomech 44(8):1499-1506 (2011)
  Understanding the mechanics of the aortic valve has been a focus of attention for many years in the biomechanics literature, with the aim of improving the longevity of prosthetic replacements. Finite element models have been extensively used to investigate stresses and deformations in the valve in considerable detail. However, the effect of uncertainties in loading, material properties and model dimensions has remained uninvestigated. This paper presents a formal statistical consideration of a selected set of uncertainties on a fluid-driven finite element model of the aortic valve and examines the magnitudes of the resulting output uncertainties. Furthermore, the importance of each parameter is investigated by means of a global sensitivity analysis. To reduce computational cost, a Bayesian emulator-based approach is adopted whereby a Gaussian process is fitted to a small set of training data and then used to infer detailed sensitivity analysis information. From the set! of uncertain parameters considered, it was found that output standard deviations were as high as 44% of the mean. It was also found that the material properties of the sinus and aorta were considerably more important in determining leaflet stress than the material properties of the leaflets themselves.
• Computational wear simulation of patellofemoral articular cartilage during in vitro testing
  - J Biomech 44(8):1507-1513 (2011)
  Though changes in normal joint motions and loads (e.g., following anterior cruciate ligament injury) contribute to the development of knee osteoarthritis, the precise mechanism by which these changes induce osteoarthritis remains unknown. As a first step toward identifying this mechanism, this study evaluates computational wear simulations of a patellofemoral joint specimen wear tested on a knee simulator machine. A multibody dynamic model of the specimen mounted in the simulator machine was constructed in commercial computer-aided engineering software. A custom elastic foundation contact model was used to calculate contact pressures and wear on the femoral and patellar articular surfaces using geometry created from laser scan and MR data. Two different wear simulation approaches were investigated—one that wore the surface geometries gradually over a sequence of 10 one-cycle dynamic simulations (termed the "progressive" approach), and one that wore the surface ge! ometries abruptly using results from a single one-cycle dynamic simulation (termed the "non-progressive" approach). The progressive approach with laser scan geometry reproduced the experimentally measured wear depths and areas for both the femur and patella. The less costly non-progressive approach predicted deeper wear depths, especially on the patella, but had little influence on predicted wear areas. Use of MR data for creating the articular and subchondral bone geometry altered wear depth and area predictions by at most 13%. These results suggest that MR-derived geometry may be sufficient for simulating articular cartilage wear in vivo and that a progressive simulation approach may be needed for the patella and tibia since both remain in continuous contact with the femur.
• Influence of simulated neuromuscular noise on the dynamic stability and fall risk of a 3D dynamic walking model
  - J Biomech 44(8):1514-1520 (2011)
  Measures that can predict risk of falling are essential for enrollment of older adults into fall prevention programs. Local and orbital stability directly quantify responses to very small perturbations and are therefore putative candidates for predicting fall risk. However, research to date is not conclusive on whether and how these measures relate to fall risk. Testing this empirically would be time consuming or may require high risk tripping experiments. Simulation studies therefore provide an important tool to initially explore potential measures to predict fall risk. This study performed simulations with a 3D dynamic walking model to explore if and how dynamic stability measures predict fall risk. The model incorporated a lateral step controller to maintain lateral stability. Neuronal noise of increasing amplitude was added to this controller to manipulate fall risk. Short-term () local instability did predict fall risk, but long-term () local instability and orbit! al stability (maxFM) did not. Additionally, was an early predictor for fall risk as it started increasing before fall risk increased. Therefore, could be a very useful tool to identify older adults whose fall risk is about to increase, so they can be enrolled in fall prevention programs before they actually fall.
• An improved multi-joint EMG-assisted optimization approach to estimate joint and muscle forces in a musculoskeletal model of the lumbar spine
  - J Biomech 44(8):1521-1529 (2011)
  Muscle force partitioning methods and musculoskeletal system simplifications are key modeling issues that can alter outcomes, and thus change conclusions and recommendations addressed to health and safety professionals. A critical modeling concern is the use of single-joint equilibrium to estimate muscle forces and joint loads in a multi-joint system, an unjustified simplification made by most lumbar spine biomechanical models. In the context of common occupational tasks, an EMG-assisted optimization method (EMGAO) is modified in this study to simultaneously account for the equilibrium at all lumbar joints (M-EMGAO). The results of this improved approach were compared to those of its conventional single-joint equivalent (S-EMGAO) counterpart, the latter method being applied to the same lumbar joints but one at a time. Despite identical geometrical configurations and passive contributions used in both models, computed outcomes clearly differed between single- and multi-! joint methods, especially at larger trunk flexed postures and during asymmetric lifting. Moreover, muscle forces predicted by L5-S1 single-joint analyses do not maintain mechanical equilibrium at other spine joints crossed by the same muscles. Assuming that the central nervous system does not attempt to balance the external moments one joint at a time and that a given muscle cannot exert different forces at different joints, the proposed multi-joint method represents a substantial improvement over its single-joint counterpart. This improved approach, hence, resolves trunk muscle forces with biological integrity but without compromising mechanical equilibrium at the lumbar joints.
• Suture augmentation following ACL injury to restore the function of the ACL, MCL, and medial meniscus in the goat stifle joint
  - J Biomech 44(8):1530-1535 (2011)
  Functional tissue engineering (FTE) approaches have shown promise in healing an injured anterior cruciate ligament (ACL) of the knee. Nevertheless, additional mechanical augmentation is needed to maintain joint stability and appropriate loading of the joint while the ACL heals. The objective of this study was to quantitatively evaluate how mechanical augmentation using sutures restores the joint kinematics as well as the distribution of loading among the ACL, medial collateral ligament, and medial meniscus (MM) in response to externally applied loads. Eight goat stifle joints were tested on a robotic/universal force–moment sensor testing system under two loading conditions: (1) a 67 N anterior tibial load (ATL) and (2) a 67 N ATL with 100 N axial compression. For each joint, four experimental conditions were tested at 30°, 60°, and 90° of flexion: the (1) intact and (2) ACL-deficient joint, as well as following (3) suture repair of the transected ACL, and (4) augm! entation using sutures passed from the femur to the tibia. Under the 67 N ATL, suture augmentation could restore the anterior tibial translation (ATT) to within 3 mm of the intact joint (p>0.05), representing a 54–76% improvement over suture repair (p<0.05). With the additional axial compression, the ATT and in-situ forces of the sutures following suture augmentation remained 2–3 times closer to normal (p<0.05). Also, the in-situ forces in the MM were 58–73% lower (p<0.05). Thus, suture augmentation may be helpful in combination with FTE approaches for ACL healing by providing the needed initial joint stability while lowering the loads on the MM.
• Hemiarthroplasty of hip joint: An experimental validation using porcine acetabulum
  - J Biomech 44(8):1536-1542 (2011)
  Biphasic properties of articular cartilage allow it to be an excellent bearing material and have been studied through several simplified experiments as well as finite element modelling. However, three-dimensional biphasic finite element (FE) models of the whole joint are rare. The current study was carried out to experimentally validate FE methodology for modelling hemiarthroplasty. Material properties such as equilibrium elastic modulus and permeability of porcine acetabular cartilage were initially derived by curve-fitting an experimental deformation curve with that obtained using FE. These properties were then used in the hemiarthroplasty hip joint modelling. Each porcine acetabular cup was loaded with 400 N using a 34 mm diameter CoCr femoral head. A specimen-specific FE model of each acetabular cup was created using μCT and a series of software processes. Each model was analysed under conditions similar to those tested experimentally. Contact stresses and contact! areas predicted by the model, immediately after loading, were then compared with the corresponding experimentally measured values. Very high peak contact stresses (maximum experimental: 14.09 MPa) were recorded. A maximum difference of 12.42% was found in peak contact stresses. The corresponding error for contact area was 20.69%. Due to a fairly good agreement in predicted and measured values of contact stresses and contact areas, the integrated methodology developed in this study can be used as a basis for future work. In addition, FE predicted total fluid load support was around 80% immediately after loading. This was lower than that observed in conforming contact problems involving biphasic cartilage and was due to a smaller local contact area and variable clearance making fluid exudation easier.
• In vivo gleno-humeral joint loads during forward flexion and abduction
  - J Biomech 44(8):1543-1552 (2011)
  To improve design and preclinical test scenarios of shoulder joint implants as well as computer-based musculoskeletal models, a precise knowledge of realistic loads acting in vivo is necessary. Such data are also helpful to optimize physiotherapy after joint replacement and fractures. This is the first study that presents forces and moments measured in vivo in the gleno-humeral joint of 6 patients during forward flexion and abduction of the straight arm. The peak forces and, even more, the maximum moments varied inter-individually to a considerable extent. Forces of up to 238%BW (percent of body weight) and moments up to 1.74%BWm were determined. For elevation angles of less than 90° the forces agreed with many previous model-based calculations. At higher elevation angles, however, the measured loads still rose in contrast to the analytical results. When the exercises were performed at a higher speed, the peak forces decreased. The force directions relative to the hum! erus remained quite constant throughout the whole motion. Large moments in the joint indicate that friction in shoulder implants is high if the glenoid is not replaced. A friction coefficient of 0.1–0.2 seems to be realistic in these cases.
• Margination of red blood cells infected by Plasmodium falciparum in a microvessel
  - J Biomech 44(8):1553-1558 (2011)
  We investigated numerically the mechanism of margination of Plasmodium falciparum malaria-infected red blood cells (Pf-IRBCs) in micro-scale blood flow. Our model illustrates that continuous hydrodynamic interaction between a Pf-IRBC in the trophozoite stage (Pf-T-IRBC) and healthy red blood cells (HRBCs) results in the margination of the Pf-T-IRBC and, thus, a longer duration of contact with endothelial cells. The Pf-T-IRBC and HRBCs first form a "train". The volume fraction of RBCs is then locally increased, to approximately 40%, and this value is maintained for a long period of time due to the formation of a long train in high-hematocrit conditions. Even in low-hematocrit conditions, the local volume fraction is instantaneously elevated to 40% and the Pf-T-IRBC can migrate to the wall. However, the short train formed in low-hematocrit conditions does not provide continuous interaction, and the Pf-T-IRBC moves back to the center of the channel.
• Finite element analysis of heel pad with insoles
  - J Biomech 44(8):1559-1565 (2011)
  To design optimal insoles for reduction of pedal tissue trauma, experimental measurements and computational analyses were performed. To characterize the mechanical properties of the tissues, indentation tests were performed. Pedal tissue geometry and morphology were obtained from magnetic resonance scan of the subject's foot. Axisymmetrical finite element models of the heel of the foot were created with 1/4 of body weight load applied. The stress, strain and strain energy density (SED) fields produced in the pedal tissues were computed. The effects of various insole designs and materials on the resulting stress, strain, and SED in the soft pedal tissues were analyzed. The results showed: (a) Flat insoles made of soft material provide some reductions in the maximum stress, strain and SED produced in the pedal tissues. These maximum values were computed near the calcaneus. (b) Flat insoles, with conical/cylindrical reliefs, provided more reductions in these maximum val! ues than without reliefs. (c) Custom insoles, contoured to match the pedal geometry provide most reductions in the maximum stress, strain and SED. Also note, the maximum stress, strain and SED computed near the calcaneus were found to be about 10 times the corresponding peak values computed on the skin surface. Based on the FEA analysis, it can be concluded that changing insole design and using different material can significantly redistribute the stress/strain inside the heel pad as well as on the skin surface.
• Fast and accurate specimen-specific simulation of trabecular bone elastic modulus using novel beam–shell finite element models
  - J Biomech 44(8):1566-1572 (2011)
  Elastic modulus and strength of trabecular bone are negatively affected by osteoporosis and other metabolic bone diseases. Micro-computed tomography-based beam models have been presented as a fast and accurate way to determine bone competence. However, these models are not accurate for trabecular bone specimens with a high number of plate-like trabeculae. Therefore, the aim of this study was to improve this promising methodology by representing plate-like trabeculae in a way that better reflects their mechanical behavior. Using an optimized skeletonization and meshing algorithm, voxel-based models of trabecular bone samples were simplified into a complex structure of rods and plates. Rod-like and plate-like trabeculae were modeled as beam and shell elements, respectively, using local histomorphometric characteristics. To validate our model, apparent elastic modulus was determined from simulated uniaxial elastic compression of 257 cubic samples of trabecular bone (4 mm�! �4 mm×4 mm; 30 μm voxel size; BIOMED I project) in three orthogonal directions using the beam–shell models and using large-scale voxel models that served as the gold standard. Excellent agreement (R2=0.97) was found between the two, with an average CPU-time reduction factor of 49 for the beam–shell models. In contrast to earlier skeleton-based beam models, the novel beam–shell models predicted elastic modulus values equally well for structures from different skeletal sites. It allows performing detailed parametric analyses that cover the entire spectrum of trabecular bone microstructures.
• Contact forces in several TKA designs during squatting: A numerical sensitivity analysis
  - J Biomech 44(8):1573-1581 (2011)
  Total knee arthroplasty (TKA) is a very successful procedure, but pain or difficulties during activities still persist in patients. Patient outcomes in TKA surgery can be affected by implant design, alignment or patient-related anatomical factors. This paper presents a numerical sensitivity analysis of several TKA types: a fixed bearing, posterior stabilized prosthesis, a high flexion fixed bearing guided motion prosthesis, a mobile bearing prosthesis and a hinge prosthesis. Each prosthesis was virtually implanted on the same cadaver leg model and it underwent a loaded squat, in 10 s, between 0° and 120°, similar to several previous experimental tests performed on knee kinematics simulators. The aim of this examination was to investigate the sensitivity of the patello-femoral (PF) and tibio-femoral (TF) contact forces to patient-related anatomical factors, and component position in the different implant types. The following parameters were used for the sensitivity study: the proximo-distal patellar position, the patellar component tilting, the tibial component position and orientation, the locations of the medial and lateral collateral ligaments with respect to femur and tibia and the patellar tendon length. The sensitivity analysis showed that PF contact forces are mostly affected by patella height (increases up to 67% for one TKA type in patella-alta configuration), by an anterior tibial component translation (increases up to 30%), and by patellar component tilting (increases up to 29%); TF contact forces are mostly affected by the anterior displacement of the insertion points of the medial collateral ligament with respect to the reference position (increases up to 48%).
• The utility of an empirically derived co-activation ratio for muscle force prediction through optimization
  - J Biomech 44(8):1582-1587 (2011)
  Biomechanical optimization models that apply efficiency-based objective functions often underestimate or negate antagonist co-activation. Co-activation assists movement control, joint stabilization and limb stiffness and should be carefully incorporated into models. The purposes of this study were to mathematically describe co-activation relationships between elbow flexors and extensors during isometric exertions at varying intensity levels and postures, and secondly, to apply these co-activation relationships as constraints in an optimization muscle force prediction model of the elbow and assess changes in predictions made while including these constraints. Sixteen individuals performed 72 isometric exertions while holding a load in their right hand. Surface EMG was recorded from elbow flexors and extensors. A co-activation index provided a relative measure of flexor contribution to total activation about the elbow. Parsimonious models of co-activation during flexion ! and extension exertions were developed and added as constraints to a muscle force prediction model to enforce co-activation. Three different PCSA data sets were used. Elbow co-activation was sensitive to changes in posture and load. During flexion exertions the elbow flexors were activated about 75% MVC (this amount varied according to elbow angle, shoulder flexion and abduction angles, and load). During extension exertions the elbow flexors were activated about 11% MVC (this amount varied according to elbow angle, shoulder flexion angle and load). The larger PCSA values appeared to be more representative of the subject pool. Inclusion of these co-activation constraints improved the model predictions, bringing them closer to the empirically measured activation levels.
• Microstructural mechanical study of a transverse osteon under compressive loading: The role of fiber reinforcement and explanation of some geometrical and mechanical microscopic properties
  - J Biomech 44(8):1588-1592 (2011)
  This Finite Element study aims at understanding the transverse osteon as a composite microstructure, and at differentiating the actions of each of its main components and their interactions. Three components of the osteon have been distinguished: the lamellae mineral–collagen matrix, the lamellae mineral–collagen reinforcement fibers and the Haversian canal content made of intracortical fluid and soft tissues. Numerical compression experiments have been performed, varying the microstructure properties. Our results show that fiber reinforcement of transverse osteons is only efficient at resisting dynamic compressive loadings, but that the improvement of the static compressive properties is very poor. Furthermore, the modeled stress distribution within the matrix and reinforcement fibers may explain why transverse osteons are often limited to a small number of lamellae (<8) and why internal lamellae could be stiffer than external ones.
• Reduced tissue hardness of trabecular bone is associated with severe osteoarthritis
  - J Biomech 44(8):1593-1598 (2011)
  This study investigated whether changes in hardness of human trabecular bone are associated with osteoarthritis. Twenty femoral heads extracted from subjects without musculoskeletal diseases (subject age: 49–83 years) and twenty femoral heads extracted from osteoarthritic subjects (subject age: 42–85 years) were tested. Sixty indentations were performed along the main trabecular direction of each sample at a fixed relative distance. Two microstructures were found on the indenting locations: packs of parallel-lamellae (PL) and secondary osteons (SO). A 25 gf load was applied for 15 s and the Vickers Hardness (HV) was assessed. Trabecular tissue extracted from osteoarthritic subjects was found to be about 13% less hard compared to tissue extracted from non-pathologic subjects. However, tissue hardness was not significantly affected by gender or age. The SO was 10% less hard than the PL for both pathologic and non-pathologic tissues. A hardness of 34.1 HV for PL and 30.8 HV for SO was found for the non-pathologic tissue. For osteoarthritic tissue, the hardness was 30.2 HV for PL and 27.1 HV for SO. In the bone tissue extracted from osteoarthritic subjects the occurrence of indenting a SO (28%) was higher than that observed in the non-pathological tissue (15%). Osteoarthritis is associated with reduced tissue hardness and alterations in microstructure of the trabecular bone tissue. Gender does not significantly affect trabecular bone hardness either in non-pathological or osteoarthritic subjects. A similar conclusion can be drawn for age, although a larger donor sample size would be necessary to definitively exclude the existence of a slight effect.
• Biomechanics for inclusive urban design: Effects of tactile paving on older adults' gait when crossing the street
  - J Biomech 44(8):1599-1604 (2011)
  In light of our ageing population it is important that the urban environment is easily accessible and hence supports older adults' independence. Tactile 'blister' paving was originally designed to provide guidance for visually impaired people at pedestrian crossings. However, as research links irregular surfaces to falls in older adults, such paving may have an adverse effect on older people. We investigated the effects of tactile paving on older adults' gait in a scenario closely resembling crossing the street. Gait analysis of 32 healthy older adults showed that tactile, as compared to smooth, paving increases the variability in timing of foot placement by 20%, thereby indicating a disturbance of the rhythmic gait pattern. Moreover, toe clearance during the swing phase increased by 7% on tactile paving, and the ability to stop upon cue from the traffic light was compromised. These results need to be viewed under the consideration of limitations associated with la! boratory studies and real world analysis is needed to fully understand their implications for urban design.
• Training multi-parameter gaits to reduce the knee adduction moment with data-driven models and haptic feedback
  - J Biomech 44(8):1605-1609 (2011)
  The purpose of this study was to evaluate gait retraining for reducing the knee adduction moment. Our primary objective was to determine whether subject-specific altered gaits aimed at reducing the knee adduction moment by 30% or more could be identified and adopted in a single session through haptic (touch) feedback training on multiple kinematic gait parameters. Nine healthy subjects performed gait retraining, in which data-driven models specific to each subject were determined through experimental trials and were used to train novel gaits involving a combination of kinematic changes to the tibia angle, foot progression and trunk sway angles. Wearable haptic devices were used on the back, knee and foot for real-time feedback. All subjects were able to adopt altered gaits requiring simultaneous changes to multiple kinematic parameters and reduced their knee adduction moments by 29–48%. Analysis of single parameter gait training showed that moving the knee medially b! y increasing tibia angle, increasing trunk sway and toeing in all reduced the first peak of the knee adduction moment with tibia angle changes having the most dramatic effect. These results suggest that individualized data-driven gait retraining may be a viable option for reducing the knee adduction moment as a treatment method for early-stage knee osteoarthritis patients with sufficient sensation, endurance and motor learning capabilities.
• Experimental modal analysis on fresh-frozen human hemipelvic bones employing a 3D laser vibrometer for the purpose of modal parameter identification
  - J Biomech 44(8):1610-1613 (2011)
  To provide a close-to-reality simulation model, such as for improved surgery planning, this model has to be experimentally verified. The present article describes the use of a 3D laser vibrometer for determining modal parameters of human pelvic bones that can be used for verifying a finite elements model. Compared to previously used sensors, such as acceleration sensors or strain gauges, the laser vibrometric procedure used here is a non-contact and non-interacting measuring method that allows a high density of measuring points and measurement in a global coordinate system. Relevant modal parameters were extracted from the measured data and provided for verifying the model. The use of the 3D laser vibrometer allowed the establishment of a process chain for experimental examination of the pelvic bones that was optimized with respect to time and effort involved. The transfer functions determined feature good signal quality. Furthermore, a comparison of the results obtain! ed from pairs of pelvic bones showed that repeatable measurements can be obtained with the method used.
• Investigation of optimal follower load path generated by trunk muscle coordination
  - J Biomech 44(8):1614-1617 (2011)
  It has been reported that the center of rotation of each vertebral body is located posterior to the vertebral body center. Moreover, it has been suggested that an optimized follower load (FL) acts posterior to the vertebral body center. However, the optimal position of the FL with respect to typical biomechanical characteristics regarding spinal stabilization, such as joint compressive force, shear force, joint moment, and muscle stress, has not been studied. A variation in the center of rotation of each vertebra was formulated in a three-dimensional finite element model of the lumbar spine with 117 pairs of trunk muscles. Then, the optimal translation of the FL path connecting the centers of rotations was estimated by solving the optimization problem that was to simultaneously minimize the compressive forces, the shear forces, and the joint moments or to minimize the cubic muscle stresses. An upright neutral standing position and a standing position with 200 N in both! hands were considered. The FL path moved posterior, regardless of the optimization criteria and loading conditions. The FL path moved 5.0 and 7.8 mm posterior in upright standing and 4.1 mm and 7.0 mm posterior in standing with 200 N in hands for each optimization scheme. In addition, it was presented that the optimal FL path may have advantages in comparison to the body center FL path. The present techniques may be important in understanding the spine stabilization function of the trunk muscles.
• Muscle extracellular matrix applies a transverse stress on fibers with axial strain
  - J Biomech 44(8):1618-1620 (2011)
  It is widely assumed that skeletal muscle contraction is isovolumic. This assumption has been verified at the single fiber and at the myofibril level. Model development and mechanical analyses often exploit this assumption when investigating skeletal muscle and evaluating muscle mechanical properties. This communication describes a method whereby individual muscle fibers and bundles of fibers, which include their constituent extracellular matrix (ECM), were tested to define the change in volume with axial strain. The results demonstrate that fibers are isovolumic, but bundles decrease in volume with strain. The loss of volume implicates a transverse force being applied to the fibers by the ECM. The nature and importance of this transverse force warrant further investigation.
• A two-parameter model of the effective elastic tensor for cortical bone
  - J Biomech 44(8):1621-1625 (2011)
  Multiscale models of cortical bone elasticity require a large number of parameters to describe the organization and composition of the tissue. We hypothesize that the macro-scale anisotropic elastic properties of different bones can be modeled retaining only two variable parameters, and setting the others to universal values identical for all bones. Cortical bone is regarded as a two-phase composite material: a dense mineralized matrix (ultrastructure) and a soft phase (pores). The ultrastructure is assumed to be a homogeneous and transversely isotropic tissue whose elastic properties in different directions are mutually dependent and can be scaled with a single parameter driving the overall rigidity. This parameter is taken to be the volume fraction of mineral fha. The pore network is modeled as an ensemble of water-filled cylinders and described only by the porosity p. The effective macroscopic elasticity tensor Cij(fha,p) is calculated with a multiscale micromechani! cs approach starting from existing models. The modeled stiffness coefficients compare favorably to four literature datasets which were chosen because they provide the full stiffness tensors of groups of human samples. Since the physical counterparts of fha and p were unknown for the datasets, their values which allow the best fit of experimental tensors by the modeled ones were determined by optimization. Optimum values of fha and p are found to be unique and realistic. These results suggest that a two-parameter model may be sufficient to model the elasticity of different samples of human femora and tibiae. Such a model would in particular be useful in large-scale parametric studies of bone mechanical response.
• Nano- and micromechanical properties of dentine: Investigation of differences with tooth side
  - J Biomech 44(8):1626-1629 (2011)
  The soft zone in dentine beneath the dentino-enamel junction is thought to play an important role in tooth function, strain distribution and fracture resistance during mastication. Recently reported asymmetry in mechanical properties with tooth side may point at a basic property of tooth function. The aim of our study was to test if this asymmetry was reflected in the nano- and micromechanical properties of dentine. We investigated the mechanical properties of dentine on the buccal and lingual side of nine extracted human teeth using nano- and microindentation. Properties were analysed on the natural log scale, using maximum likelihood to estimate the parameters. Two-sided 0.05-level likelihood ratio tests were used to assess the influences of surface (buccal versus lingual) and dentine depth, measured from the DEJ in crown dentine and from the CDJ in root dentine. Results showed the well known gradual increase in mechanical properties with increasing distance from the DEJ. Coronal dentine showed higher elastic modulus and hardness on the lingual side of teeth for all measurements, while root dentine was harder on the buccal side. Due to the subtlety of these effects and the small number of teeth studied, results failed to reach statistical significance. Results suggest that dentine nano- and micromechanical properties vary with tooth side in agreement with recent literature using macroscopic methods. They also reveal that buccal–lingual ratios of hardness are in opposite directions in crown and root dentine, suggesting compensatory functions.
• An examination of possible quadriceps force at the time of anterior cruciate ligament injury during landing: A simulation study
  - J Biomech 44(8):1630-1632 (2011)
  Anterior cruciate ligament (ACL) rupture is a common and traumatic injury. Although, identifying the mechanism of ACL injury has received considerable research attention, there are still many unanswered questions. One proposed mechanism asserts that the ACL is injured due to an aggressive quadriceps muscle contraction. However, recently it has been questioned if the magnitude of quadriceps force needed to tear the ACL is physiologically realistic under the conditions where injury occurs during landing (e.g. near full knee extension and within 50 ms after impact). To answer this question, a simple simulation model was developed to examine the upper bounds of quadriceps force that can be developed under these conditions. The model included force–length, and force–velocity properties as well as activation dynamics. Model parameters were chosen to provide a high estimate for possible quadriceps force in a young healthy man. The effects of varying quadriceps pre-activat! ion levels were also examined. When using realistic pre-activation levels, the simulated quadriceps force was less than half of what has been shown to cause ACL injury. Even when using maximum pre-activation, the quadriceps force still did not reach close to the level shown to cause injury. Therefore, we conclude that quadriceps force alone seems to be an unlikely mechanism for ACL injury.
• Tracking the scapula using the scapula locator with and without feedback from pressure-sensors: A comparative study
  - J Biomech 44(8):1633-1636 (2011)
  Background The scapula locator method has associated intra-observer and inter-observer errors caused by the dependency on the observer to locate the scapular landmarks. The potential effect of the pressures applied by the observer on the measured scapular kinematics when this method is used has also been overlooked so far. The aim of this study was to investigate the effect of using feedback on the pressures applied on the scapula using the locator on the intra-observer and inter-observer reliabilities of the method as well as on the kinematics obtained using this method. Methods Three observers tracked the scapular motion of the dominant shoulder of each subject using the locator with no reference to pressure-feedback for three trials of bilateral elevation in the scapular plane and using the locator with pressure-feedback for three other trials. Variations between the measurements obtained were used to calculate the intra-observer errors and variations between the measurements obtained by the three observers for the same subject were used to calculate inter-observer errors. Repeated-measures ANOVA tests were used to look at differences between the two methods in terms of intra-observer and inter-observer errors and scapular kinematics. Findings Using pressure-feedback reduced the intra-observer errors but had no effect on the inter-observer errors. Different scapular kinematics was measured using the two methods. Interpretations Pressure-feedback improves the reliability of the scapula locator method. Differences in the scapular kinematics suggest that unregulated pressures have an effect on the physiological scapular motion.
• Letter to the Editor
  - J Biomech 44(8):1637 (2011)
  
• Response to Letter to the Editor
  - J Biomech 44(8):1637-1638 (2011)
  

Hot off the presses! May 06 LANCET

The May 06 issue of the LANCET is now up on Pubget (About LANCET): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• The three stages of Alzheimer's disease
  - LANCET 377(9776):1465 (2011)
  
• Strengthening the regulation of herbal medicines in Europe
  - LANCET 377(9776):1466 (2011)
  
• Artesunate for severe malaria
  - LANCET 377(9776):1466 (2011)
  
• Improving tuberculosis diagnostics and treatment
  - LANCET 377(9776):1467-1468 (2011)
  
• Concerns about injectable naltrexone for opioid dependence
  - LANCET 377(9776):1468-1470 (2011)
  
• DISPACT trial: what do we learn from equivalency?
  - LANCET 377(9776):1470-1471 (2011)
  
• Stillbirths: the professional organisations' perspective
  - LANCET 377(9776):1471-1472 (2011)
  
• Case competitions to engage students in global health
  - LANCET 377(9776):1473-1474 (2011)
  
• Lead poisoning in China: a nightmare from industrialisation
  - LANCET 377(9776):1474-1476 (2011)
  
• HbA1c: an old friend in new clothes
  - LANCET 377(9776):1476-1477 (2011)
  
• Offline: The land of holy miracles
  - LANCET 377(9776):1478 (2011)
  
• UK moves to ensure "access to unlicensed herbal medicines"
  - LANCET 377(9776):1479-1480 (2011)
  
• Native American health left out in the cold
  - LANCET 377(9776):1481-1482 (2011)
  
• The happiness wars
  - LANCET 377(9776):1483-1484 (2011)
  
• Animating images
  - LANCET 377(9776):1484 (2011)
  
• Colin Sullivan: inventive pioneer of sleep medicine
  - LANCET 377(9776):1485 (2011)
  
• 17th-century childbirth: "exquisite torment and infinite grace"
  - LANCET 377(9776):1486-1487 (2011)
  
• Martin Avigdor Birnstingl
  - LANCET 377(9776):1488 (2011)
  
• Safety of workers at the Fukushima Daiichi nuclear power plant
  - LANCET 377(9776):1489-1490 (2011)
  
• Initial combination therapy for treatment of hypertension
  - LANCET 377(9776):1490-1491 (2011)
  
• Initial combination therapy for treatment of hypertension
  - LANCET 377(9776):1491 (2011)
  
• Initial combination therapy for treatment of hypertension
  - LANCET 377(9776):1491 (2011)
  
• Initial combination therapy for treatment of hypertension – Authors' reply
  - LANCET 377(9776):1492 (2011)
  
• The complexity of ABO in coronary heart disease
  - LANCET 377(9776):1492-1493 (2011)
  
• The complexity of ABO in coronary heart disease
  - LANCET 377(9776):1493 (2011)
  
• The complexity of ABO in coronary heart disease – Authors' reply
  - LANCET 377(9776):1493-1494 (2011)
  
• Department of Error
  - LANCET 377(9776):1494 (2011)
  
• Department of Error
  - LANCET 377(9776):1494 (2011)
  
• Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study
  - LANCET 377(9776):1495-1505 (2011)
  Background The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings. Methods We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2–3 sputum smears and 1–3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used. Findings We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0–1), compared with 1 day (0–1) for microscopy, 30 days (23–43) for solid culture, and 16 days (13–21) for liquid culture. Median time to detection of resistance was 20 days (10–26) for line-probe assay and 106 days (30–124) for conventional drug-susceptibility testing. Use of the MTB/RIF test ! reduced median time to treatment for smear-negative tuberculosis from 56 days (39–81) to 5 days (2–8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures. Interpretation The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment. Funding Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development.
• Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial
  - LANCET 377(9776):1506-1513 (2011)
  Background Opioid dependence is associated with low rates of treatment-seeking, poor adherence to treatment, frequent relapse, and major societal consequences. We aimed to assess the efficacy, safety, and patient-reported outcomes of an injectable, once monthly extended-release formulation of the opioid antagonist naltrexone (XR-NTX) for treatment of patients with opioid dependence after detoxification. Methods We did a double-blind, placebo-controlled, randomised, 24-week trial of patients with opioid dependence disorder. Patients aged 18 years or over who had 30 days or less of inpatient detoxification and 7 days or more off all opioids were enrolled at 13 clinical sites in Russia. We randomly assigned patients (1:1) to either 380 mg XR-NTX or placebo by an interactive voice response system, stratified by site and gender in a centralised, permuted-block method. Participants also received 12 biweekly counselling sessions. Participants, investigators, staff, and the sponsor were masked to treatment allocation. The primary endpoint was the response profile for confirmed abstinence during weeks 5–24, assessed by urine drug tests and self report of non-use. Secondary endpoints were self-reported opioid-free days, opioid craving scores, number of days of retention, and relapse to physiological opioid dependence. Analyses were by intention to treat. This trial is registered at Clinica! lTrials.gov, NCT00678418. Findings Between July 3, 2008, and Oct 5, 2009, 250 patients were randomly assigned to XR-NTX (n=126) or placebo (n=124). The median proportion of weeks of confirmed abstinence was 90·0% (95% CI 69·9–92·4) in the XR-NTX group compared with 35·0% (11·4–63·8) in the placebo group (p=0·0002). Patients in the XR-NTX group self-reported a median of 99·2% (range 89·1–99·4) opioid-free days compared with 60·4% (46·2–94·0) for the placebo group (p=0·0004). The mean change in craving was −10·1 (95% CI −12·3 to −7·8) in the XR-NTX group compared with 0·7 (−3·1 to 4·4) in the placebo group (p<0·0001). Median retention was over 168 days in the XR-NTX group compared with 96 days (95% CI 63–165) in the placebo group (p=0·0042). Naloxone challenge confirmed relapse to physiological opioid dependence in 17 patients in the placebo group compared with one in the XR-NTX group (p<0·0001). XR-NTX was well tolerated. Two patients in each group discontinued owing to! adverse events. No XR-NTX-treated patients died, overdosed, or discontinued owing to severe adverse events. Interpretation XR-NTX represents a new treatment option that is distinct from opioid agonist maintenance treatment. XR-NTX in conjunction with psychosocial treatment might improve acceptance of opioid dependence pharmacotherapy and provide a useful treatment option for many patients. Funding Alkermes.
• Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial
  - LANCET 377(9776):1514-1522 (2011)
  Background The ideal closure technique of the pancreas after distal pancreatectomy is unknown. We postulated that standardised closure with a stapler device would prevent pancreatic fistula more effectively than would a hand-sewn closure of the remnant. Methods This multicentre, randomised, controlled, parallel group-sequential superiority trial was done in 21 European hospitals. Patients with diseases of the pancreatic body and tail undergoing distal pancreatectomy were eligible and were randomly assigned by central randomisation before operation to either stapler or hand-sewn closure of the pancreatic remnant. Surgical performance was assessed with intraoperative photo documentation. The primary endpoint was the combination of pancreatic fistula and death until postoperative day 7. Patients and outcome assessors were masked to group assignment. Interim and final analysis were by intention to treat in all patients in whom a left resection was done. This trial is registered, ISRCTN18452029. Findings Between Nov 16, 2006, and July 3, 2009, 450 patients were randomly assigned to treatment groups (221 stapler; 229 hand-sewn closure), of whom 352 patients (177 stapler, 175 hand-sewn closure) were analysed. Pancreatic fistula rate or mortality did not differ between stapler (56 [32%] of 177) and hand-sewn closure (49 [28%] of 175; OR 0·84, 95% CI 0·53–1·33; p=0·56). One patient died within the first 7 days after surgery in the hand-sewn group; no deaths occurred in the stapler group. Serious adverse events did not differ between groups. Interpretation Stapler closure did not reduce the rate of pancreatic fistula compared with hand-sewn closure for distal pancreatectomy. New strategies, including innovative surgical techniques, need to be identified to reduce this adverse outcome. Funding German Federal Ministry of Education and Research.
• Stillbirths: what difference can we make and at what cost?
  - LANCET 377(9776):1523-1538 (2011)
  Worldwide, 2·65 million (uncertainty range 2·08 million to 3·79 million) stillbirths occur yearly, of which 98% occur in countries of low and middle income. Despite the fact that more than 45% of the global burden of stillbirths occur intrapartum, the perception is that little is known about effective interventions, especially those that can be implemented in low-resource settings. We undertook a systematic review of randomised trials and observational studies of interventions which could reduce the burden of stillbirths, particularly in low-income and middle-income countries. We identified several interventions with sufficient evidence to recommend implementation in health systems, including periconceptional folic acid supplementation or fortification, prevention of malaria, and improved detection and management of syphilis during pregnancy in endemic areas. Basic and comprehensive emergency obstetric care were identified as key effective interventions to reduce in! trapartum stillbirths. Broad-scale implementation of intervention packages across 68 countries listed as priorities in the Countdown to 2015 report could avert up to 45% of stillbirths according to a model generated from the Lives Saved Tool. The overall costs for these interventions are within the general estimates of cost-effective interventions for maternal care, especially in view of the effects on outcomes across maternal, fetal, and neonatal health.
• Live case demonstrations: patient safety, ethics, consent, and conflicts
  - LANCET 377(9776):1539-1541 (2011)
  
• A deadly aversion to pork
  - LANCET 377(9776):1542 (2011)