Long-term effects of lifestyle and metformin interventions in DPP on bone density.

In the Diabetes Prevention Program Outcome Study (DPPOS), a cohort at high risk of diabetes, randomization to intensive lifestyle intervention or metformin, both associated with weight loss, did not have long-term negative effects on BMD compared with the placebo group. Potential positive effects of metformin on bone warrant further investigation. INTRODUCTION: Randomization to lifestyle intervention (ILS) or metformin in the Diabetes Prevention Program (DPP) resulted in weight loss and reduced progression to diabetes. Weight loss is associated with reduced bone mineral density (BMD), but the long-term effects of these interventions on BMD are unknown. In the DPP Outcome Study (DPPOS), we determined if randomization to ILS or metformin, compared with placebo, was associated with differences in BMD approximately 16 years later. METHODS: Of 3234 DPP participants, 2779 continued in DPPOS and were offered ILS in group format. Those randomized to metformin were offered unmasked metformin. At DPPOS year 12, 1367 participants had dual-energy X-ray absorptiometry scans. BMD in metformin and ILS groups was compared to placebo using sex-specific linear regression models, adjusted for age, race/ethnicity, and weight and weight-bearing activity at DPP baseline. RESULTS: At DPPOS year 12, mean age was 66.5 (±9.5) years. Femoral neck BMD was similar in the ILS and placebo groups in men (difference = -0.021 g/cm2, 95%CI (-0.063, 0.021)) and in women (+0.014 g/cm2, 95%CI (-0.014, 0.042)). Femoral neck BMD was higher in the metformin compared to placebo group although not statistically different in men (+0.017 g/cm2, 95% CI (-0.023, 0.058)) and in women (+0.019 g/cm2, 95% CI (-0.009, 0.047)). Prevalence of osteoporosis was low and similar across treatment groups in men (0.9%; p=0.745) and women (2.4%; p=0.466). CONCLUSION: In a cohort at high risk of diabetes, lifestyle intervention or metformin did not appear to have long-term negative effects on BMD. Potential positive effects of metformin on bone warrant further research.

Traumatic brain injury in pedestrian-vehicle collisions: Convexity and suitability of some functionals used as injury metrics.

BACKGROUND AND OBJECTIVE: Abrupt accelerations or decelerations can cause large strain in brain tissues and, consequently, different forms of Traumatic Brain Injury (TBI). In order to predict the effect of the accelerations on the soft tissues of the brain, many different injury metrics have been proposed (typically, an injury metric is a real valued functional of the accelerations). The objective of this article is to make a formal and empirical comparison, in order to identify general criteria for reasonable injury metrics, and propose a general guideline to avoid ill-proposed injury metrics. METHODS: A medium-sized sample of vehicle-pedestrian collisions, from Post Mortem Human Subject (PMHS) tests, is analyzed. A statistical study has been conducted in order to determine the discriminant power of the usual metrics. We use Principal Component Analysis to reduce dimensionality and to check consistency among the different metrics. In addition, this article compares the mathematical properties of some of these functionals, trying to identify the desirable properties that any of those functionals needs to fulfill in order to be useful for optimization. RESULTS: We have found a pair-wise consistency of all the currently used metrics (any two injury metrics are always positively related). In addition, we observed that two independent principal factors explain about 72.5% of the observed variance among all collision tests. This is remarkable because it indicates that despite high number of different injury metrics, a reduced number of variables can explain the results of all these metrics. With regard to the formal properties, we found that essentially all injury mechanisms can be accounted by means of scalable, differentiable and convex functionals (we propose to call minimization suitable injury metric any metric having these three formal properties). In addition three useful functionals, usable as injury metrics, are identified on the basis of the empirical comparisons. CONCLUSIONS: The commonly used metrics are highly consistent, but also highly redundant. Formal minimal conditions of a reasonable injury metric has been identified. Future proposals of injury metrics can benefit from the results of this study.

Texting while driving: is speech-based text entry less risky than handheld text entry?

Research indicates that using a cell phone to talk or text while maneuvering a vehicle impairs driving performance. However, few published studies directly compare the distracting effects of texting using a hands-free (i.e., speech-based interface) versus handheld cell phone, which is an important issue for legislation, automotive interface design and driving safety training. This study compared the effect of speech-based versus handheld text entries on simulated driving performance by asking participants to perform a car following task while controlling the duration of a secondary text-entry task. Results showed that both speech-based and handheld text entries impaired driving performance relative to the drive-only condition by causing more variation in speed and lane position. Handheld text entry also increased the brake response time and increased variation in headway distance. Text entry using a speech-based cell phone was less detrimental to driving performance than handheld text entry. Nevertheless, the speech-based text entry task still significantly impaired driving compared to the drive-only condition. These results suggest that speech-based text entry disrupts driving, but reduces the level of performance interference compared to text entry with a handheld device. In addition, the difference in the distraction effect caused by speech-based and handheld text entry is not simply due to the difference in task duration.

A microcontinuum model for mechanical properties of esophageal tissue: experimental methodology and constitutive analysis.

Accurate material properties of tissues are a key factor for the improvement of medical procedures and treatments. Experimental data are essential in order to formulate and validate a useful constitutive model for predicting the mechanical behavior of tissues in these procedures. This study develops a comprehensive experimental protocol at multiple length scale levels in order to obtain stress-strain curves for esophagus tissue. This paper compares two different models: a conventional, non-linear elastic model, and a microcontinuum model based on fiber rearrangement. Also, a detailed description of the experimental procedure is provided. While the focus was on esophageal tissues, the experimental procedure and microcontinuum are considered widely applicable to other samples of soft tissue.

Thoracic response to shoulder belt loading: comparison of tabletop and frontal sled tests with PMHS.

OBJECTIVE: The recent refinement of high-rate optical tracking allows dramatically detailed thoracic deformation measurements to be taken during postmortem human subject (PMHS) sled tests. These data allow analysis of restraint belt geometry and the 3-dimensional thoracic deformations generated by belt impingement. One consequence of this new capability is a better understanding of complementary thoracic characterization experiments such as tabletop tests and how the thoracic response can be interpreted for applications involving more complex loading mechanisms. METHODS: This article reports a detailed evaluation of the timing, magnitude, and direction of the applied belt forces and the resulting thoracic deformations in 2 previously performed tests series involving frontal sled tests and tabletop belt-loading tests. RESULTS: In the sled tests, the posteriorly directed component (SAE x) of the belt tension (F(B)) was F(Bx) = 0.70 F(B) at the shoulder but only F(Bx) = 0.14 F(B) where the belt engaged the anterolateral torso inferiorly. The corresponding components on the tabletop were F(Bx) = 0.60 F(B) (shoulder) and F(Bx) = 0.48 F(B) (lower). CONCLUSIONS: When these components are cross-plotted with chest deflection, pronounced consequences of thoracic anterior wall deformation patterns due to flexion of the thoracic spine and the internal viscera's inertia can be seen in the effective thoracic stiffness. Supplemental materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention to view the supplemental file.

Minimization of analytical injury metrics for head impact injuries.

OBJECTIVE: To compare the predictions of the head injury criterion (HIC), currently used to predict the risk of traumatic brain injury in frontal vehicle impact and pedestrian impact tests, with the predictions of other empirical and analytical injury metrics. METHODS: The appropriateness of different criteria relative to injury metrics derived from a head finite element (FE) model is investigated for different deceleration pulses in this research. Empirical injury metrics are computed by direct calculation for different analyzed pulses. In addition, for each pulse full FE model simulations of a complete human head were performed by means of the SIMon model. The computations are used to calculate the analytical injury metrics. RESULTS: This article shows that an optimal head deceleration curve based on HIC does not minimize other analytical injury metrics. The results obtained in this study suggest that the HIC criterion does not necessarily provide the same severity ranking for different external loadings to the head as the injury metrics derived from the FE models. CONCLUSION: Countermeasures designed based only on HIC could differ significantly from those based on analytical injury measures computed by FE models. The use of multiple injury metrics is recommended given that no scalar measure seems to be positively and strongly correlated with relevant injury metrics.

Kinematics of the unrestrained vehicle occupants in side-impact crashes.

A test series involving direct right-side impact of a moving wall on unsupported, unrestrained cadavers with no arms was undertaken to better understand human kinematics and injury mechanisms during side impact at realistic speeds. The tests conducted provided a unique opportunity for a detailed analysis of the kinematics resulting from side impact. Specifically, this study evaluated the 3-dimensional (3D) kinematics of 3 unrestrained male cadavers subjected to lateral impact by a multi-element load wall carried by a pneumatically propelled rail-mounted sled reproducing a conceptual side crash impact. Three translations and 3 rotations characterize the movement of a solid body in the space, the 6 degrees of freedom (6DoF) kinematics of 15 bone segments were obtained from the 3D marker motions and computed tomography (CT)-defined relationships between the maker array mounts and the bones. The moving wall initially made contact with the lateral aspect of the pelvis, which initiated lateral motion of the spinal segments beginning with the pelvis and moving sequentially up through the lumbar spine to the thorax. Analyzing the 6DoF motions kinematics of the ribs and sternum followed right shoulder contact with the wall. Overall thoracic motion was assessed by combining the thoracic bone segments as a single rigid body. The kinematic data presented in this research provides quantified subject responses and boundary condition interactions that are currently unavailable for lateral impact.

Human surrogates for injury biomechanics research.

This article reviews the attributes of the human surrogates most commonly used in injury biomechanics research. In particular, the merits of human cadavers, human volunteers, animals, dummies, and computational models are assessed relative to their ability to characterize the living human response and injury in an impact environment. Although data obtained from these surrogates have enabled biomechanical engineers and designers to develop effective injury countermeasures for occupants and pedestrians involved in crashes, the magnitude of the traffic safety problem necessitates expanded efforts in research and development. This article makes the case that while there are limitations and challenges associated with any particular surrogate, each provides a critical and necessary component in the continued quest to reduce crash-related injuries and fatalities.

Comparison of Hybrid III child test dummies to pediatric PMHS in blunt thoracic impact response.

The limited availability of pediatric biomechanical impact response data presents a significant challenge to the development of child dummies. In the absence of these data, the development of the current generation of child dummies has been driven by scaling of the biomechanical response requirements of the existing adult test dummies. Recently published pediatric blunt thoracic impact response data provide a unique opportunity to evaluate the efficacy of these scaling methodologies. However, the published data include several processing anomalies and nonphysical features. These features are corrected by minimizing instrumentation and processing error to improve the fidelity of the individual force-deflection responses. Using these data, biomechanical impact response corridors are calculated for a 3-year-old child and a 6-year-old child. These calculated corridors differ from both the originally published postmortem human subject (PMHS) corridors and the impact response requirements of the current child dummies. Furthermore, the response of the Hybrid III 3-year-old test dummy in the same impact condition shows a similar deflection but a significantly higher force than the 3-year-old corridor. The response of the Hybrid III 6-year-old dummy, on the other hand, correlates well with the calculated 6-year-old corridor. The newly developed 3-year-old and 6-year-old blunt thoracic impact response corridors can be used to define data-driven impact response requirements as an alternative to scaling-driven requirements.

Influence of pre-collision occupant parameters on injury outcome in a frontal collision.

Optimal performance of adaptive restraint systems in the vehicle requires an accurate assessment of occupant characteristics including physical properties and pre-collision response of the occupant. To provide a feasible framework for incorporating occupant characteristics into adaptive restraint schemes, this study evaluates the sensitivity of injury risk in frontal collisions to four occupant parameters: mass, stature, posture and bracing level. The numerical approach includes using commercial multi-body software to develop occupant models that span a range of occupant parameters representative of the real-world driver population. Coupled with a multi-body model of the vehicle interior and standard restraint system, risk of occupant injuries within specific body regions are predicted through numerical simulations in conjunction with established injury risk functions. The results show occupant posture to be the most significant parameter affecting the overall risk of injury in frontal collisions. The causal relationship as predicted using the numerical model has been compared to the traffic injury epidemiology findings, and the feasibility of an analytical methodology to provide real-time estimates of injury severity has been discussed. Preliminary estimates from the study indicate that the proposed methodology will provide a framework to optimize restraint performance and potentially reduce the risk of injuries up to 35% (based on parameter-specific optimization), using accurate information regarding the pre-collision occupant characteristics.

Re-evaluating the neck injury index (NII) using experimental PMHS tests.

OBJECTIVE: The neck injury index, NII, developed in ISO 13232 (2005) as a testing and evaluation procedure for assessing the risk of injury to the AO/C1/C2 region of the cervical spine in motorcycle riders is reevaluated using an existing postmortem human subjects (PMHS) data set and resulting in a reformulated NII criterion applicable to PMHS tests. METHODS: A recent series of 36 PMHS head/neck component tests was used to examine the risk of neck injury in frontal impacts and to assess the predictive capability of NII for impacts of various orientations. Using force and moment load cell PMHS experimental data, injury risk was assessed using NII evaluated with the ISO 13232-5 algorithms. RESULTS: The injury risk predictions are compared with the injury outcomes from the head/neck PMHS. The NII criterion underestimated the injury incidence of the PMHS experimental group. The average predicted risk of injuries for the experimental injury tests based on NII across the MAIS levels was 0.7 percent, though there were 11 AIS 3+ injuries observed in the actual testing (30.6%). Using the experimental injury outcomes and the experimental force and moment time histories, the normalizing coefficients from NII are reevaluated to minimize the difference between NII risk assessment and the experimental injury outcome in the least squares (L(2)) basis. This reanalysis is compared with existing human and PMHS neck injury criteria. CONCLUSIONS: By reanalyzing the NII formulation using an existing PMHS injury data set with known forces and moments and known injury outcomes, a new NII(PMHS) is developed that uses PMHS loads to predict injury. This reformulation removes the dependency of the original NII formulation on the forces and moments from motorcyclist anthropomorphic test device (MATD) experiments and simulations yet retains the advantages of the multi-axial neck injury criterion.

Viscoelastic response of the thorax under dynamic belt loading.

OBJECTIVE: Three postmortem human surrogates (PMHS) were positioned and rigidly mounted through the spine to a tabletop test fixture for the purpose of characterizing thoracic response to diagonal belt loading with well-defined boundary conditions. METHODS: These PMHS were mounted to a stationary apparatus that supported the spine and shoulders in a configuration comparable to that seen in a 48 km/h automobile sled test at the time of maximum chest deformation. A belt restraint was positioned across the anterior torso with attachments at D-ring and buckle locations based on the geometry of a mid-sized sedan. The belt was attached to a trolley driven by a hydraulic ram linked to a universal test machine. Ramp and hold experiments were conducted at rates of 0.5, 0.9, and 1.2 m/s and hold times of 60 s. Ramp-hold displacement waveforms of up to 20 percent of the chest depth were applied to the chest while the resulting belt loads and spinal reaction loads were recorded. These data were used to identify parameters in a seven-parameter thoracic structural model mathematically analogous to a viscoelastic material model. A final test with 40 percent deflection was performed at the completion of the loading sequence. RESULTS: Model fits to ramps of different magnitudes indicated that the assumption of temporal linearity was reasonable over the range of inputs in this study. In agreement with previous studies, the spatial (force-deflection) response was only slightly nonlinear, indicating that a fully linear model would be reasonable up to the deflection levels used here. CONCLUSIONS: Pronounced variability in the instantaneous elastic behavior was observed among the three test subjects, whereas the relaxation behavior exhibited less variability.

Biomarkers of body iron stores and risk of developing type 2 diabetes.

AIM: Iron may contribute to the pathogenesis of type 2 diabetes mellitus (DM) by inducing oxidative stress and interfering with insulin secretion. Elevated ferritin levels are associated with increased DM risk among healthy individuals. However, it is yet unknown if ferritin predicts DM incidence among high-risk individuals with impaired glucose tolerance (IGT). Furthermore, the association between soluble transferrin receptors (sTfR), a novel marker of iron status, and DM risk has not yet been prospectively investigated in these individuals. We conducted this study to evaluate the association between baseline levels of ferritin and sTfR and the risk of developing DM among overweight and obese individuals at high risk of DM. METHODS: This nested case-control study (280 cases and 280 matched controls) was conducted within the placebo arm of the Diabetes Prevention Program, is a clinical trial conducted among overweight/obese individuals with IGT. Ferritin and sTfR levels were measured by immunoturbidimetric assays. Incident DM was ascertained by annual 75-g oral glucose tolerance test and semi-annual fasting glucose. RESULTS: Compared with controls, cases had higher sTfR levels (3.50 +/- 0.07 vs. 3.30 +/- 0.06 mg/l; p = 0.03), but ferritin levels were not statistically different. The multivariable odds ratios (OR) and 95% confidence intervals (95% CI) for DM incidence comparing highest with the lowest quartiles of sTfR was 2.26 (1.37-4.01) (p-trend: 0.008). CONCLUSIONS: Modestly elevated sTfR levels are associated with increased DM risk among overweight and obese individuals with IGT. Future studies should evaluate factors determining sTfR levels and examine if interventions that lower body iron stores reduce DM incidence.

Car safety seats for children: rear facing for best protection.

OBJECTIVE: To compare the injury risk between rear-facing (RFCS) and forward-facing (FFCS) car seats for children less than 2 years of age in the USA. METHODS: Data were extracted from a US National Highway Traffic Safety Administration vehicle crash database for the years 1988-2003. Children 0-23 months of age restrained in an RFCS or FFCS when riding in passenger cars, sport utility vehicles, or light trucks were included in the study. Logistic regression models and restraint effectiveness calculations were used to compare the risk of injury between children restrained in RFCSs and FFCSs. RESULTS: Children in FFCSs were significantly more likely to be seriously injured than children restrained in RFCSs in all crash types (OR=1.76, 95% CI 1.40 to 2.20). When considering frontal crashes alone, children in FFCSs were more likely to be seriously injured (OR=1.23), although this finding was not statistically significant (95% CI 0.95 to 1.59). In side crashes, however, children in FFCSs were much more likely to be injured (OR=5.53, 95% CI 3.74 to 8.18). When 1 year olds were analyzed separately, these children were also more likely to be seriously injured when restrained in FFCSs (OR=5.32, 95% CI 3.43 to 8.24). Effectiveness estimates for RFCSs (93%) were found to be 15% higher than those for FFCSs (78%). CONCLUSIONS: RFCSs are more effective than FFCSs in protecting restrained children aged 0-23 months. The same findings apply when 1 year olds are analyzed separately. Use of an RFCS, in accordance with restraint recommendations for child size and weight, is an excellent choice for optimum protection up to a child's second birthday.

Frontal sled tests comparing rear and forward facing child restraints with 1-3 year old dummies.

Although most countries recommend transitioning children from rear facing (RF) to forward facing (FF) child restraints at one year of age, Swedish data suggests that RF restraints are more effective. The objective of this study was to compare RF and FF orientations in frontal sled tests. Four dummies (CRABI 12 mo, Q1.5, Hybrid III 3 yr, and Q3) were used to represent children from 1 to 3 years of age. Restraint systems tested included both 1) LATCH and 2) rigid ISOFIX with support leg designs. Rear facing restraints with support legs provided the best results for all injury measures, while RF restraints in general provided the lowest chest displacements and neck loads.

Quantification of ankle articular cartilage topography and thickness using a high resolution stereophotography system.

OBJECTIVE: To describe the topography and to measure thicknesses, surface areas and volumes in the cartilage layers of the ankle. METHODS: Twelve cadaveric ankle joints were disarticulated and the cartilage surfaces of each bone were imaged with a highly accurate (+/-2 microm) stereophotography system (ATOS). The cartilage was then dissolved and the subchondral bone imaged. The geometric data were then used to measure the quantitative parameters in each cartilage layer. RESULTS: The mean cartilage volume across the 12 specimens ranged from 0.32+/-0.08 ml for the fibula to 2.44+/-0.48 ml for the talus. The mean thickness of both the talar (1.1+/-0.18 mm) and tibial (1.16+/-0.14 mm) cartilage was significantly thicker than the fibula (0.85+/-0.13 mm). The talus had the greatest mean maximum cartilage thickness (2.38+/-0.4 mm). CONCLUSIONS: The reported stereophotographic technique may be used as an independent gold standard for validation of the accuracy of quantitative cartilage measurements made using magnetic resonance imaging. The thickness distribution maps show that the thickest articular cartilage occurs over the talar shoulders where osteochondral lesions commonly occur and not in the centre of the talar dome as commonly believed.

Quantifying the relationship between vehicle interior geometry and child restraint systems.

The prevention of interactions of children or child restraints with other vehicle structures is critical to child passenger safety. Fifteen current vehicles and seven rear and forward facing child restraint systems were measured in an attempt to quantify the available distance between child restraints and these vehicle structures. Rear facing child restraints exhibited such small amounts of clearance that contact would be expected in the majority of frontal crashes. Upper tethers are critical in the prevention of head contact, while head contact is likely when the upper tether is not used.

Nonlinear viscoelastic behavior of human knee ligaments subjected to complex loading histories.

The nonlinear viscoelastic structural response of the major human knee ligaments when subjected to complex loading histories is investigated, with emphasis on the collateral ligaments. Bone-ligament-bone specimens are tested in knee distraction loading, where the ligaments are in the anatomical position corresponding to a fully extended knee. Temporal nonlinearities for time scales in the range of 1