Plant trait and vegetation data along a 1314 m elevation gradient with fire history in Puna grasslands, Perú.

Alpine grassland vegetation supports globally important biodiversity and ecosystems that are increasingly threatened by climate warming and other environmental changes. Trait-based approaches can support understanding of vegetation responses to global change drivers and consequences for ecosystem functioning. In six sites along a 1314 m elevational gradient in Puna grasslands in the Peruvian Andes, we collected datasets on vascular plant composition, plant functional traits, biomass, ecosystem fluxes, and climate data over three years. The data were collected in the wet and dry season and from plots with different fire histories. We selected traits associated with plant resource use, growth, and life history strategies (leaf area, leaf dry/wet mass, leaf thickness, specific leaf area, leaf dry matter content, leaf C, N, P content, C and N isotopes). The trait dataset contains 3,665 plant records from 145 taxa, 54,036 trait measurements (increasing the trait data coverage of the regional flora by 420%) covering 14 traits and 121 plant taxa (ca. 40% of which have no previous publicly available trait data) across 33 families.

Advanced error modeling and Bayesian uncertainty quantification in mechanistic liquid chromatography modeling.

Current mechanistic chromatography process modeling methods lack the ability to account for the impact of experimental errors beyond detector noise (e.g. pump delays and variable feed composition) on the uncertainty in calibrated model parameters and the resulting model-predicted chromatograms. This paper presents an uncertainty quantification method that addresses this limitation by determining the probability distribution of parameters in calibrated models, taking into consideration multiple realistic sources of experimental error. The method, which is based on Bayes' theorem and utilizes Markov chain Monte Carlo with an ensemble sampler, is demonstrated to be robust and extensible using synthetic and industrial data. The corresponding software is freely available as open-source code at https://github.com/modsim/CADET-Match.

Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma.

INTRODUCTION: Several studies have linked increased risk of osteosarcoma with tall stature, high birthweight, and early puberty, although evidence is inconsistent. We used genetic risk scores (GRS) based on established genetic loci for these traits and evaluated associations between genetically inferred birthweight, height, and puberty timing with osteosarcoma. METHODS: Using genotype data from two genome-wide association studies, totaling 1039 cases and 2923 controls of European ancestry, association analyses were conducted using logistic regression for each study and meta-analyzed to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were conducted by case diagnosis age, metastasis status, tumor location, tumor histology, and presence of a known pathogenic variant in a cancer susceptibility gene. RESULTS: Genetically inferred higher birthweight was associated with an increased risk of osteosarcoma (OR =1.59, 95% CI 1.07-2.38, P = 0.02). This association was strongest in cases without metastatic disease (OR =2.46, 95% CI 1.44-4.19, P = 9.5 ×10-04). Although there was no overall association between osteosarcoma and genetically inferred taller stature (OR=1.06, 95% CI 0.96-1.17, P = 0.28), the GRS for taller stature was associated with an increased risk of osteosarcoma in 154 cases with a known pathogenic cancer susceptibility gene variant (OR=1.29, 95% CI 1.03-1.63, P = 0.03). There were no significant associations between the GRS for puberty timing and osteosarcoma. CONCLUSION: A genetic propensity to higher birthweight was associated with increased osteosarcoma risk, suggesting that shared genetic factors or biological pathways that affect birthweight may contribute to osteosarcoma pathogenesis.

Advanced score system and automated search strategies for parameter estimation in mechanistic chromatography modeling.

Least squares estimation of unknown parameters from measurement data is a well-established standard method in chromatography modeling but can suffer from critical disadvantages. The description of real-world systems is generally prone to unaccounted mechanisms, such as dispersion in external holdup volumes, and systematic measurement errors, such as caused by pump delays. In this scenario, matching the shape between simulated and measured chromatograms has been found to be more important than the exact peak positions. We have therefore developed a new score system that separately accounts for the shape, position and height of individual peaks. A genetic algorithm is used for optimizing these multiple objectives. Even for non-conflicting objectives, this approach shows superior convergence in comparison to single-objective gradient search, while conflicting objectives indicate incomplete models or inconsistent data. In the latter case, Pareto optima provide important information for understanding the system and improving experiments. The proposed method is demonstrated with synthetic and experimental case studies of increasing complexity. All software is freely available as open source code (https://github.com/modsim/CADET-Match).

Multi-state steric mass action model and case study on complex high loading behavior of mAb on ion exchange tentacle resin.

Tentacle resins for IEX are increasingly applied in preparative chromatography for their higher selectivity and higher capacities in comparison to IEX resins without tentacles. However, tentacle resins are often observed to cause unusual elution behavior of monoclonal antibodies under high loading conditions. Understanding this elution behavior is important for a quality by design approach, as it is now mandated by regulatory agencies. A model-based analysis of load, wash and gradient elution is performed for a monoclonal antibody (mAb) on Fractogel SO3-. Four experiments with increasing loaded mass show complex peak shapes and formation of a shoulder under overloaded conditions. We hypothesize that the observed peak shapes are caused by mAbs binding in multiple states on the tentacle ion-exchange resin. A new multi-state SMA binding model is used for testing this hypothesis. A two-state binding model is found to quantitatively reproduce all four experiments. An in-depth analysis reveals that the shoulder formation under overloaded conditions can be explained by multi-state binding that particularly manifests in rapid but weak re-adsorption of eluting molecules near the column end. The introduced multi-state SMA model combines features of the so-called spreading model (multiple bound states) and of the standard SMA model (salt dependency). It is by no means limited to ion-exchange chromatography on tentacle resins, but the same concept can be applied for studying systems that are based on other physical mechanisms. The new model can potentially improve mechanistic understanding and facilitate quantitative simulation of various phenomena, such as caused by reorientation, reconformation or unfolding of bound species. Similar concepts can be applied for studying surface-induced aggregation and denaturation.

Quantitative metrics of spinal cord injury recovery in the rat using motion capture, electromyography and ground reaction force measurement.

Toward improving the quantitative tools available for evaluation of locomotion after a spinal cord injury, we characterized selected biomechanical and physiological parameters that could be used to assess the level of recovery of locomotion after a mid-thoracic spinal cord lateral hemisection. Specifically we defined quantitative measures of muscle activation and coordination, body weight support, propulsive force, and pre-toe contact activation. Generation of this ensemble of recovery measures was based on kinematics, ground reaction forces, and EMG in rats from the hindlimb ipsilateral to the hemisection during quadrupedal running on a trackway. We derived muscle activation levels using inverse dynamics and static optimization applied to a model of the hindlimb musculoskeletal system. Rats exhibited a phased recovery pattern: progressive recovery of general muscle activity beginning within 2-3 days post-injury, followed by recovery of propulsive force and intralimb coordination of antagonistic muscles 12-13 days post-injury. Even at 12-13 days post-injury however, body weight support and the normal pre-paw contact EMG burst were significantly impaired. These data are consistent with a differential rate of recovery of general motor pool recruitment, and coordination among motor pools. The results demonstrate the discriminative potential of these physiologically based measures in quantifying the progressive recovery of gait performance after a lateral spinal cord hemisection.

The validity and utility of the California Family Risk Assessment under practice conditions in the field: A prospective study.

OBJECTIVE: Analysis of the validity and implementation of a child maltreatment actuarial risk assessment model, the California Family Risk Assessment (CFRA). QUESTIONS ADDRESSED: (1) Is there evidence of the validity of the CFRA under field operating conditions? (2) Do actuarial risk assessment results influence child welfare workers' service delivery decisions? (3) How frequently are CFRA risk scores overridden by child welfare workers? (4) Is there any difference in the predictive validity of CFRA risk assessments and clinical risk assessments by child welfare workers? METHOD: The study analyzes 7,685 child abuse/neglect reports originating in 5 California counties followed prospectively for 2 years to identify further substantiated child abuse/neglect. Measures of model calibration and discrimination were used to assess CFRA validity and compare its accuracy with the accuracy of clinical predictions made by child welfare workers. The extent of use of an override feature of the CFRA and child welfare worker reliance on CFRA risk scores for making service decisions were analyzed. RESULTS: Imperfect but better-than-chance predictive validity was found for the CFRA on a range of measures in a large temporal validation sample (n=6,543). For 114 cases where both CFRA risk assessments and child welfare worker clinical risk assessments were available, the CFRA exhibited evidence of imperfect but better-than-chance predictive validity, while child welfare worker risk assessments were found to be invalid. Child welfare workers overrode CFRA risk assessments in only 114 (1.5%) of 7,685 cases and provided in-home services in statistically significantly larger proportions of higher- versus lower-risk cases, consistent with heavy reliance on the CFRA. CONCLUSIONS/PRACTICE IMPLICATIONS: Until research identifies actuarial models exhibiting superior predictive validity when applied in every-day practice, the CFRA is, and will be a valuable tool for assessing risk in order to make in-home service-provision decisions.

Application of a rat hindlimb model: a prediction of force spaces reachable through stimulation of nerve fascicles.

A device to generate standing or locomotion through chronically placed electrodes has not been fully developed due in part to limitations of clinical experimentation and the high number of muscle activation inputs of the leg. We investigated the feasibility of functional electrical stimulation paradigms that minimize the input dimensions for controlling the limbs by stimulating at nerve fascicles, utilizing a model of the rat hindlimb, which combined previously collected morphological data with muscle physiological parameters presented herein. As validation of the model, we investigated the suitability of a lumped-parameter model for the prediction of muscle activation during dynamic tasks. Using the validated model, we found that the space of forces producible through activation of muscle groups sharing common nerve fascicles was nonlinearly dependent on the number of discrete muscle groups that could be individually activated (equivalently, the neuroanatomical level of activation). Seven commonly innervated muscle groups were sufficient to produce 78% of the force space producible through individual activation of the 42 modeled hindlimb muscles. This novel, neuroanatomically derived reduction in input dimension emphasizes the potential to simplify controllers for functional electrical stimulation to improve functional recovery after a neuromuscular injury.

Tactical and subject considerations of in-custody deaths proximal to use of conductive energy devices.

Conductive Energy Devices (CEDs) are used by many law enforcement agencies as a safer way to gain control of subjects, particularly those who are armed, physically resistive, or under the influence of illicit stimulant drugs. This study is an extensive voluntary survey of all police agencies that had a reported CED-related death. The list of deaths was obtained by cross referencing the published lists from Amnesty International and the Arizona Republic occurring between September 1999 and May 31, 2005. One hundred eighteen unique proximity deaths in subjects who had CED activations were identified. These cases involved 96 law enforcement jurisdictions in 26 different states. Each agency was surveyed, with 60 (63%) agencies responding, resulting in data from 65% (77 of 118) of the CED proximity deaths. The majority of deaths were among men (96%), white (46%), and individuals 31 to 40 years of age (38%). Among the 77 subjects, 20 (26%) were armed at some point during the incident including 4 (20%) with a firearm, 8 (40%) with a knife/cutting weapon, and 5 (25%) with a club/baton/blunt force weapon. Undesirable behaviors were also common with 58 (75%) exhibiting noncompliance, 53 (69%) with severe aggression, and 39 (51%) with mild aggression.

A three-dimensional model of the rat hindlimb: musculoskeletal geometry and muscle moment arms.

As a first step towards developing a dynamic model of the rat hindlimb, we measured muscle attachment and joint center coordinates relative to bony landmarks using stereophotogrammetry. Using these measurements, we analyzed muscle moment arms as functions of joint angle for most hindlimb muscles, and tested the hypothesis that postural change alone is sufficient to alter the function of selected muscles of the leg. We described muscle attachment sites as second-order curves. The length of the fit parabola and residual errors in the orthogonal directions give an estimate of muscle attachment sizes, which are consistent with observations made during dissection. We modeled each joint as a moving point dependent on joint angle; relative endpoint errors less than 7% indicate this method as accurate. Most muscles have moment arms with a large range across the physiological domain of joint angles, but their moment arms peak and vary little within the locomotion domain. The small variation in moment arms during locomotion potentially simplifies the neural control requirements during this phase. The moment arms of a number of muscles cross zero as angle varies within the quadrupedal locomotion domain, indicating they are intrinsically stabilizing. However, in the bipedal locomotion domain, the moment arms of these muscles do not cross zero and thus are no longer intrinsically stabilizing. We found that muscle function is largely determined by the change in moment arm with joint angle, particularly the transition from quadrupedal to bipedal posture, which may alter an intrinsically stabilizing arrangement or change the control burden.