Improving Social and Play Outcomes for Students With Significant Disabilities During Recess.

For students with autism, recess is often a missed opportunity to develop social competence and relationships. Although interventions have been developed to promote interactions and social skills for students with average or above-average intellectual functioning, there has been less focus on students with autism who have below-average intellectual functioning or who meet the criteria for intellectual disability. In this single-case design study, we tested the efficacy of a combined peer-mediated and social skills instruction intervention on the interactions, play, and social skills of three students with autism who met their state's criteria for alternate assessment for students with significant cognitive disabilities. Social skills instruction featured video models that portrayed same-aged peers demonstrating individualized social skills on the playground. For all three students, there were substantial increases in interactions, play and social skills, and students and their peers provided positive feedback about the intervention.

Seasonal overturn and stratification changes drive deep-water warming in one of Earth's largest lakes.

Most of Earth's fresh surface water is consolidated in just a few of its largest lakes, and because of their unique response to environmental conditions, lakes have been identified as climate change sentinels. While the response of lake surface water temperatures to climate change is well documented from satellite and summer in situ measurements, our understanding of how water temperatures in large lakes are responding at depth is limited, as few large lakes have detailed long-term subsurface observations. We present an analysis of three decades of high frequency (3-hourly and hourly) subsurface water temperature data from Lake Michigan. This unique data set reveals that deep water temperatures are rising in the winter and provides precise measurements of the timing of fall overturn, the point of minimum temperature, and the duration of the winter cooling period. Relationships from the data show a shortened winter season results in higher subsurface temperatures and earlier onset of summer stratification. Shifts in the thermal regimes of large lakes will have profound impacts on the ecosystems of the world's surface freshwater.

Lake Huron's Phosphorus Contributions to the St. Clair-Detroit River Great Lakes Connecting Channel.

The United States and Canada called for a 40% load reduction of total phosphorus from 2008 levels entering the western and central basins of Lake Erie to achieve a 6000 MTA target and help reduce its central basin hypoxia. The Detroit River is a significant source of total phosphorus to Lake Erie; it in turn has been reported to receive up to 58% of its load from Lake Huron when accounting for resuspended sediment loads previously unmonitored at the lake outlet. Key open questions are where does this additional load originate, what drives its variability, and how often does it occur. We used a hydrodynamic model, satellite images of resuspension events and ice cover, wave hindcasts, and continuous turbidity measurements at the outlet of Lake Huron to determine where in Lake Huron the undetected load originates and what drives its variability. We show that the additional sediment load, and likely phosphorus, is from wave-induced Lake Huron sediment resuspension, primarily within 30 km of the southeastern shore. When the flow is from southwest or down the center of the lake, the resuspended sediment is not detected at Canada's sampling station at the head of the St. Clair River.

Diagnosis and treatment of a boy with IPEX syndrome presenting with diabetes in early infancy.

IPEX syndrome (Immune dysregulation, Polyendocrinopathy, X-linked) should be tested for in males under 6 months old presenting with diabetes, even without other IPEX features. Early diagnosis and bone marrow transplantation can improve outcomes.

Unexpected rip currents induced by a meteotsunami.

A tragic drowning event occurred along southeastern beaches of Lake Michigan on a sunny and calm July 4, 2003, hours after a fast-moving convective storm had crossed the lake. Data forensics indicates that a moderate-height (~0.3 m) meteotsunami was generated by the fast-moving storm impacting the eastern coast of the lake. Detailed Nearshore Area (DNA) modeling forensics on a high-resolution spatial O(1 m) grid reveals that the meteotsunami wave generated unexpected rip currents, changing the nearshore condition from calm to hazardous in just a few minutes and lasting for several hours after the storm. Cross-comparison of rip current incidents and meteotsunami occurrence databases suggests that meteotsunamis present severe water safety hazards and high risks, more frequently than previously recognized. Overall, meteorological tsunamis are revealed as a new generation mechanism of rip currents, thus posing an unexpected beach hazard that, to date, has been ignored.

Prospective Design, Rapid Prototyping, and Testing of Smart Dressings, Drug Delivery Patches, and Replacement Body Parts Using Microscopy Aided Design and ManufacturE (MADAME).

Natural materials exhibit smart properties including gradients in biophysical properties that engender higher order functions, as well as stimuli-responsive properties which integrate sensor and/or actuator capacities. Elucidation of mechanisms underpinning such smart material properties (i), and translation of that understanding (ii), represent two of the biggest challenges in emulating natural design paradigms for design and manufacture of disruptive materials, parts, and products. Microscopy Aided Design And ManufacturE (MADAME) stands for a computer-aided additive manufacturing platform that incorporates multidimensional (multi-D) printing and computer-controlled weaving. MADAME enables the creation of composite design motifs emulating e.g., patterns of woven protein fibers as well as gradients in different caliber porosities, mechanical, and molecular properties, found in natural tissues, from the skin on bones (periosteum) to tree bark. Insodoing, MADAME provides a means to manufacture a new genre of smart materials, products and replacement body parts that exhibit advantageous properties both under the influence of as well as harnessing dynamic mechanical loads to activate material properties (mechanoactive properties). This Technical Report introduces the MADAME technology platform and its associated machine-based workflow (pipeline), provides basic technical background of the novel technology and its applications, and discusses advantages and disadvantages of the approach in context of current 3 and 4D printing platforms.

Meteotsunamis in the Laurentian Great Lakes.

The generation mechanism of meteotsunamis, which are meteorologically induced water waves with spatial/temporal characteristics and behavior similar to seismic tsunamis, is poorly understood. We quantify meteotsunamis in terms of seasonality, causes, and occurrence frequency through the analysis of long-term water level records in the Laurentian Great Lakes. The majority of the observed meteotsunamis happen from late-spring to mid-summer and are associated primarily with convective storms. Meteotsunami events of potentially dangerous magnitude (height > 0.3 m) occur an average of 106 times per year throughout the region. These results reveal that meteotsunamis are much more frequent than follow from historic anecdotal reports. Future climate scenarios over the United States show a likely increase in the number of days favorable to severe convective storm formation over the Great Lakes, particularly in the spring season. This would suggest that the convectively associated meteotsunamis in these regions may experience an increase in occurrence frequency or a temporal shift in occurrence to earlier in the warm season. To date, meteotsunamis in the area of the Great Lakes have been an overlooked hazard.

Particle backtracking improves breeding subpopulation discrimination and natal-source identification in mixed populations.

We provide a novel method to improve the use of natural tagging approaches for subpopulation discrimination and source-origin identification in aquatic and terrestrial animals with a passive dispersive phase. Our method integrates observed site-referenced biological information on individuals in mixed populations with a particle-tracking model to retrace likely dispersal histories prior to capture (i.e., particle backtracking). To illustrate and test our approach, we focus on western Lake Erie's yellow perch (Perca flavescens) population during 2006-2007, using microsatellite DNA and otolith microchemistry from larvae and juveniles as natural tags. Particle backtracking showed that not all larvae collected near a presumed hatching location may have originated there, owing to passive drift during the larval stage that was influenced by strong river- and wind-driven water circulation. Re-assigning larvae to their most probable hatching site (based on probabilistic dispersal trajectories from the particle backtracking model) improved the use of genetics and otolith microchemistry to discriminate among local breeding subpopulations. This enhancement, in turn, altered (and likely improved) the estimated contributions of each breeding subpopulation to the mixed population of juvenile recruits. Our findings indicate that particle backtracking can complement existing tools used to identify the origin of individuals in mixed populations, especially in flow-dominated systems.

Record-setting algal bloom in Lake Erie caused by agricultural and meteorological trends consistent with expected future conditions.

In 2011, Lake Erie experienced the largest harmful algal bloom in its recorded history, with a peak intensity over three times greater than any previously observed bloom. Here we show that long-term trends in agricultural practices are consistent with increasing phosphorus loading to the western basin of the lake, and that these trends, coupled with meteorological conditions in spring 2011, produced record-breaking nutrient loads. An extended period of weak lake circulation then led to abnormally long residence times that incubated the bloom, and warm and quiescent conditions after bloom onset allowed algae to remain near the top of the water column and prevented flushing of nutrients from the system. We further find that all of these factors are consistent with expected future conditions. If a scientifically guided management plan to mitigate these impacts is not implemented, we can therefore expect this bloom to be a harbinger of future blooms in Lake Erie.

Molecular paleontology: a biochemical model of the ancestral ribosome.

Ancient components of the ribosome, inferred from a consensus of previous work, were constructed in silico, in vitro and in vivo. The resulting model of the ancestral ribosome presented here incorporates ∼20% of the extant 23S rRNA and fragments of five ribosomal proteins. We test hypotheses that ancestral rRNA can: (i) assume canonical 23S rRNA-like secondary structure, (ii) assume canonical tertiary structure and (iii) form native complexes with ribosomal protein fragments. Footprinting experiments support formation of predicted secondary and tertiary structure. Gel shift, spectroscopic and yeast three-hybrid assays show specific interactions between ancestral rRNA and ribosomal protein fragments, independent of other, more recent, components of the ribosome. This robustness suggests that the catalytic core of the ribosome is an ancient construct that has survived billions of years of evolution without major changes in structure. Collectively, the data here support a model in which ancestors of the large and small subunits originated and evolved independently of each other, with autonomous functionalities.

Bone as an inspiration for a novel class of mechanoactive materials.

Fortuitous combinations of anisotropic stiffness and permeability coefficients in a poroelastic structure (e.g. bone) result in counterintuitive flow when the structure is subjected to tension or compression. Nonlinearities in flow and transport result when loading is asymmetrical (tension and compression are not balanced over the course of a cycle), boundary conditions are asymmetrical (area available for inflow or outflow) or uptake of the transported agent is factored in (ratchet effect). These properties can be exploited for the development of flow directing materials, e.g. wound dressings that prevent development of stress concentrators while augmenting transport of pharmaceuticals to the wound site, as well as transport of drainage away from the wound site, via convective flow. The dressings are designed as carriers of pharmaceutical agents. Normally, the delivery of these agents is diffusion driven, e.g. as in nicotine, pain abatement, and hormone replacement therapy patches. However, by designing the structure of the pharmaceutical doped dressings to mimic the relationship between stiffness and permeability coefficients shown to produce counterintuitive flow in bone, it is possible to deliver the pharmaceuticals to the wound site and imbibe exudant from the wound in an accelerated fashion via convective transport. This unprecedented approach harnesses the mass and movement of the patient to provide the impetus for flow to and from the wound. It has a range of further applications in not only the medical sector but also the textile industry as well as in microfluidics.

Idealization of pericellular fluid space geometry and dimension results in a profound underprediction of nano-microscale stresses imparted by fluid drag on osteocytes.

To date, no published study has examined quantitatively the effect of geometric and dimensional idealization on prediction of the mechanical signals imparted by fluid drag to cell surfaces. We hypothesize that this idealization affects the magnitude and range of imparted forces predicted to occur at a subcellular level. Hence, we used computational fluid dynamics to predict magnitudes and spatial variation of fluid velocity and pressure, as well as shear stress, on the cell surface in two- and three-dimensional models of actual and idealized pericellular canalicular geometries. Furthermore, variation in actual pericellular space dimensions was analyzed statistically based on high-resolution transmitted electron micrographs (TEM). Accounting for the naturally occurring protrusions of the pericellular space delineating lamina limitans resulted in predictions of localized stress spikes on the cell surface, up to five times those predicted using idealized geometries. Predictions accounting for actual pericellular geometries approached those required to trigger cell activity in in vitro models. Furthermore, statistical analysis of TEM-based dimensions showed significant variation in the width of the canalicular space as well as the diameter of the cell process, both of which decrease with increasing distance from the cell body. For the first time to our knowledge, this study shows the influence of physiologic geometry per se on the nano-scale flow regimes in bone, and the profound influence of physiologic geometry on force magnitudes and variations imparted locally to cells through load-induced fluid flow.

Open access to novel dual flow chamber technology for in vitro cell mechanotransduction, toxicity and pharamacokinetic studies.

BACKGROUND: A major stumbling block for researchers developing experimental models of mechanotransduction is the control of experimental variables, in particular the transmission of the mechanical forces at the cellular level. A previous evaluation of state of the art commercial perfusion chambers showed that flow regimes, applied to impart a defined mechanical stimulus to cells, are poorly controlled and that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable. METHODS: This study provides a novel chamber design to provide both physiologically-based flow regimes, improvements in control of experimental variables, as well as ease of use compared to commercial chambers. This novel design achieves controlled stresses through five gasket designs and both single- and dual-flow regimes. RESULTS: The imparted shear stress within the gasket geometry is well controlled. Fifty percent of the entire area of the 10 x 21 mm universal gasket (Gasket I, designed to impart constant magnitude shear stresses in the center of the chamber where outcome measures are taken), is exposed to target stresses. In the 8 mm diameter circular area at the center of the chamber (where outcome measures are made), over 92% of the area is exposed to the target stress (+/- 2.5%). In addition, other gasket geometries provide specific gradients of stress that vary with distance from the chamber inlet. Bench-top testing of the novel chamber prototype shows improvements, in the ease of use as well as in performance, compared to the other commercial chambers. The design of the chamber eliminates flow deviations due to leakage and bubbles and allows actual flow profiles to better conform with those predicted in computational models. CONCLUSION: The novel flow chamber design provides predictable and well defined mechanical forces at the surface of a cell monolayer, showing improvement over previously tested commercial chambers. The predictability of the imparted stress improves both experiment repeatability as well as the accuracy of inter-study comparisons. Carefully controlling the stresses on cells is critical in effectively mimicking in vivo situations. Overall, the improved perfusion flow chamber provides the needed resolution, standardization and in vitro model analogous to in vivo conditions to make the step towards greater use in research and the opportunity to enter the diagnostic and therapeutic market.

Design of tissue engineering scaffolds as delivery devices for mechanical and mechanically modulated signals.

New approaches to tissue engineering aim to exploit endogenous strategies such as those occurring in prenatal development and recapitulated during postnatal healing. Defining tissue template specifications to mimic the environment of the condensed mesenchyme during development allows for exploitation of tissue scaffolds as delivery devices for extrinsic cues, including biochemical and mechanical signals, to drive the fate of mesenchymal stem cells seeded within. Although a variety of biochemical signals that modulate stem cell fate have been identified, the mechanical signals conducive to guiding pluripotent cells toward specific lineages are less well characterized. Furthermore, not only is spatial and temporal control of mechanical stimuli to cells challenging, but also tissue template geometries vary with time due to tissue ingrowth and/or scaffold degradation. Hence, a case study was carried out to analyze flow regimes in a testbed scaffold as a first step toward optimizing scaffold architecture. A pressure gradient was applied to produce local (nm-micron) flow fields conducive to migration, adhesion, proliferation, and differentiation of cells seeded within, as well as global flow parameters (micron-mm), including flow velocity and permeability, to enhance directed cell infiltration and augment mass transport. Iterative occlusion of flow channel dimensions was carried out to predict virtually the effect of temporal geometric variation (e.g., due to tissue development and growth) on delivery of local and global mechanical signals. Thereafter, insights from the case study were generalized to present an optimization scheme for future development of scaffolds to be implemented in vitro or in vivo. Although it is likely that manufacture and testing will be required to finalize design specifications, it is expected that the use of the rational design optimization will reduce the number of iterations required to determine final prototype geometries and flow conditions. As the range of mechanical signals conducive to guiding cell fate in situ is further elucidated, these refined design criteria can be integrated into the general optimization rubric, providing a technological platform to exploit nature's endogenous tissue engineering strategies for targeted tissue generation in the lab or the clinic.

The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction.

BACKGROUND: In vitro mechanotransduction studies are designed to elucidate cell behavior in response to a well-defined mechanical signal that is imparted to cultured cells, e.g. through fluid flow. Typically, flow rates are calculated based on a parallel plate flow assumption, to achieve a targeted cellular shear stress. This study evaluates the performance of specific flow/perfusion chambers in imparting the targeted stress at the cellular level. METHODS: To evaluate how well actual flow chambers meet their target stresses (set for 1 and 10 dyn/cm2 for this study) at a cellular level, computational models were developed to calculate flow velocity components and imparted shear stresses for a given pressure gradient. Computational predictions were validated with micro-particle image velocimetry (microPIV) experiments. RESULTS: Based on these computational and experimental studies, as few as 66% of cells seeded along the midplane of commonly implemented flow/perfusion chambers are subjected to stresses within +/-10% of the target stress. In addition, flow velocities and shear stresses imparted through fluid drag vary as a function of location within each chamber. Hence, not only a limited number of cells are exposed to target stress levels within each chamber, but also neighboring cells may experience different flow regimes. Finally, flow regimes are highly dependent on flow chamber geometry, resulting in significant variation in magnitudes and spatial distributions of stress between chambers. CONCLUSION: The results of this study challenge the basic premise of in vitro mechanotransduction studies, i.e. that a controlled flow regime is applied to impart a defined mechanical stimulus to cells. These results also underscore the fact that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable.

Nano-microscale models of periosteocytic flow show differences in stresses imparted to cell body and processes.

In order to understand how local changes in mechanical environment are translated into cellular activity underlying tissue level bone adaptation, there is a need to explore fluid flow regimes at small scales such as the osteocyte. Recent developments in computational fluid dynamics (CFD) provide impetus to elucidate periosteocytic flow through development of a nanomicroscale model to study local effects of fluid flow on the osteocyte cell body, which contains the cellular organelles, and on the osteocyte processes, which connect the cell to the entire cellular network distributed throughout bone tissue. For each model, fluid flow was induced via a pressure gradient and the velocity profile and wall shear stress at the cell-fluid interface were calculated using a CFD software package designed for nano/micro-electromechanical-systems device development. Periosteocytic flow was modeled, taking into consideration the nanoscale dimensions of the annular channels and the flow pathways of the periosteocytic flow volume, to analyze the local effects of fluid flow on the osteocyte cell body (within the lacuna) and its processes (within the canaliculi). Based on the idealized model presented in this article, the osteocyte cell body is exposed primarily to effects of hydrodynamic pressure and the cell processes (CP) are exposed primarily to fluid shear stress, with highest stress gradients at sites where the process meets the cell body and where two CP link at the gap junction. Hence, this model simulates subcellular effects of fluid flow and suggests, for the first time to our knowledge, major differences in modes of loading between the domain of the cell body and that of the cell process.