Kenneth R. Diller

University of Texas at Austin, Austin, Texas, United States

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Publications (251)388.6 Total impact

  • Kenneth R. Diller
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    ABSTRACT: Mammals and birds that regulate the core body temperature have an elaborate and highly effective thermoregulatory system. This system depends on the ability to move heat between the body core and surface via the convection of blood. Glabrous areas of skin, located in humans primarily on the palms, soles, ears, and selected facial sites, contain a vascular network with large-bore shunt vessels called arteriovenous anastomoses (AVAs) that have a highly dynamic and specialized control. Under conditions of core energy conservation, AVAs tightly vasoconstrict. Under conditions of core heat rejection, they vasodilate so that a significant fraction of the cardiac output can flow through them to exchange heat with the environment. A primary site of control is the preoptic anterior hypothalamus (POAH). This paper presents evidence that humans have a parallel controller peripheral to the POAH lying along the spinal cord, consistent with prior evidence in other mammalian and avian species. The ability to thermally access the spinal controller simply and safely provides an opportunity to exercise management of the body core temperature independent of the POAH to induce therapeutic hypothermia, which can have life-saving consequences for multiple medical conditions. Data are presented demonstrating the efficacy of selective thermal stimulation (STS) to the spinal cord as a means to regulate blood flow to the AVAs on demand. STS can be used in combination with dedicated heat exchangers placed onto glabrous skin to produce large heat fluxes into and out of the body for therapeutic purposes. This technology provides the basis for a new generation of medical heat transfer devices.
    No preview · Chapter · Dec 2015
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    ABSTRACT: The goal of this study was to investigate the persistence of cold-induced vasoconstriction following cessation of active skin-surface cooling. This study demonstrates a hysteresis effect that develops between skin temperature and blood perfusion during the cooling and subsequent rewarming period. An Arctic Ice cryotherapy unit was applied to the knee region of 6 healthy subjects for 60 minutes of active cooling followed by 120 min of passive rewarming. Multiple laser Doppler flowmetry perfusion probes were used to measure skin blood flow (expressed as cutaneous vascular conductance, CVC). Skin surface cooling produced a significant reduction in CVC (P<0.001) that persisted throughout the duration of the rewarming period. In addition, there was a hysteresis effect between CVC and skin temperature during the cooling and subsequent rewarming cycle (P<0.01). Mixed model regression showed a significant difference in the slopes of the CVC-skin temperature curves during cooling and rewarming (P<0.001). Piecewise regression was used to investigate the temperature thresholds for acceleration of CVC during the cooling and rewarming periods. The two thresholds were shown to be significantly different (P=0.003). The results show that localized cooling causes significant vasoconstriction that continues beyond the active cooling period despite skin temperatures returning towards baseline values. The significant and persistent reduction in skin perfusion may contribute to non-freezing cold injury associated with cryotherapy.
    No preview · Article · Dec 2015 · Journal of Biomechanical Engineering
  • Kenneth Diller

    No preview · Article · Dec 2015 · Cryobiology
  • Kenneth R. Diller
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    ABSTRACT: Our bodies depend on an exquisitely sensitive and refined temperature control system to maintain a state of health and homeostasis. The exceptionally broad range of physical activities that humans engage in and the diverse array of environmental conditions we face require remarkable strategies and mechanisms for regulating internal and external heat transfer processes. On the occasions for which the body suffers trauma, therapeutic temperature modulation is often the approach of choice for reversing injury and inflammation and launching a cascade of healing. The focus of human thermoregulation is maintenance of the body core temperature within a tight range of values, even as internal rates of energy generation may vary over an order of magnitude, environmental convection, and radiation heat loads may undergo large changes in the absence of any significant personal control, surface insulation may be added or removed, all occurring while the body's internal thermostat follows a diurnal circadian cycle that may be altered by illness and anesthetic agents. An advanced level of understanding of the complex physiological function and control of the human body may be combined with skill in heat transfer analysis and design to develop life-saving and injury-healing medical devices. This paper will describe some of the challenges and conquests the author has experienced related to the practice of heat transfer for maintenance of health and enhancement of healing processes.
    No preview · Article · Oct 2015 · Journal of Heat Transfer
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    ABSTRACT: Cryotherapy involves the surface application of low temperatures to enhance the healing of soft tissue injuries. Typical devices embody a remote source of chilled water that is pumped through a circulation bladder placed on the treatment site. In contrast, the present device uses thermoelectric refrigeration modules to bring the cooling source directly to the tissue to be treated, thereby achieving significant improvements in control of therapeutic temperature while having a reduced size and weight. A prototype system was applied to test an oscillating cooling and heating protocol for efficacy in regulating skin blood perfusion in the treatment area. Data on 12 human subjects indicate that thermoelectric coolers (TECs) delivered significant and sustainable changes in perfusion for both heating (increase by (±SE) 173.0 ± 66.0%, P < 0.005) and cooling (decrease by (±SE) 57.7 ± 4.2%, P < 0.0005), thus supporting the feasibility of a TEC-based device for cryotherapy with local temperature regulation.
    No preview · Article · Sep 2015 · Journal of Medical Devices
  • John P Abraham · Brian Plourde · Lauren Vallez · John Stark · Kenneth R Diller
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    ABSTRACT: The objective of this study is to develop and present a simple procedure for evaluating the temperature and exposure-time conditions that lead to causation of a deep-partial thickness burn and the effect that the immediate post-burn thermal environment can have on the process. A computational model has been designed and applied to predict the time required for skin burns to reach a deep-partial thickness level of injury. The model includes multiple tissue layers including the epidermis, dermis, hypodermis, and subcutaneous tissue. Simulated exposure temperatures ranged from 62.8 to 87.8°C (145-190°F). Two scenarios were investigated. The first and worst case scenario was a direct exposure to water (characterized by a large convection coefficient) with the clothing left on the skin following the exposure. A second case consisted of a scald insult followed immediately by the skin being washed with cool water (20°C). For both cases, an Arrhenius injury model was applied whereby the extent and depth of injury were calculated and compared for the different post-burn treatments. In addition, injury values were compared with experiment data from the literature to assess verification of the numerical methodology. It was found that the clinical observations of injury extent agreed with the calculated values. Furthermore, inundation with cool water decreased skin temperatures more quickly than the clothing insulating case and led to a modest decrease in the burn extent. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.
    No preview · Article · Jul 2015 · Burns: journal of the International Society for Burn Injuries
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    ABSTRACT: Relatively little is understood about the practice of teaching for adaptability. Our prior research demonstrates that challenge-based instruction (CBI) can foster Adaptive Expertise (AE). AE is a combination of 1) traditional routine expertise as defined by content knowledge and its correct application and 2) the skills and habits to use that knowledge in new ways on novel problems. The experiments reported in this paper investigate the hypotheses that 1) both the nature of the learning environment (adaptive or routine) and the level of expertise of the learner (adaptive or routine) are important for understanding the development of innovation and efficiency, and 2) innovation and efficiency co-develop in the CBI environment. In Experiment 1, we examined students' exam performance, coding for both innovation and efficiency, across a complete implementation of the CBI biotransport course. We assessed students' level of innovation and efficiency on routine and adaptive problems at four time points at the grain size of exam questions. In Experiment 2, we interviewed eight students three times over the course of their biotransport class. Students solved the same heat transfer problem on each interview, talking aloud as they solved the problem. This design enabled the use of text analysis and clustering learning analytics methods to examine how students' use of innovation and efficiency changed over the course of the interviews in small time segments. Both experiments demonstrated gains in innovation and efficiency, and appropriate use of them given the context of the task. Experiment 2 additionally demonstrated the co-developing nature of the two elements of AE.
    Full-text · Article · Jan 2015
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    ABSTRACT: We have investigated thermal operating characteristics of 13 commercially available cryotherapy units (CTUs) and their associated cooling pads using IR imaging. Quantitative examination of the temperature profiles from pad IR images shows diverse, non-uniform temperature distribution patterns. The extent of heterogeneity of the temperature fields was quantified via standard image analysis methods, including thresholding, spatial gradient diagrams, and frequency histogram distributions. A primary conclusion of this study is that it is a misnomer to characterize the thermal performance of a CTU and cooling pad combination in terms of a single therapeutic temperature.
    No preview · Article · Mar 2014 · Journal of Biomechanical Engineering
  • Alfred S Song · Amer M. Najjar · Kenneth R Diller
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    ABSTRACT: This study was conducted to compare the heat shock responses of cells grown in two- (2D) and three-dimensional (3D) culture environments as indicated by the level of Heat Shock Protein 70 expression and the incidence of apoptosis and necrosis of prostate cancer cell lines in response to graded thermal stress. PC3 cells were stably transduced with a dual reporter system composed of two tandem expression cassettes - a conditional heat shock protein promoter driving the expression of green fluorescent protein (HSPp-GFP) and a CMV promoter controlling the constitutive expression of a "beacon" red fluorescent protein (CMVp-RFP). Two- and three-dimensional cultures of PC3 prostate cancer cells were grown in 96-well plates for evaluation of their time-dependent response to supraphysiological temperature. To induce controlled thermal stress, culture plates were placed on a flat copper surface of a circulating water manifold that maintained the specimens within +/-0.1 degree C of a target temperature. Stress protocols included various combinations of temperature, ranging from 37-57 degree C, and exposure times of up to 2 hours. The majority of protocols were focused on temperature and time permutations where the response gradient was greatest. Post-treatment analysis by flow cytometry analysis was used to measure the incidences of apoptosis (annexin V-FITC stain), necrosis (propidium iodide (PI) stain) and HSP70 transcription (GFP expression). Cells grown in 3D compared to 2D culture showed reduced incidence of apoptosis and necrosis and a higher level of HSP70 expression in response to heat shock at the temperatures tested. Cells responded differently to thermal stress when grown in 2D and 3D cultures. Three dimensional culture appears to enhance survival plausibly by activating protective processes related to enhanced HSP70 expression. These differences highlight the importance of selecting physiologically relevant 3D models in assessing cellular thermal stress responses in experimental settings.
    No preview · Article · Mar 2014 · Journal of Biomechanical Engineering
  • Sepideh Khoshnevis · Natalie K Craik · Kenneth R Diller
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    ABSTRACT: Localized cooling is widely used in treating soft tissue injuries by modulating swelling, pain, and inflammation. One of the primary outcomes of localized cooling is vasoconstriction within the underlying skin. It is thought that in some instances, cryotherapy may be causative of tissue necrosis and neuropathy via cold-induced ischaemia leading to nonfreezing cold injury (NFCI). The purpose of this study is to quantify the magnitude and persistence of vasoconstriction associated with cryotherapy. Data are presented from testing with four different FDA approved cryotherapy devices. Blood perfusion and skin temperature were measured at multiple anatomical sites during baseline, active cooling, and passive rewarming periods. Local cutaneous blood perfusion was depressed in response to cooling the skin surface with all devices, including the DonJoy (DJO, p = 2.6 × 10(-8)), Polar Care 300 (PC300, p = 1.1 × 10(-3)), Polar Care 500 Lite (PC500L, p = 0.010), and DeRoyal T505 (DR505, p = 0.016). During the rewarming period, parasitic heat gain from the underlying tissues and the environment resulted in increased temperatures of the skin and pad for all devices, but blood perfusion did not change significantly, DJO (n.s.), PC300 (n.s.), PC500L (n.s.), and DR505 (n.s.). The results demonstrate that cryotherapy can create a deep state of vasoconstriction in the local area of treatment. In the absence of independent stimulation, the condition of reduced blood flow persists long after cooling is stopped and local temperatures have rewarmed towards the normal range, indicating that the maintenance of vasoconstriction is not directly dependent on the continuing existence of a cold state. The depressed blood flow may dispose tissue to NFCI.
    No preview · Article · Feb 2014 · Knee Surgery Sports Traumatology Arthroscopy
  • Sepideh Khoshnevis · Natalie Craik · Kenneth R. Diller
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    ABSTRACT: Localized cooling is commonly used following orthopedic surgery and in sports medicine to reduce swelling, pain, inflammation, metabolism, muscle spasm, and bleeding[1,2]. The therapeutic application of cold therapy has a long history dating from the time of Hippocrates and has been widely documented in the literature[3,4]. Nonetheless, there remains to the present time considerable controversy over the appropriate protocol for application of cryotherapy and the risk factors associated with its use[5].
    No preview · Conference Paper · Jun 2013
  • Natalie K. Craik · Sepideh Khoshnevis · Kenneth R. Diller
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    ABSTRACT: Orthopedic surgery and sports medicine commonly use cryotherapy to reduce inflammation, alleviate pain, lower the chance of secondary hypoxic injury, and decrease hematoma formation [1,2]. Methods of cryotherapy vary widely in their sophistication, ranging from bags of ice or freezable gel packs to liquid perfusion cryotherapy devices. These perfusion cryotherapy devices circulate near 0°C water through a flexible bladder, resulting in localized tissue cooling.
    No preview · Conference Paper · Jun 2013
  • Kenneth R. Diller
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    ABSTRACT: This presentation will describe the design of several new classes of devices for low temperature therapeutic procedures and the results of initial tests on humans. The devices are used for cryotherapy and for induction of core temperature reduction. Their operation is based on new methods to induce targeted behaviors of the human thermoregulatory system. More than 300 human trials have been conducted that will be presented and discussed. Extensive data records include skin and core temperature measurements, and superficial and deep cutaneous blood flow. Computer simulation models for local and systemic heat transfer behavior during therapeutic cooling include integrated effects such as regional modulation of blood flow, local thermal boundary conditions, and thermoregulatory control schemes.
    No preview · Article · Jun 2013 · Cryobiology
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    ABSTRACT: This paper presents an updated and augmented version of the Wissler human thermoregulation model that has been developed continuously over the past 50 years. The existing Fortran code is translated into C with extensive embedded commentary. A graphical user interface (GUI) has been developed in Python to facilitate convenient user designation of input and output variables and formatting of data presentation. Use of the code with the GUI is described and demonstrated. New physiological elements were added to the model to represent the hands and feet, including the unique vascular structures adapted for heat transfer associated with glabrous skin. The heat transfer function and efficacy of glabrous skin is unique within the entire body based on the capacity for a very high rate of blood perfusion and the novel capability for dynamic regulation of blood flow. The model was applied to quantify the absolute and relative contributions of glabrous skin flow to thermoregulation for varying levels of blood perfusion. The model also was used to demonstrate how the unique features of glabrous skin blood flow may be recruited to implement thermal therapeutic procedures. We have developed proprietary methods to manipulate the control of glabrous skin blood flow in conjunction with therapeutic devices and simulated the effect of these methods with the model.
    No preview · Article · Feb 2013 · Journal of Biomechanical Engineering
  • Sepideh Khoshnevis · Kenneth R. Diller
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    ABSTRACT: Cryotherapy has been used in the treatment of soft tissue trauma and other ailments since the time of Hippocrates. Currently it is commonly applied in conjunction with surgical procedures and by athletic trainers and physical therapists to control pain, swelling, bleeding, and inflammation. Localized cooling also results in slowing of the nerve conduction velocity and reduced muscle spasm and secondary hypoxic injury1,2. Cooling is commonly used for soft tissue injuries in combination with rest, compression and elevation to minimize inflammation.
    No preview · Conference Paper · Jun 2012
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    ABSTRACT: Glabrous (hairless) skin found on the hands, feet, face, and ears is a unique component of the thermoregulatory system. Its anatomy and control physiology differ markedly from those of the rest of the skin. Glabrous regions contain vascular networks capable of supporting large blood flows due to the presence of highly tortuous and densely packed arteriovenous anastomoses (AVAs) and associated venous collecting networks [1]. When dilated, these vessels bring large volumes of blood close to the body surface where they function as highly efficient heat exchangers. Furthermore, the manner in which this blood flow is controlled is very unique, exhibiting, for example, rapid and high-magnitude responses, as well as a greater sensitivity to central core signals [1]. In this light, glabrous skin is an important but often overlooked tool the body uses to rapidly and finely adjust energy balance to maintain thermal equilibrium.
    No preview · Conference Paper · Jun 2012
  • Kenneth R. Diller
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    ABSTRACT: Bioheat transfer is a field with origins in medical applications that date to thousands of years ago. It has long been appreciated that manipulation of temperature and energy could have significant therapeutic benefits. However, prior to the Second World War, nearly all work in this field was based on empirical studies, many of which were guided by brilliant insights of medical and life scientists. In more recent times, the principles and methods of heat transfer have been applied systematically, and often times in conjunction with highly synergistic collaborations with physicians and biologists, to achieve remarkable advances that have translated to important innovations in life science and medicine. The following discussion presents a limited range of comments concerning work accomplished by researchers associated with the ASME Bioengineering Division.
    No preview · Conference Paper · Jun 2012
  • Vanessa Svihla · Anthony J. Petrosino · Kenneth R. Diller
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    ABSTRACT: Engineering design is a collaborative and complex process, and our understanding of how to support student teams in learning to design remains limited. By considering in-situ student design teams in a capstone biomedical engineering course, we are a?orded the opportunity to contrast two versions of a non-sponsored project, then consider expert perceptions of their later sponsored designs. Data from two cohorts of the course yield compelling contrasts for authentic design learning experiences. We found that a non-sponsored redesign project led students to values customer needs and to use them to de?ne the design problem, whereas in a kit-based version this did not occur. We also found that greater perceived opportunities to negotiate one's understanding within a team predicted more innovative team designs.
    No preview · Article · Jan 2012 · International Journal of Engineering Education
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    ABSTRACT: Sub-lethal temperature elevations in the tumour incurred during laser cancer therapy can induce heat shock protein (HSP) expression leading to enhanced tumour survival and recurrence. Nanoshells utilised in combination with laser therapy can potentially enable selective heat deposition, greater thermal injury, and diminished HSP expression in the tumour. The study objective was to measure the distribution of temperature and HSP expression in prostate tumours in response to laser therapy alone or with nanoshells to determine if these combinatorial therapies can minimise HSP expression. PC3 cells were inoculated in the backs of CB17-Prkd c SCID/J mice and treated with external laser irradiation (wavelength of 810 nm, irradiance of 5 W/cm(2), spot size of 5 mm, and heating duration of 3 min) alone or in combination with gold nanoshells (diameter of 55 nm and outer gold shell thickness of 10 nm) introduced into the tumour 24 h prior to laser treatment. Magnetic resonance temperature imaging was used to measure the distribution of temperature elevation in the tumours during laser treatment. Tumours were sectioned 16 h following laser treatment, stained for Hsp27 and Hsp70, imaged with a confocal microscope, and HSP expression levels were quantified as a function of depth in the tumours. Maximum temperature elevations at the tumour surface were 28°C for laser treatment only and 50°C for laser heating in combination with gold nanoshells. Laser therapy alone caused significant induction of HSP expression in the first few millimeters of the tumour depth, whereas decreasing HSP expression occurred with greater tumour depth. Tumours treated with laser and nanoshells experienced substantial temperatures (73-78°C) at the tumour surface and temperatures greater than 53°C in the first few millimeters which eliminated HSP expression. Inclusion of nanoshells in laser therapy can provide a mechanism for enhancing heat deposition capable of eliminating HSP expression within a larger tumour region compared to laser heating alone.
    No preview · Article · Dec 2011 · International Journal of Hyperthermia
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    ABSTRACT: We discuss and give examples of the use of selective laser sintering to fabricate solid macroscopic models of microscopic specimens that have been imaged with a confocal microscope. The digital image processing necessary to create structurally sound models of both translucent and opaque specimens is presented. The fabricated models offer the ultimate in data visualization since they can be physically handled and manipulated to investigate the shape and features of the specimen. Such a powerful visualization tool is useful in both research and educational environments.
    No preview · Article · Aug 2011 · Journal of Microscopy

Publication Stats

3k Citations
388.60 Total Impact Points

Institutions

  • 1975-2015
    • University of Texas at Austin
      • • Department of Biomedical Engineering
      • • Institute for Computational Engineering and Sciences
      • • Department of Mechanical Engineering
      • • Department of Electrical & Computer Engineering
      Austin, Texas, United States
  • 1989-1991
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 1988
    • Umeå University
      Umeå, Västerbotten, Sweden
  • 1985
    • Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB
      Stuttgart, Baden-Württemberg, Germany
  • 1982-1985
    • Concordia University Texas
      Austin, Texas, United States
  • 1971-1972
    • Massachusetts Institute of Technology
      • Department of Mechanical Engineering
      Cambridge, Massachusetts, United States