Predictive Radiation Oncology - A New NCI-DOE Scientific Space and Community.

With a widely attended virtual kickoff event on January 29, 2021, the National Cancer Institute (NCI) and the Department of Energy (DOE) launched a series of 4 interactive, interdisciplinary workshops-and a final concluding "World Café" on March 29, 2021-focused on advancing computational approaches for predictive oncology in the clinical and research domains of radiation oncology. These events reflect 3,870 human hours of virtual engagement with representation from 8 DOE national laboratories and the Frederick National Laboratory for Cancer Research (FNL), 4 research institutes, 5 cancer centers, 17 medical schools and teaching hospitals, 5 companies, 5 federal agencies, 3 research centers, and 27 universities. Here we summarize the workshops by first describing the background for the workshops. Participants identified twelve key questions-and collaborative parallel ideas-as the focus of work going forward to advance the field. These were then used to define short-term and longer-term "Blue Sky" goals. In addition, the group determined key success factors for predictive oncology in the context of radiation oncology, if not the future of all of medicine. These are: cross-discipline collaboration, targeted talent development, development of mechanistic mathematical and computational models and tools, and access to high-quality multiscale data that bridges mechanisms to phenotype. The workshop participants reported feeling energized and highly motivated to pursue next steps together to address the unmet needs in radiation oncology specifically and in cancer research generally and that NCI and DOE project goals align at the convergence of radiation therapy and advanced computing.

Sample test array and recovery (STAR) platform at the National Ignition Facility.

We have developed the Sample Test Array and Recovery (STAR) platform for the National Ignition Facility (NIF) for studying the thermal and hydrodynamic responses of materials in extreme environments. The STAR platform expands the range of obtainable fluences and quadruples the rate that materials experiments can be conducted at the NIF. Example configurations are demonstrated for fluences spanning 0.56-34 J/cm2 with environmental isolation for post-shot material recovery and inspection and up to 1740 J/cm2 without isolation, with surface heating rates of up to 2 × 1014 K/s. An example experiment involving thermally driven shock and spallation of aluminum alloy 7075 is briefly discussed.

Molecular and Kinetic Models for High-Rate Thermal Degradation of Polyethylene.

Thermal degradation of polyethylene is studied under the extremely high rate temperature ramps expected in laser-driven and X-ray ablation experiments-from 1010 to 1014 K/s in isochoric, condensed phases. The molecular evolution and macroscopic state variables are extracted as a function of density from reactive molecular dynamics simulations using the ReaxFF potential. The enthalpy, dissociation onset temperature, bond evolution, and observed cross-linking are shown to be rate dependent. These results are used to parametrize a kinetic rate model for the decomposition and coalescence of hydrocarbons as a function of temperature, temperature ramp rate, and density. The results are contrasted to first-order random-scission macrokinetic models often assumed for pyrolysis of linear polyethylene under ambient conditions.

Complications of hand-assisted laparoscopic renal surgery: single-center ten-year experience.

OBJECTIVES: To review our perioperative complications during the first decade of using hand-assisted laparoscopic nephrectomy using a sleeve (HALN). HALN is a minimally invasive procedure first reported by our group in 1997. METHODS: After institutional review board approval, the charts of the patients who had undergone HALN, hand-assisted laparoscopic partial nephrectomy, or hand-assisted laparoscopic nephroureterectomy from 1997 to 2007, at our institution, were retrospectively reviewed. Standard laparoscopic procedures were not included. The relevant patient characteristics, operative details, American Society of Anesthesiologists score, body mass index, comorbidities, medications, and complications were recorded. RESULTS: A total of 227 consecutive patients had undergone Hand-assisted laparoscopic renal surgery, and all their charts were reviewed. Of these 227, 134 were radical HALN, 37 were nonradical HALN, 42 were hand-assisted laparoscopic partial nephrectomy, and 15 were hand-assisted laparoscopic nephroureterectomy. Complications developed in 59 patients (26%): 8% major and 18% minor. The procedure-specific complication rate was 29% for radical HALN, 27% for nonradical HALN, 33% for hand-assisted laparoscopic nephroureterectomy, and 17% for hand-assisted laparoscopic partial nephrectomy. Complications included blood transfusion in 6%, urinary retention in 4%, ileus in 4%, and wound infection in 4%. From 2003 through 2007 (n = 163), our overall complication rate was 22% (8% major and 13% minor). From 1997 to 2002 (n = 65), the overall complication rate was 38% (P = .02). The American Society of Anesthesiologists score and the use of systemic steroids were associated with the occurrence of perioperative complications. CONCLUSIONS: Our results have shown that hand assistance provides a safe, minimally invasive laparoscopic procedure. Our complications rates were comparable to those with other standard and hand-assist series, although the spectrum of complications varied. Hand-assisted laparoscopic renal surgery could be a method by which to improve patient access to minimally invasive nephron-sparing surgery.

Adhesion hysteresis from interdependent capillary and electrostatic forces.

Adhesion hysteresis commonly occurs at the nanoscale in humid atmospheres, yet mechanisms are not entirely understood. Here, the adhesion forces between silicon (111) oxide surfaces and tungsten oxide probes have been examined using interfacial force microscopy. The results show that the adhesion forces during surface approach and separation differ not only in magnitude but also in mechanism, arising mainly from capillary and electrostatic forces, respectively. Surface contact leads to a transient intersurface potential on dewetting. This mechanism of adhesion hysteresis differs in not relying singly on hysteretic wetting. Furthermore, by biasing the surfaces, nonadditivity is demonstrated between the capillary and electrostatic forces at the onset of condensation. These results hold important implications on the interpretation of force in nanoprobe geometries in humid atmospheres.

Superplastic nanowires pulled from the surface of common salt.

Superplastic nanowires were formed by touching the NaCl(100) surface with a Au tip in a transmission electron microscope. The nanowires were stretched < or =2.2 microm, or 280%, and bent >90 degrees upon compression, when showered with the electron beam. More surprisingly, no dislocations were observable during the elongation due to fast diffusion. Mechanical measurements in humid atmospheres suggest that salt nanowires also form in ambient environments.

Emergency room follow-up trends in urolithiasis: single-center report.

OBJECTIVES: Over 1 million emergency room visits are made annually for renal colic and urinary stone disease in the United States. This study seeks to determine patterns of follow-up for patients diagnosed with ureterolithiasis in a single emergency department. METHODS: A retrospective review identified 556 patients diagnosed with ureterolithiasis in the emergency department at the University of Wisconsin Hospital over a 2-year period. RESULTS: Of these patients, 130 met inclusion criteria including first-time stone formers and no prior urological visit within the past 5 years. Fourteen patients seen in the emergency room at their initial visit received immediate urological consultation. Of the remaining 116 patients discharged by the emergency room, 71 (61%) patients followed up with a urologist, 27 (23%) patients followed up with a primary care physician, 10 (9%) patients returned to the emergency department for their initial follow-up, and 8 (7%) patients had no further follow-up. Of the 44 patients with ureteral calculi 5 mm or greater, 38 (86%) patients either received urological consultation in the emergency department or followed up with a urologist as an outpatient (P < .05). CONCLUSIONS: This study demonstrates that most patients seen in the emergency department at our institution for ureterolithiasis with > 4 mm ureteral stones follow up with a urologist on an outpatient basis. Alternatively, based on the overall subset of patients identified, it is conceivable that a significant percentage of patients never see a urologist.

Adhesion from tethered ligand-receptor bonds with microsecond lifetimes.

According to classical thermodynamics, biological ligand-receptor bonds should have a median lifetime of about 2 ms, and nearly half should have lifetimes of nanoseconds to microseconds. As a result, it is clear that many "weak" bonds are indispensable for cellular adhesion, signaling, and other critical events. However, the forces required to rupture such weak bonds and the adhesion they provide between surfaces are largely unknown because of their propensity to dissociate rapidly from a measuring probe. To measure such weak bond forces quantitatively, we followed nature's example of adhering surfaces with many weak ligand-receptor bonds. Analogously to how multiplicity promotes stronger adhesion between cellular membranes, multiple bonds created significant adhesion between model cellular surfaces. Specifically, we used an automated surface forces apparatus to measure the adhesion between complementary surfaces bearing dense populations of streptavidin receptors and flexible PEG tethers that each anchored a weakly binding ligand (HABA, or 2-(4-hydroxyphenylazo) benzoic acid). We show that this short-lived bond (<100 mus) leads to low forces of dissociation and only a small fraction being simultaneously bound. These results are significant because the HABA-streptavidin bond energy ( approximately 10.5kBT) is similar to the average found in nature (14.7kBT). The measurements exemplify how a single ligand-receptor bond may fall apart and rejoin many times before completing a cellular function yet can still exhibit strength in numbers.

Bimodal polymer mushrooms: compressive forces and specificity toward receptor surfaces.

End-grafted poly(ethylene glycol) (or PEG) polymer chains are used to extend the in vivo circulation time of targeted liposomes and nanoparticles; however, the most efficacious structure for also imparting high target specificity remains unknown. Using the surface force apparatus, we have measured the specific and nonspecific forces between bimodal mixtures of grafted polymer mushrooms and model receptor surfaces. Specifically, supported lipid membranes anchoring 2000 or 5000 Da PEG with a controlled fraction of PEG(2000) bearing biotin ligands were compressed against opposing streptavidin surfaces. The presence of the longer 5000 Da chain increased the steric repulsion of the bimodal mushroom layer and thus decreased the net adhesive force when shorter chains were ligated. However, the 5000 Da chain did not detectably alter the distance where ligand-receptor binding occurs and adhesion begins. This latter result is in good agreement with theoretical predictions based on summing the repulsive steric and attractive bridging forces. Further, all ligated structures adhered to receptors under both static and dynamic fluid flow conditions. The dynamic movement of the flexible PEG tethers permitted ligand-receptor bonds to form far beyond the equilibrium edge of the bimodal mushroom layer. This work demonstrates that liposome targeting should be enhanced by grafting ligands to liposomes with a tether that has a contour length longer than the equilibrium height of the bimodal mushroom layer.

The role of flexible tethers in multiple ligand-receptor bond formation between curved surfaces.

Ligands mounted to surfaces via extensible tethers are present in nature and represent a growing class of molecules used to engineer adhesion in drug targeting, biosensing, self-assembling nanostructures, and in other biophysical research. Using a continuum approach with geometric and thermodynamic arguments, we derive a number of analytical expressions that relate key properties of single-tethered ligand-receptor interactions to multiple bond formation between curved surfaces. The theoretical predictions are in good agreement with measurements made with the surface forces apparatus. We establish that, when ligated, many tethers commonly used in biophysical research exhibit a discrete binding range that can be accurately measured with force spectroscopy. The distribution of bound ligated tethers is independent of the surfaces' interaction radius, R. The bridging force scales linearly with R, the tether's effective spring constant and grafting density, and with the ligand-receptor bond energy when the surfaces are in direct contact. These results are contrasted to bridging forces that evolve between plane-parallel geometries. Last, we show how our simple analytical reductions can be used to predict adhesive forces for STEALTH liposomes and other targeted and self-assembled nanoparticles.