Conceptual and Experimental Tools to Understand Spatial Effects and Transport Phenomena in Nonlinear Biochemical Networks Illustrated with Patchy Switching.

Many biochemical systems are spatially heterogeneous and exhibit nonlinear behaviors, such as state switching in response to small changes in the local concentration of diffusible molecules. Systems as varied as blood clotting, intracellular calcium signaling, and tissue inflammation are all heavily influenced by the balance of rates of reaction and mass transport phenomena including flow and diffusion. Transport of signaling molecules is also affected by geometry and chemoselective confinement via matrix binding. In this review, we use a phenomenon referred to as patchy switching to illustrate the interplay of nonlinearities, transport phenomena, and spatial effects. Patchy switching describes a change in the state of a network when the local concentration of a diffusible molecule surpasses a critical threshold. Using patchy switching as an example, we describe conceptual tools from nonlinear dynamics and chemical engineering that make testable predictions and provide a unifying description of the myriad possible experimental observations. We describe experimental microfluidic and biochemical tools emerging to test conceptual predictions by controlling transport phenomena and spatial distribution of diffusible signals, and we highlight the unmet need for in vivo tools.

Long-range structural defects by pathogenic mutations in most severe glucose-6-phosphate dehydrogenase deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common blood disorder, presenting multiple symptoms, including hemolytic anemia. It affects 400 million people worldwide, with more than 160 single mutations reported in G6PD. The most severe mutations (about 70) are classified as class I, leading to more than 90% loss of activity of the wild-type G6PD. The crystal structure of G6PD reveals these mutations are located away from the active site, concentrating around the noncatalytic NADP+-binding site and the dimer interface. However, the molecular mechanisms of class I mutant dysfunction have remained elusive, hindering the development of efficient therapies. To resolve this, we performed integral structural characterization of five G6PD mutants, including four class I mutants, associated with the noncatalytic NADP+ and dimerization, using crystallography, small-angle X-ray scattering (SAXS), cryogenic electron microscopy (cryo-EM), and biophysical analyses. Comparisons with the structure and properties of the wild-type enzyme, together with molecular dynamics simulations, bring forward a universal mechanism for this severe G6PD deficiency due to the class I mutations. We highlight the role of the noncatalytic NADP+-binding site that is crucial for stabilization and ordering two ß-strands in the dimer interface, which together communicate these distant structural aberrations to the active site through a network of additional interactions. This understanding elucidates potential paths for drug development targeting G6PD deficiency.

Exons as units of phenotypic impact for truncating mutations in autism.

Autism spectrum disorders (ASD) are a group of related neurodevelopmental diseases displaying significant genetic and phenotypic heterogeneity. Despite recent progress in understanding ASD genetics, the nature of phenotypic heterogeneity across probands remains unclear. Notably, likely gene-disrupting (LGD) de novo mutations affecting the same gene often result in substantially different ASD phenotypes. Nevertheless, we find that truncating mutations affecting the same exon frequently lead to strikingly similar intellectual phenotypes in unrelated ASD probands. Analogous patterns are observed for two independent proband cohorts and several other important ASD-associated phenotypes. We find that exons biased toward prenatal and postnatal expression preferentially contribute to ASD cases with lower and higher IQ phenotypes, respectively. These results suggest that exons, rather than genes, often represent a unit of effective phenotypic impact for truncating mutations in autism. The observed phenotypic patterns are likely mediated by nonsense-mediated decay (NMD) of splicing isoforms, with autism phenotypes usually triggered by relatively mild (15-30%) decreases in overall gene dosage. We find that each ASD gene with recurrent mutations can be characterized by a parameter, phenotype dosage sensitivity (PDS), which quantifies the relationship between changes in a gene's dosage and changes in a given disease phenotype. We further demonstrate analogous relationships between exon LGDs and gene expression changes in multiple human tissues. Therefore, similar phenotypic patterns may be also observed in other human genetic disorders.

Heterogeneity in Alcohol-Related Severity and Interests in Going to Treatment in Community Adults with Alcohol Use Disorder (AUD).

RATIONALE: Alcohol use disorder (AUD) is highly prevalent among adults in the US and is associated with substantial personal and societal costs. Yet only a small percentage of adults with AUD initiate treatment, including those with severe AUD symptoms who are most in need of treatment. In this paper we use latent profile analysis (LPA) to describe differences in symptoms of AUD severity and alcohol-related consequences among untreated adults with severe AUD symptoms who were recruited from the community. Identification of such differences will result in better understanding of this population and will improve methods of treatment outreach. METHOD: The LPAs were conducted on the baseline data of 403 (50% male, 77% White, M age = 40.74 with severe AUD recruited from the community and enrolled in a trial of an intervention designed to encourage treatment initiation. Participants reported no prior AUD treatment history. The LPAs were based on indicators of AUD severity, alcohol-related negative consequences, and self-reported intention to initiate AUD treatment. RESULTS: The LPAs revealed 4 profiles. Profile membership was predicted by baseline participant sex and whether they were living with a partner and was associated with baseline past 30-days alcohol consumption. CONCLUSIONS: The findings characterize and describe the variability among adults in the community with untreated severe AUD on variables that tend to motivate such individuals to seek treatment, which could significantly advance treatment outreach efforts.

Improved statistical methods enable greater sensitivity in rhythm detection for genome-wide data.

Robust methods for identifying patterns of expression in genome-wide data are important for generating hypotheses regarding gene function. To this end, several analytic methods have been developed for detecting periodic patterns. We improve one such method, JTK_CYCLE, by explicitly calculating the null distribution such that it accounts for multiple hypothesis testing and by including non-sinusoidal reference waveforms. We term this method empirical JTK_CYCLE with asymmetry search, and we compare its performance to JTK_CYCLE with Bonferroni and Benjamini-Hochberg multiple hypothesis testing correction, as well as to five other methods: cyclohedron test, address reduction, stable persistence, ANOVA, and F24. We find that ANOVA, F24, and JTK_CYCLE consistently outperform the other three methods when data are limited and noisy; empirical JTK_CYCLE with asymmetry search gives the greatest sensitivity while controlling for the false discovery rate. Our analysis also provides insight into experimental design and we find that, for a fixed number of samples, better sensitivity and specificity are achieved with higher numbers of replicates than with higher sampling density. Application of the methods to detecting circadian rhythms in a metadataset of microarrays that quantify time-dependent gene expression in whole heads of Drosophila melanogaster reveals annotations that are enriched among genes with highly asymmetric waveforms. These include a wide range of oxidation reduction and metabolic genes, as well as genes with transcripts that have multiple splice forms.

Prophylactic dexamethasone effectively reduces the incidence of pain flare following spine stereotactic body radiotherapy (SBRT): a prospective observational study.

PURPOSE: The purpose of this study was to determine the incidence of pain flare (PF) in patients receiving spine stereotactic body radiotherapy (SBRT) treated with prophylactic oral dexamethasone (DEX) 1 h before and for 4 days following SBRT. METHODS: Forty-seven patients were accrued on this prospective observational study. The first cohort of 24 patients was treated with 4 mg, while a second cohort of 23 patients treated with 8 mg of DEX. The Brief Pain Inventory (BPI) was used to score pain and functional interference each day during SBRT and for 10 days following. Comparisons between the 4 and 8 mg cohorts, in addition to our previously reported steroid naïve patients post SBRT (n = 41), were also performed. RESULTS: The total incidence of PF was 19 % (9/47). The incidence in the 4 and 8 mg cohorts was 25 % (6/24) and 13 % (3/23), respectively, and the difference was not statistically significant (p = 0.46). Comparing functional interference, the 4 mg cohort had better profile in walking ability (p < 0.005) and relationships with others (p < 0.035) compared to the 8 mg cohort. Compared to our previously reported steroid naïve cohort, prophylactic DEX significantly reduced the incidence of PF (68 vs. 19 %, p < 0.0001, respectively), patients had lower worst pain scores, and improved general activity interference outcome. CONCLUSION: We recommend prophylactic DEX for patients treated with spine SBRT. Our current practice is based on the 4 mg protocol primarily due to the improved functional interference outcomes. A randomized trial is required to finalize the optimal regimen and schedule.

Brief, cognitive-behavioral intervention to promote treatment seeking in adults with severe alcohol use disorder: A randomized controlled trial.

BACKGROUND AND AIMS: There is little RCT evidence that brief interventions improve treatment seeking in individuals with severe alcohol use disorder (AUD) or treatment seeking reduces alcohol use. The aim was to test the efficacy of a brief intervention to increase treatment seeking in treatment naïve adults with severe AUD and measure its effects on alcohol use. DESIGN: Parallel group, non-pharmacologic RCT with intervention (n = 197) and active control (n = 203) conditions, with blinded assessors conducting follow-ups at 1, 3 and 6 months. SETTING: Online recruitment in a 17-county region of upstate New York, USA. PARTICIPANTS: Inclusion criteria consisted of ages ≥18 years, Alcohol Use Disorders Identification Test score ≥16, exceeds recommended limits for alcohol use and no history of AUD treatment. n = 400; 50% female; 79% white; mean age, 40.7; mean education, 14.6 years. INTERVENTION AND COMPARATOR: One-session telephone-delivered interventions: Cognitive-Behavioral Therapy for Treatment Seeking (CBT-TS; intervention), review of a National Institute on Alcohol Abuse and Alcoholism pamphlet on AUD treatment (control). MEASUREMENTS: Self-report of any AUD treatment use over 3 months (primary outcome) and two standard measures of alcohol use over 6 months (secondary outcomes). FINDINGS: Intent-to-treat analyses were used. Assessment follow-up rates were ≥93%. Any alcohol-related treatment use over 3-month follow-up was obtained by 38 (19%) intervention participants and 36 (18%) control participants, a non-significant difference, χ2 [1] = 0.16, P = 0.689. Secondary analysis showed a significant interaction term between sex and intervention assignment (ß = -1.197, P = 0.027). The interaction suggested CBT-TS was effective in men (22% vs 13%), although the evidence was somewhat weak (P = 0.071), and it was not effective in women (17% vs 24%). CONCLUSIONS: A one-session cognitive-behavioral therapy intervention to increase treatment seeking in treatment naïve adults with severe alcohol use disorder did not increase treatment seeking.

Alcohol-related consequences and the intention to seek care in treatment naïve women and men with severe alcohol use disorder.

INTRODUCTION: Research on treatment utilization for alcohol use disorder (AUD) is based primarily on clinical samples and community samples of low AUD severity that may not need formal care. Using a community sample of adults with untreated but severe AUD symptoms, we tested the hypothesis that alcohol-related consequences, but not alcohol consumption levels, are associated with the intention to seek AUD treatment, examined associations of specific types of alcohol-related consequences with intention, and explored sex differences in these associations. METHODS: The sample was recruited using social media ads for a randomized controlled trial to test a brief intervention to promote AUD treatment seeking. This report is based on analysis of baseline data collected prior to treatment intervention. Multiple linear regressions examined associations of measures of alcohol consumption, alcohol-related consequences broadly, and specific alcohol-related consequences with the intention to seek treatment. Moderating effects of sex on associations were explored. RESULTS: Subjects (n = 349) averaged 41 years of age, 48% were female, 6% were Latinx, 80% were white, 15% were Black, and 92% met criteria for severe AUD. Alcohol consumption measures were not associated with intention to seek treatment whereas interpersonal- and intrapersonal- consequences were associated with intention. Sex served as a moderator, with intrapersonal consequences (e.g., sad mood) showing a stronger association with intention in women and social responsibility consequences (particularly financial) associated with intention in men. CONCLUSION: Select alcohol-related consequences may be keys to understanding increased intention to seek AUD treatment including intrapersonal consequences in women and financial consequences in men.

Alcohol use during COVID-19 in adults with severe untreated AUD.

Evidence demonstrating increased alcohol use during COVID-19 comes from low- to moderate-alcohol use samples and has yet to use adults with severe but untreated AUD. Using a community sample of adults with severe AUD, this exploratory, cross-sectional study examined associations of COVID-19 alcohol use. Participants were recruited for a phase-II RCT. Only baseline measures, completed prior to randomization, were analyzed in the present study. Key variables were alcohol consumption, COVID-19-related worries and experiences, and qualitative responses of 1) alcohol use and 2) positive changes during COVID-19. 176 pariticpants recruited since COVID-19 were on average 41.4 years old, 49.1% female, and 79% White. Participants drank alcohol nearly 23 of the past 30 days, consumed 7 standard drinks per drinking day, and nearly 90% reported increased alcohol use. More heavy episodic drinking was reported in the first six-months of COVID-19 and more COVID-related concerns in the most recent six-months. Participants reported drinking increased due to "more time on their hands", but the pandemic also "strengthened relationships". Results affirm an increase in alcohol use during COVID-19 in adults with severe, untreated AUD. Findings underscore the need to understand how alcohol use and pandemic-related circumstances may influence one another for adults with severe AUD.

Insights into characteristics of light absorbing carbonaceous aerosols over an urban location in Southeast Asia.

Light absorbing carbonaceous aerosols (LACA) consisting of black carbon (BC) and brown carbon (BrC) have received considerable attention because of their climate and health implications, but their sources, characteristics and fates remain unclear in Southeast Asia (SEA). In this study, we investigated spatio-temporal characteristics of LACA, their radiative properties and potential sources in Singapore under different weather conditions. Hourly BC concentrations, measured from May 2017 to March 2018, ranged from 0.31 µg/m3 to 14.37 µg/m3 with the mean value being 2.44 ±â€¯1.51 µg/m3. High mass concentrations of BC were observed during the south-west monsoon (SWM, 2.60 ±â€¯1.56 µg/m3) while relatively low mass concentrations were recorded during the north-east monsoon (NEM, 1.68 ±â€¯0.96 µg/m3). There was a shift in the Absorption Ångström exponent (AAE) from 1.1 to 1.4 when the origin of LACA changed from fossil fuel (FF) to biomass burning (BB) combustion. This shift is attributed to the presence of secondary BrC in LACA, derived from transboundary BB emissions during the SWM. Lower AAE values were observed when local traffic emissions were dominant during the NEM. This explanation is supported by measurements of water-soluble organic carbon (WSOC) in LACA and the corresponding AAE values determined at 365 nm using a UV-vis spectrophotometer. The AAE values, indicative of the presence of brown carbon (BrC), showed that photochemically aged LACA contribute to an enhancement in the light absorption of aerosols. In addition, spatio-temporal characteristics of BC in the intra-urban environment of Singapore were investigated across diverse outdoor and indoor microenvironments. High variability of BC was evident across these microenvironments. Several air pollution hotspots with elevated BC concentrations were identified. Overall, the results stress a need to control anthropogenic emissions of BC and BrC in order to mitigate near-term climate change impacts and provide health benefits.

Stereotactic Body Radiation Therapy Boost for Intermediate-Risk Prostate Cancer: A Phase 1 Dose-Escalation Study.

PURPOSE: High-dose-rate brachytherapy boost plus external beam radiation therapy is an established option for intermediate-risk prostate cancer (PCa). Stereotactic body radiation therapy (SBRT) boost can potentially mimic high-dose-rate boost and could be a viable alternative. Here we report the long-term outcomes of a phase 1 dose-escalation trial of single-fraction SBRT boost. METHODS AND MATERIALS: Patients had intermediate-risk PCa and were accrued to 3 different SBRT single-fraction dose-level cohorts (10 Gy, 12.5 Gy, and 15 Gy). All received supplemental radiation therapy afterwards (37.5 Gy in 15 fractions). Three gold fiducials were implanted for image guidance. Patients were simulated and treated with a foley catheter and intrarectal balloon. A T2 magnetic resonance imaging scan was used for contouring, and a cine magnetic resonance imaging scan was used to calculate patient-specific internal target volume margins. Toxicity and quality-of-life data were collected using Common Terminology Criteria for Adverse Events v3.0 and the Expanded Prostate Cancer Index Composite. RESULTS: 30 patients were accrued, 10 in each cohort. Median follow-up was 72 months. 60% had unfavorable intermediate-risk PCa. Two patients in the 15 Gy cohort developed late grade ≥3 gastrointestinal and genitourinary toxicity, with 1 patient suffering from a grade-4 rectal fistula after a rectal ulcer was biopsied repeatedly. Two patients had biochemical failure. Median PSA nadir was 0.4 ng/mL with 10 Gy, 0.09 ng/mL with 12.5 Gy and 0.07 ng/mL with 15 Gy. Median PSA at 4 years as well as proportion achieving a nadir <0.2 ng/mL improved significantly with higher doses. There was no significant change in quality of life from baseline in any of the domains, and the minimal clinically important change was not statistically different between the 3 cohorts. CONCLUSIONS: Other than a grade 4 toxicity, which may in part be due to repeated biopsies of a rectal ulcer, single-fraction SBRT boost was feasible and well tolerated. Larger studies are warranted to better document the outcomes of such an approach.

A calmodulin-binding site on cyclin E mediates Ca2+-sensitive G1/s transitions in vascular smooth muscle cells.

Calcium transients are known to control several transition points in the eukaryotic cell cycle. For example, we have previously shown that a coordinate elevation in the intracellular free calcium ion concentration is required for G1- to S-phase cell cycle progression in vascular smooth muscle cells (VSMC). However, the molecular basis for this Ca2+ sensitivity was not known. Using buffers with differing [Ca2+], we found that the kinase activity of mouse and human cyclin E/CDK2, but not other G1/S-associated cell cycle complexes, was responsive to physiological changes in [Ca2+]. We next determined that this Ca2+-responsive kinase activity was dependent on a direct interaction between calmodulin (CaM), one of the major Ca2+-signal transducers of eukaryotic cells, and cyclin E. Pharmacological inhibition of CaM abrogated the Ca2+ sensitivity of cyclin E/CDK2 and retarded mouse VSMC proliferation by causing G1 arrest. We next defined the presence of a highly conserved 22 amino acid N-terminal CaM-binding motif in mammalian cyclin E genes (dissociation constant, 1.5+/-0.1 micromol/L) and showed its essential role in mediating Ca2+-sensitive kinase activity of cyclin E/CDK2. Mutant human cyclin E protein, lacking this CaM-binding motif, was incapable of binding CaM or responding to [Ca2+]. Taken together, these findings reveal CaM-dependent cyclin E/CDK2 activity as a mediator of the known Ca2+ sensitivity of the G1/S transition of VSMC.

Activation of p53 by Dishevelled independent of Wnt or planar polarity pathways.

Dishevelled is a key component of the Wnt signaling and planar polarity pathways. We discovered that in selective cell types, it potently activates the transcriptional activity of the tumor suppressor p53. This action, however, is not dependent on the downstream of either the Wnt or the planar polarity pathways. Dishevelled signals to the first 50 amino acids of p53, which is the transactivation domain. The level of phosphorylation on several serine residues within that region of p53 increases in response to disheveled activation, partially contributing to p53 activation. The MAP kinase pathway and E1B55k may also be involved in this dishevelled-p53 connection. Our data provide evidence that there is a novel signaling pathway from Dishevelled to p53.

Stretchable and Degradable Semiconducting Block Copolymers.

This paper describes the synthesis and characterization of a class of highly stretchable and degradable semiconducting polymers. These materials are multi-block copolymers (BCPs) in which the semiconducting blocks are based on the diketopyrrolopyrrole (DPP) unit flanked by furan rings and the insulating blocks are poly(ε-caprolactone) (PCL). The combination of stiff conjugated segments with flexible aliphatic polyesters produces materials that can be stretched >100%. Remarkably, BCPs containing up to 90 wt% of insulating PCL have the same field-effect mobility as the pure semiconductor. Spectroscopic (ultraviolet-visible absorption) and morphological (atomic force microscopic) evidence suggests that the semiconducting blocks form aggregated and percolated structures with increasing content of the insulating PCL. Both PDPP and PCL segments in the BCPs degrade under simulated physiological conditions. Such materials could find use in wearable, implantable, and disposable electronic devices.

Effects of flexibility and branching of side chains on the mechanical properties of low-bandgap conjugated polymers.

This paper describes effects of the flexibility, length, and branching of side chains on the mechanical properties of low-bandgap semiconducting polymers. The backbones of the polymer chains comprise a diketopyrrolopyrrole (DPP) motif flanked by two furan rings and copolymerized by Stille polycondensation with thiophene (DPP2FT). The side chains of the DPP fall into three categories: linear alkyl (C8, C14, or C16), branched alkyl (ethylhexyl, EH, or hexyldecyl, HD), and linear oligo(ethylene oxide) (EO3, EO4, or EO5). Polymers bearing C8 and C14 side chains are obtained in low yields and thus not pursued. Thermal, mechanical, and electronic properties are plotted against the number of carbon and oxygen atoms in the side chain. We obtain consistent trends in the thermal and mechanical properties for branched alkyl and linear oligo(ethylene oxide) side chains. For example, the glass transition temperature (T g) and elastic modulus decrease with increasing number of carbon and oxygen atoms, whereas the crack-onset strain increases. Among polymers with side chains of 16 carbon and oxygen atoms (C16, HD, and EO5), C16 exhibits the highest T g and the greatest susceptibility to fracture. Hole mobility, as measured in thin-film transistors, appears to be a poor predictor of electronic performance for polymers blended with [60]PCBM in bulk heterojunction (BHJ) solar cells. For example, while EO3 and EO4 exhibit the lowest mobilities (< 10-2 cm2 V-1 s-1) in thin-film transistors, solar cells made using these materials performed the best (efficiency > 2.6%) in unoptimized devices. Conversely, C16 exhibits the highest mobility (≈ 0.2 cm2 V-1 s-1) but produces poor solar cells (efficiency < 0.01%). We attribute the lack of correlation between mobility and power conversion efficiency to unfavorable morphology in the BHJ solar cells. Given the desirable properties measured for EO3 and EO4, the use of flexible oligo(ethylene oxide) side chains is a successful strategy to impart mechanical deformability to organic solar cells, without sacrificing electronic performance.

Metallic Nanoislands on Graphene for Monitoring Swallowing Activity in Head and Neck Cancer Patients.

There is a need to monitor patients with cancer of the head and neck postradiation therapy, as diminished swallowing activity can result in disuse atrophy and fibrosis of the swallowing muscles. This paper describes a flexible strain sensor comprising palladium nanoislands on single-layer graphene. These piezoresistive sensors were tested on 14 disease-free head and neck cancer patients with various levels of swallowing function: from nondysphagic to severely dysphagic. The patch-like devices detected differences in (1) the consistencies of food boluses when swallowed and (2) dysphagic and nondysphagic swallows. When surface electromyography (sEMG) is obtained simultaneously with strain data, it is also possible to differentiate swallowing vs nonswallowing events. The plots of resistance vs time are correlated to specific events recorded by video X-ray fluoroscopy. Finally, we developed a machine-learning algorithm to automate the identification of bolus type being swallowed by a healthy subject (86.4%. accuracy). The algorithm was also able to discriminate between swallows of the same bolus from either the healthy subject or a dysphagic patient (94.7% accuracy). Taken together, these results may lead to noninvasive and home-based systems for monitoring of swallowing function and improved quality of life.

Stereotactic Ablative Radiation Therapy for Pulmonary Metastases: Histology, Dose, and Indication Matter.

PURPOSE: To assess the association between colorectal cancer (CRC) histology, dose, and local failure (LF) after stereotactic ablative radiation therapy (SABR) for pulmonary metastases, and to describe subsequent cancer progression, change of systemic therapy (CST), survival, and their association with treatment indications. METHODS AND MATERIALS: From a prospective SABR cohort, 180 pulmonary metastases in 120 patients were identified. Treatment indications were single metastasis, oligometastases, oligoprogression, and dominant areas of progression. Doses of 48 to 52 Gy/4 to 5 fractions were delivered. Since 2010 the dose for peripheral CRC metastases was increased to 60 Gy/4 fractions. Cumulative incidence function (CIF) was used to report LF, progression probability, and CST. The Kaplan-Meier method estimated overall survival (OS). Univariate and multivariable analyses to assess variable associations were conducted. RESULTS: Median follow-up was 22 months (interquartile range, 14-33 months). At 24 months, the CIF of LF was 23.6% (95% confidence interval [CI] 15.1%-33.3%) and 8.3% (95% CI 2.6%-18.6%), respectively, for CRC and non-CRC metastases (P<.001). This association remained significant after adjusting for confounders (subdistribution hazard ratio [SHR] 13.6, 95% CI 4.2-44.1, P<.001). Among CRC metastases, 56 and 45 received <60 Gy and 60 Gy, respectively. Delivering 60 Gy was independently associated with a lower hazard of LF (SHR 0.271, 95% CI 0.078-0.940, P=.040). At 12 months the CIF of progression was 41.67% (95% CI 21.69%-60.56%), 42.51% (95% CI 29.09%-55.29%), 62.96% (95% CI 41.25%-78.53%), and 78.57% (95% CI 42.20%-93.48%), respectively, for patients treated for single metastasis, oligometastases, oligoprogression, and dominant area of progression (P<.001). A CST was observed, respectively, in 4 (17%), 17 (31%), 12 (44%), and 10 (71%) patients with a median time of 13.1, 11.1, 8.4, and 8.4 months. CONCLUSION: Colorectal cancer lung metastases are associated with a higher hazard of LF and require higher SABR doses. Outcomes for patients with oligometastases and oligoprogression treated with SABR seem favorable. Prospective clinical trials are needed to confirm these benefits.

Practicality of exchanging transparent 3D CT for radiography for pelvic fractures.

OBJECTIVE: We assess the utility of transparent 3D reconstructed CT images for evaluation of traumatic pelvic bony injuries compared to traditional radiographs. METHODS: Radiographs and 3D reconstructed CT were anonymized and randomized before review by 4 board certified physicians using a standardized questionnaire and compared to a gold-standard axial CT by a fifth board certified physician. RESULTS: 49 patients were included. We found significant agreement (K=[0.5-0.92], p<0.001) and comparable accuracy (K=[0.36-0.38], p<0.02) and ghost images of radiographs and transparent 3D reconstructed CT without a difference in confidence (p=0.38). CONCLUSION: Transparent 3D reconstructed CT images may be sufficient for pelvic trauma injury without the use of radiographs.

SERS-enhanced piezoplasmonic graphene composite for biological and structural strain mapping.

Thin-film optical strain sensors have the ability to map small deformations with spatial and temporal resolution and do not require electrical interrogation. This paper describes the use of graphene decorated with metallic nanoislands for sensing of tensile deformations of less than 0.04% with a resolution of less than 0.002%. The nanoisland-graphene composite films contain gaps between the nanoislands, which when functionalized with benzenethiolate behave as hot spots for surface-enhanced Raman scattering (SERS). Mechanical strain increases the sizes of the gaps; this increase attenuates the electric field, and thus attenuates the SERS signal. This compounded, SERS-enhanced "piezoplasmonic" effect can be quantified using a plasmonic gauge factor, and is among the most sensitive mechanical sensors of any type. Since the graphene-nanoisland films are both conductive and optically active, they permit simultaneous electrical stimulation of myoblast cells and optical detection of the strains produced by the cellular contractions.