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Advances in renewable and sustainable energy technologies critically depend on our ability to design and realize materials with optimal properties. Materials discovery and design efforts ideally involve close coupling between materials prediction, synthesis and characterization. The increased use of computational tools, the generation of materials databases, and advances in experimental methods have substantially accelerated these activities. It is therefore an opportune time to consider future prospects for materials by design approaches. The purpose of this Roadmap is to present an overview of the current state of computational materials prediction, synthesis and characterization approaches, materials design needs for various technologies, and future challenges and opportunities that must be addressed. The various perspectives cover topics on computational techniques, validation, materials databases, materials informatics, high-throughput combinatorial methods, advanced characterization approaches, and materials design issues in thermoelectrics, photovoltaics, solid state lighting, catalysts, batteries, metal alloys, complex oxides and transparent conducting materials. It is our hope that this Roadmap will guide researchers and funding agencies in identifying new prospects for materials design.

Anatomic subsite risk factors for gastric cancer differ substantially, and subsite-specific distribution of risk factors (such as Helicobacter pylori) can vary by race and ethnicity and neighborhood socioeconomic status (nSES). We examined differences in gastric cancer incidence by subsite, stratified by race and ethnicity and nSES, using Surveillance Epidemiology and End Results Program 2000-2014 data for 77,881 incident gastric cancer cases (cardia, n = 23,651; non-cardia, n = 35,825; overlapping or unspecified, n = 18,405). Compared with non-Hispanic whites, cardia cancer multivariable-adjusted incidence rate ratios were 35%-47% lower for blacks, Hispanics, Asian or Pacific Islanders, and American Indian or Alaska Natives; conversely, non-cardia incidence rate ratios were 1.7- to 3.9-fold higher for blacks, Hispanics, Asian or Pacific Islanders, and American Indian or Alaska Natives. Higher adjusted incidence rate ratios with decreasing nSES (lowest vs highest nSES quintile) were observed for all gastric (1.3-fold) and non-cardia (1.3-fold) cancers but were borderline significant for cardia cancers (1.1-fold). In conclusion, non-cardia cancer incidence is higher in minorities and varies by nSES, but cardia cancer incidence is higher in non-Hispanic whites and does not vary substantially by nSES. Clarifying reasons for higher cardia risk in non-Hispanic whites and targeted interventions to address non-cardia cancer risk in minorities could lessen the burden of gastric cancer.

PurposeGeneralized competing event (GCE) models improve stratification of patients according to their risk of cancer events relative to competing causes of mortality. The potential impact of such methods on clinical trial power and cost, however, is uncertain. We sought to test the hypothesis that GCE models can reduce estimated clinical trial cost in elderly patients with cancer.MethodsPatients with nonmetastatic head and neck (n = 9,677), breast (n = 22,929), or prostate cancer (n = 51,713) were sampled from the SEER-Medicare database. Using multivariable Cox proportional hazards models, we compared risk scores for all-cause mortality (ACM) and cancer-specific mortality (CSM) with GCE-based risk scores for each disease. We applied a cost function to estimate the cost and duration of clinical trials with a primary end point of overall survival in each population and in high-risk subpopulations. We conducted sensitivity analyses to examine model uncertainty.ResultsFor the purpose of enriching subpopulations, GCE models reduced estimated clinical trial cost compared with Cox models of ACM and CSM in all disease sites. The relative cost reductions with GCE models compared with ACM and CSM models, respectively, were -68.4% and -14.4% in prostate cancer, -38.8% and -18.3% in breast cancer, and -17.1% and -4.1% in head and neck cancer. Cost savings in breast and prostate cancers were on the order of millions of dollars. The GCE model also reduced relative clinical trial duration compared with CSM and ACM models for all disease sites. The optimal risk score cutoff for clinical trial enrollment occurred near the top tertile for all disease sites.ConclusionGCE models have significant potential to improve clinical trial efficiency and reduce cost, with a potentially large impact in prostate and breast cancers.

Behavioral economic theories of substance abuse posit that deficits in substance-free reward increase risk for substance misuse, but little research has examined potential moderators of this relationship, including dispositional risk factors. Here, we tested the hypothesis that young adult heavy drinkers with family histories of alcohol misuse would show a stronger association specifically between low evening substance-free reinforcement and alcohol problems compared to those without a family history of alcohol misuse. Participants were 317 college students reporting heavy episodic drinking (Mage = 18.8, SD = 1.1, 61% female, 79% White) who completed a questionnaire about engagement and enjoyment in rewarding activities not involving substance use after 7 p.m., along with measures of personal and parental alcohol use/problems. Evening substance-free reinforcement was negatively associated with typical drinking level for women, but not for men. Family history status did not show a significant association with typical alcohol consumption or evening substance-free reinforcement (operationalized as activity participation × enjoyment), but did show a significant association with alcohol problems. Evening substance-free reinforcement was significantly negatively related to alcohol problems for both men and women. However, the presence of a family history of alcohol misuse moderated this relationship, such that only individuals with familial risk for alcohol misuse who reported lower evening substance-free reinforcement evidenced greater alcohol-related problems. These findings suggest that lower evening substance-free reinforcement is associated with alcohol misuse among young adults, and that this association is exacerbated among individuals with familial risk for developing alcohol problems. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PurposeCancer ascertainment using large-scale electronic health records is a challenge. Our aim was to propose and apply a structured approach for evaluating multiple candidate approaches for cancer ascertainment using colorectal cancer (CRC) ascertainment within the US Department of Veterans Affairs (VA) as a use case.MethodsThe proposed approach for evaluating cancer ascertainment strategies includes assessment of individual strategy performance, comparison of agreement across strategies, and review of discordant diagnoses. We applied this approach to compare three strategies for CRC ascertainment within the VA: administrative claims data consisting of International Classification of Diseases, Ninth Revision (ICD9) diagnosis codes; the VA Central Cancer Registry (VACCR); and the newly accessible Oncology Domain, consisting of cases abstracted by local cancer registrars. The study sample consisted of 1,839,043 veterans with index colonoscopy performed from 1999 to 2014. Strategy-specific performance was estimated based on manual record review of 100 candidate CRC cases and 100 colonoscopy controls. Strategies were further compared using Cohen's κ and focused review of discordant CRC diagnoses.ResultsA total of 92,197 individuals met at least one CRC definition. All three strategies had high sensitivity and specificity for incident CRC. However, the ICD9-based strategy demonstrated poor positive predictive value (58%). VACCR and Oncology Domain had almost perfect agreement with each other (κ, 0.87) but only moderate agreement with ICD9-based diagnoses (κ, 0.51 and 0.57, respectively). Among discordant cases reviewed, 15% of ICD9-positive but VACCR- or Oncology Domain-negative cases had incident CRC.ConclusionEvaluating novel strategies for identifying cancer requires a structured approach, including validation against manual record review, agreement among candidate strategies, and focused review of discordant findings. Without careful assessment of ascertainment methods, analyses may be subject to bias and limited in clinical impact.

BackgroundPrevious studies have reported conflicting information regarding the prognostic role of p16 in nonoropharyngeal head and neck squamous cell carcinoma (HNSCC).MethodsUsing the US Veterans Affairs database, we analyzed 1448 patients with locoregionally advanced HNSCC and known p16 status diagnosed between 2005 and 2015 and treated with surgery, radiotherapy, or chemoradiotherapy. Tumor p16 status was determined through manual review of pathology reports of primary tumor specimens. Oropharyngeal (n = 1061) or nonoropharyngeal (n = 387; hypopharyngeal, laryngeal, or oral cavity) tumor site was determined from tumor registry data and manually reviewed for accuracy. We used multivariable Cox regression to analyze the effect of p16 status on overall survival (OS), cancer-specific survival (CSS), and competing mortality (CM) for oropharyngeal or nonoropharyngeal tumor sites. All statistical tests were two-sided.ResultsIn multivariable models adjusting for treatment, stage, age, comorbidity, and body mass index, patients with p16-positive tumors had improved OS, CSS, and CM compared with patients with p16-negative tumors in both oropharyngeal (OS: hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.40 to 0.71, P < .001; CSS: HR = 0.50, 95% CI = 0.35 to 0.73, P < .001; CM: HR = 0.59, 95% CI = 0.38 to 0.93, P = .02) and nonoropharyngeal primary sites (OS: HR = 0.41, 95% CI = 0.25 to 0.69, P < .001; CSS: HR = 0.37, 95% CI = 0.18 to 0.77, P = .008; CM: HR = 0.46, 95% CI = 0.23 to 0.95, P = .04). The prognostic impact of p16 status did not statistically significantly differ by primary tumor site for OS, CSS, or CM (Pinteraction > .05).ConclusionsOur findings support the hypothesis that p16 has a similar prognostic role in both nonoropharyngeal and oropharyngeal cancer. Consideration should be given to increased testing for p16 in laryngeal, hypopharyngeal, and oral cavity primaries.

ObjectivesTo develop a training program designed to meet the specific needs of medical physicists as they transition into a clinical role with direct patient care responsibilities.Materials and methodsThe training program was designed in collaboration with the faculty at the UC San Diego School of Medicine and incorporates training techniques that have been shown to be effective in improving communication skills. The program emphasizes experiential, practice-based learning over didactic presentations.ResultsThe training program is comprised of 5 components: 1) a 1-day Clinician-Patient Communication Workshop run by the UC San Diego School of Medicine, 2) Communication Strategies for Radiation Oncology, which consists of two, 2-hour sessions designed to provide trainees with patient communication skills that are specific to patient interactions in radiation oncology, 3) Simulated Patient Interactions, in which trainees perform mock physicist-patient consults with trained patient actors, 4) Faculty-Observed Patient Consults, and 5) a Case-Based Treatment Toxicity Course. A competency assessment mechanism was also developed to provide a clear set of objectives and to guide trainer feedback. [Correction added after first online publication on November 7, 2018: The phrase ", which consists of two, 2-hour" was added above.] CONCLUSIONS: The training program that we have developed incorporates an array of established education techniques and provides a comprehensive, accessible, means of improving medical physicists' patient communication skills.

Background: There are many tools to assist with cigarette smoking cessation (e.g., counseling, pharmacotherapy). However, tool use among cancer patients is understudied despite the consequences of continued smoking after a cancer diagnosis. Objectives: Study aims included describing and comparing cessation tool use among individuals with and without cancer who were currently smoking and who quit to determine if there are different preferences among those with cancer. Methods: Participants (N = 203) completed an online survey about demographics, cigarette use, and cessation tool use. Results: Eighty-nine participants reported being diagnosed with cancer (45 quit after diagnosis, 44 currently smoking) and 114 reported not having cancer (57 quit, 57 currently smoking). Individuals with cancer who were smoking used more evidence-based resources than those with cancer who quit (B = 1.86, SE = 0.50, p < 0.0001). Individuals with cancer who were smoking used more total cessation resources than participants without cancer who were smoking (B = 2.00, SE = 0.58, p = 0.001), but there was no difference in use of evidence-based resources between these two groups (p > 0.05). Lastly, individuals with cancer who quit also used more total cessation tools (B = 1.23, SE = 0.41, p = 0.003) and evidence-based tools (B = 1.03, SE = 0.36, p = 0.005) than those without cancer who quit. Conclusions: Individuals with cancer may be using more resources before successfully quitting. Cancer patients may need additional help to quit smoking, and further research is needed to better understand unique barriers that preclude quitting among this vulnerable population. [ABSTRACT FROM AUTHOR]

Necroptosis is a lytic and pro-inflammatory form of programmed cell death executed by the terminal effector, the MLKL (mixed lineage kinase domain-like) pseudokinase. Downstream of death and Toll-like receptor stimulation, MLKL is trafficked to the plasma membrane via the Golgi-, actin- and microtubule-machinery, where activated MLKL accumulates until a critical lytic threshold is exceeded and cell death ensues. Mechanistically, MLKL’s lytic function relies on disengagement of the N-terminal membrane-permeabilising four-helix bundle domain from the central autoinhibitory brace helix: a process that can be experimentally mimicked by introducing the R30E MLKL mutation to induce stimulus-independent cell death. Here, we screened a library of 429 kinase inhibitors for their capacity to block R30E MLKL-mediated cell death, to identify co-effectors in the terminal steps of necroptotic signalling. We identified 13 compounds — ABT-578, AR-A014418, AZD1480, AZD5363, Idelalisib, Ipatasertib, LJI308, PHA-793887, Rapamycin, Ridaforolimus, SMI-4a, Temsirolimus and Tideglusib — each of which inhibits mammalian target of rapamycin (mTOR) signalling or regulators thereof, and blocked constitutive cell death executed by R30E MLKL. Our study implicates mTOR signalling as an auxiliary factor in promoting the transport of activated MLKL oligomers to the plasma membrane, where they accumulate into hotspots that permeabilise the lipid bilayer to cause cell death. [ABSTRACT FROM AUTHOR]

PurposeCompared with conventional radiation therapy, intensity modulated radiation therapy (IMRT) may reduce acute toxicity from anal cancer treatment, potentially leading to improved long-term outcomes. We analyze the effect of IMRT on short- and long-term outcomes among a large sample of US veterans.Methods and materialsFrom a national Veterans Affairs database, we identified 779 patients (n = 403 conventional radiation therapy, n = 376 IMRT) with locally advanced anal squamous cell carcinoma diagnosed between 2000 and 2015 and treated with concurrent chemoradiation therapy. Radiation treatment planning and dosimetric constraints were not standardized across patients. We analyzed the effect of IMRT on short-term outcomes (acute toxicity, treatment breaks, and incomplete chemotherapy) and long-term outcomes (survival and ostomy placement) in multivariable logistic regression, Fine-Gray, and frailty models, adjusting for potential confounders.ResultsIMRT was associated with decreased radiation treatment breaks ≥5 days (odds ratio [OR] 0.58; 95% confidence interval [CI] 0.37-0.91; P = .02), increased rates of receiving 2 cycles of mitomycin C chemotherapy (OR 2.04; 95% CI 1.22-3.45; P = .007), increased rates of receiving 2 cycles of any chemotherapy (OR 3.45; 95% CI 1.82-6.25; P < .001), and decreased risk of ostomy related to tumor recurrence or progression (subdistribution hazard ratio 0.60; 95% CI 0.37-0.99; P = .045). IMRT was not associated with a decrease in grade 3 to 4 hematologic toxicity (P = .79), hospitalization for gastrointestinal toxicity (P = .59), or cancer-specific survival (P = 0.18).ConclusionsAmong a large sample of US veterans with anal cancer, IMRT was associated with higher rates of receiving 2 chemotherapy cycles, decreased radiation treatment breaks, and decreased rates of ostomy placement. IMRT appears to offer substantial benefits over conventional radiation therapy for patients undergoing concurrent chemoradiation therapy for anal cancer.

Behavioral economic theory suggests that increased engagement in constructive, substance-free activities that are in the service of long-term goals (e.g., college graduation, career development, health) can decrease alcohol use and related problems. However, engaging in activities such as these in the high-risk college environment requires the ability to self-regulate by avoiding rewarding but risky behaviors (e.g., drinking) while also effectively organizing behavior in the pursuit of delayed academic and career-related rewards. The current secondary data analyses evaluated self-regulation as a potential mechanism of behavior change in an alcohol intervention trial that compared a standard alcohol-focused brief motivational intervention (BMI) plus a behavioral economic substance-free activity session (SFAS) with an alcohol BMI plus relaxation training (reaction time [RT]) session (Murphy et al., 2012). Participants were 82 first-year undergraduate students (50% women; Mage = 18.5, SD = .71) who reported 2 or more past-month heavy drinking episodes. After completing a baseline assessment and an individual alcohol-focused BMI, participants were randomized to either the SFAS or the RT session. The BMI + SFAS condition reported greater mean self-regulation at 1 month compared with BMI + RT. Furthermore, self-regulation at 1 month significantly mediated the relation between condition and alcohol-related outcomes at 6-month follow-up. Although preliminary, these results suggest that brief behavioral economic intervention elements that an attempt to increase future goal pursuit and substance-free activities can enhance the short-term efficacy of standard alcohol BMIs and that this effect may be due in part to increases in self-regulation. (PsycINFO Database Record

PurposeThe survival benefit of combined radiation therapy (RT) and androgen deprivation therapy (ADT) compared with ADT alone for clinically lymph node-positive prostate cancer remains controversial.Methods and materialsWe identified patients with clinically node-positive, nonmetastatic prostate cancer diagnosed between 2000 and 2015 and treated with ADT (n = 450) or ADT-RT (n = 198) from a national Veterans Affairs database. We compared prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) between treatment groups using multivariable competing-risks regression and Cox regression, respectively. An interaction term between ADT-RT and prostate-specific antigen (PSA) level (dichotomized about the median) was included in the multivariable models.ResultsADT-RT was associated with improved PCSM among patients with PSA levels less than the median of 26 ng/mL (sub-distribution hazard ratio, 0.50; 95% confidence interval [CI] 0.28-0.88; P = .02) but not greater than the median (hazard ratio [HR], 1.15; 95% CI 0.67-1.96; P = .62) (P = .038 for interaction). ADT-RT was also associated with improved ACM among patients with PSA levels less than the median (HR, 0.38; 95% CI 0.25-0.57; P

A positive surgical margin (PSM) following cancer resection oftentimes necessitates adjuvant treatments and carries significant financial and prognostic implications. We sought to compare PSM rates for the ten most common solid cancers in the United States, and to assess trends over time. Over 10 million patients were identified in the National Cancer Data Base from 1998-2012, and 6.5 million had surgical margin data. PSM rates were compared between two time periods, 1998-2002 and 2008-2012. PSM was positively correlated with tumor category and grade. Ovarian and prostate cancers had the highest PSM prevalence in women and men, respectively. The highest PSM rates for cancers affecting both genders were seen for oral cavity tumors. PSM rates for breast cancer and lung and bronchus cancer in both men and women declined over the study period. PSM increases were seen for bladder, colon and rectum, and kidney and renal pelvis cancers. This large-scale analysis appraises the magnitude of PSM in the United States in order to focus future efforts on improving oncologic surgical care with the goal of optimizing value and improving patient outcomes.

Symptoms of posttraumatic stress (PTS) show significant comorbidity with alcohol use, but little is known about the mechanisms that might account for this comorbidity. Deficits in reward functioning have long been implicated in alcohol misuse and more recently in PTS reactions, but no study has examined whether reward deprivation may serve as a transdiagnostic risk factor for comorbid PTS-alcohol misuse. The current cross-sectional study sought to test the behavioral economic hypothesis that reward deprivation would be related to both PTS symptoms and alcohol problems, and would mediate the relation between PTS symptoms and alcohol problems in college students. We recruited a diverse sample of urban college students (N = 203, Mage = 21.5 years, SD = 5.5; 79.5% female; 56.8% White, 28.1% Black, .9% Asian, 9.8% Multiracial) who endorsed both alcohol use and PTS symptoms. Reward deprivation (lack of access to, and ability to, experience reward) was related to alcohol problems, and a lack of access to reward was related to PTS symptoms. Furthermore, reward access mediated the relation between PTS symptoms and alcohol problems and craving, after controlling for alcohol use, age, gender, and race. These data provide preliminary support for behavioral economic models of alcohol comorbidity and suggest that treatments for combined PTS and alcohol misuse should attempt to reduce barriers to accessing natural rewards. (PsycINFO Database Record

The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib.

PURPOSE:To study the effects of immunosuppression on treatment toxicity, long-term cancer recurrence risk, and survival among human immunodeficiency virus (HIV)-positive anal cancer patients. METHODS AND MATERIALS:From a nationwide retrospective cohort of veterans with anal cancer we identified 142 HIV-positive patients with stage I-III disease, diagnosed between 2000 and 2015 and treated with definitive-intent chemotherapy and radiation. We used regression models to study the impact of pretreatment CD4 counts and longitudinal posttreatment CD4 counts on outcomes including acute toxicity, long-term ostomy rates, cancer recurrence, cancer-specific survival, and overall survival. All models were adjusted for potential confounders. RESULTS:The median pretreatment CD4 count was 375 cells/mm3, which dropped to 157 cells/mm3 after treatment. Each 100-cell/mm3 decrease in pretreatment CD4 count was associated with an increased risk of acute hematologic toxicity (odds ratio 1.19, 95% confidence interval [CI] 1.01-1.42, P=.04) and hospitalization for hematologic toxicity (odds ratio 1.24, 95% CI 1.00-1.54, P=.049) but not gastrointestinal toxicity, tumor recurrence, or cancer-specific mortality (P>.05). Each 100-cells/mm3 decrease in posttreatment CD4 count increased the risk of recurrence by 54% (hazard ratio 1.54, 95% CI 1.09-2.17, P=.01) and cancer mortality by 46% at a trend level (hazard ratio 1.46, 95% CI 0.99-2.14, P=.06). Neither pre- nor posttreatment CD4 count influenced long-term ostomy rates or overall survival (all P>.05). CONCLUSIONS:Lower pretreatment CD4 counts were associated with acute hematologic toxicity, and lower posttreatment CD4 count levels were associated with an increased risk of tumor recurrence. These results suggest that immune surveillance may play an important role in long-term disease control in anal cancer.

Purpose: Treatments for locoregionally advanced head and neck cancer (LAHNC) negatively impact swallowing function, but the long-term incidence of severe toxicity requiring esophageal dilation is not well-documented in the population. The aim of this study was to compare the incidence of long-term esophageal dilation across varying treatments for LAHNC. Methods and Materials: We identified 5,223 patients with LAHNC diagnosed from 2000 to 2009 in the SEER-Medicare database. We compared the incidence of esophageal dilation for surgery alone vs. surgery plus adjuvant radiotherapy (RT) and chemoradiotherapy (CRT) vs. definitive RT or CRT. Results: The cumulative incidence of esophageal dilation for all sites at 10 years, according to treatment group were as follows: CRT, 14% (95% confidence interval (CI), 12-17%); definitive RT, 13% (95% CI, 10-16%); surgery alone, 5% (95% CI, 3-7%); surgery and CRT, 15% (95% CI, 11-19%); surgery and adjuvant RT: 10% (95% CI, 8-13%). There was no significant difference in the incidence of esophageal dilation between surgery plus adjuvant RT/CRT or definitive RT/CRT (p = 0.37), but the incidence was significantly increased in both groups compared to surgery alone (p = 0.003). On multivariable analysis, chemotherapy was associated with significantly increased incidence of esophageal dilation (HR 2.9, 95% CI 1.5-5.5, p < 0.001) in oropharyngeal cancers. Conclusions: The incidence of esophageal dilation is similar in LAHNC patients undergoing RT with or without surgery. Chemoradiotherapy increases the long-term risk of esophageal dilation events over surgery alone.

Background and purposePre- and mid-radiotherapy FDG-PET metrics have been proposed as biomarkers of recurrence and survival in patients treated for stage III non-small cell lung cancer. We evaluated these metrics in patients treated with definitive radiation therapy (RT). We also evaluated outcomes after progression on mid-radiotherapy PET/CT.Material and methodsSeventy-seven patients treated with RT with or without chemotherapy were included in this retrospective study. Primary tumor and involved nodes were delineated. PET metrics included metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax. For mid-radiotherapy PET, both absolute value of these metrics and percentage decrease were analyzed. The influence of PET metrics on time to death, local recurrence, and regional/distant recurrence was assessed using Cox regression.Results91% of patients had concurrent chemotherapy. Median follow-up was 14months. None of the PET metrics were associated with overall survival. Several were positively associated with local recurrence: pre-radiotherapy MTV, and mid-radiotherapy MTV and TLG (p=0.03-0.05). Ratio of mid- to pre-treatment SUVmax was associated with regional/distant recurrence (p=0.02). 5/77 mid-radiotherapy scans showed early out-of-field progression. All of these patients died.ConclusionsSeveral PET metrics were associated with risk of recurrence. Progression on mid-radiotherapy PET/CT was a poor prognostic factor.