Successful kinetic impact into an asteroid for planetary defence.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation1,2. Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid1-3. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation1. NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft4. Although past missions have utilized impactors to investigate the properties of small bodies5,6, those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos7 demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary.

Olfactory flow in the sea catfish, Ariopsis felis (L.): Origin, regulation, and resampling.

The olfactory epithelium of the sea catfish, Ariopsis felis, is found on a pinnate array of lamellae (the olfactory rosette) housed within a nasal chamber. The nasal anatomy of A. felis suggests an ability to capture external water currents. We prepared models from X-ray micro-computed tomography scans of two preserved specimens of A. felis. We then used dye visualisation and computational fluid dynamics to show that an external current induced a flow of water through a) the nasal chamber and b) the sensory channels of the olfactory rosette. The factors responsible for inducing flow through the nasal chamber are common to fishes from two other orders. The dye visualisation experiments, together with observations of sea catfishes in vivo, indicate that flow through the nasal chamber is regulated by a mobile nasal flap. The position of the nasal flap - elevated (significant flow) or depressed (reduced flow) - is controlled by the sea catfish's movements. Flow in the sensory channels of the olfactory rosette can pass through either a single channel or, via multiple pathways, up to four consecutive channels. Flow through consecutive sensory channels (olfactory resampling) is more extensive at lower Reynolds numbers (200 and 300, equivalent to swimming speeds of 0.5-1.0 total lengths s-1), coinciding with the mean swimming speed of the sea catfishes observed in vivo (0.6 total lengths s-1). Olfactory resampling may also occur, via a vortex, within single sensory channels. In conclusion, olfactory flow in the sea catfish is regulated and thoroughly sampled by novel mechanisms.

Changing multiple health behaviors in cancer survivors: smoking and exercise.

Research regarding cross-behavioral relationships between the cognitive mechanisms motivating health behavior change is lacking for cancer survivors. This study investigated these relationships to inform the development of multiple health behavior change (MHBC) interventions for this at-risk population. Eligible participants included cancer survivors attending an intake appointment for smoking cessation services. This cross-sectional survey study assessed participants' self-efficacy and motivation (stage of change) for smoking cessation and exercise, as well as self-reported health behaviors. Analyses evaluated cross-behavioral associations between cognitive mechanisms and their relationships with smoking and exercise behaviors. Seventy-six participants completed the survey questionnaire. The correlation between self-efficacy scores for smoking cessation and exercise was statistically significant (r = .45, 95% CI [.09, .67]), as were correlations between self-efficacy and reported levels of exercise ((r = .44, 95% CI [.20, .65]) strenuous); ((r = .36, 95% CI [.12, .59]) moderate), exercise self-efficacy and smoking behavior (r = -.27, 95% CI [-.46, -.05]), and smoking self-efficacy and smoking behavior (r = -0.41, 95% CI [-.61, -.18]). For cancer survivors, associations between exercise self-efficacy and smoking cessation self-efficacy may offer an opportunity to leverage MHBC; specifically, this positive association may facilitate exercise intervention in survivors seeking smoking cessation services..

Disease burden and pain in obese cancer patients with chemotherapy-induced peripheral neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) and obesity are prevalent in cancer survivors and decrease quality of life; however, the impact of the co-occurrence of these conditions has garnered little attention. This study investigated differences between obese and non-obese cancer survivors with CIPN and predictors of symptom burden and pain. METHODS: Patients with CIPN were administered the MD Anderson Symptom Inventory and a modified version of pain descriptors from the McGill Pain Inventory. Independent t tests assessed group differences between obese and non-obese survivors, and linear regression analyses explored predictors of patient outcomes. RESULTS: Results indicated a significant difference in symptom severity scores for obese (M = 32.89, SD = 25.53) versus non-obese (M = 19.35, SD = 16.08) patients (t(37.86) = -2.49, p = .02). Significant differences were also found for a total number of pain descriptors endorsed by obese (M = 4.21, SD = 3.45) versus non-obese (M = 2.42, SD = 2.69) participants (t(74) = -2.53, p = .01). Obesity was a significant predictor of symptom severity and total pain descriptors endorsed. Other significant predictors included age and months since treatment. CONCLUSIONS: Cancer survivors with CIPN and co-occurring obesity may be more at risk for decreased quality of life through increased symptom severity and pain compared to non-obese survivors. This paper identified risk factors, including obesity, age, and months since treatment, that can be clinically identified for monitoring distress in CIPN patients. Future research should focus on the longitudinal relationship between obesity and CIPN, and robust interventions to address the multifaceted issues faced by cancer survivors.

Examining pain, body image, and depressive symptoms in patients with lymphedema secondary to breast cancer.

OBJECTIVE: Depression and reduced quality of life are often reported in patients with upper-extremity lymphedema secondary to breast cancer treatment. Little is known about how pain and body image influence depression in patients with lymphedema. The current study examined the association of pain intensity and body integrity beliefs with depressive symptoms and the extent to which body image dissatisfaction mediated these associations. METHODS: A cross-sectional sample of patients with lymphedema secondary to breast cancer treatment completed self-report questionnaires of pain, body image, and depressive symptoms. Hierarchical regression analyses and tests of mediation were conducted to examine the associations among the variables of interest. RESULTS: Pain intensity and body integrity beliefs were positively associated with depressive symptoms. Further, body image dissatisfaction mediated the relationship between pain and depressive symptoms, indicating that higher levels of pain led to higher states of body image dissatisfaction, which, in turn, led to greater depressive symptoms. Body image dissatisfaction also mediated the relationship between body integrity beliefs and depressive symptoms, suggesting that greater body integrity beliefs led to higher dissatisfaction with one's body and subsequently to greater depressive symptoms. CONCLUSIONS: Our findings provide preliminary evidence that pain intensity and body image are important factors in understanding depressive symptoms in patients with lymphedema. Clinical implications include screening for pain and body image concerns in this population to identify patients who are in distress. Counseling interventions targeting body image dissatisfaction can also be potentially helpful for patients with lymphedema.

Grasping the 'teachable moment': time since diagnosis, symptom burden and health behaviors in breast, colorectal and prostate cancer survivors.

BACKGROUND: A cancer diagnosis may provide a 'teachable moment' in cancer recovery. To better understand factors influencing lifestyle choices following diagnosis, we examined associations between time since diagnosis and symptom burden with recommended dietary (e.g., five or more fruit/vegetable servings/day), physical activity (e.g., >150 active min, 3-5 times/week), and smoking behaviors (i.e., eliminate tobacco use) in cancer survivors. METHODS: We analyzed cross-sectional survey data collected from breast (n = 528), colorectal (n = 106), and prostate (n = 419) cancer survivors following active treatment at The University of Texas MD Anderson Cancer Center. Four regression models were tested for behaviors of interest. Additionally, we assessed symptom burden as a potential moderator and/or mediator between time since diagnosis and behaviors. RESULTS: Respondents were mostly female (55%) and non-Hispanic White (68%) with a mean age of 62.8 ± 11.4 years and mean time since diagnosis of 4.6 ± 3.1 years. In regression models, greater time since diagnosis predicted lower fruit and vegetable consumption (B = -0.05, p = 0.02) and more cigarette smoking (B = 0.06, p = 0.105). Greater symptom burden was a significant negative predictor for physical activity (B = -0.08, p < .001). We did not find evidence that symptom burden moderated or mediated the association between time since diagnosis and health behaviors. CONCLUSION: We assessed the prevalence of recommended behaviors in the context of other challenges that survivors face, including time since diagnosis and symptom burden. Our results provide indirect evidence that proximity to a cancer diagnosis may provide a teachable moment to improve dietary and smoking behaviors and that symptom burden may impede physical activity following diagnosis. Copyright © 2015 John Wiley & Sons, Ltd.

Inhibitory control effects in adolescent binge eating and consumption of sugar-sweetened beverages and snacks.

Inhibitory control and sensitivity to reward are relevant to the food choices individuals make frequently. An imbalance of these systems can lead to deficits in decision-making that are relevant to food ingestion. This study evaluated the relationship between dietary behaviors - binge eating and consumption of sweetened beverages and snacks - and behavioral control processes among 198 adolescents, ages 14 to 17. Neurocognitive control processes were assessed with the Iowa Gambling Task (IGT), a generic Go/No-Go task, and a food-specific Go/No-Go task. The food-specific version directly ties the task to food cues that trigger responses, addressing an integral link between cue-habit processes. Diet was assessed with self-administered food frequency and binge eating questionnaires. Latent variable models revealed marked gender differences. Inhibitory problems on the food-specific and generic Go/No-Go tasks were significantly correlated with binge eating only in females, whereas inhibitory problems measured with these tasks were the strongest correlates of sweet snack consumption in males. Higher BMI percentile and sedentary behavior also predicted binge eating in females and sweet snack consumption in males. Inhibitory problems on the generic Go/No-Go, poorer affective decision-making on the IGT, and sedentary behavior were associated with sweetened beverage consumption in males, but not females. The food-specific Go/No-Go was not predictive in models evaluating sweetened beverage consumption, providing some initial discriminant validity for the task, which consisted of sweet/fatty snacks as no-go signals and no sugar-sweetened beverage signals. This work extends research findings, revealing gender differences in inhibitory function relevant to behavioral control. Further, the findings contribute to research implicating the relevance of cues in habitual behaviors and their relationship to snack food consumption in an understudied population of diverse adolescents not receiving treatment for eating disorders.

Roles of progranulin and FRamides in neural versus non-neural tissues on dietary restriction-related longevity and proteostasis in C. elegans.

Dietary restriction (DR) mitigates loss of proteostasis associated with aging that underlies neurodegenerative conditions including Alzheimer's disease and related dementias. Previously, we observed increased translational efficiency of certain FMRFamide-like neuropeptide ( flp ) genes and the neuroprotective growth factor progranulin gene prgn-1 under dietary restriction in C. elegans . Here, we tested the effects of flp-5 , flp-14 , flp-15 and pgrn-1 on lifespan and proteostasis under both standard and dietary restriction conditions. We also tested and distinguished function based on their expression in either neuronal or non-neuronal tissue. Lowering the expression of pgrn-1 and flp genes selectively in neural tissue showed no difference in survival under normal feeding conditions nor under DR in two out of three experiments performed. Reduced expression of flp-14 in non-neuronal tissue showed decreased lifespan that was not specific to DR. With respect to proteostasis, a genetic model of DR from mutation of the eat-2 gene that showed increased thermotolerance compared to fully fed wild type animals demonstrated no change in thermotolerance in response to knockdown of pgrn-1 or flp genes. Finally, we tested effects on motility in a neural-specific model of proteotoxicity and found that neuronal knockdown of pgrn-1 and flp genes improved motility in early life regardless of diet. However, knocking these genes down in non-neuronal tissue had variable results. RNAi targeting flp-14 increased motility by day seven of adulthood regardless of diet. Interestingly, non-neuronal RNAi of pgrn-1 decreased motility under standard feeding conditions while DR increased motility for this gene knockdown by day seven (early mid-life). Results show that pgrn-1 , flp-5 , flp-14 , and flp-15 do not have major roles in diet-related changes in longevity or whole-body proteostasis. However, reduced expression of these genes in neurons increases motility early in life in a neural-specific model of proteotoxicity, whereas knockdown of non-neuronal expression mostly increases motility in mid-life under the same conditions.

Neuronal CBP-1 is required for enhanced body muscle proteostasis in response to reduced translation downstream of mTOR.

Background: The ability to maintain muscle function decreases with age and loss of proteostatic function. Diet, drugs, and genetic interventions that restrict nutrients or nutrient signaling help preserve long-term muscle function and slow age-related decline. Previously, it was shown that attenuating protein synthesis downstream of the mechanistic target of rapamycin (mTOR) gradually increases expression of heat shock response (HSR) genes in a manner that correlates with increased resilience to protein unfolding stress. Here, we investigate the role of specific tissues in mediating the cytoprotective effects of low translation. Methods: This study uses genetic tools (transgenic C. elegans , RNA interference and gene expression analysis) as well as physiological assays (survival and paralysis assays) in order to better understand how specific tissues contribute to adaptive changes involving cellular cross-talk that enhance proteostasis under low translation conditions. Results: We use the C. elegans system to show that lowering translation in neurons or the germline increases heat shock gene expression and survival under conditions of heat stress. In addition, we find that low translation in these tissues protects motility in a body muscle-specific model of proteotoxicity that results in paralysis. Low translation in neurons or germline also results in increased expression of certain muscle regulatory and structural genes, reversing reduced expression normally observed with aging in C. elegans . Enhanced resilience to protein unfolding stress requires neuronal expression of cbp-1 . Conclusion: Low translation in either neurons or the germline orchestrate protective adaptation in other tissues, including body muscle.

Identification and Optimization of Small Molecule Pyrazolopyrimidine TLR7 Agonists for Applications in Immuno-oncology.

Small molecule toll-like receptor (TLR) 7 agonists have gathered considerable interest as promising therapeutic agents for applications in cancer immunotherapy. Herein, we describe the development and optimization of a series of novel TLR7 agonists through systematic structure-activity relationship studies focusing on modification of the phenylpiperidine side chain. Additional refinement of ADME properties culminated in the discovery of compound 14, which displayed nanomolar reporter assay activity and favorable drug-like properties. Compound 14 demonstrated excellent in vivo pharmacokinetic/pharmacodynamic profiles and synergistic antitumor activity when administered in combination with aPD1 antibody, suggesting opportunities of employing 14 in immuno-oncology therapies with immune checkpoint blockade agents.

Discovery of Novel TLR7 Agonists as Systemic Agent for Combination With aPD1 for Use in Immuno-oncology.

We have designed and developed novel and selective TLR7 agonists that exhibited potent receptor activity in a cell-based reporter assay. In vitro, these agonists significantly induced secretion of cytokines IL-6, IL-1ß, IL-10, TNFa, IFNa, and IP-10 in human and mouse whole blood. Pharmacokinetic and pharmacodynamic studies in mice showed a significant secretion of IFNα and TNFα cytokines. When combined with aPD1 in a CT-26 tumor model, the lead compound showed strong synergistic antitumor activity with complete tumor regression in 8/10 mice dosed using the intravenous route. Structure-activity relationship studies enabled by structure-based designs of TLR7 agonists are disclosed.

The integrated stress response protects against ER stress but is not required for altered translation and lifespan from dietary restriction in Caenorhabditis elegans.

The highly conserved integrated stress response (ISR) reduces and redirects mRNA translation in response to certain forms of stress and nutrient limitation. It is activated when kinases phosphorylate a key residue in the alpha subunit of eukaryotic translation initiation factor 2 (eIF2). General Control Nonderepressible-2 (GCN2) is activated to phosphorylate eIF2α by the presence of uncharged tRNA associated with nutrient scarcity, while protein kinase R-like ER kinase-1 (PERK) is activated during the ER unfolded protein response (UPRER). Here, we investigated the role of the ISR during nutrient limitation and ER stress with respect to changes in protein synthesis, translationally driven mRNA turnover, and survival in Caenorhabditis elegans. We found that, while GCN2 phosphorylates eIF2α when nutrients are restricted, the ability to phosphorylate eIF2α is not required for changes in translation, nonsense-mediated decay, or lifespan associated with dietary restriction (DR). Interestingly, loss of both GCN2 and PERK abolishes increased lifespan associated with dietary restriction, indicating the possibility of other substrates for these kinases. The ISR was not dispensable under ER stress conditions, as demonstrated by the requirement for PERK and eIF2α phosphorylation for decreased translation and wild type-like survival. Taken together, results indicate that the ISR is critical for ER stress and that other translation regulatory mechanisms are sufficient for increased lifespan under dietary restriction.

Supporting tool suite for production proteomics.

SUMMARY: The large amount of data produced by proteomics experiments requires effective bioinformatics tools for the integration of data management and data analysis. Here we introduce a suite of tools developed at Vanderbilt University to support production proteomics. We present the Backup Utility Service tool for automated instrument file backup and the ScanSifter tool for data conversion. We also describe a queuing system to coordinate identification pipelines and the File Collector tool for batch copying analytical results. These tools are individually useful but collectively reinforce each other. They are particularly valuable for proteomics core facilities or research institutions that need to manage multiple mass spectrometers. With minor changes, they could support other types of biomolecular resource facilities.

Initial experience with the use of porcine acellular dermal matrix (Strattice) for abdominal wall reinforcement after transverse rectus abdominis myocutaneous flap breast reconstruction.

Reestablishing anterior rectus fascial integrity remains a clinical challenge after transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction. The main concerns include herniation and bulging due to abdominal weakness. Mesh-assisted closure of the fascial defect has improved bulging and herniation rates but infection, extrusion, and encapsulation are serious concerns with mesh use. Biologic tissue matrices may overcome some of these mesh-related complications. The initial experience of using Strattice for fascial closure after TRAM flap procedure is described in this article. Strattice was in-lain and sutured between the anterior and posterior layers of the rectus fascia, at the rectus muscle donor site. The abdominal wall was closed with progressive tension sutures. Postoperative complications at the donor site were assessed. A total of 16 unilateral and 9 bilateral reconstructions were performed in 25 patients. Length of hospital stay was 2 to 3 days which is shorter than with mesh repair (typically 4-5 days). During a mean follow-up period of 14.0 months, complications occurred in 7 patients (28%): seroma formation (2), minor skin separation (2), superficial skin infection (2), and superficial wound dehiscence (1). Complications were not directly related to Strattice and all, except one (superficial skin infection), were resolved without surgical intervention. In all patients, routine abdominal functions were restored 4 months postoperatively. Strattice is a safe, alternative option to synthetic mesh for fascial repair following TRAM flap breast reconstruction. When used in conjunction with progressive tension suture closure of the abdominal wall, dynamic reconstruction of the abdominal wall with resumption of abdominal function is possible with Strattice.

Racial and ethnic disparities in physical abuse reporting and child protective services interventions in the United States.

BACKGROUND: Minorities are more prevalent than the general population in the child protection system; however, racial/ ethnic disparities in physical abuse and child protective services interventions are not understood. METHODS: Bivariate and multivariate analyses evaluated racial/ethnic differences in reported and substantiated physical abuse, physical abuse deaths, and interventions provided in all reported maltreatment from the 2006 National Child Abuse and Neglect Data System. RESULTS: In bivariate analyses, African American (25%), Asian/ Pacific Islander (21%), and multiracial children (21%) have a higher prevalence of substantiated physical abuse than whites (20%). Native Americans (0.21%), African Americans (0.15%), Asians/Pacific Islanders (0.12%), and Latinos (0.11%) are more likely to die from physical abuse than whites (0.09%). African Americans have higher odds than whites of reported (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.11-1.14) and substantiated (OR, 1.27; 95% CI, 1.23-1.31) physical abuse. Latinos have higher odds of reported physical abuse (OR, 1.18; 95% CI, 1.16-1.20) and lower odds of substantiated physical abuse (OR, 0.93; 95% CI, 0.90-0.96). Native Americans have lower odds (OR, 0.53; 95% CI, 0.49-0.56) and Asian/Pacific Islanders higher odds (OR, 1.34; 95% CI, 1.26-1.44) of reported physical abuse vs whites. Latinos have significantly lower odds than whites of receiving support services. CONCLUSIONS: Compared with whites, African Americans are at increased risk. Latino, Asian/Pacific Islander, and multiracial children have greater odds of reports, and Native Americans have lower odds of reports for physical abuse. Significant disparities exist in interventions provided to minority families. Understanding these disparities has the potential to improve reporting, prevention, and interventions.

Safety risk management for low molecular weight process-related impurities in monoclonal antibody therapeutics: Categorization, risk assessment, testing strategy, and process development with leveraging clearance potential.

Process-related impurities (PRIs) derived from manufacturing process should be minimized in final drug product. ICH Q3A provides a regulatory road map for PRIs but excludes biologic drugs like monoclonal antibodies (mAbs) that contain biological PRIs (e.g. host cell proteins and DNA) and low molecular weight (LMW) PRIs (e.g., fermentation media components and downstream chemical reagents). Risks from the former PRIs are typically addressed by routine tests to meet regulatory expectations, while a similar routine-testing strategy is unrealistic and unnecessary for LMW PRIs, and thus a risk-assessment-guided testing strategy is often utilized. In this report, we discuss a safety risk management strategy including categorization, risk assessment, testing strategy, and its integrations with other CMC development activities, as well as downstream clearance potentials. The clearance data from 28 mAbs successfully addressed safety concerns but did not fully reveal the process clearance potentials. Therefore, we carried out studies with 13 commonly seen LMW PRIs in a typical downstream process for mAbs. Generally, Protein A chromatography and cation exchange chromatography operating in bind-and-elute mode showed excellent clearances with greater than 1,000- and 100-fold clearance, respectively. The diafiltration step had better clearance (greater than 100-fold) for the positively and neutrally charged LMW PRIs than for the negatively charged or hydrophobic PRIs. We propose that a typical mAb downstream process provides an overall clearance of 5,000-fold. Additionally, the determined sieving coefficients will facilitate diafiltration process development. This report helps establish effective safety risk management and downstream process design with robust clearance for LMW PRIs.

Migration of covered stents from hemodialysis A-V access to the pulmonary artery: percutaneous stent retrieval and procedural trends.

Details are presented of two patients with end-stage renal disease (ESRD) who recently experienced migration of a Viabahn covered stent from a peripheral hemodialysis A-V access to the right lower lobe pulmonary artery. Successful percutaneous retrieval was achieved in one patient using a dual snare approach, facilitated by ex vivo product testing. The second patient was managed conservatively. A review of the institution's A-V access salvage procedures, indicated a concomitant trend toward greater use of stent-assisted procedures, and a higher utilization of covered versus uncovered stents.

Characteristics and outcomes of patients with COVID-19 at a district general hospital in Surrey, UK.

BACKGROUND: This retrospective cohort study aims to define the clinical findings and outcomes of every patient admitted to a district general hospital in Surrey with COVID-19 in March 2020, providing a snapshot of the first wave of infection in the UK. This study is the first detailed insight into the impact of frailty markers on patient outcomes and provides the infection rate among healthcare workers. METHODS: Data were obtained from medical records. Outcome measures were level of oxygen therapy, discharge and death. Patients were followed up until 21 April 2020. RESULTS: 108 patients were included. 34 (31%) died in hospital or were discharged for palliative care. 43% of patients aged over 65 died. The commonest comorbidities were hypertension (49; 45%) and diabetes (25; 23%). Patients who died were older (mean difference ±SEM, 13.76±3.12 years; p<0.0001) with a higher NEWS2 score (median 6, IQR 2.5-7.5 vs median 2, IQR 2-6) and worse renal function (median differences: urea 2.7 mmol/L, p<0.01; creatinine 4 µmol/L, p<0.05; eGFR 14 mL/min, p<0.05) on admission compared with survivors. Frailty markers were identified as risk factors for death. Clinical Frailty Scale (CFS) was higher in patients over 65 who died than in survivors (median 5, IQR 4-6 vs 3.5, IQR 2-5; p<0.01). Troponin and creatine kinase levels were higher in patients who died than in those who recovered (p<0.0001). Lymphopenia was common (median 0.8, IQR 0.6-1.2; p<0.005). Every patient with heart failure died (8). 26 (24%) were treated with continuous positive airway pressure (CPAP; median 3 days, IQR 2-7.3) and 9 (8%) were intubated (median 14 days, IQR 7-21). All patients who died after discharge (4; 6%) were care home residents. 276 of 699 hospital staff tested were positive for COVID-19. CONCLUSIONS: This study identifies older patients with frailty as being particularly vulnerable and reinforces government policy to protect this group at all costs.

Preparation of heteroaryloxetanes and heteroarylazetidines by use of a Minisci reaction.

Introduction of oxetan-3-yl and azetidin-3-yl groups into heteroaromatic bases was achieved by using a radical addition method (Minisci reaction). To demonstrate utility, the process was used to introduce an oxetane or azetidine into heteroaromatic systems that have found important uses in the drug discovery industry, such as the marketed EGFR inhibitor gefitinib, a quinolinecarbonitrile Src tyrosine kinase inhibitor, and the antimalarial hydroquinine.