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Waves impart momentum and exert force on obstacles in their path. The transfer of wave momentum is a fundamental mechanism for contactless manipulation, yet the rules of conventional scattering intrinsically limit the radiation force based on the shape and the size of the manipulated object. Here, we show that this intrinsic limit can be broken for acoustic waves with subwavelength-structured surfaces (metasurfaces), where the force becomes controllable by the arrangement of surface features, independent of the object’s overall shape and size. Harnessing such anomalous metasurface scattering, we demonstrate complex actuation phenomena: self-guidance, where a metasurface object is autonomously guided by an acoustic wave, and tractor beaming, where a metasurface object is pulled by the wave. Our results show that bringing the metasurface physics of acoustic waves, and its full arsenal of tools, to the domain of mechanical manipulation opens new frontiers in contactless actuation and enables diverse actuation mechanisms that are beyond the limits of traditional wave-matter interactions. Here, the authors demonstrate that acoustic waves can actuate and guide large objects based on subwavelength meta-patterns on their surface.

Background. Healthy volunteer wild-type influenza challenge models offer a unique opportunity to evaluate multiple aspects of this important virus. Such studies have not been performed in the United States in more than a decade, limiting our capability to investigate this virus and develop countermeasures. We have completed the first ever wild-type influenza A challenge study under an Investigational New Drug application (IND). This dose-finding study will lead to further development of this model both for A(H1N1)pdm09 and other strains of influenza. Methods. Volunteers were admitted to an isolation unit at the National Institutes of Health Clinical Center for a minimum of 9 days. A reverse genetics, cell-based, Good Manufacturing Practice (GMP)–produced, wild-type A (H1N1)pdm09 virus was administered intranasally. Escalating doses were given until a dose was reached that produced disease in a minimum of 60% of volunteers. Results. An optimal dose of 107 tissue culture infectious dose 50 was reached that caused mild to moderate influenza disease in 69% of individuals with mean viral shedding for 4–5 days and significant rises in convalescent influenza antibody titers. Viral shedding preceded symptoms by 12–24 hours and terminated 2–3 days prior to symptom resolution, indicating that individuals may be infectious before symptom development. As expected, nasal congestion and rhinorrhea were most common, but interestingly, fever was observed in only 10% of individuals. Conclusions. This study represents the first healthy volunteer influenza challenge model using a GMP-produced wild-type virus under an IND. This unique clinical research program will facilitate future studies of influenza pathogenesis, animal model validation, and the rapid, efficient, and cost-effective evaluation of efficacy of novel vaccines and therapeutics.

Background Most published studies evaluating digital breast tomosynthesis (DBT) included a separate 2-dimensional full-field digital mammogram (FFDM) for DBT screening protocols, increasing radiation from screening mammography. Synthesized mammography (SM) creates a 2-dimensional image from the DBT source data, and if used in place of FFDM, it reduces radiation of DBT screening. This study evaluated the implementation of SM + DBT in routine screening practice in terms of recall rates, cancer detection rates (CDR), % of minimal cancers, % of node-positive cancers, and positive predictive values (PPV). Materials and methods A multivariate retrospective institutional analysis was performed on 31,979 women who obtained screening mammography (10/2013–12/2015) with cohorts divided by modality (SM + DBT, FFDM + DBT, and FFDM). We adjusted for comparison mammograms, age, breast density, and the interpreting radiologist. Recall type was analyzed for differences (focal asymmetry, asymmetry, masses, calcifications, architectural distortion). Results SM + DBT significantly decreased the recall rate compared to FFDM (5.52 vs. 7.83%, p  < 0.001) with no differences in overall CDR ( p  = 0.66), invasive and/or in situ CDR, or percentages of minimal and node-negative cancers. PPV1 significantly increased with SM + DBT relative to FFDM (9.1 vs. 6.2%, p  = 0.02). SM + DBT did not differ significantly in recall rate or overall CDR compared to FFDM + DBT. There were statistically significant differences in certain findings recalled by screening modality (e.g., focal asymmetries). Conclusions SM + DBT reduces false positives compared to FFDM, while maintaining the CDR and other desirable audit outcome data. SM + DBT is more accurate than FFDM alone, and is a desirable alternative to FFDM + DBT, given the added benefit of radiation reduction.

Adherence to diet and medical therapies are key to improving heart failure (HF) outcomes; however, nonadherence is common. While mobile apps may be a promising way to support patients with adherence via education and monitoring, HF patient perspectives regarding the use of apps for HF management in unknown. This data is critical for these tools to be successfully developed, implemented, and adopted to optimize adherence and improve HF outcomes. To determine patients' needs, motivations, and challenges on the use of mobile apps to support HF management. A qualitative descriptive study using focus groups (n = 4,60 minutes) was conducted among HF patients from outpatient HF clinics in Toronto, Canada. The Diffusion of Innovation theory informed a ten-question interview guide. Interview transcripts were independently coded by two researchers and analyzed using content analysis. Nineteen HF patients (65 ± 10 yrs, 12 men) identified a total of four key themes related to the use of mobile apps. The theme 'Factors impacting technology use by patients' identified motivations and challenges to app use, including access to credible information, easy and accessible user-interface. Three themes described patients' needs on the use of mobile apps to support HF management: 1) 'Providing patient support through access to information and self-monitoring', apps could provide education on HF-related content (e.g., diet, medication, symptoms); 2) 'Facilitating connection and communication', through information sharing with healthcare providers and connecting with other patients; 3) 'Patient preferences', app features such as reminders for medication, and visuals to show changes in HF symptoms were favoured. HF patients perceive several benefits and challenges to app use for HF self-management. Capitalizing on the benefits and addressing the challenges during the app development process may maximize adoption of such tools in this patient population.

Objectives. Although the hepatitis C epidemic in the United States disproportionately affects correctional populations, the last national estimates of seroprevalence and disease burden among these populations are more than a decade old. We investigated routine hepatitis C surveillance conducted in state prison systems and updated previous estimates. Methods. We surveyed all U.S. state correctional departments to determine which state prison systems had performed routine hepatitis C screening since 2001. Using seroprevalence data for these prison systems, we estimated the national hepatitis C seroprevalence among prisoners in 2006 and the share of the epidemic borne by correctional populations. Results. Of at least 12 states performing routine testing from 2001 to 2012, seroprevalences of hepatitis C ranged from 9.6% to 41.1%. All but one state with multiple measurements demonstrated declining seroprevalence. We estimated the national state prisoner seroprevalence at 17.4% in 2006. Based on the estimated total U.S. correctional population size, we projected that 1,857,629 people with hepatitis C antibody were incarcerated that year. We estimated that correctional populations represented 28.5%–32.8% of the total U.S. hepatitis C cases in 2006, down from 39% in 2003. Conclusions. Our results provide an important updated estimate of hepatitis C seroprevalence and suggest that correctional populations bear a declining but still sizable share of the epidemic. Correctional facilities remain important sites for hepatitis C case finding and therapy implementation. These results may also assist future studies in projecting the societal costs and benefits of providing new treatment options in prison systems.

Background Background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) may be associated with breast cancer risk, but previous studies of the association are equivocal and limited by incomplete blinding of BPE assessment. In this study, we evaluated the association between BPE and breast cancer based on fully blinded assessments of BPE in the unaffected breast. Methods The Imaging and Epidemiology (IMAGINE) study is a multicenter breast cancer case-control study of women receiving diagnostic, screening, or follow-up breast MRI, recruited from three comprehensive cancer centers in the USA. Cases had a first diagnosis of unilateral breast cancer and controls had no history of or current breast cancer. A single board-certified breast radiologist with 12 years’ experience, blinded to case-control status and clinical information, assessed the unaffected breast for BPE without view of the affected breast of cases (or the corresponding breast laterality of controls). The association between BPE and breast cancer was estimated by multivariable logistic regression separately for premenopausal and postmenopausal women. Results The analytic dataset included 835 cases and 963 controls. Adjusting for fibroglandular tissue (breast density), age, race/ethnicity, BMI, parity, family history of breast cancer, BRCA1 / BRCA2 mutations, and other confounders, moderate/marked BPE (vs minimal/mild BPE) was associated with breast cancer among premenopausal women [odds ratio (OR) 1.49, 95% CI 1.05–2.11; p  = 0.02]. Among postmenopausal women, mild/moderate/marked vs minimal BPE had a similar, but statistically non-significant, association with breast cancer (OR 1.45, 95% CI 0.92–2.27; p  = 0.1). Conclusions BPE is associated with breast cancer in premenopausal women, and possibly postmenopausal women, after adjustment for breast density and confounders. Our results suggest that BPE should be evaluated alongside breast density for inclusion in models predicting breast cancer risk.

Precision medicine is essential for the modern care of a patient with cancer. Comprehensive molecular profiling of the tumor itself is necessary to determine the presence or absence of certain targetable abnormalities or biomarkers. In particular, lung cancer is a disease for which targetable genomic alterations will soon guide therapy in the majority of cases. In this comprehensive review of solid tumor-based biomarkers, we describe the genomic alterations for which targeted agents have been approved by the United States Food and Drug Administration (FDA). While focusing on alterations leading to approvals in a tumor-agnostic fashion (MSI-h, TMB-h, NTRK) and on those alterations with approvals in multiple malignancies (BRAF, ERBB2, RET, BRCA, PD-L1), we also describe several biomarkers or indications that are likely to lead to an approved drug in the near future (e.g., KRAS G12C, PD-L1 amplification, HER2 overexpression in colon cancer, HER2 mutations in lung cancer). Finally, we detail the current landscape of additional actionable alterations (EGFR, ALK, ROS1, MET) in lung cancer, a biomarker-rich malignancy that has greatly benefitted from the precision oncology revolution.

Nonadherence to diet and medical therapies in heart failure (HF) contributes to poor HF outcomes. Mobile apps may be a promising way to improve adherence because they increase knowledge and behavior change via education and monitoring. Well-designed apps with input from health care providers (HCPs) can lead to successful adoption of such apps in practice. However, little is known about HCPs' perspectives on the use of mobile apps to support HF management. The aim of this study is to determine HCPs' perspectives (needs, motivations, and challenges) on the use of mobile apps to support patients with HF management. A qualitative descriptive study using one-on-one semistructured interviews, informed by the diffusion of innovation theory, was conducted among HF HCPs, including cardiologists, nurses, and nurse practitioners. Transcripts were independently coded by 2 researchers and analyzed using content analysis. The 21 HCPs (cardiologists: n=8, 38%; nurses: n=6, 29%; and nurse practitioners: n=7, 33%) identified challenges and opportunities for app adoption across 5 themes: participant-perceived factors that affect app adoption-these include patient age, technology savviness, technology access, and ease of use; improved delivery of care-apps can support remote care; collect, share, and assess health information; identify adverse events; prevent hospitalizations; and limit clinic visits; facilitating patient engagement in care-apps can provide feedback and reinforcement, facilitate connection and communication between patients and their HCPs, support monitoring, and track self-care; providing patient support through education-apps can provide HF-related information (ie, diet and medications); and participant views on app features for their patients-HCPs felt that useful apps would have reminders and alarms and participative elements (gamification, food scanner, and quizzes). HCPs had positive views on the use of mobile apps to support patients with HF management. These findings can inform effective development and implementation strategies of HF management apps in clinical practice.

Small cell carcinoma of the breast is a rare, aggressive form of breast cancer that is associated with extremely poor outcomes [ 1 ]. In an effort to identify possible targets for treatment, we utilized comprehensive genomic profiling in small cell carcinoma of the breast. Under an IRB approved protocol, we identified patients with small cell carcinoma of the breast and small cell carcinoma of the lung profiled by Caris Life Sciences between 2007 and 2015. Tumors were assessed with up to 25 immunohistochemical stains, in situ hybridization of cMET, EGFR, HER2, PIK3CA, and TOP2A, and next generation sequencing as well as Sanger sequencing of 47 genes. 19 patients with small cell carcinoma of the breast were identified, median age was 58 years (range 37–79) and 42 % had metastatic disease at presentation; for comparison, 58 patients with small cell carcinoma of the lung were identified (66 [36–86], 65 % metastatic). By immunohistochemistry, 31 % of small cell carcinoma of the breast patients expressed ER, 13 % expressed PR, and 16 % expressed AR; small cell carcinoma of the lung patients expressed ER 0 %, PR 2 %, and AR 6 %. Small cell carcinoma of the breast and small cell carcinoma of the lung patients had similar patterns of other immunohistochemical expression (0 v 0 % PDL1, 50 v 42 % PD1, and 77 v 95 % TOP2A, respectively). All small carcinoma of the breast and small cell carcinoma of the lung patients were negative for HER2 and cMET amplification by in situ hybridization. Next generation sequencing revealed TP53 mutations in 75 % of patients both with small cell carcinoma of the breast and small cell carcinoma of the lung and PIK3CA mutations in 33 % of small cell carcinoma of the breast patients but no small cell carcinoma of the lung patients (Fisher’s exact test p  = 0.005, OR 0.02 [0.00–0.52]). No other mutations were found in small cell carcinoma of the breast patients and no other mutation occurred in over 10 % of small cell carcinoma of the lung patients except RB1 in 19 % ( p  = 0.31). Small cell carcinoma of the breast is an aggressive tumor with few therapeutic options. Molecular profiling suggests many similarities between small cell carcinoma of the breast and small cell carcinoma of the lung with the exception an increased incidence of PIK3CA mutations in small cell carcinoma of the breast, which may have therapeutic implications.