Comparing Patient and Provider Priorities Around Amputation Level Outcomes Using Multiple Criteria Decision Analysis.

BACKGROUND: Patients with chronic limb threatening ischemia may require a transmetatarsal amputation (TMA) or a transtibial amputation. When making an amputation-level decision, these patients face a tradeoff-a TMA preserves more limb and may provide better mobility but has a lower probability of primary wound healing and may therefore result in additional same or higher level amputation surgeries with an associated negative impact on function. Understanding differences in how patients and providers prioritize these tradeoffs and other outcomes may enhance shared decision-making. OBJECTIVES: Compare patient priorities with provider perceptions of patient priorities using Multiple Criteria Decision Analysis (MCDA). METHODS: The MCDA Analytic Hierarchy Process was chosen due to its low cognitive burden and ease of implementation. We included 5 criteria (outcomes): ability to walk, healing after amputation surgery, rehabilitation program intensity, limb length, and ease of use of prosthetic/orthotic device. A national sample of dysvascular lower-limb amputees and providers were recruited from the Veterans Health Administration with the MCDA administered online to providers and telephonically to patients. RESULTS: Twenty-six dysvascular amputees and 38 providers participated. Fifty percent of patients had undergone a TMA; 50%, a transtibial amputation. When compared to providers, patients placed higher value on TMA (72% vs. 63%). Patient versus provider priorities were ability to walk (47% vs. 42%), healing (18% vs. 28%), ease of prosthesis use (17% vs. 13%), limb length (11% vs. 13%), and then rehabilitation intensity (7% vs. 6%). LIMITATIONS: Our sample may not generalize to other populations. CONCLUSIONS: Provider perceptions aligned with patient values on amputation level but varied around the importance of each outcome. IMPLICATIONS: These findings illuminate some differences between patients' values and provider perceptions of patient values, suggesting a role for shared decision-making. Embedding this MCDA framework into a future decision aid may facilitate these discussions.

Exploring the Value of Improvisational Theater in Medical Education for Advancing the Doctor-Patient Relationship and Health Equity.

PURPOSE: Health care inequities persist, and it is difficult to teach health professions students effectively about implicit bias, structural inequities, and caring for patients from underrepresented or minoritized backgrounds. Improvisational theater (improv), where performers create everything in a spontaneous and unplanned manner, may help teach health professions trainees about advancing health equity. Core improv skills, discussion, and self-reflection can help improve communication; build trustworthy relationships with patients; and address bias, racism, oppressive systems, and structural inequities. METHOD: Authors integrated a 90-minute virtual improv workshop using basic exercises into a required course for first-year medical students at University of Chicago in 2020. Sixty randomly chosen students took the workshop and 37 (62%) responded to Likert-scale and open-ended questions about strengths, impact, and areas for improvement. Eleven students participated in structured interviews about their experience. RESULTS: Twenty-eight (76%) of 37 students rated the workshop as very good or excellent, and 31 (84%) would recommend it to others. Over 80% of students perceived their listening and observation skills improved, and that the workshop would help them take better care of patients with experiences different than their own. Six (16%) students experienced stress during the workshop but 36 (97%) felt safe. Eleven (30%) students agreed there were meaningful discussions about systemic inequities. Qualitative interview analysis showed that students thought the workshop helped develop interpersonal skills (communication, relationship building, empathy); helped personal growth (insights into perception of self and others, ability to adapt to unexpected situations); and felt safe. Students noted the workshop helped them to be in the moment with patients and respond to the unexpected in ways more traditional communication curricula have not. The authors developed a conceptual model relating improv skills and equity teaching methods to advancing health equity. CONCLUSIONS: Improv theater exercises can complement traditional communication curricula to advance health equity.

The Development and Pilot Study of a Multiple Criteria Decision Analysis (MCDA) to Compare Patient and Provider Priorities around Amputation-Level Outcomes.

Background. Patients with chronic limb-threatening ischemia who are facing a lower-limb amputation often require a transmetatarsal amputation (TMA) or a transtibial amputation (TTA). A TMA preserves more of the patient's limb and may provide better mobility but has a lower probability of primary wound healing relative to a TTA and may result in additional amputation surgeries. Understanding the differences in how patients and providers prioritize key outcomes may enhance the amputation decisional process. Purpose. To develop and pilot test a multiple criteria decision analysis (MCDA) tool to elicit patient values around amputation-level selection and compare those with provider perceptions of patient values. Methods. We conducted literature reviews to identify and measure the performance of criteria important to patients. Because the quantitative literature was sparse, we developed a Sheffield elicitation framework exercise to elicit criteria performance from subject matter experts. We piloted our MCDA among patients and providers to understand tool acceptability and preliminarily assess differences in patient and provider priorities. Results. Five criteria of importance were identified: ability to walk, healing after amputation surgery, rehabilitation intensity, limb length, and prosthetic/orthotic device ease. Patients and providers successfully completed the MCDA and identified challenges in doing so. We propose potential solutions to these challenges. The results of the pilot test suggest differences in patient and provider outcome priorities. Limitations. The pilot test study enrolled a small sample of providers and patients. Conclusions. We successfully implemented the pilot study to patients and providers, received helpful feedback, and identified solutions to improve the tool. Implications. Once modified, our MCDA tool will be suitable for wider rollout. Highlights: Patients and providers have successfully completed our MCDA, and patients feel the MCDA may be useful in clinical practice.We encountered several methodologic challenges and identified approaches to ease participant burden.When data are sparse, using the Sheffield elicitation framework is helpful in creating a performance matrix, although patients relied largely on their amputation experiences to complete the exercise. Blinding the alternatives may help patients better understand the process.

Improvisational and Standup Comedy, Graphic Medicine, and Theatre of the Oppressed to Teach Advancing Health Equity.

Ninety-minute virtual workshops that used improvisational comedy, standup comedy, graphic medicine, and Theatre of the Oppressed were implemented in 2020 within a required health equity course at the University of Chicago Pritzker School of Medicine to train 90 first-year medical students in advancing health equity. Learning objectives were to (1) deepen understanding of diverse human experiences by developing relationship skills, such as empathy, active listening, engagement, and observation; (2) recognize how diverse patients perceive students and how students perceive them to gain insight into one's identity and how intersectional systems of oppression can stigmatize and marginalize different identities; and (3) engage in free, frank, fearless, and safe conversations about structural racism, colonialism, White and other social privileges, and systemic factors that lead to health inequities. With a 61% (109/180 [90 students × 2 workshops per student]) survey response rate, 72% of respondents thought workshops were very good or excellent, and 83% agreed or strongly agreed they would recommend workshops to others. Key recommendations are to (1) incorporate experiential storytelling and discussion; (2) define clear learning goals for each workshop, map exercises to these goals, and explain their relevance to students; and (3) create a safe, courageous, brave space for exploration and discussion. For health equity, transformation happens as students share their perspectives of curriculum content from their intersectional identities, experiences, and varied privileges; are challenged by others' perspectives; and attempt to understand how others can experience the same content differently. The arts create a powerful form of sharing beyond routine conversations or discussions, which is critical for honest dialogue on difficult topics, such as racism, homophobia, and White privilege and other social privileges. Educators should enable students to have the space, time, and courage to share their true perspectives and engage in authentic discussions that may be uncomfortable but transformative.

Assessing the Effectiveness of a Primary Care Provider Office-Based Intervention for Increasing Organ Donor Registration Rates in Two New York State Counties.

Introduction: Despite strong public support, organ donor registration rates (RR) continue to lag while need only grows. In the United States, the traditional registration site is the Department of Motor Vehicles (DMV), however Primary care provider (PCP) offices have been considered as alternate locations for increasing RR. Methods: Twelve PCP offices across 2 New York Counties were subjected to a control week where participants received only a registration opportunity and an intervention week with the addition of a motivational poster and informational brochure. Zip code level sociodemographic data were obtained for each site. RR from the DMV over the same period served as historical control. Results: There were 1292 participants in the control phase and 1099 in the experimental phase. New registration rate for the control was 33.8% (289/897); experimental phase 7.88% (61/769); DMV registration 21.02% (1902/9050). The intervention was associated with a significant decrease in registrations (OR 0.181 (95% CI 0.135-0.244, P < 0.001)). Offices were clustered based on sociodemographic factors and regressed in 2 clusters. Lower educational attainment was associated with lower registration in the first but not second cluster (OR = 0.948 (0.923-0.974, P < 0.001)). Conclusions: This study provided evidence that PCP offices were a feasible site for organ donor registration and calls into question the efficacy of written materials-only interventions for increasing organ donor RR. It reiterated the negative effect of lower educational attainment on registration and suggested future studies focus on more active methods of engagement.

Assessment of muscle activity and fatigue during laparoscopic surgery.

BACKGROUND: Cumulative musculoskeletal stress during operative procedures can contribute to the development of chronic musculoskeletal injury among surgeons. This is a concern in laparoscopic specialties where trainees may incur greater risk by learning poor operative posture or technique early in training. This study conducted an initial investigation of the physical stress encountered during the conduct of foregut laparoscopic surgery. METHODS: Subjects were divided into two groups based on their surgical experience level, high experience (HE), consisting of two attending surgeons, and low experience (LE), consisting of two fellow surgeons and a surgical chief resident. Nine distinct foregut laparoscopic procedures were observed for data collection within these groups. Electromyographic (EMG) activity was collected at the bilateral neck, shoulders, biceps, triceps, and lower back for each procedure. Physical workload was measured using percent reference voluntary contractions (%RVC) for each surgeon's muscle activities. Fatigue development was assessed using the median frequency of EMG data between two consecutive cases. Subjects completed a NASA-TLX survey when surgery concluded. RESULTS: LE surgeons experienced higher levels of %RVC in the lower back muscles compared to HE surgeons. LE fatigue level was also higher than HE surgeons across most muscle groups. A decrease in median frequency in six of the ten muscle groups after performing two consecutive cases, the largest decrements being in the biceps and triceps indicated fatigue development across consecutive cases for both surgeon groups. CONCLUSION: Surgeons developed fatigue in consecutive cases while performing minimally invasive surgery (MIS). HE surgeons demonstrated a lower overall physical workload while also demonstrating different patterns in muscle work. The findings from this study can be used to inform further ergonomic studies and the data from this study can be used to develop surgical training programs focused on the importance of surgeon ergonomics and minimizing occupational injury risk.

Risk Prediction Model of 90-Day Mortality After Esophagectomy for Cancer.

Importance: Ninety-day mortality rates after esophagectomy are an indicator of the quality of surgical oncologic management. Accurate risk prediction based on large data sets may aid patients and surgeons in making informed decisions. Objective: To develop and validate a risk prediction model of death within 90 days after esophagectomy for cancer using the International Esodata Study Group (IESG) database, the largest existing prospective, multicenter cohort reporting standardized postoperative outcomes. Design, Setting, and Participants: In this diagnostic/prognostic study, we performed a retrospective analysis of patients from 39 institutions in 19 countries between January 1, 2015, and December 31, 2019. Patients with esophageal cancer were randomly assigned to development and validation cohorts. A scoring system that predicted death within 90 days based on logistic regression ß coefficients was conducted. A final prognostic score was determined and categorized into homogeneous risk groups that predicted death within 90 days. Calibration and discrimination tests were assessed between cohorts. Exposures: Esophageal resection for cancer of the esophagus and gastroesophageal junction. Main Outcomes and Measures: All-cause postoperative 90-day mortality. Results: A total of 8403 patients (mean [SD] age, 63.6 [9.0] years; 6641 [79.0%] male) were included. The 30-day mortality rate was 2.0% (n = 164), and the 90-day mortality rate was 4.2% (n = 353). Development (n = 4172) and validation (n = 4231) cohorts were randomly assigned. The multiple logistic regression model identified 10 weighted point variables factored into the prognostic score: age, sex, body mass index, performance status, myocardial infarction, connective tissue disease, peripheral vascular disease, liver disease, neoadjuvant treatment, and hospital volume. The prognostic scores were categorized into 5 risk groups: very low risk (score, ≥1; 90-day mortality, 1.8%), low risk (score, 0; 90-day mortality, 3.0%), medium risk (score, -1 to -2; 90-day mortality, 5.8%), high risk (score, -3 to -4: 90-day mortality, 8.9%), and very high risk (score, ≤-5; 90-day mortality, 18.2%). The model was supported by nonsignificance in the Hosmer-Lemeshow test. The discrimination (area under the receiver operating characteristic curve) was 0.68 (95% CI, 0.64-0.72) in the development cohort and 0.64 (95% CI, 0.60-0.69) in the validation cohort. Conclusions and Relevance: In this study, on the basis of preoperative variables, the IESG risk prediction model allowed stratification of an individual patient's risk of death within 90 days after esophagectomy. These data suggest that this model can help in the decision-making process when esophageal cancer surgery is being considered and in informed consent.

Testing Cancer Immunotherapy in a Human Immune System Mouse Model: Correlating Treatment Responses to Human Chimerism, Therapeutic Variables and Immune Cell Phenotypes.

Over the past decade, immunotherapies have revolutionized the treatment of cancer. Although the success of immunotherapy is remarkable, it is still limited to a subset of patients. More than 1500 clinical trials are currently ongoing with a goal of improving the efficacy of immunotherapy through co-administration of other agents. Preclinical, small-animal models are strongly desired to increase the pace of scientific discovery, while reducing the cost of combination drug testing in humans. Human immune system (HIS) mice are highly immune-deficient mouse recipients rtpeconstituted with human hematopoietic stem cells. These HIS-mice are capable of growing human tumor cell lines and patient-derived tumor xenografts. This model allows rapid testing of multiple, immune-related therapeutics for tumors originating from unique clinical samples. Using a cord blood-derived HIS-BALB/c-Rag2nullIl2rγnullSIRPαNOD (BRGS) mouse model, we summarize our experiments testing immune checkpoint blockade combinations in these mice bearing a variety of human tumors, including breast, colorectal, pancreatic, lung, adrenocortical, melanoma and hematological malignancies. We present in-depth characterization of the kinetics and subsets of the HIS in lymph and non-lymph organs and relate these to protocol development and immune-related treatment responses. Furthermore, we compare the phenotype of the HIS in lymph tissues and tumors. We show that the immunotype and amount of tumor infiltrating leukocytes are widely-variable and that this phenotype is tumor-dependent in the HIS-BRGS model. We further present flow cytometric analyses of immune cell subsets, activation state, cytokine production and inhibitory receptor expression in peripheral lymph organs and tumors. We show that responding tumors bear human infiltrating T cells with a more inflammatory signature compared to non-responding tumors, similar to reports of "responding" patients in human immunotherapy clinical trials. Collectively these data support the use of HIS mice as a preclinical model to test combination immunotherapies for human cancers, if careful attention is taken to both protocol details and data analysis.

Evaluation of Wood Composite Sandwich Panels as a Promising Renewable Building Material.

During this study, full-size wood composite sandwich panels, 1.2 m by 2.4 m (4 ft by 8 ft), with a biaxial corrugated core were evaluated as a building construction material. Considering the applications of this new building material, including roof, floor, and wall paneling, sandwich panels with one and two corrugated core(s) were fabricated and experimentally evaluated. Since primary loads applied on these sandwich panels during their service life are live load, snow load, wind, and gravity loads, their bending and compression behavior were investigated. To improve the thermal characteristics, the cavities within the sandwich panels created by the corrugated geometry of the core were filled with a closed-cell foam. The R-values of the sandwich panels were measured to evaluate their energy performance. Comparison of the weight indicated that fabrication of a corrugated panel needs 74% less strands and, as a result, less resin compared to a strand-based composite panel, such as oriented strand board (OSB), of the same size and same density. Bending results revealed that one-layer core sandwich panels with floor applications under a 4.79 kPa (100 psf) bending load are able to meet the smallest deflection limit of L/360 when the span length (L) is 137.16 cm (54 in) or less. The ultimate capacity of two-layered core sandwich panels as a wall member was 94% and 158% higher than the traditional walls with studs under bending and axial compressive loads, respectively. Two-layered core sandwich panels also showed a higher ultimate capacity compared to structural insulated panels (SIP), at 470% and 235% more in bending and axial compression, respectively. Furthermore, normalized R-values, the thermal resistance, of these sandwich panels, even with the presence of thermal bridging due to the core geometry, was about 114% and 109% higher than plywood and oriented strand board, respectively.

In vivo anti-V-ATPase antibody treatment delays ovarian tumor growth by increasing antitumor immune responses.

Tumor acidity is the key metabolic feature promoting cancer progression and is modulated by pH regulators on a cancer cell's surface that pump out excess protons/lactic acid for cancer cell survival. Neutralizing tumor acidity improves the therapeutic efficacy of current treatments including immunotherapies. Vacuolar-ATPase (V-ATPase) proton pumps encompass unique plasma membrane-associated subunit isoforms, making this molecule an important target for anticancer therapy. Here, we examined the in vivo therapeutic efficacy of an antibody (a2v-mAB) targeting specific V-ATPase-'V0a2' surface isoform in controlling ovarian tumor growth. In vitro a2v-mAb treatment inhibited the proton pump activity in ovarian cancer (OVCA) cells. In vivo intraperitoneal a2v-mAb treatment drastically delayed ovarian tumor growth with no measurable in vivo toxicity in a transplant tumor model. To explore the possible mechanism causing delayed tumor growth, histochemical analysis of the a2v-mAb-treated tumor tissues displayed high immune cell infiltration (M1-macrophages, neutrophils, CD103+ cells, and NK cells) and an enhanced antitumor response (iNOS, IFN-y, IL-1α) compared to control. There was marked decrease in CA-125-positive cancer cells and an enhanced active caspase-3 expression in a2v-mAb-treated tumors. RNA-seq analysis of a2v-mAb tumor tissues further revealed upregulation of apoptosis-related and toll-like receptor pathway-related genes. Indirect coculture of a2v-mAb-treated OVCA cells with human PBMCs in an unbuffered medium led to an enhanced gene expression of antitumor molecules IFN-y, IL-17, and IL-12-A in PBMCs, further validating the in vivo antitumor responses. In conclusion, V-ATPase inhibition using a monoclonal antibody directed against the V0a2 isoform increases antitumor immune responses and could therefore constitute an effective treatment strategy in OVCA.

The synthesis of one H-2 labeled and two H-3 labeled leukotriene C4 synthase inhibitors.

As part of a medicinal chemistry program aimed at developing a leukotriene C4 synthase inhibitor for the treatment of asthma, two tritium-labeled and one stable isotope-labeled compounds were required. The synthesis of the tritium-labeled compounds used a standard bromination-tritiodehalogentation approach. One of the tritium-labeled compounds was observed to exchange its tritium label slowly with the solvent. The stable isotope-labeled compound was prepared in seven steps (3% overall yield) from [2 H6 ]acetone in a modification of the route used by medicinal chemistry.

Soft crystal martensites: An in situ resonant soft x-ray scattering study of a liquid crystal martensitic transformation.

Liquid crystal blue phases (BPs) are three-dimensional soft crystals with unit cell sizes orders of magnitude larger than those of classic, atomic crystals. The directed self-assembly of BPs on chemically patterned surfaces uniquely enables detailed in situ resonant soft x-ray scattering measurements of martensitic phase transformations in these systems. The formation of twin lamellae is explicitly identified during the BPII-to-BPI transformation, further corroborating the martensitic nature of this transformation and broadening the analogy between soft and atomic crystal diffusionless phase transformations to include their strain-release mechanisms.

Sculpted grain boundaries in soft crystals.

Engineering the grain boundaries of crystalline materials represents an enduring challenge, particularly in the case of soft materials. Grain boundaries, however, can provide preferential sites for chemical reactions, adsorption processes, nucleation of phase transitions, and mechanical transformations. In this work, "soft heteroepitaxy" is used to exert precise control over the lattice orientation of three-dimensional liquid crystalline soft crystals, thereby granting the ability to sculpt the grain boundaries between them. Since these soft crystals are liquid-like in nature, the heteroepitaxy approach introduced here provides a clear strategy to accurately mold liquid-liquid interfaces in structured liquids with a hitherto unavailable level of precision.

An Analytical Mobile App for Shared Decision Making About Prenatal Screening: Protocol for a Mixed Methods Study.

BACKGROUND: Decisions about prenatal screening to assess the risk of genetic conditions such as Down syndrome are complex and should be well informed. Moreover, the number of available tests is increasing. Shared decision making (SDM) about testing could be facilitated by decision aids powered by mobile technology. OBJECTIVE: In this mixed methods study, we aim to (1) assess women's needs and preferences regarding using an app for considering prenatal screening, (2) develop a decision model using the analytical hierarchy process, and (3) develop an analytical app and assess its usability and usefulness. METHODS: In phase 1, we will assess the needs of 90 pregnant women and their partners (if available). We will identify eligible participants in 3 clinical sites (a midwife-led birthing center, a family practice clinic, and an obstetrician-led hospital-based clinic) in Quebec City and Montreal, Canada. Using semistructured interviews, we will assess participants' attitudes toward mobile apps for decision making about health, their current use of apps for health purposes, and their expectations of an app for prenatal testing decisions. Self-administered questionnaires will collect sociodemographic information, intentions to use an app for prenatal testing, and perceived importance of decision criteria. Qualitative data will be transcribed verbatim and analyzed thematically. Quantitative data will be analyzed using descriptive statistics and the analytic hierarchy process (AHP) method. In phase 2, we will develop a decision model using the AHP whereby users can assign relative importance to criteria when deciding between options. We will validate the model with potential users and a multidisciplinary team of patients, family physicians, primary care researchers, decision sciences experts, engineers, and experts in SDM, genetics, and bioethics. In phase 3, we will develop a prototype of the app using the results of the first 2 phases, pilot test its usefulness and usability among a sample of 15 pregnant women and their partners (if available), and improve it through 3 iterations. Data will be collected with a self-administered questionnaire. Results will be analyzed using descriptive statistics. RESULTS: Recruitment for phase 1 will begin in 2019. We expect results to be available in 2021. CONCLUSIONS: This study will result in a validated analytical app that will provide pregnant women and their partners with up-to-date information about prenatal screening options and their risks and benefits. It will help them clarify their values and enable them to weigh the options to make informed choices consistent with their preferences and values before meeting face-to-face with their health care professional. The app will be easy to update with the latest information and will provide women with a user-friendly experience using their smartphones or tablets. This study and the resulting app will contribute to high-quality SDM between pregnant women and their health care team. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13321.

Stop hedging your bets: reasons for non-adherence to a tri-modality regimen in the treatment of esophageal cancer in a multidisciplinary setting.

BACKGROUND: In locally-advanced esophageal cancer (LAEC), providers' concerns regarding eventual surgical candidacy can persuade physicians to defer to definitive doses of 50 Gy or higher preoperatively. We report the successful completion rate of tri-modality therapy (TMT) (documented at the outset) and reasons for TMT non-adherence at a large multi-disciplinary esophageal program. METHODS: LAEC patients diagnosed 2007-2016 from a prospective institutional database were subdivided into CRT/S+ [completed chemoradiation (CRT) and surgery] and CRT/S- (CRT and no subsequent surgery) groups. Chart review provided surgery non-adherence reasons. RESULTS: A total of 283 patients met planned TMT criteria: 164 (58.0%) patients received 50 or 50.4 Gy CRT, 27 patients (9.5%) received greater than 50.4 Gy, and 92 patients received less than 50 Gy (32.5%, only 8 patients received CRT to 41.4 Gy); 221 (78.1%) completed surgery (CRT/S+), while 62 (21.9%) failed to advance to surgery (CRT/S-): 25 of 62 CRT/S- patients (40.3%) evidenced metastatic progression before surgery, 4 (6.5%) were deemed unresectable intraoperatively, 4 (6.5%) expired prior to planned surgery (3 from unknown causes, 1 suicide), 8 (12.9%) experienced significant CRT-related medical decompensation and were withdrawn from surgical consideration, 16 (25.8%) voluntarily declined surgery post-CRT (largely due to long-term quality of life concerns), and 5 (8.1%) failed to advance for unknown reasons. Four of the 16 patients who voluntarily declined surgery after CRT received less than 50 Gy. The 22.2% of CRT/S+ patients achieved pathologic complete response (21.6% for adenocarcinoma and 29.0% for squamous cell carcinoma). CONCLUSIONS: Our institution's 78% surgery completion rate among TMT-indicated patients highlights the benefits of upfront multidisciplinary care. Metastatic disease development most commonly truncated TMT with a low rate failing due to medical decompensation. Given the number of patients who voluntarily declined surgery following CRT, TMT counseling and involvement of a patient advocate are paramount prior to treatment planning.

Hierarchical Assembly of Plasmonic Nanoparticle Heterodimer Arrays with Tunable Sub-5 nm Nanogaps.

Nanoparticle assemblies have generated intense interest because of their novel optical, electronic, and magnetic properties that open up numerous opportunities in fundamental and applied nanophotonics, -electronics, and -magnetics. However, despite the great scientific and technological potential of these structures, it remains an outstanding challenge to reliably fabricate such assemblies with both nanometer-level structural control and precise spatial arrangements on a macroscopic scale. It is the combination of these two features that is key to realizing nanoparticle assemblies' potential, particular for device applications. To address this challenge, we propose a hierarchical assembly approach consisting of both template-particle and particle-particle interactions, whereby the former ensures precise addressability of assemblies on a surface and the latter provides nanometer-level structural control. Template-particle interactions are harnessed via chemical-pattern-directed assembly, and the particle-particle interactions are controlled using DNA-directed self-assembly. To demonstrate the potential of this hierarchical assembly approach, we demonstrate the fabrication of a particularly fascinating assembly: the nanoparticle heterodimer, which possesses a surprisingly rich set of plasmonic properties and is a promising candidate to enable a variety of imaging and sensing applications. Each heterodimer is placed on the surface at predetermined locations, and the precise control of the nanogaps is confirmed by far-field scattering measurements of individual dimers. We further demonstrate that the gap size can be effectively tuned by varying the DNA length. By correlating measured spectra with finite-difference time-domain (FDTD) simulations, we determine the gap sizes to be 4.2 and 5.0 nm-with subnm deviation-for the two DNA lengths investigated. This is one of the best gap uniformities ever demonstrated for surface-bound nanoparticle assemblies. The estimated surface-enhanced Raman scattering (SERS) enhancement factor of these heterodimers is on the order of 105-106 with high reproducibility and predictable polarization-dependence. This hierarchical fabrication technique-employing both template-particle and particle-particle interactions-constitutes a novel platform for the realization of functional nanoparticle assemblies on surfaces and thereby creates new opportunities to implement these structures in a variety of applications.