Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses.

The emergence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed. Here, we utilized a targeted donor selection strategy to isolate a large panel of human broadly neutralizing antibodies (bnAbs) to sarbecoviruses. Many of these bnAbs are remarkably effective in neutralizing a diversity of sarbecoviruses and against most SARS-CoV-2 VOCs, including the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor-binding domain (RBD). Consistent with targeting of conserved sites, select RBD bnAbs exhibited protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model in vivo. These bnAbs provide new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and provide a molecular basis for effective design of pan-sarbecovirus vaccines.

Population genomic structure of a widespread, urban-dwelling mammal: The eastern grey squirrel (Sciurus carolinensis).

Urbanization is a persistent and widespread driver of global environmental change, potentially shaping evolutionary processes due to genetic drift and reduced gene flow in cities induced by habitat fragmentation and small population sizes. We tested this prediction for the eastern grey squirrel (Sciurus carolinensis), a common and conspicuous forest-dwelling rodent, by obtaining 44K SNPs using reduced representation sequencing (ddRAD) for 403 individuals sampled across the species' native range in eastern North America. We observed moderate levels of genetic diversity, low levels of inbreeding, and only a modest signal of isolation-by-distance. Clustering and migration analyses show that estimated levels of migration and genetic connectivity were higher than expected across cities and forested areas, specifically within the eastern portion of the species' range dominated by urbanization, and genetic connectivity was less than expected within the western range where the landscape is fragmented by agriculture. Landscape genetic methods revealed greater gene flow among individual squirrels in forested regions, which likely provide abundant food and shelter for squirrels. Although gene flow appears to be higher in areas with more tree cover, only slight discontinuities in gene flow suggest eastern grey squirrels have maintained connected populations across urban areas in all but the most heavily fragmented agricultural landscapes. Our results suggest urbanization shapes biological evolution in wildlife species depending strongly on the composition and habitability of the landscape matrix surrounding urban areas.

Geriatric Psychiatrists' Perspectives on Palliative Care: Results From A National Survey.

OBJECTIVES: Older adults with psychiatric illnesses often have medical comorbidities that require symptom management and impact prognosis. Geriatric psychiatrists are uniquely positioned to meet the palliative care needs of such patients. This study aims to characterize palliative care needs of geriatric psychiatry patients and utilization of primary palliative care skills and subspecialty referral among geriatric psychiatrists. METHODS: National, cross-sectional survey study of geriatrics psychiatrists in the United States. RESULTS: Respondents (n = 397) reported high palliative care needs among their patients (46-73% of patients). Respondents reported using all domains of palliative care in their clinical practice with varied comfort. In multivariate modeling, only frequency of skill use predicted comfort with skills. Respondents identified that a third of patients would benefit from referral to specialty palliative care. CONCLUSIONS: Geriatric psychiatrists identify high palliative care needs in their patients. They meet these needs by utilizing primary palliative care skills and when available referral to subspecialty palliative care.

Model for an Academic Medicine Interest Group: A student-led initiative.

Academic physicians are responsible for the education of medical students, residents, and other practicing physicians through clinical rotations lectures, seminars, research, and conferences. Therefore, the increasing need to recruit academic physicians holds immense value within the healthcare system. Academic Medicine Interest Group (AMIG) is a collective made up of students who share an interest in the growth and advancement of academic medicine. We present a guide and model on establishing an AMIG. We found that AMIG fostered professional growth by providing leadership, research, and teaching opportunities. Strategic planning, effective leadership, and group organization were all necessary for the success of the group.

Comparison of two frailty definitions in women with systemic lupus erythematosus.

OBJECTIVES: Frailty is a risk factor for adverse health in systemic lupus erythematosus (SLE). The Fried phenotype (FP) and the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI) are common frailty metrics reflecting distinct approaches to frailty assessment. We aimed to 1) compare frailty prevalence according to both metrics in women with SLE and describe differences between frail and non-frail participants using each method and 2) evaluate for cross-sectional associations between each metric and self-report disability. METHODS: Women aged 18-70 years with SLE were enrolled. FP and SLICC-FI were measured, and agreement calculated using a kappa statistic. Physician-reported disease activity and damage, Patient Reported Outcome Measurement Information System (PROMIS) computerized adaptive tests, and Valued Life Activities (VLA) self-report disability were assessed. Differences between frail and non-frail participants were evaluated cross-sectionally, and the association of frailty with disability was determined for both metrics. RESULTS: Of 67 participants, 17.9% (FP) and 26.9% (SLICC-FI) were frail according to each metric (kappa = 0.41, p< 0.01). Compared with non-frail women, frail women had greater disease damage, worse PROMIS scores, and greater disability (all p< 0.01 for FP and SLICC-FI). After age adjustment, frailty remained associated with a greater odds of disability (FP: odds ratio [OR] 4.7, 95% confidence interval [CI] 1.2-18.8; SLICC-FI: OR 4.6, 95% CI 1.3-15.8). CONCLUSION: Frailty is present in 17.9-26.9% of women with SLE. These metrics identified a similar, but non-identical group of women as frail. Further studies are needed to explore which metric is most informative in this population.

Mapping the Design Space of Technology-Based Solutions for Better Chronic Pain Care: Introducing the Pain Tech Landscape.

OBJECTIVES: Technology has substantial potential to transform and extend care for persons with chronic pain, a burdensome and costly condition. To catalyze the development of impactful applications of technology in this space, we developed the Pain Tech Landscape (PTL) model, which integrates pain care needs with characteristics of technological solutions. METHODS: Our interdisciplinary group representing experts in pain and human factors research developed PTL through iterative discussions. To demonstrate one potential use of the model, we apply data generated from a narrative review of selected pain and technology journals (2000-2020) in the form of heat map overlays, to reveal where pain tech research attention has focused to date. RESULTS: The PTL comprises three two-dimensional planes, with pain care needs on each x axis (measurement to management) and technology applications on the y axes according to a) user agency (user- to system-driven), b) usage time frame (temporary to lifelong), and c) collaboration (single-user to collaborative). Heat maps show that existing applications reside primarily in the "user-driven/management" quadrant (e.g., self-care apps). Examples of less developed areas include artificial intelligence and Internet of Things (i.e., Internet-linked household objects), and collaborative/social tools for pain management. CONCLUSIONS: Collaborative development between the pain and tech fields in early developmental stages using the PTL as a common language could yield impactful solutions for chronic pain management. The PTL could also be used to track developments in the field over time. We encourage periodic reassessment and refinement of the PTL model, which can also be adapted to other chronic conditions.

Dietary Inflammatory Potential and the Risk of Serrated and Adenomatous Colorectal Polyps.

Studies of dietary inflammation potential and risks of colorectal cancer precursors are limited, particularly for sessile serrated lesions (SSLs). This study examines the association using the energy-adjusted dietary inflammatory index (E-DIITM), a measure of anti- and/or pro-inflammatory diet, in a large US colonoscopy-based case-control study of 3246 controls, 1530 adenoma cases, 472 hyperplastic polyp cases, and 180 SSL cases. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. Analyses were stratified by participant characteristics, and urinary prostaglandin E2 metabolite (PGE-M) and high-sensitivity plasma C-reactive protein (hs-CRP) levels, inflammation biomarkers. Highest E-DII™ intake was associated with significantly increased risks of colorectal adenomas (OR 1.36, 95% CI 1.11, 1.67), and hyperplastic polyps (OR 1.43, 95% CI 1.06, 1.98), compared with participants consuming the lowest E-DII™ quartile. A similar, but non-significant, increased risk was also observed for SSLs (OR 1.41, 95% CI 0.82, 2.41). The positive association was stronger in females (pinteraction <0.001), normal weight individuals (ptrend 0.01), and in individuals with lower inflammatory biomarkers (ptrend 0.02 and 0.01 for PGE-M and hs-CRP, respectively). A high E-DII™ is associated with colorectal polyp risk, therefore promoting an anti-inflammatory diet may aid in preventing colorectal polyps.

Close proximity to blast: No long-term or lasting effect on cognitive performance in service members with and without TBI during blast exposure.

OBJECTIVE: Blast related characteristics may contribute to the diversity of findings on whether mild traumatic brain injury sustained during war zone deployment has lasting cognitive effects. This study aims to evaluate whether a history of blast exposure at close proximity, defined as exposure within 30 feet, has long-term or lasting influences on cognitive outcomes among current and former military personnel. METHOD: One hundred participants were assigned to one of three groups based on a self-report history of blast exposure during combat deployments: 47 close blast, 14 non-close blast, and 39 comparison participants without blast exposure. Working memory, processing speed, verbal learning/memory, and cognitive flexibility were evaluated using standard neuropsychological tests. In addition, assessment of combat exposure and current post-concussive, posttraumatic stress, and depressive symptoms, and headache was performed via self-report measures. Variables that differed between groups were controlled as covariates. RESULTS: No group differences survived Bonferroni correction for family-wise error rate; the close blast group did not differ from non-close blast and comparison groups on measures of working memory, processing speed, verbal learning/memory, or cognitive flexibility. Controlling for covariates did not alter these results. CONCLUSION: No evidence emerged to suggest that a history of close blast exposure was associated with decreased cognitive performance when comparisons were made with the other groups. Limited characterization of blast contexts experienced, self-report of blast distance, and heterogeneity of injury severity within the groups are the main limitations of this study.

Use of a Novel Standardized Administration Protocol Reduces Agitation Pro Re Nata (PRN) Medication Requirements: The Birmingham Agitation Management (BAM) Initiative.

BACKGROUND: Agitation management is a principal challenge on inpatient psychiatric units. Overreliance on common prescribing strategies of pro re nata (PRN) medication administration is problematic, given the tendencies to have overlapping or unclear indications. OBJECTIVE: Piloted project to determine whether a standardized protocol for agitation intervention may reduce PRN medication administration. METHODS: The Birmingham Agitation Management (BAM) interdisciplinary team uniquely connected the Brøset Violence Checklist (BVC) for assessment of agitation severity to a standardized PRN medication order set. Nurses on the piloted unit were trained on how to score the BVC and administer medications. Patients were assessed by the BVC every 4 hours and, based on their score, would receive no medication, low-dose benzodiazepine, high-dose benzodiazepine, or high-dose benzodiazepine plus antipsychotic. The primary end point compared the number of PRNs administered after novel protocol implementation with a retrospective cohort. Secondary measures included analysis of medication-related effects, seclusion, and physical restraint rates. RESULTS: 377 patients were included in the final analyses (184 pre-BAM, 193 BAM intervention group). No significant differences were seen in patient characteristics between groups. The total number of PRNs administered decreased by 42.5%, with both the mean and median number of administrations decreasing significantly (95% confidence interval [CI] = [1.68-5.75]; P < 0.001). A trend was noted between the number of PRNs administered and seclusion rates, but did not reach statistical significance (95% CI = [-7.28 to 60.31]; P = 0.124). CONCLUSIONS: In seemingly the first initiative of its kind, we found that a standardized agitation management protocol can help decrease the total number of PRN administrations for agitation without worsening of restraint rates and may possibly reduce the risk of adverse effects. These results require validation in specific, larger populations.

The relationship of caregiver self-efficacy to caregiver outcomes: a correlation and mediation analysis.

OBJECTIVES: Caregivers of individuals with Alzheimer's disease and related dementias experience significant burden and adverse outcomes. Enhancing caregiver self-efficacy has the potential to mitigate these negative impacts, yet little is known about its relationship with other aspects of caregiving. This study examined the relationship between self-efficacy and outcomes; identified factors associated with self-efficacy; examined the mediating role of self-efficacy; and analyzed whether there were racial/ethnic differences. METHODS: Data from caregivers (N = 243) were collected from the Caring for the Caregiver Network study. Participants' level of self-efficacy, depression, burden, and positive aspects of caregiving was assessed using validated measures. RESULTS: Two self-efficacy subscales predicted caregiver depression, burden, and positive aspects of caregiving. Being White, a spouse, or having a larger social network predicted lower self-efficacy for obtaining respite. Higher income and lower preparedness predicted lower self-efficacy for controlling upsetting thoughts and responding to disruptive behaviors. Self-efficacy for controlling upsetting thoughts mediated the relationship between preparedness and depression along with the relationship between preparedness and burden. Race/ethnicity did not improve model fit. CONCLUSION: Self-efficacy plays an important role in caregiver outcomes. These findings indicate that strategies to improve caregiver self-efficacy should be an integral component of caregiver interventions.

Survivin Expression in Luminal Breast Cancer and Adjacent Normal Tissue for Immuno-Oncology Applications.

Survivin (BIRC5) is a tumor-associated antigen (TAA) overexpressed in various tumors but present at low to undetectable levels in normal tissue. Survivin is known to have a high expression in breast cancer (e.g., Ductal Carcinoma in situ (DCIS) and triple negative breast cancer). Previous studies have not compared survivin expression levels in DCIS tumor samples to levels in adjacent, normal breast tissue from the same patient. To ensure the effective use of survivin as a target for T cell immunotherapy of breast cancer, it is essential to ascertain the varying levels of survivin expression between DCIS tumor tissue samples and the adjacent normal breast tissue taken from the same patient simultaneously. Next-generation sequencing of RNA (RNA-seq) in normal breast tissue and tumor breast tissue from five women presenting with DCIS for lumpectomy was used to identify sequence variation and expression levels of survivin. The identity of both tumor and adjacent normal tissue samples were corroborated by histopathology. Survivin was overexpressed in human breast tissue tumor samples relative to the corresponding adjacent human normal breast tissue. Wild-type survivin transcripts were the predominant species identified in all tumor tissue sequenced. This study demonstrates upregulated expression of wild type survivin in DCIS tumor tissue versus normal breast tissue taken from the same patient at the same time, and provides evidence that developing selective cytotoxic T lymphocyte (CTL) immunotherapy for DCIS targeting survivin warrants further study.

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill.

Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca(2+) dysregulation is present through altered Ca(2+) homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

The Relationship Between Pain and Psychological Distress During the COVID-19 Pandemic: Is Social Technology Use Protective?

OBJECTIVES: The COVID-19 pandemic and resulting shelter-in-place orders have profoundly changed the everyday social environment. This study examines the relationship between pain and psychological distress (depression, anxiety, and loneliness) among U.S. adults ages 54 and older during the pandemic. We also test whether use of technology for social purposes moderates the association between pain severity and psychological distress. METHODS: Using cross-sectional data on 1,014 adults ages 54 and older (pain free, n = 637; mild pain, n = 106; moderate pain, n = 227; and severe pain, n = 64) from the 2020 Health and Retirement Study COVID-19 Project (Early, Version 1.0), we conducted regression analyses to test the association between pain severity and psychological outcomes and to assess social technology use frequency as a moderator. RESULTS: Compared with their pain-free peers, participants with mild-to-moderate pain reported more depressive symptoms and greater loneliness; those with severe pain reported higher levels of depression, anxiety, and loneliness. Social technology use was associated with lower levels of depression and loneliness. However, interaction analyses show that social technology use predicted an increase in depression for individuals with pain but a decrease in depression among pain-free individuals. For anxiety and loneliness, no significant effects of social technology use were observed. CONCLUSION: Older adults with pain are at high risk of depression, anxiety, and loneliness during the pandemic. Although social technologies have become a common alternative to face-to-face interactions during the COVID-19 crisis, and overall they can provide mental health benefits, our results suggest that social technologies can be detrimental to psychological well-being among people with pain. These findings can inform technology-based interventions aiming to promote well-being among older adults with pain.

Which Pain Treatment Goals Are Important to Community-Dwelling Older Adults?

OBJECTIVE: In this cross-sectional study of 237 older adults, we ascertained the importance of seven pain treatment goals and identified factors associated with their perceived importance. METHODS: Participants (mean age = 72 years) ranked each goal (e.g., pain reduction; finding a cure) on a 1 (not at all important) to 10 (extremely important) scale. We used general linear models to identify sociodemographic and pain factors independently associated with the perceived importance of each goal and repeated measures mixed models to examine their relative importance. RESULTS: The goal with the lowest adjusted score was "minimize harmful side effects from pain medications" with a mean (standard error [SE]) of 6.75 (0.239), while the highest ranked goals, "finding a cure," and "reducing my pain" had mean scores of 8.06 (0.237) and 7.89 (0.235), respectively. Pain reduction did not differ significantly from the average of the other 6 goals (P = .072) but was significantly different when compared with the goals of minimizing side effects (P < .0001) and finding a cause for the pain (P = .047), and different from the average of the five other goals excluding finding a cure (P = .021). We did not identify differences in the importance of the seven goals by gender or race/ethnicity. Age was inversely associated with the goals of minimizing harmful side effects and decreasing pain's effects on everyday activities. Pain reduction was rated more important than all other goals but finding a cure. CONCLUSIONS: Future research is needed to establish the benefits of eliciting treatment goals when delivering pain care to older adults.

Prevalence of lifetime nonmedical opioid use among U.S. Health Center Patients aged 45 years and older with psychiatric disorders.

OBJECTIVE: Despite recent concerns over the increase in opioid misuse among aging adults, little is known about the prevalence of lifetime nonmedical opioid use in underserved, vulnerable middle-aged and older patients with psychiatric disorders. This study aims to determine the lifetime prevalence of nonmedical opioid use among underserved, vulnerable U.S. adults aged ≥45 years with psychiatric disorders. METHOD: A nationally representative sample (n = 3,294) was obtained from the 2014 Health Center Patient Survey which collects data on psychiatric disorders, opioid use, and other health information from underserved, vulnerable U.S. primary care populations. Predictor variables included self-reported panic disorder, generalized anxiety disorder, schizophrenia, or bipolar disorder. The outcome variable was self-reported lifetime nonmedical opioid use. Frequencies, counts, and unadjusted and adjusted logistic regression models were conducted with the cross-sectional survey dataset. RESULTS: Patients with bipolar disorder had the highest lifetime nonmedical opioid use rate (20.8%), followed by schizophrenia (19.3%), panic disorder (16.5%), and generalized anxiety disorder (14.5%). Nonmedical opioid use was significantly associated with bipolar disorder (OR 3.46, 95% CI [1.33, 8.99]) and generalized anxiety disorder (OR 2.03 95% CI [1.08, 3.83]). CONCLUSION: Our findings demonstrate a high prevalence of lifetime nonmedical opioid use in underserved, vulnerable middle-aged and older health center patients with psychiatric disorders. Given the prevalence, health center professionals should monitor, prevent, and treat new or reoccurring signs and symptoms of nonmedical opioid use in this high-risk group of aging patients with psychiatric disorders.

The influence of candidates' physical attributes on patient ratings in simulated assessments of clinical practice.

BACKGROUND: We have previously shown that clinical examiners' scoring is not negatively impacted when a candidate has a tattoo, unnatural hair colour, or a regional accent. We investigated whether these physical attributes in exam candidates impact patient scoring. METHODS: Simulated/real patients were randomly assigned to watch five videos of simulated candidate performances of a cranial nerve examination: clear fail, borderline, good, 'clear pass' without an attribute, and 'clear pass' with one of the attributes (tattoo, purple hair, accent). Participants scored domains of communication and professionalism. We compared scores for the clear pass candidates with and without attributes. RESULTS: One hundred and eighty three patients participated. The total scores for the candidates with tattoos and purple hair were higher than the candidate with no physical attribute (p < 0.001). For the candidate with a Liverpool English accent no difference was identified (p = 0.120). CONCLUSIONS: The presence of certain physical attributes (tattoos or purple hair) was associated with higher scores given by patients to candidates in a simulated physical examination station.

Palliative care for case managers: Building capacity to extend community-based palliative care to underserved older adults.

Palliative care has demonstrated effectiveness in alleviating the biological, emotional, social, and spiritual symptoms that accompany serious illness, and improving quality of life for seriously ill individuals and their family members. Despite increasing availability, there are significant disparities in access to and utilization of palliative care, particularly among diverse, low-income, and community-dwelling older adults with chronic illness. Training frontline service providers is a novel approach to expanding access to palliative care among underserved elders. This article presents a process and outcome evaluation of a palliative care curriculum that was developed and piloted for geriatric case managers in a large urban area. We describe the background, planning, design, implementation, and preliminary outcomes associated with a pilot implementation of the curriculum. We conclude with implications for replicating efforts to enhance frontline providers' knowledge, skills, and self-efficacy in extending palliative care to communities that lack access to critical supports for their burdensome symptoms.

Prescription Opioids Dispensed to Patients with Cancer with Bone Metastasis: 2011-2017.

Opioid therapy is a first-line approach for moderate-to-severe pain associated with cancer with bone metastasis (CBM). The decade-long decline in opioid prescribing in the U.S. would not be expected to affect patients with CBM. We investigated trends in opioids dispensed to patients with CBM using data from a large commercial claims database. From 2011 quarter 2 to 2017 quarter 4, the percentage of patients with CBM prescribed at least 1 day of opioids in a quarter declined from 28.1% to 24.5% (p < .001) for privately insured patients aged 18-64 years and from 39.1% to 30.5% (p < .001) for Medicare Advantage (MA) patients aged 65 years or older. Among patients with at least 1 day of opioids in a quarter, the average morphine milligram equivalents dispensed declined by 37% and 11% (p < .001 for both) for privately insured and MA patients, respectively. Our findings raise concerns about potential unintended consequences related to population-level reduction in opioid prescribing.

Staff and participant perceptions of optimal recruitment and retention strategies for biomedical cohort studies in the Caribbean.

PURPOSE: To identify staff and participants perspectives of best practices that facilitate achieving enrollment and retention targets in biomedical cohort studies in Caribbean populations. METHODS: Eight focus group discussions (FGDs) were held with research stakeholders including research (i) nurses/study supervisors, (ii) field staff/data collectors, and (iii) rural and urban participants of the Third Jamaica Health and Lifestyle Survey (a national NCD risk factor survey with biospecimen collection) to capture qualitative data on experiences with recruitment, training, retention challenges and potential solutions or strategies for strengthening future efforts. RESULTS: Our findings indicate that trained, experienced study staff with good interpersonal communication skills enhanced the proficiency of field operations and attracted study participants. Targeted community and stakeholder engagement alongside strong support from the coordinating center increased the reach and efficiency of the data collectors. Timely participant feedback, gender-appropriate approaches, and socioeconomic balance enhanced equitable enrollment and retention of participants of cohort studies particularly the hard to reach groups. CONCLUSION: Well-functioning research teams using traditional and social media promotion, applying gender-appropriate and personalized approaches together with strategies for reaching the less accessible socioeconomic groups, are effective for recruiting and retaining members of a Caribbean cohort. These strategies may also enhance the recruitment of other Black populations in the Diaspora including the US and Caribbean into biomedical studies including cancer research.

Radiative heat transfer in the extreme near field.

Radiative transfer of energy at the nanometre length scale is of great importance to a variety of technologies including heat-assisted magnetic recording, near-field thermophotovoltaics and lithography. Although experimental advances have enabled elucidation of near-field radiative heat transfer in gaps as small as 20-30 nanometres (refs 4-6), quantitative analysis in the extreme near field (less than 10 nanometres) has been greatly limited by experimental challenges. Moreover, the results of pioneering measurements differed from theoretical predictions by orders of magnitude. Here we use custom-fabricated scanning probes with embedded thermocouples, in conjunction with new microdevices capable of periodic temperature modulation, to measure radiative heat transfer down to gaps as small as two nanometres. For our experiments we deposited suitably chosen metal or dielectric layers on the scanning probes and microdevices, enabling direct study of extreme near-field radiation between silica-silica, silicon nitride-silicon nitride and gold-gold surfaces to reveal marked, gap-size-dependent enhancements of radiative heat transfer. Furthermore, our state-of-the-art calculations of radiative heat transfer, performed within the theoretical framework of fluctuational electrodynamics, are in excellent agreement with our experimental results, providing unambiguous evidence that confirms the validity of this theory for modelling radiative heat transfer in gaps as small as a few nanometres. This work lays the foundations required for the rational design of novel technologies that leverage nanoscale radiative heat transfer.