Belief Updating during Social Interactions: Neural Dynamics and Causal Role of Dorsomedial Prefrontal Cortex.

In competitive interactions, humans have to flexibly update their beliefs about another person's intentions in order to adjust their own choice strategy, such as when believing that the other may exploit their cooperativeness. Here we investigate both the neural dynamics and the causal neural substrate of belief updating processes in humans. We used an adapted prisoner's dilemma game in which participants explicitly predicted the coplayer's actions, which allowed us to quantify the prediction error between expected and actual behavior. First, in an EEG experiment, we found a stronger medial frontal negativity (MFN) for negative than positive prediction errors, suggesting that this medial frontal ERP component may encode unexpected defection of the coplayer. The MFN also predicted subsequent belief updating after negative prediction errors. In a second experiment, we used transcranial magnetic stimulation (TMS) to investigate whether the dorsomedial prefrontal cortex (dmPFC) causally implements belief updating after unexpected outcomes. Our results show that dmPFC TMS impaired belief updating and strategic behavioral adjustments after negative prediction errors. Taken together, our findings reveal the time course of the use of prediction errors in social decisions and suggest that the dmPFC plays a crucial role in updating mental representations of others' intentions.

Gene transfer agents: The ambiguous role of selfless viruses in genetic exchange and bacterial evolution.

Gene transfer agents (GTAs) are genetic elements derived from ancestral bacteriophages that have become domesticated by the host. GTAs are present in diverse prokaryotic organisms, where they can facilitate horizontal gene transfer under certain conditions. Unlike typical bacteriophages, GTAs do not exhibit any preference for the replication or transfer of the genes encoding them; instead, they exhibit a remarkable capacity to package chromosomal, and sometimes extrachromosomal, DNA into virus-like capsids and disseminate it to neighboring cells. Because GTAs resemble defective prophages, identification of novel GTAs is not trivial. The detection of candidates relies on the genetic similarity to known GTAs, which has been fruitful in α-proteobacterial lineages but challenging in more distant bacteria. Here we consider several fundamental questions: What is the true prevalence of GTAs in prokaryote genomes? Given there are high costs for GTA production, what advantage do GTAs provide to the bacterial host to justify their maintenance? How is the bacterial chromosome recognized and processed for inclusion in GTA particles? This article highlights the challenges in comprehensively understanding GTAs' prevalence, function and DNA packaging method. Going forward, broad study of atypical GTAs and use of ecologically relevant conditions are required to uncover their true impact on bacterial chromosome evolution.

The Dose Comparison of Intrathecal Morphine for Postoperative Analgesia in Total Knee Arthroplasty Under Spinal Anesthesia: A Single Institute Retrospective Study.

Background and purpose of the study Intrathecal morphine (ITM) provides effective postoperative analgesia in patients undergoing total knee arthroplasty (TKA) under spinal anesthesia. However, the ideal dose at which maximal analgesic effects can be delivered with minimal side effects is not clearly known. This retrospective study is aimed to compare two different doses of ITM with respect to analgesia benefits and side effects. Methods This is a retrospective, descriptive, single-center study approved by the Institutional Review Board (IRB) at the University of Alabama at Birmingham. Three patient groups were selected: a control group receiving continuous adductor canal block (CCACB) under spinal anesthesia, and two experimental groups receiving single-dose adductor canal block (SSACB) under spinal anesthesia with either 100 mcg or 150 mcg of ITM. The sample size included 75 patients (25 per group) who were 18 years and older, American Society of Anesthesiology (ASA) class 1-3 who were undergoing primary TKA. Patients with chronic pain or opioid use exceeding 30 days and those undergoing surgeries other than primary TKA were excluded. Outcome data, including opioid use (from which post-operative oral morphine equivalents (OME) were calculated), antiemetic use, visual analog pain scale (VAS) scores, distance ambulated at 24 hours, and length of hospital stay, were extracted by chart review. Results In the post-anesthesia care unit (PACU), patients in both ITM groups experienced significantly lower opioid consumption and pain scores compared to the control group (p<.001). Furthermore, cumulative OME at 24 hours was significantly less in the ITM groups compared to the control, but there was no difference between ITM doses (p=0.004; mean cumulative OME for control was 77.2 OME vs 43.4 OME for 100 mcg ITM vs 42.6 OME for 150 mcg ITM). Antiemetic usage did not increase in the ITM groups. Although there was no statistically significant difference in ambulation at 24 hours, both ITM groups exhibited a trend toward greater average ambulation distance compared to the control group (p=0.095; mean distance walked for control was 67.6 feet, 76.6 feet for 100 mcg ITM vs 98.8 feet for 150 mcg ITM). Hospital length of stay did not significantly differ between the groups. Conclusion ITM doses of 100 mcg and 150 mcg provide effective analgesia for patients undergoing lower extremity total knee arthroplasty under spinal anesthesia. Patients receiving ITM had better pain scores in the immediate post-operative period and had overall less oral morphine equivalent consumption when compared to control. In addition, the safety and side effect profile for ITM is similar for both doses as there was no incidence of respiratory depression and antiemetic usage did not differ between all study arms. Future studies should explore the use of higher ITM doses and consider a broader patient population to further understand the advantages and potential drawbacks of ITM in TKA surgery.

Targeted Crystallization of Rare Earth Carbonate Polymorphs at Hydrothermal Conditions via Mineral Replacement Reactions.

The interaction between rare earth element (REE)-rich (La, Pr, Nd, Dy) aqueous solutions, dolomite (CaMg(CO3)2), and aragonite (CaCO3) at low temperature hydrothermal conditions (25-220 °C) is studied. The experiments result in the solvent-mediated surface precipitation and subsequent pseudomorphic mineral replacement of the dolomite and aragonite seeds by newly formed REE-carbonates. The host grains are replaced from periphery inward. The newly formed REE-bearing carbonates in La-, Pr-, and Nd-doped systems follow the crystallization sequence: lanthanite [REE2(CO3)3·8H2O] → kozoite [orthorhombic REECO3(OH)] → hydroxylbastnasite [hexagonal REECO3(OH)]. The interaction of Dy-bearing solutions with dolomite results only in the crystallization of kozoite [orthorhombic DyCO3(OH)]. However, experiments with aragonite reveal a two-step crystallization pathway: tengerite [Dy2(CO3)3·2-3(H2O)] → kozoite [orthorhombic DyCO3(OH)]. The temperature, the dissolution rate of the host mineral, and the ionic radii of the REE3+ in question are found to control the kinetics of the replacement reaction, the polymorph selection, and the crystallization pathways toward bastnasite. The findings allow to gain a more in-depth understanding of the formation REE-bearing carbonates, particularly the mineral bastnasite, which is the main source of REEs for industry. This knowledge can be used to improve REE separation, exploration, exploitation methods, as well to produce carbonate minerals with tailored structures.

Struggling with the basics: food and housing insecurity among college students across twenty-two colleges and universities.

OBJECTIVES: To quantify the number and type of students failing to secure basic needs. PARTICIPANTS: Students attending 22 postsecondary schools in the United States in Fall 2019. METHODS: The Adult Food Security Module and part of the #RealCollege Survey were used to measure food and housing insecurity, respectively. Logistic and linear regression models were used to assess the relationship between selected factors and basic needs insecurities. RESULTS: Participants (n = 22,153) were classified as 44.1% and 52.3% food insecure and housing insecure, respectively. Homeless students or those who experienced childhood food insecurity were at the greatest odds of college food insecurity. Year in school was the largest contributor to being housing insecure, with PhD or EdD students being 1,157% more likely to experience housing insecurity compared to freshmen. CONCLUSIONS: High prevalence of basic needs insecurities remain. Current campus initiatives may be insufficient, calling for a more holistic approach at the campus, state, and national levels.

A retrospective cohort study of bladder cancer following the COVID-19 pandemic: Are patients presenting with more aggressive disease?

Background: The COVID-19 pandemic has resulted in delays in the treatment of patients with urological malignancies. The management of bladder cancer (BC) in particular poses a significant challenge given the recurrent nature of the disease and the intense follow-up regime required for many cases. The aim of this study was to evaluate potential changes in the presentation and operative management of BC in our hospital following the pandemic. Materials and methods: This is a retrospective cohort study. Potential BC cases were identified through the histopathology database between March 2019 and February 2021. Details were obtained on patient demographics, procedure type such as biopsy, resection or excision, grade and stage of BC. Cases were divided into two groups: period one (pre-COVID between March 2019 and February 2020) and period two (post-COVID between March 2020 and February 2021). Results: A total of 207 procedures for confirmed BC were performed during the study period, 126 in period one and 81 in period two. New cases accounted for 52.4% (n = 66) and 53.1% (n = 43) of cases during periods one and two respectively. There was a higher rate of invasive disease (43.2% vs 26.2%) as well as high grade disease (47.4% vs 35.8%) in period two than in period one. Conclusion: Fewer BC procedures were performed in the COVID period. The higher rate of more advanced stage and grade of disease seen in period two suggests patients are presenting later. This should be considered when allocating resources in the management of non-COVID related diseases. Further studies are needed to assess the long-term impact of COVID-19 on bladder cancer outcome.

Food insecurity among university students in the United States amidst the COVID-19 pandemic.

OBJECTIVE: This study reports on food insecurity (FI) amidst the COVID-19 pandemic. PARTICIPANTS AND METHODS: College students in four regions of the US completed the two-item validated Hunger Vital Sign™ screening tool on Qualtrics. RESULTS: FI increased significantly after March 2020 among US students (worry about food running out: 25% to 35%; food did not last: 17% to 21%) with significant regional increase in the Midwest and South. An adjusted multivariable logistic regression model indicated students that ran out of food were significantly at greater odds of experiencing hardship with paying bills (AOR: 5.59, 95% CI =3.90-8.06). CONCLUSIONS: The findings identified an increase in the prevalence of FI among college students during the pandemic. Suggestions of how to address FI are discussed.

Turnaround times for molecular testing of pediatric viral cerebrospinal fluid samples in United Kingdom laboratories.

BACKGROUND: Rapid molecular testing has revolutionized the management of suspected viral meningitis and encephalitis by providing an etiological diagnosis in < 90 min with potential to improve outcomes and shorten inpatient stays. However, use of molecular assays can vary widely. AIM: To evaluate current practice for molecular testing of pediatric cerebrospinal fluid (CSF) samples across the United Kingdom using a structured questionnaire. METHODS: A structured telephone questionnaire survey was conducted between July and August 2020. Data was collected on the availability of viral CSF nucleic acid amplification testing (NAAT), criteria used for testing and turnaround times including the impact of the coronavirus disease 2019 pandemic. RESULTS: Of 196/212 (92%) microbiology laboratories responded; 63/196 (32%) were excluded from final analysis as they had no on-site microbiology laboratory and outsourced their samples. Of 133 Laboratories included in the study, 47/133 (35%) had onsite facilities for viral CSF NAAT. Hospitals currently undertaking onsite NAAT (n = 47) had much faster turnaround times with 39 centers (83%) providing results in ≤ 24 h as compared to those referring samples to neighboring laboratories (5/86; 6%). CONCLUSION: Onsite/near-patient rapid NAAT (including polymerase chain reaction) is recommended wherever possible to optimize patient management in the acute setting.

Comparison of the Utilization of Tranexamic Acid and Tourniquet Use in Total Knee Arthroplasty: A Retrospective Case Series.

INTRODUCTION: Total knee arthroplasty (TKA) carries a high risk for significant blood loss due to bone cuts and extensive soft tissue involvement in the knee region. The use of tranexamic acid (TXA) or a tourniquet are two methods commonly employed to prevent significant blood loss and avoid the need for blood transfusion. TXA has been shown to reduce both intraoperative and postoperative bleeding as well as the probability that a patient will require a blood transfusion. The purpose of this study is to compare the efficacy of TXA and tourniquet use, both alone and in combination, in reducing blood loss during TKA. METHODS: Data for this retrospective cohort study were obtained by searching records of patients who underwent TKA at a tertiary care center from January 2019 to October 2020. Data from 526 subjects were available. A chart review was conducted to determine if the patient received TXA only, tourniquet only, or both TXA and tourniquet during the TKA procedure. Primary outcomes for this study including procedure length in minutes, estimated blood loss in cubic centimeters, and total infusion pressor (phenylephrine) administered intraoperatively in milligrams were recorded for the study. Data were summarized using means and standard errors. Statistical methods used for analysis include one-way ANOVA, probability plots, the Shapiro-Wilk test for normality, the Kruskal-Wallis test, and Tukey's test. RESULTS: Data were available for 526 subjects. 122 subjects received tourniquet only (Tourniquet group), 104 received intravenous (IV) TXA only, 264 received both tourniquet and IV TXA (Tourniquet + TXA), and 36 received neither tourniquet nor TXA (None). The groups did not significantly differ in procedure length (p = 0.140) or infusion pressor total (p > 0.20). The groups did significantly differ in estimated blood loss (p < 0.001). Subjects who did not receive either TXA or tourniquet had significantly more blood loss than the Tourniquet and Tourniquet + TXA groups. Similarly, the TXA group had significantly more blood loss than both the Tourniquet and Tourniquet + TXA groups. CONCLUSION: This study supports the conclusion that the use of a tourniquet is superior to the use of TXA in reducing intraoperative blood loss during TKA. All groups that underwent TKA using a tourniquet, either alone or in combination with TXA, exhibited significantly lower levels of blood loss compared to the control (no intervention) group.

Can early phase cardiac [123I]mIBG images be used to diagnose Lewy body disease?

PURPOSE: Some studies have suggested that cardiac [123I]metaiodobenzylguanidine images obtained 15-20 min after tracer administration are as accurate for dementia with Lewy bodies (DLB) diagnosis as standard images acquired after a delay of 3-4 h; some suggest delayed imaging is preferable. We compare early and delayed heart-to-mediastinum ratios (HMR) in a well-characterised research dataset and make recommendations for clinical practice. METHODS: Images were acquired using a Siemens gamma camera with medium energy collimators. Early images were obtained at 20 min and delayed at 4 h (± 30) min. In total 167 pairs of images were reviewed: 30 controls, 39 people with dementia and 98 with mild cognitive impairment. HMR normal cutoff values derived from control data were ≥2.10 for early imaging and ≥1.85 for delayed. RESULTS: HMR tended to drop between early and delayed for abnormal images, but increase for normal images. Histograms of early and delayed HMR showed a slightly better separation of results into two groups for delayed imaging. Accuracy results were slightly higher for delayed imaging than early imaging (73 vs. 77%), sensitivity 63 vs. 65% and specificity 82 vs. 88%. However, this was not statistically significant - in total only 8/167 (5%) of scans changed designation between early and delayed imaging. CONCLUSION: We suggest that a delayed image could be acquired only if the early result is borderline. This removes the need for delayed imaging in about 70% of patients. Adopting this protocol in clinical practice would reduce the time most patients have to wait and could free up scanner time.

Using geographic information systems to characterize food environments around historically black colleges and universities: Implications for nutrition interventions.

ObjectiveTo understand the distribution of healthy and unhealthy food stores near historically black colleges and universities (HBCUs). Participants and methods: Using ArcGIS Pro's network analysis tools and ReferenceUSA database, this study characterized the healthy (favorable) and unhealthy (unfavorable) retail food stores within a 5-mile radius, 15-min driving, and 15-min walking distance from each HBCU in North Carolina. Results: Most retail food stores within a 5-mile buffer radius of the 10 HBCUs in North Carolina were unfavorable. Within 15-min driving from each HBCU, 1082 stores (76.0%) were unfavorable food stores, while 332 (24.0%) were favorable. Additionally, there were four favorable and 35 unfavorable retail food stores within the 15-min walking distance of each HBCU. Conclusions: Favorable food retail stores around HBCUs in North Carolina are limited. Researchers, policy makers, and community stakeholders should work together to improve food environments surrounding HBCUs.

Retrospective Case Series Comparing the Efficacy of Thoracic Epidural With Continuous Paravertebral and Erector Spinae Plane Blocks for Postoperative Analgesia After Thoracic Surgery.

Perioperative pain management for thoracic surgery plays a vital role in recovery and improved outcomes. In this retrospective study we compare three different regional anesthesia techniques utilized at one institute to provide postoperative analgesia for thoracic surgery. Continuous thoracic epidural analgesia (TEA), thoracic paravertebral block (PVB) and erector spinae plane (ESP) block are compared for postoperative pain management, opioid requirements, postoperative nausea and vomiting (PONV), respiratory events and length of stay. In this study, pairwise comparisons were also performed among the regional techniques with respect to mentioned outcomes.

Examining the effects of social determinants of health on COVID-19 related stress, family's stress and discord, and personal diagnosis of COVID-19.

BACKGROUND: COVID-19 is a significant threat to people's mental health and social well-being. The research examined the effects of social determinants of health on COVID-19 related stress, family's stress and discord, and personal diagnosis of COVID-19. METHODS: In November 2020, the data collection was conducted from 97 counties in North Carolina (N = 1500). Adult residents in North Carolina completed an online COVID-19 impact survey conducted using quota-based sampling on race, income, and county to provide a rapid quasi-representative assessment of COVID impact. The study investigated the variables in a structural model through structural equation modeling. For data analysis, IBM SPSS 26 and AMOS 27 were deployed. RESULTS: Social determinants of health had direct effects on COVID-19 related stress (ß = 0.66, p < 0.001, r 2 = 0.43), family's stress and discord (ß = 0.73, p < 0.001, r 2 = 0.53), and personal diagnosis of COVID-19 (ß = 0.52, p < 0.001, r 2 = 0.27). These findings indicate that underserved populations experienced higher stress and discord at both individual and family levels and more severe COVID-19 symptoms. Moreover, black participants, whose family income and food access declined significantly more, had worse stress, discord, and COVID-19 symptoms than white participants. CONCLUSIONS: The study suggests that the government and health professionals enhance mental health and family support service accessibility for underprivileged populations through telehealth and community health programs to prevent associated social and health issues such as suicide, violence, and cancer.

Effect of High-frequency (10-kHz) Spinal Cord Stimulation in Patients With Painful Diabetic Neuropathy: A Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments. Objective: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN). Design, Setting, and Participants: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A1c (HbA1c) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated. Interventions: Implanted medical device delivering 10-kHz SCS. Main Outcomes and Measures: The prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA1c over 6 months. Results: Of 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001). Conclusions and Relevance: Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN. Trial Registration: ClincalTrials.gov Identifier: NCT03228420.

College student sleep quality and mental and physical health are associated with food insecurity in a multi-campus study.

OBJECTIVE: To assess the relationship between food insecurity, sleep quality, and days with mental and physical health issues among college students. DESIGN: An online survey was administered. Food insecurity was assessed using the ten-item Adult Food Security Survey Module. Sleep was measured using the nineteen-item Pittsburgh Sleep Quality Index (PSQI). Mental health and physical health were measured using three items from the Healthy Days Core Module. Multivariate logistic regression was conducted to assess the relationship between food insecurity, sleep quality, and days with poor mental and physical health. SETTING: Twenty-two higher education institutions. PARTICIPANTS: College students (n 17 686) enrolled at one of twenty-two participating universities. RESULTS: Compared with food-secure students, those classified as food insecure (43·4 %) had higher PSQI scores indicating poorer sleep quality (P < 0·0001) and reported more days with poor mental (P < 0·0001) and physical (P < 0·0001) health as well as days when mental and physical health prevented them from completing daily activities (P < 0·0001). Food-insecure students had higher adjusted odds of having poor sleep quality (adjusted OR (AOR): 1·13; 95 % CI 1·12, 1·14), days with poor physical health (AOR: 1·01; 95 % CI 1·01, 1·02), days with poor mental health (AOR: 1·03; 95 % CI 1·02, 1·03) and days when poor mental or physical health prevented them from completing daily activities (AOR: 1·03; 95 % CI 1·02, 1·04). CONCLUSIONS: College students report high food insecurity which is associated with poor mental and physical health, and sleep quality. Multi-level policy changes and campus wellness programmes are needed to prevent food insecurity and improve student health-related outcomes.

Quantifying cell death induced by doxorubicin, hyperthermia or HIFU ablation with flow cytometry.

Triggered release and targeted drug delivery of potent anti-cancer agents using hyperthermia-mediated focused-ultrasound (FUS) is gaining momentum in the clinical setting. In early phase studies, tissue biopsy samples may be harvested to assess drug delivery efficacy and demonstrate lack of instantaneous cell death due to FUS exposure. We present an optimised tissue cell recovery method and a cell viability assay, compatible with intra-cellular doxorubicin. Flow cytometry was used to determine levels of cell death with suspensions comprised of: (i) HT29 cell line exposed to hyperthermia (30 min at 47 °C) and/or doxorubicin, or ex-vivo bovine liver tissue exposed to (ii) hyperthermia (up to 2 h at 45 °C), or (iii) ablative high intensity FUS (HIFU). Flow cytometric analysis revealed maximal cell death in HT29 receiving both heat and doxorubicin insults and increases in both cell granularity (p < 0.01) and cell death (p < 0.01) in cells recovered from ex-vivo liver tissue exposed to hyperthermia and high pressures of HIFU (8.2 MPa peak-to-peak free-field at 1 MHz) relative to controls. Ex-vivo results were validated with microscopy using pan-cytokeratin stain. This rapid, sensitive and highly quantitative cell-viability method is applicable to the small masses of liver tissue typically recovered from a standard core biopsy (5-20 mg) and may be applied to tissues of other histological origins including immunostaining.

Systemic lupus erythematosus presenting as Guillain-Barré syndrome.

A 37-year-old woman developed progressive symmetrical weakness with areflexia, consistent with Guillain-Barré syndrome. After initially briefly responding to intravenous immunoglobulin, her weakness progressed markedly. Further investigation identified a new diagnosis of systemic lupus erythematosus with lupus nephritis. Following additional plasma exchange and corticosteroids, the lupus activity remitted and she made a complete neurological recovery.

Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device.

Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically. Using an ultrasound-guided extracorporeal clinical FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model with ribs, we present an optimised strategy for rapidly inducing (5-15 min) and sustaining (>30 min) mild hyperthermia (ΔT <+4°C) in large tissue volumes (≤92 cm3). We describe successful clinical translation in a first-in-human clinical trial of targeted drug delivery of LTSLs (TARDOX: a phase I study to investigate drug release from thermosensitive liposomes in liver tumours), in which targeted tumour hyperthermia resulted in localised chemo-ablation. The heating strategy is potentially applicable to other indications and ultrasound-guided FUS devices.