Use of TSAR, Thermal Shift Analysis in R, to identify Folic Acid as a Molecule that Interacts with HIV-1 Capsid.

Thermal shift assay (TSA) is a versatile biophysical technique for studying protein interactions. Here, we report a free, open-source software tool TSAR (Thermal Shift Analysis in R) to expedite and automate the analysis of thermal shift data derived either from individual experiments or large screens of chemical libraries. The TSAR package incorporates multiple, dynamic workflows to facilitate the analysis of TSA data and returns publication-ready graphics or processed results. Further, the package includes a graphic user interface (GUI) that enables easy use by non-programmers, aiming to simplify TSA analysis while diversifying visualization. To exemplify the utility of TSAR we screened a chemical library of vitamins to identify molecules that interact with the capsid protein (CA) of human immunodeficiency virus type 1 (HIV-1). Our data show that hexameric CA interacts with folic acid in vitro.

The reality of advanced airway management during out of hospital cardiac arrest; why did paramedics deviate from their allocated airway management strategy during the AIRWAYS-2 randomised trial?

Background: AIRWAYS-2 was a large multi-centre cluster randomised controlled trial investigating the effect on functional outcome of a supraglottic airway device (i-gel) versus tracheal intubation (TI) as the initial advanced airway during out-of-hospital cardiac arrest. We aimed to understand why paramedics deviated from their allocated airway management algorithm during AIRWAYS-2. Methods: This study employed a pragmatic sequential explanatory design utilising retrospective study data collected during the AIRWAYS-2 trial. Airway algorithm deviation data were analysed to categorise and quantify the reasons why paramedics did not follow their allocated strategy of airway management during AIRWAYS-2. Recorded free text entries provided additional context to the paramedic decision-making related to each category identified. Results: In 680 (11.7%) of 5800 patients the study paramedic did not follow their allocated airway management algorithm. There was a higher percentage of deviations in the TI group (399/2707; 14.7%) compared to the i-gel group (281/3088; 9.1%). The predominant reason for a paramedic not following their allocated airway management strategy was airway obstruction, occurring more commonly in the i-gel group (109/281; 38.7%) versus (50/399; 12.5%) in the TI group. Conclusion: There was a higher proportion of deviations from the allocated airway management algorithm in the TI group (399; 14.7%) compared to the i-gel group (281; 9.1%). The most frequent reason for deviating from the allocated airway management algorithm in AIRWAYS-2 was obstruction of the patient's airway by fluid. This occurred in both groups of the AIRWAYS-2 trial, but was more frequent in the i-gel group.

Deliberate self-poisoning in Australian adolescents is increased on school days.

Deliberate self-poisoning (DSP) in adolescents is increasing dramatically. Life at school is one of the most important life influences for this age group. This study aimed to investigate whether the frequency of DSP is higher during school term compared to holidays and whether this difference has become greater over time. This is an ecological study using Poisons Information Centre (PIC) data for all DSPs in 10-19 year olds from New South Wales, Tasmania and Australian Capital Territory that occurred between 2005 and 2018. For each call, the date of the poisoning was assigned as 'term' or 'holiday'. To control for population growth, calls were expressed as per 100,000 of the population per day. Multivariable Poisson regression was performed to investigate the combined impact of various predictors (state, sex, year, holiday/term, day of week, age) on call number. 26,432 calls were included in the analysis (73.6% female, 24.1% male and 2.3% unknown). Poisson regression showed significant effects for all predictors, with an increased likelihood of DSP during the school term compared with holidays and on Monday-Thursday compared with Saturday but only during the school term. DSP doubled between 2012 and 2017 and the disparity between DSP that occurs during term vs. holiday increased over that time frame. We conclude that some of the increase in DSP is likely due to school-specific stressors, hence the school environment is the ideal setting for self-harm prevention initiatives.

Engineering Thermal Transport across Layered Graphene-MoS2 Superlattices.

Layering two-dimensional van der Waals materials provides a high degree of control over atomic placement, which could enable tailoring of vibrational spectra and heat flow at the sub-nanometer scale. Here, using spatially resolved ultrafast thermoreflectance and spectroscopy, we uncover the design rules governing cross-plane heat transport in superlattices assembled from monolayers of graphene (G) and MoS2 (M). Using a combinatorial experimental approach, we probe nine different stacking sequences, G, GG, MG, GGG, GMG, GGMG, GMGG, GMMG, and GMGMG, and identify the effects of vibrational mismatch, interlayer adhesion, and junction asymmetry on thermal transport. Pure G sequences display evidence of quasi-ballistic transport, whereas adding even a single M layer strongly disrupts heat conduction. The experimental data are described well by molecular dynamics simulations, which include thermal expansion, accounting for the effect of finite temperature on the interlayer spacing. The simulations show that an increase of ∼2.4% in the layer separation of GMGMG, relative to its value at 300 K, can lead to a doubling of the thermal resistance. Using these design rules, we experimentally demonstrate a five-layer GMGMG superlattice "thermal metamaterial" with an ultralow effective cross-plane thermal conductivity comparable to that of air.

High Current Density in Monolayer MoS2 Doped by AlOx.

Semiconductors require stable doping for applications in transistors, optoelectronics, and thermoelectrics. However, this has been challenging for two-dimensional (2D) materials, where existing approaches are either incompatible with conventional semiconductor processing or introduce time-dependent, hysteretic behavior. Here we show that low-temperature (<200 °C) substoichiometric AlOx provides a stable n-doping layer for monolayer MoS2, compatible with circuit integration. This approach achieves carrier densities >2 × 1013 cm-2, sheet resistance as low as ∼7 kΩ/□, and good contact resistance ∼480 Ω·µm in transistors from monolayer MoS2 grown by chemical vapor deposition. We also reach record current density of nearly 700 µA/µm (>110 MA/cm2) along this three-atom-thick semiconductor while preserving transistor on/off current ratio >106. The maximum current is ultimately limited by self-heating (SH) and could exceed 1 mA/µm with better device heat sinking. With their 0.1 nA/µm off-current, such doped MoS2 devices approach several low-power transistor metrics required by the international technology roadmap.

The experiences of EMS providers taking part in a large randomised trial of airway management during out of hospital cardiac arrest, and the impact on their views and practice. Results of a survey and telephone interviews.

AIMS: To explore EMS experiences of participating in a large trial of airway management during out-of-hospital cardiac arrest (AIRWAYS-2), specifically to explore: 1. Any changes in views and practice as a result of trial participation. 2. Experiences of trial training. 3. Experiences of enrolling critically unwell patients without consent. 4. Barriers and facilitators for out-of-hospital trial participation. METHODS: An online questionnaire was distributed to 1523 EMS providers who participated in the trial. In-depth telephone interviews explored the responses to the online questionnaire. Quantitative data were collated and presented using simple descriptive statistics. Qualitative data collected during the online survey were analysed using content analysis. Interpretive Phenomenological Analysis was used for qualitative interview data. RESULTS: Responses to the online questionnaire were received from 33% of the EMS providers who participated in AIRWAYS-2, and 19 providers were interviewed. EMS providers described barriers and facilitators to trial participation and changes in their views and practice. The results are presented in five distinct themes: research process; changes in airway management views and practice; engagement with research; professional identity; professional competence. CONCLUSIONS: Participation in the AIRWAYS-2 trial was enjoyable and EMS providers valued the study training and support. There was enhanced confidence in airway management as a result of taking part in the trial. EMS providers indicated existing variability in training, experience and confidence in tracheal intubation, and expressed a preference for the method of airway management to which they had been randomised. There was support for the stepwise approach to airway management, but also concern regarding the potential loss of tracheal intubation from 'standard' EMS practice. The views and practices of the EMS providers expressed in this research will usefully inform the design of future similar trials.

Plant functional trait response to environmental drivers across European temperate forest understorey communities.

Functional traits respond to environmental drivers, hence evaluating trait-environment relationships across spatial environmental gradients can help to understand how multiple drivers influence plant communities. Global-change drivers such as changes in atmospheric nitrogen deposition occur worldwide, but affect community trait distributions at the local scale, where resources (e.g. light availability) and conditions (e.g. soil pH) also influence plant communities. We investigate how multiple environmental drivers affect community trait responses related to resource acquisition (plant height, specific leaf area (SLA), woodiness, and mycorrhizal status) and regeneration (seed mass, lateral spread) of European temperate deciduous forest understoreys. We sampled understorey communities and derived trait responses across spatial gradients of global-change drivers (temperature, precipitation, nitrogen deposition, and past land use), while integrating in-situ plot measurements on resources and conditions (soil type, Olsen phosphorus (P), Ellenberg soil moisture, light, litter mass, and litter quality). Among the global-change drivers, mean annual temperature strongly influenced traits related to resource acquisition. Higher temperatures were associated with taller understoreys producing leaves with lower SLA, and a higher proportional cover of woody and obligate mycorrhizal (OM) species. Communities in plots with higher Ellenberg soil moisture content had smaller seeds and lower proportional cover of woody and OM species. Finally, plots with thicker litter layers hosted taller understoreys with larger seeds and a higher proportional cover of OM species. Our findings suggest potential community shifts in temperate forest understoreys with global warming, and highlight the importance of local resources and conditions as well as global-change drivers for community trait variation.

Ultrahigh thermal isolation across heterogeneously layered two-dimensional materials.

Heterogeneous integration of nanomaterials has enabled advanced electronics and photonics applications. However, similar progress has been challenging for thermal applications, in part due to shorter wavelengths of heat carriers (phonons) compared to electrons and photons. Here, we demonstrate unusually high thermal isolation across ultrathin heterostructures, achieved by layering atomically thin two-dimensional (2D) materials. We realize artificial stacks of monolayer graphene, MoS2, and WSe2 with thermal resistance greater than 100 times thicker SiO2 and effective thermal conductivity lower than air at room temperature. Using Raman thermometry, we simultaneously identify the thermal resistance between any 2D monolayers in the stack. Ultrahigh thermal isolation is achieved through the mismatch in mass density and phonon density of states between the 2D layers. These thermal metamaterials are an example in the emerging field of phononics and could find applications where ultrathin thermal insulation is desired, in thermal energy harvesting, or for routing heat in ultracompact geometries.

High-Field Transport and Velocity Saturation in Synthetic Monolayer MoS2.

Two-dimensional semiconductors such as monolayer MoS2 are of interest for future applications including flexible electronics and end-of-roadmap technologies. Most research to date has focused on low-field mobility, but the peak current-driving ability of transistors is limited by the high-field saturation drift velocity, vsat. Here, we measure high-field transport as a function of temperature for the first time in high-quality synthetic monolayer MoS2. We find that in typical device geometries (e.g. on SiO2 substrates) self-heating can significantly reduce current drive during high-field operation. However, with measurements at varying ambient temperature (from 100 to 300 K), we extract electron vsat = (3.4 ± 0.4) × 106 cm/s at room temperature in this three-atom-thick semiconductor, which we benchmark against other bulk and layered materials. With these results, we estimate that the saturation current in monolayer MoS2 could exceed 1 mA/µm at room temperature, in digital circuits with near-ideal thermal management.

Temperature-Dependent Thermal Boundary Conductance of Monolayer MoS2 by Raman Thermometry.

The electrical and thermal behavior of nanoscale devices based on two-dimensional (2D) materials is often limited by their contacts and interfaces. Here we report the temperature-dependent thermal boundary conductance (TBC) of monolayer MoS2 with AlN and SiO2, using Raman thermometry with laser-induced heating. The temperature-dependent optical absorption of the 2D material is crucial in such experiments, which we characterize here for the first time above room temperature. We obtain TBC ∼ 15 MW m-2 K-1 near room temperature, increasing as ∼ T0.65 in the range 300-600 K. The similar TBC of MoS2 with the two substrates indicates that MoS2 is the "softer" material with weaker phonon irradiance, and the relatively low TBC signifies that such interfaces present a key bottleneck in energy dissipation from 2D devices. Our approach is needed to correctly perform Raman thermometry of 2D materials, and our findings are key for understanding energy coupling at the nanoscale.

Detection of methylation on dsDNA using nanopores in a MoS2 membrane.

Methylation at the 5-carbon position of the cytosine nucleotide base in DNA has been shown to be a reliable diagnostic biomarker for carcinogenesis. Early detection of methylation and intervention could drastically increase the effectiveness of therapy and reduce the cancer mortality rate. Current methods for detecting methylation involve bisulfite genomic sequencing, which are cumbersome and demand a large sample size of bodily fluids to yield accurate results. Hence, more efficient and cost effective methods are desired. Based on our previous work, we present a novel nanopore-based assay using a nanopore in a MoS2 membrane, and the methyl-binding protein (MBP), MBD1x, to detect methylation on dsDNA. We show that the dsDNA translocation was effectively slowed down using an asymmetric concentration of buffer and explore the possibility of profiling the position of methylcytosines on the DNA strands as they translocate through the 2D membrane. Our findings advance us one step closer towards the possible use of nanopore sensing technology in medical applications such as cancer detection.

Low Variability in Synthetic Monolayer MoS2 Devices.

Despite much interest in applications of two-dimensional (2D) fabrics such as MoS2, to date most studies have focused on single or few devices. Here we examine the variability of hundreds of transistors from monolayer MoS2 synthesized by chemical vapor deposition. Ultraclean fabrication yields low surface roughness of ∼3 Šand surprisingly low variability of key device parameters, considering the atomically thin nature of the material. Threshold voltage variation and very low hysteresis suggest variations in charge density and traps as low as ∼1011 cm-2. Three extraction methods (field-effect, Y-function, and effective mobility) independently reveal mobility from 30 to 45 cm2/V/s (10th to 90th percentile; highest value ∼48 cm2/V/s) across areas >1 cm2. Electrical properties are remarkably immune to the presence of bilayer regions, which cause only small conduction band offsets (∼55 meV) measured by scanning Kelvin probe microscopy, an order of magnitude lower than energy variations in Si films of comparable thickness. Data are also used as inputs to Monte Carlo circuit simulations to understand the effects of material variability on circuit variation. These advances address key missing steps required to scale 2D semiconductors into functional systems.

Emergency medical service provider decision-making in out of hospital cardiac arrest: an exploratory study.

BACKGROUND: There are approximately 60,000 out-of-hospital cardiac arrests (OHCA) in the United Kingdom (UK) each year. Within the UK there are well-established clinical practice guidelines that define when resuscitation should be commenced in OHCA, and when resuscitation should cease. Background literature indicates that decision-making in the commencement and cessation of resuscitation efforts in OHCA is complex, and not comprehensively understood. No relevant research from the UK has been published to date and this research study seeks to explore the influences on UK Emergency Medical Service (EMS) provider decision-making when commencing and ceasing resuscitation attempts in OHCA. The aim of this research to explore the influences on UK Emergency Medical Services provider decision-making when commencing and ceasing resuscitation attempts in OHCA. METHODS: Four focus groups were convened with 16 clinically active EMS providers. Four case vignettes were discussed to explore decision-making within the focus groups. Thematic analysis was used to analyse transcripts. RESULTS: This research found that there are three stages in the decision-making process when EMS providers consider whether to commence or cease resuscitation attempts in OHCA. These stages are: the call; arrival on scene; the protocol. Influential factors present at each of the three stages can lead to different decisions and variability in practice. These influences are: factual information available to the EMS provider; structural factors such as protocol, guidance and research; cultural beliefs and values; interpersonal factors; risk factors; personal values and beliefs. CONCLUSIONS: An improved understanding of the circumstantial, individual and interpersonal factors that mediate the decision-making process in clinical practice could inform the development of more effective clinical guidelines, education and clinical decision support in OHCA. These changes have the potential to lead to greater consistency. and EMS provider confidence, with the potential for improved patient outcome from OHCA.

Photoresponse of Natural van der Waals Heterostructures.

Van der Waals heterostructures consisting of two-dimensional materials offer a platform to obtain materials by design and are very attractive owing to unique electronic states. Research on 2D van der Waals heterostructures (vdWH) has so far been focused on fabricating individually stacked atomically thin unary or binary crystals. Such systems include graphene, hexagonal boron nitride, and members of the transition metal dichalcogenide family. Here we present our experimental study of the optoelectronic properties of a naturally occurring vdWH, known as franckeite, which is a complex layered crystal composed of lead, tin, antimony, iron, and sulfur. We present here that thin film franckeite (60 nm < d < 100 nm) behaves as a narrow band gap semiconductor demonstrating a wide-band photoresponse. We have observed the band-edge transition at ∼1500 nm (∼830 meV) and high external quantum efficiency (EQE ≈ 3%) at room temperature. Laser-power-resolved and temperature-resolved photocurrent measurements reveal that the photocarrier generation and recombination are dominated by continuously distributed trap states within the band gap. To understand wavelength-resolved photocurrent, we also calculated the optical absorption properties via density functional theory. Finally, we have shown that the device has a fast photoresponse with a rise time as fast as ∼1 ms. Our study provides a fundamental understanding of the optoelectronic behavior in a complex naturally occurring vdWH, and may pave an avenue toward developing nanoscale optoelectronic devices with tailored properties.

Home or hospital for people with dementia and one or more other multimorbidities: What is the potential to reduce avoidable emergency admissions? The HOMEWARD Project Protocol.

INTRODUCTION: Older people with multimorbidities frequently access 999 ambulance services. When multimorbidities include dementia, the risk of ambulance use, accident and emergency (A&E) attendance and hospital admission are all increased, even when a condition is treatable in the community. People with dementia tend to do poorly in the acute hospital setting and hospital admission can result in adverse outcomes. This study aims to provide an evidence-based understanding of how older people living with dementia and other multimorbidities are using emergency ambulance services. It will also provide evidence of how paramedics make decisions about taking this group of patients to hospital, and what resources would allow them to make more person-focused decisions to enable optimal patient care. METHODS AND ANALYSIS: Phase 1: retrospective data analysis: quantitative analysis of ambulance service data will investigate: how often paramedics are called to older people with dementia; the amount of time paramedics spend on scene and the frequency with which these patients are transported to hospital. Phase 2: observational case studies: detailed case studies will be compiled using qualitative methods, including non-participant observation of paramedic decision-making, to understand why older people with multimorbidities including dementia are conveyed to A&E when they could be treated at home or in the community. Phase 3: needs analysis: nominal groups with paramedics will investigate and prioritise the resources that would allow emergency, urgent and out of hours care to be effectively delivered to these patients at home or in a community setting. ETHICS AND DISSEMINATION: Approval for the study has been obtained from the Health Research Authority (HRA) with National Health Service (NHS) Research Ethics Committee approval for phase 2 (16/NW/0803). The dissemination strategy will include publishing findings in appropriate journals, at conferences and in newsletters. We will pay particular attention to dissemination to the public, dementia organisations and ambulance services.

Energy Dissipation in Monolayer MoS2 Electronics.

The advancement of nanoscale electronics has been limited by energy dissipation challenges for over a decade. Such limitations could be particularly severe for two-dimensional (2D) semiconductors integrated with flexible substrates or multilayered processors, both being critical thermal bottlenecks. To shed light into fundamental aspects of this problem, here we report the first direct measurement of spatially resolved temperature in functioning 2D monolayer MoS2 transistors. Using Raman thermometry, we simultaneously obtain temperature maps of the device channel and its substrate. This differential measurement reveals the thermal boundary conductance of the MoS2 interface with SiO2 (14 ± 4 MW m-2 K-1) is an order magnitude larger than previously thought, yet near the low end of known solid-solid interfaces. Our study also reveals unexpected insight into nonuniformities of the MoS2 transistors (small bilayer regions) which do not cause significant self-heating, suggesting that such semiconductors are less sensitive to inhomogeneity than expected. These results provide key insights into energy dissipation of 2D semiconductors and pave the way for the future design of energy-efficient 2D electronics.

Sensitivity of blood and tissue diagnostics for gastrointestinal cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: Gastrointestinal (GI) cytomegalovirus (CMV) disease is the most common manifestation of tissue-invasive CMV infection in solid organ transplant (SOT) recipients, but the diagnostic yields of blood and tissue testing have not been systematically assessed in a large patient cohort. METHODS: We retrospectively identified consecutive SOT recipients with biopsy-confirmed GI CMV disease who had both tissue and blood (CMV polymerase chain reaction or antigenemia) diagnostic testing performed within 14 days of diagnosis. Descriptive statistics and logistic regression were used to assess the association between patient factors and viremia and the diagnostic yield of tests performed on biopsy specimens. RESULTS: A total of 101 patients (73% donor seropositive/recipient seronegative [D+/R-], 22% recipient seropositive [R+]) had GI CMV disease (58% upper, 22% lower, and 20% both) at a median of 185 days (range, 21-6345 days) post transplant. In multivariate analysis, R+ CMV serostatus (odds ratio [OR] 0.1 [0.0-0.4], P < 0.001) and diagnosis >6 months post transplant (OR 0.3 [0.1-0.9], P = 0.03) were each independently associated with absence of CMV viremia at time of diagnosis. In the subset of patients (n = 29) in whom both histopathology and viral culture were performed on biopsy specimens, 11 (39%) had CMV detected only by culture and had similar clinical characteristics and outcomes to those with positive histopathology (P > 0.05 for all comparisons). CONCLUSIONS: The sensitivity of viremia in SOT recipients with GI CMV disease is significantly lower in CMV-seropositive patients and in those >6 months post transplant. Addition of viral culture to endoscopic biopsy specimens significantly increases the diagnostic yield for GI CMV disease.

Comparison of Single-fraction and Multi-fraction Stereotactic Radiotherapy for Patients with 18F-fluorodeoxyglucose Positron Emission Tomography-staged Pulmonary Oligometastases.

AIM: To compare outcomes of single-fraction and multi-fraction stereotactic ablative body radiotherapy (SABR) for pulmonary metastases. MATERIALS AND METHODS: A retrospective review from two academic institutions of patients with one to three pulmonary metastases staged with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans. For single-fraction SABR, 26 Gy was prescribed for peripheral targets and 18 Gy for central targets. In the multi-fraction cohort, 48 Gy/4 or 50 Gy/5 was prescribed for peripheral targets and 50 Gy/5 was prescribed for central targets. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were delivered using heterogeneity corrections. Conformity indices at an intermediate dose (R50%) and at a high dose (R100%) were used to assess a relationship with the planning target volume (PTV). Overall survival, local and distant progression and toxicity rates were analysed from the date of treatment completion. RESULTS: Between February 2010 and June 2013, 65 patients with 85 pulmonary metastases were reviewed. The median follow-up was 2.1 years. Metastases most commonly originated from colorectal cancer (31%), followed by non-small cell lung cancer (25%). 3D-CRT was used in 52 targets, IMRT in 21 and VMAT in 12. 3D-CRT showed a lower median R50% (P=0.01), but a higher median R100% than IMRT/VMAT (P=0.04). The R50% index was inversely correlated to the PTV with all techniques (P=0.01). Overall survival at 1 and 2 years in all patients was 93% (95% confidence interval 87-100%) and 71% (95% confidence interval 58-86%), respectively. The 2 year freedom from local and distant progression was 93% (95% confidence interval 86-100%) and 38% (95% confidence interval 27-55%), respectively. There were no significant differences between overall survival (P=0 .14), time to distant progression (P=0.06) or toxicity rates (P=0.75) between single- and multi-fraction cohorts. CONCLUSION: We report comparable local control, overall survival and toxicity rates between single-fraction and multi-fraction SABR treatments in patients with FDG-PET-staged pulmonary oligometastases. We propose a guideline for R50% conformity incorporating 3D-CRT/IMRT/VMAT techniques with heterogeneity corrected planning algorithms.

Left ventricular rotational mechanics in Tanzanian children with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a common inherited hemoglobinopathy. Adults with SCD manifest both systolic and diastolic cardiac dysfunction, though the age of onset of dysfunction has not been defined. Left ventricular (LV) rotational mechanics have not been studied in children with SCD. The aim of this study was to investigate whether cardiac rotational mechanics differed between children with SCD and age-matched controls. METHODS: Basal and apical LV short-axis images were acquired prospectively in 213 patients with SCD (mean age, 14.1 ± 2.6 years) and 49 controls (mean age, 13.3 ± 2.8 years) from the Muhimbili Sickle Cohort in Dar es Salaam, Tanzania. The magnitude of basal and apical rotation, net twist angle, torsion, and untwist rate were obtained by two-dimensional speckle-tracking. The timing of events was normalized to aortic valve closure. RESULTS: Mean basal rotation was significantly lower in patients with SCD compared with controls (P = .012), although no difference was observed in apical rotation (P = .37). No statistically significant differences in torsion or net twist angle were detected. Rotation rate at the apex (P = .001) and base (P = .0004) were significantly slower in subjects with SCD compared with controls. Mean peak untwisting rate was also significantly slower in patients with SCD (P = .006). No associations were found between hemoglobin concentration and apical rotation, basal rotation, net twist, and torsion. CONCLUSION: This study demonstrates alterations in LV rotational mechanics in children with SCD, including lower basal rotation, peak differential twist, and untwist rate. These abnormalities denote subclinical changes in LV systolic and diastolic performance in children with SCD. Future work may reveal an association between rotational metrics and long-term patient outcomes.