Bluetongue disease in sheep in New South Wales - April 2023.

In 2016, bluetongue virus (BTV), serotype 16 (BTV-16), was detected in New South Wales (NSW) in sentinel cattle for the first time. Over the next 6 years, BTV-16 has been detected regularly and over an increasing area of the BTV zone in NSW. In April 2023, disease was reported in sheep on two farms on the Northern Tablelands of NSW. The consistent clinical signs included reduced exercise tolerance, facial swelling, serous nasal discharges with encrustation of the nasal plane, subcutaneous oedema of the neck and brisket and variable congestion of the coronary band. Affected sheep were mainly mature ewes and rams, with an estimated morbidity of 20% over a period of 6-8 weeks. Although there were several unexpected deaths, no veterinary examination was sought. Predominantly BTV-16 RNA was detected in sick sheep, with an incidence of infection of approximately 40% in a cross section of one flock. These events represent the first confirmation of disease due to bluetongue virus in NSW. As these cases occurred in a region with a high density of sheep, if there is ongoing transmission of BTV-16 during subsequent summers, further disease might be expected.

A liquid metal dropper for experiments on the wettability of liquid metals on plasma facing components.

A liquid metal dropper has been developed as a part of the Ion-Gas-Neutral Interactions with Surfaces 2 (IGNIS-2) facility at The Pennsylvania State University. The dropper has the capability of directly applying drops to candidate plasma facing materials for nuclear fusion reactors to enable measurements of their liquid metal wetting properties. The results presented here are specific to the use of lithium in the dropper. This paper discusses the design choices of the liquid metal dropper and its chamber, including the heating and temperature control and the dropper's motorized operation. Lithium drops of masses ranging from 0.05 g up to 0.13 g, equivalent to drop diameters between 5.6 mm to 1 cm, have been consistently dispensed by the dropper. A new algorithm is developed and used to automate the analysis of the contact angle between the liquid drops and substrate material for efficient analysis of video data recorded to study the wetting properties of candidate plasma-facing components.

The Hunter-8 Scale Prehospital Triage Workflow for Identification of Large Vessel Occlusion and Brain Haemorrhage.

OBJECTIVE: The Hunter-8 prehospital stroke scale predicts large vessel occlusion in hyperacute ischemic stroke patients (LVO) at hospital admission. We wished to test its performance in the hands of paramedics as part of a prehospital triage algorithm. We aimed to determine (a) the proportion of patients identified by the Hunter-8 algorithm, receiving reperfusion therapies, (b) whether a call to stroke team improved this, and (c) performance for LVO detection using an expanded LVO definition. METHODS: A prehospital workflow combining pre-morbid functional status, time from symptom onset, and the Hunter-8 scale was implemented from July 2019. A telephone call to the stroke team was prompted for potential treatment candidates. Classic LVO was defined as a proximal middle cerebral artery (MCA-M1), terminal internal carotid artery, or tandem occlusion. Extended LVO added proximal MCA-M2 and basilar occlusions. RESULTS: From July 2019 to April 2021, there were 363 Hunter-8 activations, 320 analyzed: 181 (56.6%) had confirmed ischemic strokes, 13 (4.1%) transient ischemic attack, 91 (28.5%) stroke mimics, and 35 (10.9%) intracranial hemorrhage. Fifty-two patients (16.3%) received reperfusion therapies, 35 with Hunter-8 ≥ 8. The stroke doctor changed the final destination for 76 patients (23.7%), and five received reperfusion therapies. The AUCs for classic and extended LVO were 0.73 (95% CI 0.66-0.79) and 0.72 (95% CI 0.65-0.77), respectively. CONCLUSION: The Hunter-8 workflow resulted in 28.7% of confirmed ischemic stroke patients receiving reperfusion therapies, with no secondary transfers to the comprehensive stroke center. The role of communication with stroke team needs to be further explored.

Neuroimaging Findings in CHANTER Syndrome: A Case Series.

Recently, a distinct clinicoradiologic entity involving cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) on MR imaging was identified. Patients present in an unresponsive state following exposure to drugs of abuse. Very little information exists regarding this entity, particularly in the radiology literature. We identify and describe 3 patients at our institution with similar clinical and radiographic findings. Multifocal restricted diffusion in the brain is typically associated with poor outcomes. By contrast, CHANTER involves intraventricular obstructive hydrocephalus that, when treated, can lead to substantial recovery. This novel syndrome should be on the differential in patients who present in an unresponsive state after recent opioid use in the context of the above imaging findings. Additional diagnoses on the differential can include ischemic stroke, hypoxic-ischemic encephalopathy, "chasing the dragon," leukoencephalopathy, opioid-associated amnestic syndrome, and pediatric opioid-use-associated neurotoxicity with cerebellar edema.

Osimertinib and anti-HER3 combination therapy engages immune dependent tumor toxicity via STING activation in trans.

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR.

Development of a novel 3D-printed multifunctional thorax model simulator for the simulation-based training of tube thoracostomy.

Tube thoracostomy is a high-acuity, low-occurrence (HALO) procedure with significant morbidity when performed incorrectly; this is amendable through simulation. Commercially available trainers exist but often have limited realism or exorbitant cost. Three-dimensional (3D) printing produces realistic and cost-effective models suitable for simulation, but no simulator has been developed for tube thoracostomy. The aim of this paper is to describe the initial development of a multifunctional 3D-printed thorax trainer for the instruction of tube thoracostomy. The thorax model was developed in conjunction with a multi-disciplinary team using 3D-printing capable software. An existing ribcage model was modified and printed in separate elements, including bony portions (ribcage, sternum and clavicles), flexible joints, skin, heart and lungs and then assembled. The total printing cost was $180 CAD. Future research will focus on incorporating the model's ability to simulate other HALO procedures and evaluating it as a training adjunct.

RéSUMé: La thoracostomie par tube est une procédure de haute acuité et de faible occurrence (HALO) avec une morbidité significative lorsqu'elle est mal exécutée; ceci est modifiable par simulation. Il existe des formateurs disponibles dans le commerce, mais ils sont souvent d'un réalisme limité ou d'un coût exorbitant. L'impression tridimensionnelle (3D) produit des modèles réalistes et rentables adaptés à la simulation, mais aucun simulateur n'a été développé pour la thoracostomie tubulaire. L'objectif de ce document est de décrire le développement initial d'un simulateur de thorax multifonctionnel imprimé en 3D pour l'enseignement de la thoracostomie tubulaire. Le modèle du thorax a été développé en collaboration avec une équipe pluridisciplinaire utilisant un logiciel capable d'imprimer en 3D. Un modèle de cage thoracique existant a été modifié et imprimé en éléments séparés, comprenant des parties osseuses (cage thoracique, sternum et clavicules), des articulations souples, la peau, le cœur et les poumons, puis assemblé. Le coût total d'impression était de 180 $ CAN. Les recherches futures se concentreront sur l'incorporation de la capacité du modèle à simuler d'autres procédures HALO et à l'évaluer en tant que complément de formation.

Detection of Optic Neuritis on Routine Brain MRI without and with the Assistance of an Image Postprocessing Algorithm.

BACKGROUND AND PURPOSE: At times, there is a clinical need for using routine brain MR imaging performed close to the time of onset of patients' visual symptoms to firmly establish the diagnosis of optic neuritis. Our aim was to assess the diagnostic performance of radiologists in detecting optic neuritis on routine brain MR images and whether this performance could be enhanced using a postprocessing algorithm. MATERIALS AND METHODS: In this retrospective case-control study of 60 patients (37 women, 23 men; mean age, 47.2 [SD, 17.9] years), 2 blinded neuroradiologists evaluated T2-weighted FLAIR and contrast-enhanced T1WI from brain MR imaging for the presence of imaging evidence of optic neuritis. Images were processed using an image-processing algorithm that aimed to selectively accentuate the signal intensity of diseased optic nerves. We assessed the effect of image processing on the contrast-to-noise ratio between the optic nerves and normal-appearing white matter and on the diagnostic performance of the neuroradiologists, including the interobserver reliability. RESULTS: The average sensitivity of readers was 55%, 56.5%, and 30.0% on FLAIR, coronal contrast-enhanced T1WI, and axial contrast-enhanced T1WI, respectively. Sensitivities were lower in the absence of fat saturation on FLAIR (P = .001) and coronal contrast-enhanced T1WI (P = .04). Processing increased the contrast-to-noise ratio of diseased (P value range = .03 to <.001) but not of control optic nerves. Processing did not improve the sensitivity but improved the specificity and positive predictive value. Interobserver agreement improved from slight to good. CONCLUSIONS: Detection of optic neuritis on routine brain MR imaging is challenging. Specificity, positive predictive value, and interobserver agreement can be improved by postprocessing of MR images.

Role of neuroimaging before reperfusion therapy. Part 1 - IV thrombolysis - Review.

This review paper summarises the yield of the different imaging modalities in the evaluation of patients for IV thrombolysis. Non-contrast CT and CTA or brain MRI combined with MRA are the recommended sequences for the evaluation of patients within the 4.5 hours time window. Multimodal MRI (DWI/PWI), and more recently, CT perfusion, offer reliable surrogate of salvageable penumbra, the target mismatch, which is now currently used as selection criteria for revascularisation treatment in an extended time window. Those sequences may also help the physician for the management of other limited cases when the diagnosis of acute ischemic stroke is difficult. Another approach the DWI/FLAIR mismatch has been proposed to identify among wake-up stroke patients those who have been experiencing an acute ischemic stroke evolving from less than 4.5hrs. Other biomarkers, such as the clot imaging on MRI and CT, help to predict the recanalisation rate after IVT, while the impact of the presence microbleeds on MRI remains to be determined.

Validated image ordering guidelines for odontogenic infections.

Overuse of computed tomography (CT) is a prevalent problem across multiple disciplines in healthcare and is common in the workup of odontogenic infections. To address this problem, an imaging pathway was created through collaboration of the oral maxillofacial surgery and emergency medicine departments to reduce unnecessary CT orders. A prospective study was implemented to assess the success of the imaging pathway to guide in the selection of the most appropriate radiological imaging modality when managing an odontogenic infection. Subjects included were adults, presenting through the emergency department for confirmed odontogenic infection. The primary outcome was the rate of unnecessary CT scans performed after the introduction of the pathway. Statistics were performed via the t-test, χ2 test, and multiple regression analysis; P < 0.05 was considered significant. Between February 1 and December 15, 2019, 100 patients met the inclusion criteria and were enrolled. The rate of unnecessary CT scans was 25.6%, compared to 56.6% prior to the introduction of the imaging pathway. The pathway did not misclassify any patient to not receive a CT when it was medically necessary. Use of the imaging pathway has the potential to reduce unnecessary CT imaging for odontogenic infections, without negatively affecting patient outcomes.

Factors associated with typical enteropathogenic Escherichia coli infection among children <5 years old with moderate-to-severe diarrhoea in rural western Kenya, 2008-2012.

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37-3.17), and convulsions (aOR 2.83, 95% CI 1.12-7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3-3.6) and wasted (OR 2.5, 95% CI 1.3-4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47-5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

Evaluating the Utility of a Postprocessing Algorithm for MRI Evaluation of Optic Neuritis.

BACKGROUND AND PURPOSE: MR imaging is useful for the detection and/or confirmation of optic neuritis. The objective of this study was to determine whether a postprocessing algorithm selectively increases the contrast-to-noise ratio of abnormal optic nerves in optic neuritis, facilitating this diagnosis on MR imaging. MATERIALS AND METHODS: In this retrospective case-control study, coronal FLAIR images and coronal contrast-enhanced T1WI from 44 patients (31 eyes with clinically confirmed optic neuritis and 28 control eyes) underwent processing using a proprietary postprocessing algorithm designed to detect and visually highlight regions of contiguous increases in signal intensity by increasing the signal intensities of regions that exceed a predetermined threshold. For quantitative evaluation of the effect on image processing, the contrast-to-noise ratio of equivalent ROIs and the contrast-to-noise ratio between optic nerves and normal-appearing white matter were measured on baseline and processed images. The effect of image-processing on diagnostic performance was evaluated by masked reviews of baseline and processed images by 6 readers with varying experience levels. RESULTS: In abnormal nerves, processing resulted in an increase in the median contrast-to-noise ratio from 17.8 to 85.0 (P < .001) on FLAIR and from 19.4 to 93.7 (P < .001) on contrast-enhanced images. The contrast-to-noise ratio for control optic nerves was not affected by processing (P = 0.13). Image processing had a beneficial effect on radiologists' diagnostic performance, with an improvement in sensitivities for 5/6 readers and relatively unchanged specificities. Interobserver agreement improved following processing. CONCLUSIONS: Processing resulted in a selective increase in the contrast-to-noise ratio for diseased nerves and corresponding improvement in the detection of optic neuritis on MR imaging by radiologists.

Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers.

BACKGROUND: Whole-genome sequencing (WGS) is a powerful method for revealing the diversity and complexity of the somatic mutation burden of tumours. Here, we investigated the utility of tumour and matched germline WGS for understanding aetiology and treatment opportunities for high-risk individuals with familial breast cancer. PATIENTS AND METHODS: We carried out WGS on 78 paired germline and tumour DNA samples from individuals carrying pathogenic variants in BRCA1 (n = 26) or BRCA2 (n = 22) or from non-carriers (non-BRCA1/2; n = 30). RESULTS: Matched germline/tumour WGS and somatic mutational signature analysis revealed patients with unreported, dual pathogenic germline variants in cancer risk genes (BRCA1/BRCA2; BRCA1/MUTYH). The strategy identified that 100% of tumours from BRCA1 carriers and 91% of tumours from BRCA2 carriers exhibited biallelic inactivation of the respective gene, together with somatic mutational signatures suggestive of a functional deficiency in homologous recombination. A set of non-BRCA1/2 tumours also had somatic signatures indicative of BRCA-deficiency, including tumours with BRCA1 promoter methylation, and tumours from carriers of a PALB2 pathogenic germline variant and a BRCA2 variant of uncertain significance. A subset of 13 non-BRCA1/2 tumours from early onset cases were BRCA-proficient, yet displayed complex clustered structural rearrangements associated with the amplification of oncogenes and pathogenic germline variants in TP53, ATM and CHEK2. CONCLUSIONS: Our study highlights the role that WGS of matched germline/tumour DNA and the somatic mutational signatures can play in the discovery of pathogenic germline variants and for providing supporting evidence for variant pathogenicity. WGS-derived signatures were more robust than germline status and other genomic predictors of homologous recombination deficiency, thus impacting the selection of platinum-based or PARP inhibitor therapy. In this first examination of non-BRCA1/2 tumours by WGS, we illustrate the considerable heterogeneity of these tumour genomes and highlight that complex genomic rearrangements may drive tumourigenesis in a subset of cases.

Implementation of a stable, high-power optical lattice for quantum gas microscopy.

We describe the design and implementation of a stable high-power 1064 nm laser system to generate optical lattices for experiments with ultracold quantum gases. The system is based on a low-noise laser amplified by an array of four heavily modified, high-power fiber amplifiers. The beam intensity is stabilized and controlled with a nonlinear feedback loop. Using real-time monitoring of the resulting optical lattice, we find the stability of the lattice site positions to be well below the lattice spacing over the course of hours. The position of the harmonic trap produced by the Gaussian envelope of the lattice beams is stable to about one lattice spacing and the long-term (six-month) relative root-mean-square stability of the lattice spacing itself is 0.5%.

Image Processing to Improve Detection of Mesial Temporal Sclerosis in Adults.

In this retrospective case-control study, we investigated whether an image-processing algorithm designed to exaggerate the intensity of diseased hippocampi on FLAIR images can improve the diagnostic accuracy and interobserver reliability of radiologists in detecting mesial temporal sclerosis-related hippocampal signal alteration. Herein, we share the results of this study that showed that the image processing improved the confidence of radiologists in detecting mesial temporal sclerosis-related signal alteration, allowing an improved sensitivity, specificity, and interobserver reliability.

Effect of caffeinated gum on a battery of rugby-specific tests in trained university-standard male rugby union players.

BACKGROUND: Caffeine has been shown to enhance strength, power and endurance, characteristics that underpin performance in rugby. Caffeinated gum has attracted interest as a novel vehicle for delivering caffeine, because absorption of caffeine from gum is quick. Rapid absorption of caffeine may be useful during rugby matches when there is limited time for supplementation such as at half-time or when substitutes enter play. The purpose of this study was to determine whether a low dose of caffeine in gum improves performance in a battery of rugby-specific tests. METHODS: In a double-blind, randomized, placebo-controlled, crossover design, 17 male university-standard rugby players (mass: 85.6 ± 6.3 kg; height: 179.4 ± 6.2 cm; age: 20.4 ± 1.2 years) chewed caffeinated gum (200 mg caffeine) or a placebo gum on two occasions separated by a week. After a standardized warm-up, gum was chewed for 5 min. Subsequently, participants performed three countermovement jumps, followed by an Illinois agility test, 6 × 30 m repeated sprints, and the Yo-Yo IR-2 test; each test was separated by short rest periods. RESULTS: Caffeinated gum enhanced countermovement jump by 3.6% (caffeine: 43.7 ± 7.6 cm vs. placebo: 42.2 ± 6.2 cm; d = 0.22, 95% CI [0.006, 0.432]; p = 0.044). There was a greater resistance to fatigue during the 6 × 30 m repeated sprint test (fatigue index caffeine: 102.2 ± 0.9% vs. placebo: 103.3 ± 1.2%; d = 1.03, 95% CI [0.430, 1.613]; p = 0.001), and performance on the Yo-Yo IR2 was improved by 14.5% (caffeine: 426 ± 105 m, placebo: 372 ± 91 m; d = 0.55, 95% CI [0.130, 0.957]; p = 0.010). Caffeine gum had no significant effect on the Illinois agility test (caffeine 16.22 ± 1.08 s vs. placebo 15.88 ± 1.09 s; d = - 0.31, 95% CI [- 0.855, 0.240]; p = 0.271). CONCLUSIONS: In university-standard rugby players, a low dose of caffeine (200 mg) supplied in chewing gum enhanced performance on the Yo-Yo IR-2 test and the countermovement jump test and reduced fatigue index during repeated sprints. These improvements in a battery of rugby-specific tests may transfer to enhanced performance in rugby matches.

Using Correlative Properties of Neighboring Pixels to Improve Gray-White Differentiation in Pediatric Head CT Images.

BACKGROUND AND PURPOSE: A lower radiation dose can have a detrimental effect on the quality of head CT images. The aim of this study performed in a pediatric population was to test whether an image-processing algorithm (Correlative Image Enhancement) based on the correlation among intensities of neighboring pixels can improve gray-white differentiation in head CTs. MATERIALS AND METHODS: Sixty baseline head CT images with normal findings obtained from scans of 30 children were processed using Correlative Image Enhancement to produce corresponding enhanced images. Gray-white differentiation in baseline and enhanced images was assessed quantitatively by calculating the contrast-to-noise ratio and conspicuity in equivalent ROIs in gray and white matter. Two masked readers rated the images for visibility of gray-white differentiation on a 5-point Likert scale. Differences in both quantitative and qualitative measures of gray-white differentiation between baseline and enhanced images were tested for statistical significance. P values < .05 were considered significant. RESULTS: Image processing resulted in improvement in the contrast-to-noise ratio (from 1.86 ± 0.94 to 2.26 ± 1.00, P = .02) as well as conspicuity (from 37.28 ± 11.56 to 46.4 ± 11.5, P < .001). This was accompanied by improved subjective visibility of gray-white differentiation as reported by both readers (P < .01). CONCLUSIONS: Image processing using Correlative Image Enhancement had a beneficial effect on quantitative measures of gray-white differentiation. This translated into improved perception of gray-white differentiation by readers. Further studies are needed to assess the effect of such image processing on the detection of disease processes using head CTs.

Vibriosis, not cholera: toxigenic Vibrio cholerae non-O1, non-O139 infections in the United States, 1984-2014.

Toxigenic strains of Vibrio cholerae serogroups O1 and O139 have caused cholera epidemics, but other serogroups - such as O75 or O141 - can also produce cholera toxin and cause severe watery diarrhoea similar to cholera. We describe 31 years of surveillance for toxigenic non-O1, non-O139 infections in the United States and map these infections to the state where the exposure probably originated. While serogroups O75 and O141 are closely related pathogens, they differ in how and where they infect people. Oysters were the main vehicle for O75 infection. The vehicles for O141 infection include oysters, clams, and freshwater in lakes and rivers. The patients infected with serogroup O75 who had food traceback information available ate raw oysters from Florida. Patients infected with O141 ate oysters from Florida and clams from New Jersey, and those who only reported being exposed to freshwater were exposed in Arizona, Michigan, Missouri, and Texas. Improving the safety of oysters, specifically, should help prevent future illnesses from these toxigenic strains and similar pathogenic Vibrio species. Post-harvest processing of raw oysters, such as individual quick freezing, heat-cool pasteurization, and high hydrostatic pressurization, should be considered.

Nondestructive Biological Evidence Collection with Alternative Swabs and Adhesive Lifters.

In forensic science, biological material is typically collected from evidence via wet/dry double swabbing with cotton swabs, which is effective but can visibly damage an item's surface. When an item's appearance must be maintained, dry swabbing and tape-lifting may be employed as collection techniques that are visually nondestructive to substrates' surfaces. This study examined the efficacy of alternative swab matrices and adhesive lifters when collecting blood and fingerprints from glass, painted drywall, 100% cotton, and copy paper. Data were evaluated by determining the percent profile and quality score for each STR profile generated. Hydraflock(®) swabs, BVDA Gellifters(®) , and Scenesafe FAST™ tape performed as well as or better than cotton swabs when collecting fingerprints from painted drywall and 100% cotton. Collection success was also dependent on the type of biological material sampled and the substrate on which it was deposited. These results demonstrated that alternative swabs and adhesive lifters can be effective for nondestructive DNA collection from various substrates.

Functional advantage of educated KIR2DL1(+) natural killer cells for anti-HIV-1 antibody-dependent activation.

Evidence from the RV144 HIV-1 vaccine trial implicates anti-HIV-1 antibody-dependent cellular cytotoxicity (ADCC) in vaccine-conferred protection from infection. Among effector cells that mediate ADCC are natural killer (NK) cells. The ability of NK cells to be activated in an antibody-dependent manner is reliant upon several factors. In general, NK cell-mediated antibody-dependent activation is most robust in terminally differentiated CD57(+) NK cells, as well as NK cells educated through ontological interactions between inhibitory killer immunoglobulin-like receptors (KIR) and their major histocompatibility complex class I [MHC-I or human leucocyte antigen (HLA-I)] ligands. With regard to anti-HIV-1 antibody-dependent NK cell activation, previous research has demonstrated that the epidemiologically relevant KIR3DL1/HLA-Bw4 receptor/ligand combination confers enhanced activation potential. In the present study we assessed the ability of the KIR2DL1/HLA-C2 receptor/ligand combination to confer enhanced activation upon direct stimulation with HLA-I-devoid target cells or antibody-dependent stimulation with HIV-1 gp140-pulsed CEM.NKr-CCR5 target cells in the presence of an anti-HIV-1 antibody source. Among donors carrying the HLA-C2 ligand for KIR2DL1, higher interferon (IFN)-γ production was observed within KIR2DL1(+) NK cells than in KIR2DL1(-) NK cells upon both direct and antibody-dependent stimulation. No differences in KIR2DL1(+) and KIR2DL1(-) NK cell activation were observed in HLA-C1 homozygous donors. Additionally, higher activation in KIR2DL1(+) than KIR2DL1(-) NK cells from HLA-C2 carrying donors was observed within less differentiated CD57(-) NK cells, demonstrating that the observed differences were due to education and not an overabundance of KIR2DL1(+) NK cells within differentiated CD57(+) NK cells. These observations are relevant for understanding the regulation of anti-HIV-1 antibody-dependent NK cell responses.