Insight into the emerging insect to human pathogen Photorhabdus revealing geographic differences in immune cell tropism.

Background: Photorhabdus asymbiotica is a species of the insect pathogenic Photorhabdus genus that has been isolated as an etiological agent in human infections. Since then, multiple isolates have been identified worldwide; however, actual clinical infections have so far only been identified in North America, Australia, and Nepal. Previous research on the clinical isolates had shown that the strains differed in their behaviour when infecting cultured human cells. Methods: In this study, we investigate the differences between the pathogenic activities of P. asymbiotica isolates from different geographic locations. Pathogenicity was analysed using infection assays with both cultured cell lines (THP-1, CHO, and HEK cells) and primary immune cells, and peripheral blood mononuclear cells (PBMCs) isolated from human blood. Results: Here, we present the findings from the Australian (Kingscliff) and North American (ATCC43949) clinical isolates, and non-clinical soilborne nematode isolates from Thailand (PB68) and Northern Europe (HIT and JUN) of P. asymbiotica. We also show the first findings from a new clinical isolate of P. luminescens (Texas), the first non-asymbiotica species to cause a human infection, confirming its ability to infect and survive inside human immune cells. Conclusion: Here for the first time, we show how P. asymbiotica selectively infects certain immune cells while avoiding others and that infectivity varies depending on growth temperature. We also show that the tropism varies depending on the geographic location a strain is isolated from, with only the European HIT and JUN strains lack the ability to survive within mammalian cells in tissue culture.

Distinct Longitudinal Changes in EEG Measures Reflecting Functional Network Disruption in ALS Cognitive Phenotypes.

Amyotrophic lateral sclerosis (ALS) is characterised primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. We have shown previously that resting-state EEG captures dysfunction in motor and cognitive networks in ALS. However, the longitudinal development of these dysfunctional patterns, especially in networks linked with cognitive-behavioural functions, remains unclear. Longitudinal studies on non-motor changes in ALS are essential to further develop our understanding of disease progression, improve care and enhance the evaluation of new treatments. To address this gap, we examined 124 ALS individuals with 128-channel resting-state EEG recordings, categorised by cognitive impairment (ALSci, n = 25), behavioural impairment (ALSbi, n = 58), or non-impaired (ALSncbi, n = 53), with 12 participants meeting the criteria for both ALSci and ALSbi. Using linear mixed-effects models, we characterised the general and phenotype-specific longitudinal changes in brain network, and their association with cognitive performance, behaviour changes, fine motor symptoms, and survival. Our findings revealed a significant decline in [Formula: see text]-band spectral power over time in the temporal region along with increased [Formula: see text]-band power in the fronto-temporal region in the ALS group. ALSncbi participants showed widespread ß-band synchrony decrease, while ALSci participants exhibited increased co-modulation correlated with verbal fluency decline. Longitudinal network-level changes were specific of ALS subgroups and correlated with motor, cognitive, and behavioural decline, as well as with survival. Spectral EEG measures can longitudinally track abnormal network patterns, serving as a candidate stratification tool for clinical trials and personalised treatments in ALS.

Acute pancreatitis as a risk factor of chronic pancreatitis and pancreatic cancer. An overview.

This is an overview of relation between acute and chronic pancreatitis and between acute pancreatitis and pancreatic cancer. Acute pancreatitis and recurrent acute pancreatitis are an etiological factor of chronic pancreatitis. Population-based studies have calculated the risk of acute recurrent pancreatitis after the first attack of acute pancreatitis to be 20% and development of chronic pancreatitis after first attack of acute pancreatitis is 10%. An important risk factor is tobacco smoking. Acute and chronic pancreatitis are risk factors for pancreatic cancer. The risk of acute pancreatitis is related to the number of recurrences of acute pancreatitis, but not the etiology of acute pancreatitis. Acute pancreatitis, as well as chronic pancreatitis, are risk factors for pancreatic cancer. After an attack of acute pancreatitis or recurrent acute pancreatitis a patient should be regarded as a high risk.

Insulin-Like Growth Factor-Binding Protein 5 Promotes the Cell Proliferation and Osteogenic Potential of Dental Pulp Stem Cells Dependent on Its Nuclear Localisation Sequence.

OBJECTIVES: Dental pulp stem cells (DPSCs) have been extensively used for tissue regeneration owing to their notable capabilities. Insulin-like growth factor-binding protein 5 (IGFBP5) regulates osteogenic differentiation of mesenchymal stem cells (MSCs); however, the underlying regulatory mechanisms require further investigation. MATERIALS AND METHODS: Carboxyfluorescein succinimidyl ester, an alkaline phosphatase (ALP) activity assay and Alizarin Red staining were used to reveal the role of IGFBP5 in DPSCs. Protein expression levels were determined using western blotting. Immunofluorescence was used to observe cell sub-localisation. Subcutaneous transplantation in nude mice was used to observe the osteogenesis of DPSCs in vivo. RESULTS: IGFBP5 enhanced the proliferation and osteogenic differentiation of DPSCs. Deletion of the nuclear localisation sequence (NLS) of IGFBP5 prevented its nuclear import and abolished all its promoting effects on DPSCs; ivermectin stimulation attenuated the enhancement of ALP activity by IGBFP5. Bone-like tissue formation promoted by IGFBP5 in vivo vanishes when the NLS is deleted. Inhibition of IGFBP5 nuclear import attenuated the IGFBP5-induced phosphorylation of JNK (p-JNK) and phosphorylated ERK (p-ERK) in DPSCs. CONCLUSION: Our findings suggest that cell proliferation and osteogenic differentiation effects exerted by IGFBP5 on DPSCs are closely associated with their entry into the nucleus, thereby providing a novel potential target for tissue regeneration.

Precise Localization of Urine Leak After Renal Transplantation on Radionuclide Renography: Added Value of the Unclamped Drainage Tube and SPECT-CT.

Identifying and localizing the site of post-renal transplantation urine leaks is important for patient management and treatment planning. Renal scintigraphy is a proven modality for confirming urine leaks after complicated post-renal transplantation. Routinely, renogram studies are performed with a clamped extraperitoneal drain. This results in the spread of radioactivity in the abdominal region, which makes localization of the leak site difficult in the planar images. Here we are trying to give an insight into minimalizing the accumulated urine volume by an unclamped extraperitoneal drain in order to precisely localize the site of the leak.

Vaccination governance in protracted conflict settings: the case of northwest Syria.

BACKGROUND: Effective vaccination governance in conflict-affected regions poses unique challenges. This study evaluates the governance of vaccination programs in northwest Syria, focusing on effectiveness, efficiency, inclusiveness, data availability, vision, transparency, accountability, and sustainability. METHODS: Using a mixed-methods approach, and adapting Siddiqi's framework for health governance, data were collected through 14 key informant interviews (KIIs), a validating workshop, and ethnographic observations. Findings were triangulated to provide a comprehensive understanding of vaccination governance. RESULTS: The study highlights innovative approaches used to navigate the complex health governance landscape to deliver vaccination interventions, which strengthened sub-national vaccination structures such as The Syria Immunisation Group (SIG). The analysis revealed several key themes. Effectiveness and efficiency were demonstrated through cold-chain reliability and extensive outreach activities, though formal reports lacked detailed analysis of vaccine losses and linkage between disease outbreak data and coverage statistics. Key informants and workshop participants rated the vaccination strategy positively but identified inefficiencies due to irregular funding and bureaucracy. Inclusiveness and data availability were prioritised, with outreach activities targeting vulnerable groups. However, significant gaps in demographic data and reliance on paper-based systems hindered comprehensive coverage analysis. Digitalisation efforts were noted but require further support. The SIG demonstrated a clear strategic vision supported by international organizations such as the World Health Organization, yet limited partner participation in strategic planning raised concerns about broader ownership and engagement. While the SIG was perceived as approachable, the lack of public documentation and financial disclosure limited transparency. Internal information sharing was prevalent, but public communication strategies were insufficient. Accountability and sustainability faced challenges due to a decentralized structure and reliance on diverse donors. Despite stabilizing factors such as decentralization and financial continuity, fragmented oversight and reliance on donor funding remained significant concerns. DISCUSSION: The study highlights the complexities of vaccination governance in conflict-affected areas. Comparisons with other conflict zones underscore the importance of local organisations and international support. The SIG's role is pivotal, but its legitimacy, transparency, and inclusivity require improvement. The potential transition to early recovery in Syria poses additional challenges to SIG's sustainability and integration into national programs. CONCLUSION: The governance of vaccination in northwest Syria is multifaceted, involving multiple stakeholders and lacking a legitimate government. Enhancing transparency, local ownership, and participatory decision-making are crucial for improving governance. The role of international bodies is essential, emphasising the need for structured feedback mechanisms and transparent monitoring processes to ensure the program's success and sustainability.

Super-resolution ultrasound imaging reveals temporal cerebrovascular changes with disease progression in female 5×FAD mouse model of Alzheimer's disease: correlation with pathological impairments.

BACKGROUND: Vascular dysfunction is closely associated with the progression of Alzheimer's disease (AD). A critical research gap exists that no studies have explored the in vivo temporal changes of cerebrovascular alterations with AD progression in mouse models, encompassing both structure and flow dynamics at micron-scale resolution across the early, middle, and late stages of the disease. METHODS: In this study, ultrasound localisation microscopy (ULM) was applied to image the cerebrovascular alterations of the transgenic female 5×FAD mouse model across different stages of disease progression: early (4 months), moderate (7 months), and late (12 months). Age-matched non-transgenic (non-Tg) littermates were used as controls. Immunohistology examinations were performed to evaluate the influence of disease progression on the ß-amyloid (Aß) load and microvascular alterations, including morphological changes and the blood-brain barrier (BBB) leakage. FINDINGS: Our findings revealed a significant decline in both vascular density and flow velocity in the retrosplenial cortex of 5×FAD mice at an early stage, which subsequently became more pronounced in the visual cortex and hippocampus as the disease progressed. Additionally, we observed a reduction in vascular length preceding diminished flow velocities in cortical penetrating arterioles during the early stages. The quantification of vascular metrics derived from ULM imaging showed significant correlations with those obtained from vascular histological images. Immunofluorescence staining identified early vascular abnormalities in the retrosplenial cortex. As the disease advanced, there was an exacerbation of Aß accumulation and BBB disruption in a regionally variable manner. The vascular changes observed through ULM imaging exhibited a negative correlation with amyloid load and were associated with the compromise of the BBB integrity. INTERPRETATION: Through high-resolution, in vivo imaging of cerebrovasculature, this study reveals significant spatiotemporal dysfunction in cerebrovascular dynamics accompanying disease progression in a mouse model of AD, enhancing our understanding of its pathophysiology. FUNDING: This study is supported by grants from National Key Research and Development Program of China (2020YFA0908800), National Natural Science Foundation of China (12074269, 82272014, 82327804, 62071310), Shenzhen Basic Science Research (20220808185138001, JCYJ20220818095612027, JCYJ20210324093006017), STI 2030-Major Projects (2021ZD0200500) and Guangdong Natural Science Foundation (2024A1515012591, 2024A1515011342).

Characterization and functional analysis of Litopenaeus vannamei Na+/K+/2Cl- cotransporter 1 under nitrite stress.

The function of Litopenaeus vannamei Na+/K+/2Cl- cotransporter 1 (NKCC1) under nitrite stress was investigated. The full-length cDNA sequence of the L. vannamei NKCC1 gene was cloned using the rapid amplification of cDNA ends (RACE) technique, and the sequence was analysed using bioinformatics tools. Expression and localisation of NKCC1 in tissues were assessed using real-time quantitative PCR and in situ hybridisation, respectively. The impact of nitrite stress on the survival, physiology, biochemistry and tissue structure of L. vannamei was investigated following silencing of NKCC1 by RNA interference. The 3143 bp cDNA sequence of L. vannamei NKCC1 encodes a polypeptide of 918 amino acids. It is evolutionarily conserved. NKCC1 expression was highest in gill tissue, particularly within cuticle and gill epithelial cells. After silencing NKCC1, an increase in shrimp survival was observed, accompanied by a significant reduction in nitrite entry into the body (P < 0.05). Moreover, the oxidative stress enzyme system remained unaffected and damage to gill tissue was alleviated. The results suggest that NKCC1 is involved in regulating nitrite uptake, and plays a crucial role in facilitating nitrite entry into the organism through gill tissue. The findings provide a vital experimental basis for addressing concerns related to nitrite toxicity.

Bilateral Todd's paralysis in a patient with left fronto-opercular epilepsy.

Postictal paresis ("Todd's paralysis") is commonly observed as a unilateral, transient motor weakness, lasting minutes to hours, after focal or focal to bilateral tonic-clonic seizures, contralateral to the epileptogenic zone. Bilateral postictal paresis is exceedingly rare and could be misinterpreted, especially if the preceding convulsive phase was not witnessed. An 18-year-old right-handed male patient with refractory focal epilepsy with seizure onset at age 3 years, was admitted for presurgical video-EEG monitoring. His seizures were predominantly nocturnal, consisting of a laryngeal somatosensory aura, occasionally evolving to bilateral tonic or tonic-clonic seizures with occasional asymmetrical limb extension during the tonic phase (right arm extension). Postictally, consciousness recovery was fast, if ever lost. At that stage, we documented severe dysarthria and bilateral symmetrical arm paresis lasting several minutes. The ictal pattern and interictal epileptiform activity were projected on the fronto-central midline. Brain MRI was highly suggestive of a bottom-of-sulcus dysplasia with underlying transmantle sign on the left premotor, fronto-opercular region and an FDG-PET-CT showed a concordant left fronto-operculo-insular hypometabolism. A complete lesionectomy was performed, with the additional guidance of intraoperative electrocorticography, resulting in sustained seizure freedom. Anatomo-pathology confirmed a type 2b focal cortical dysplasia. We speculate that, in our patient, a left fronto-opercular ictal onset with an early spread to both primary motor cortices and relative sparing of consciousness networks allowed the emergence of a clinically detectable postictal bilateral paresis.

Genetic evidence for efficacy of targeting IL-2, IL-6 and TYK2 signalling in the prevention of type 1 diabetes: a Mendelian randomisation study.

AIMS/HYPOTHESIS: We aimed to investigate the genetic evidence that supports the repurposing of drugs already licensed or in clinical phases of development for prevention of type 1 diabetes. METHODS: We obtained genome-wide association study summary statistics for the risk of type 1 diabetes, whole-blood gene expression and serum protein levels and investigated genetic polymorphisms near seven potential drug target genes. We used co-localisation to examine whether the same genetic variants that are associated with type 1 diabetes risk were also associated with the relevant drug target genetic proxies and used Mendelian randomisation to evaluate the direction and magnitude of the associations. Furthermore, we performed Mendelian randomisation analysis restricted to functional variants within the drug target genes. RESULTS: Co-localisation revealed that the blood expression levels of IL2RA (encoding IL-2 receptor subunit α [IL2RA]), IL6R (encoding IL-6 receptor [IL6R]) and IL6ST (encoding IL-6 cytokine family signal transducer [IL6ST]) shared the same causal variant with type 1 diabetes liability near the corresponding genes (posterior probabilities 100%, 96.5% and 97.0%, respectively). The OR (95% CI) of type 1 diabetes per 1-SD increase in the genetically proxied gene expression of IL2RA, IL6R and IL6ST were 0.22 (0.17, 0.27), 1.98 (1.48, 2.65) and 1.90 (1.45, 2.48), respectively. Using missense variants, genetically proxied TYK2 (encoding tyrosine kinase 2) expression levels were associated with type 1 diabetes risk (OR 0.61 [95% CI 0.54, 0.69]). CONCLUSIONS/INTERPRETATION: Our findings support the targeting of IL-2, IL-6 and TYK2 signalling in prevention of type 1 diabetes. DATA AVAILABILITY: The analysis code is available at https://github.com/jkoskenniemi/T1DSCREEN , which also includes instructions on how to download the original GWAS summary statistics.

Automated Room-Level Localisation Using Building Plan Information.

Building Management Systems (BMSs) are transitioning from utilising wired installations to wireless Internet of Things (IoT) sensors and actuators. This shift introduces the requirement of robust localisation methods which can link the installed sensors to the correct Control Units (CTUs) which will facilitate continued communication. In order to lessen the installation burden on the technicians, the installation process should be made more complicated by the localisation method. We propose an automated version of the fingerprinting-based localisation method which estimates the location of sensors with room-level accuracy. This approach can be used for initialisation and maintenance of BMSs without introducing additional manual labour from the technician installing the sensors. The method is extended to two proposed localisation methods which take advantage of knowledge present in the building plan regarding the distribution of sensors in each room to estimate the location of groups of sensors at the same time. Through tests using a simulation environment based on a Bluetooth-based measurement campaign, the proposed methods showed an improved accuracy from the baseline automated fingerprinting method. The results showed an error rate of 1 in 20 sensors (if the number of sensors per room is known) or as few as 1 per 200 sensors (if a group of sensors are deployed and detected together for one room at a time).

Intraoperative parathyroid hormone assay benefits surgery for primary hyperparathyroidism when preoperative localisation is negative or not performed.

INTRODUCTION: Parathyroid localisation is now routine before first-time surgery for patients with primary hyperparathyroidism (PHPT). The aim of this study was to investigate the contribution of intraoperative parathyroid hormone (PTH) (ioPTH) in patients in whom localisation was either not undertaken or negative for a tumour. METHODS: This was a retrospective study of patients undergoing first-time parathyroidectomy for PHPT in a regional endocrine centre. Data were collected prospectively (Microsoft Excel) and the all-Wales electronic patient record portal was used to retrieve missing data. Statistical analysis appropriate for nonparametric data was undertaken, with statistical significance reached when p<0.05. RESULTS: Between 1 July 2002 and 31 December 2022, 1,490 patients underwent a first-time parathyroidectomy for PHPT. Of this cohort, 1,133 patients had at least one positive imaging modality; the study group consisted of 343 patients that had negative imaging, and 13 that had no preoperative localisation. Patients with MEN-1 (n=26), an incorrect diagnosis (n=4), or less than six months follow-up (n=6) were excluded. Of the remaining 321, 106 patients underwent surgery without ioPTH (Group A), 215 cases with ioPTH (Group B). In Group B there were more women (170 female/45 male; 79% vs 67 female/37 male; 63% p=0.002, chi-squared), lower calcium (median [range] 2.77 [2.63-3.24] mmol/l; vs 2.85 [2.60-4.52] p=0.001) and lower PTH (12.0pmol/l [3.4-39.5] vs 14.4 [3.9-97.0] p=0.001) and smaller weights of resected tissue (320mg [50-9,000] vs 454 [46-8,280] p=0.02) (Student's t-test). The rate of multiple gland disease was similar (Group A 29%; Group B 27%). The rate of normocalcaemia at 6 months was significantly higher when ioPTH was used (Group B 202/215; 94% vs Group A 90/106; 85%) (p=0.014, chi-square test). The sensitivity and specificity of ioPTH was 98.5% [confidence interval (CI) 96.2-99.6] and 91.2% [80.7-97.0] (positive predictive value 99.9%, CI 93.6-100.0). CONCLUSION: Despite milder hyperparathyroidism and smaller tumour weight, the outcome in patients in whom ioPTH was used was superior, with failure rates 2.5-fold higher in the cohort where ioPTH was not utilised. The results of this study demonstrate that ioPTH is a valuable adjunct for the surgeon in cases where localisation has failed or not been undertaken.

Vessel recovery using ultrasound localisation microscopy: An in silico comparative study between minimum variance and delay-and-sum beamformers.

The use of particle localisation and tracking algorithms on Contrast Enhanced Ultrasound (CEUS) or other ultrasound mode image data containing sparse microbubble (MB) populations, can produce super-resolved vascularization maps. Typically such data stem from conventional delay and sum (DAS) beamforming that is used widely in ultrasound imaging modes. Recently, adaptive beamforming has shown significant improvement in spatial resolution, but its value to super-resolution image analysis approaches is not fully understood. The in silico study here evaluates the performance of combining minimum variance beamformers (MV BF), established to provide improved lateral resolution, compared to DAS BFs with single particle detection. The isolated effect of a range of simplified image-affecting factors such as flow profile, pulse length, noise, vessel separations and data availability is considered. The study aims to assess the vessel recovery performance using the different beamformers and investigate the link with MB detection and localisation. The MV BF was shown to provide improved microvessel position accuracy compared to conventional DAS BFs. In particular, vessel separations between 0.3-4 λ provided superior localisation uncertainty with the MV. In addition, for a separation of 0.36λ, vessel recovery was achieved with both methods but the use of MV eliminated artifacts that appear as additional vessels. These results were found to be linked to improved MB detection and localisation for the MV BF, which is proposed as suitable for testing in Ultrasound Localisation Microscopy (ULM) imaging using patient data.

Development of a novel Bluetooth Low Energy device for proximity and location monitoring in grazing sheep.

Monitoring animal location and proximity can provide useful information on behaviour and activity, which can act as a health and welfare indicator. However, tools such as global navigation satellite systems (GNSS) can be costly, power-hungry and often heavy, thus not viable for commercial uptake in small ruminant systems. Developments in Bluetooth Low Energy (BLE) could offer another option for animal monitoring, however, BLE signal strength can be variable, and further information is needed to understand the relationship between signal strength and distance in an outdoor environment and assess factors which might affect its interpretation in on-animal scenarios. A calibration of a purpose-built device containing a BLE reader, alongside commercial BLE beacons, was conducted in a field environment to explore how signal strength changed with distance and investigate whether this was affected by device height, and thus animal behaviour. From this calibration, distance prediction equations were developed whereby beacon distance from a reader could be estimated based on signal strength. BLE as a means of localisation was then trialled, firstly using a multilateration approach to locate 16 static beacons within an ∼5 400 m2 section of paddock using 6 BLE readers, followed by an on-sheep validation where two localisation approaches were trialled in the localisation of a weaned lamb within ∼1.4 ha of adjoining paddocks, surrounded by nine BLE readers. Validation was conducted using 1 days' worth of data from a lamb fitted with both a BLE beacon and separate GNSS device. The calibration showed a decline in signal strength with increasing beacon distance from a reader, with a reduced range and earlier decline in the proportion of beacons reported at lower reader and beacon heights. The distance prediction equations indicated a mean underestimation of 12.13 m within the static study, and mean underestimation of 1.59 m within the on-sheep validation. In the static beacon localisation study, the multilateration method produced a mean localisation error of 22.02 m, whilst in the on-sheep validation, similar mean localisation errors were produced by both methods - 19.00 m using the midpoint and 23.77 m using the multilateration method. Our studies demonstrate the technical feasibility of localising sheep in an outdoor environment using BLE technology; however, potential commercial application of such a system would require improvements in BLE range and accuracy.

Transient Expression Vector Construction, Subcellular Localisation, and Evaluation of Antiviral Potential of Flagellin BP8-2.

This study used the DNA of Bacillus amyloliquefaciens Ba168 as a template to amplify the flagellin BP8-2 gene and ligate it into the fusion expression vector pCAMBIA1300-35S-EGFP after digestion for the construction of the expression vector pCAMBIA1300-EGFP-BP8-2. Next, using Nicotiana benthamiana as receptor material, transient expression was carried out under the mediation of Agrobacterium tumefaciens C58C1. Finally, the transient expression and subcellular localisation of flagellin BP8-2 protein were analysed using the imaging of co-transformed GFP under laser confocal microscopy. The results showed that flagellin BP8-2 was localised in the cell membrane and nucleus, and the RT-PCR results showed that the BP8-2 gene could be stably expressed in tobacco leaf cells. Furthermore, there was stronger antiviral activity against tobacco mosaic virus (TMV) infection in Nicotiana glutinosa than in BP8-2 and ningnanmycin, with an inhibitory effect of 75.91%, protective effect of 77.45%, and curative effect of 68.15%. TMV movement and coat protein expression were suppressed, and there was a high expression of PR-1a, PAL, and NPR1 in BP8-2-treated tobacco leaf. These results suggest that flagellin BP8-2 inhibits TMV by inducing resistance. Moreover, BP8-2 has low toxicity and is easily biodegradable and eco-friendly. These results further enrich our understanding of the antiviral mechanisms of proteins and provide alternatives for controlling viral diseases in agriculture.

The acoustic change complex evoked by location-change sounds in the elderly.

OBJECTIVE: We have shown that the acoustic change complex (ACC) can be elicited by changing the horizontal sound location in young individuals. In this study, we aimed to evaluate the application of ACC within the elderly and its relationship with behavioural results. DESIGN: The minimum audible angle (MAA), as well as onset cortical auditory evoked potentials (onset-CAEPs) and ACC elicited by the stimuli of location-change white noise (±45 to ±2 degrees) were recorded. Latencies and amplitudes were analysed using repeated-measures ANOVA. Pearson correlation analysis was conducted to examine the relationship between ACC and MAA. STUDY SAMPLE: Ten older adults with normal hearing (NH) and twenty with presbycusis. RESULTS: The ACC was effectively elicited with angular variations in elderly participants. The onset-CAEP N1 latency, ACC N1'-P2' amplitude, and N1' latency were all associated with the angle shifts, with the N1' latency being the most predictive factor for angle discrimination. The consistency between MAA and ACC made them complementary for the clinical evaluation of sound localisation. CONCLUSIONS: The utilisation of ACC, evoked by location-change sounds, presented a promising clinical objective measure for evaluating sound localisation abilities in the elderly.

Unveiling the limits of precision in iterative MINFLUX.

In single-molecule microscopy, a big question is how precisely we can estimate the location of a single molecule. Our research shows that by using iterative localisation microscopy and factoring in the prior information, we can boost precision and reduce the number of photons needed. Leveraging the Van Trees inequality aids in determining the optimal precision achievable. Our approach holds promise for wider application in discerning the optimal precision across diverse imaging scenarios, encompassing various illumination strategies, point spread functions and overarching control methodologies.

Similar performance in sound localisation with unsynchronised and synchronised automatic gain controls in bilateral cochlear implant recipients.

OBJECTIVE: One proposed method to improve sound localisation for bilateral cochlear implant (BiCI) users is to synchronise the automatic gain control (AGC) of both audio processors. In this study we tested whether AGC synchronisation in a dual-loop front-end processing scheme with a 3:1 compression ratio improves sound localisation acuity. DESIGN: Source identification in the frontal hemifield was tested in in an anechoic chamber as a function of (roving) presentation level. Three different methods of AGC synchronisation were compared to the standard unsynchronised approach. Both root mean square error (RMSE) and signed bias were calculated to evaluate sound localisation in the horizontal plane. STUDY SAMPLE: Six BiCI users. RESULTS: None of the three AGC synchronisation methods yielded significant improvements in either localisation error or bias, neither across presentation levels nor for individual presentation levels. For synchronised AGC, the pooled mean (standard deviation) localisation error of the three synchronisation methods was 24.7 (5.8) degrees RMSE, for unsynchronised AGC it was 27.4 (7.5) degrees. The localisation bias was 5.1 (5.5) degrees for synchronised AGC and 5.0 (3.8) for unsynchronised. CONCLUSIONS: These findings do not support the hypothesis that the tested AGC synchronisation configurations improves localisation acuity in bilateral users of MED-EL cochlear implants.

UAV-UGV Collaborative Localisation with Minimum Sensing.

This paper presents a novel methodology to localise Unmanned Ground Vehicles (UGVs) using Unmanned Aerial Vehicles (UAVs). The UGVs are assumed to be operating in a Global Navigation Satellite System (GNSS)-denied environment. The localisation of the ground vehicles is achieved using UAVs that have full access to the GNSS. The UAVs use range sensors to localise the UGV. One of the major requirements is to use the minimum number of UAVs, which is two UAVs in this paper. Using only two UAVs leads to a significant complication that results an estimation unobservability under certain circumstances. As a solution to the unobservability problem, the main contribution of this paper is to present a methodology to treat the unobservability problem. A Constrained Extended Kalman Filter (CEKF)-based solution, which uses novel kinematics and heuristics-based constraints, is presented. The proposed methodology has been assessed based on the stochastic observability using the Posterior Cramér-Rao Bound (PCRB), and the results demonstrate the successful operation of the proposed localisation method.

Targeted axillary dissection reduces residual nodal disease in clinically node- positive breast cancer after neoadjuvant chemotherapy.

BACKGROUND: Any advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer. METHODS: A combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed. RESULTS: Overall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046). CONCLUSIONS: TAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.