Post mortem blood bromazolam concentrations and co-findings in 96 coronial cases within England and Wales.

Bromazolam is a newly emerging benzodiazepine drug which is not licensed for medicinal use. It may be sourced as a New Psychoactive Substance (NPS) for its desired effects or be consumed unknowingly via counterfeit Xanax® or Valium® preparations. As part of our Coronial workload, we observed an increase in the detection of bromazolam from September 2021 to November 2022. We report a series of 96 cases in which bromazolam was quantitated by high resolution accurate mass - mass spectrometry (HRAM - MS) in post-mortem blood. The mean (SD) post-mortem blood bromazolam concentration from our case series was 64.6 ( ± 79.4) µg/L (range <1-425 µg/L). Routine toxicological screening results have also been reported; the most commonly encountered drugs taken in combination with bromazolam were cocaine, gabapentinoids and diazepam. In 48% of cases at least one further designer benzodiazepine drug was also present (etizolam, flualprazolam, flubromazolam, flubromazepam). It is essential that laboratories providing toxicological investigations are aware of the limitations of their assays; and inclusion of bromazolam within targeted screening panels using LC-MS/MS is encouraged. Bromazolam has not been associated with death in isolation from resulting toxic concentrations; however, it is likely to enhance adverse clinical effects when taken in combination with stimulant and/or centrally-acting depressant drugs (poly-drug deaths). Bromazolam, similar to other benzodiazepines, may also impair cognition and decision making skills.

Rethinking the 'one-stop' neck lump clinic: a novel pathway beyond coronavirus disease 2019.

OBJECTIVES: UK guidelines advocate 'one-stop' neck lump assessment for cancer referrals. This paper reports the pilot of a novel pre-clinic ultrasound pathway, presents outcomes, and discusses strengths and limitations in the context of the coronavirus disease 2019 pandemic. METHODS: Two-week-wait cancer referral patients with a neck lump were allocated a pre-clinic ultrasound scan followed by a clinic appointment. Demographic, patient journey and outcome data were collected and analysed. RESULTS: Ninety-nine patients underwent ultrasound assessment with or without biopsy on average 8 days following referral. Patients were followed up on average 14.1 days (range, 2-26 days) after initial referral. At the first clinic appointment, 45 patients were discharged, 10 were scheduled for surgery, 12 were diagnosed with cancer, 6 were referred to another specialty and cancer was excluded in 19 patients. Retrospectively, four ultrasounds were performed unnecessarily. CONCLUSION: Pre-clinic ultrasound scanning is an alternative to the one-stop neck lump pathway. This study demonstrates fewer clinic visits, faster diagnosis and a low proportion of unnecessary scans, whilst minimising face-to-face consultations and aerosol-generating procedures.

Sodium nitrite poisoning: A series of 20 fatalities in which post-mortem blood nitrite and nitrate concentrations are reported.

Sodium nitrite has several industrial applications however its accidental or intentional ingestion has been associated with severe toxicity and death. We present a series of 20 cases over 2 years in which evidence of sodium nitrite ingestion was found at the scene and supported by biochemical analysis of post-mortem blood nitrite and nitrate levels. Routine toxicological screening was performed on post-mortem blood samples received at University Hospitals of Leicester (UHL) NHS Trust, including ethanol analysis by headspace gas chromatography-flame ionisation detection (HS GC-FID), drug screening by high resolution accurate mass-mass spectrometry (HRAM-MS) and confirmatory drug quantitation by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cases in which the history indicated the possibility of nitrite salts present at the scene, purchase of a suicide kit or a dusky-ash appearance of skin on post-mortem were referred to a specialist laboratory for nitrite and nitrate analysis. Analysis was based upon the gas-phase chemiluminescent reaction between nitric oxide (NO) and ozone; NO levels were determined using an NOA 280A, Sievers NO analyser. Twenty post-mortem cases in which sodium nitrite ingestion was the most probable cause of death were reported between January 2020 and February 2022; mean age was 31 years (range 14-49) with 9/20 (45%) female. 16/20 (80%) of cases had a history of depression and / or mental health issues. In half of the cases, anti-depressant / anti-psychotic drugs were prescribed; these drugs were detected in 8/20 (40%) cases. Ethanol was detected in 4/20 (20%) cases and anti-emetic drugs in 7/20 (35%) cases; anti-emetic drugs may be used to aid retention of sodium nitrite. Illicit drugs (amphetamine, cannabis and cocaine) were present in 3/20 cases (15%). Nitrite was found to be elevated in all but one case (95%), and nitrate was elevated in 17/20 (85%) cases. This paper highlights a surge in numbers of deaths across England and Wales due to sodium nitrite toxicity. Although, nitrite poisoning remains a rare cause of death, it is worthwhile considering its use in individuals with suicidal ideation given its unregulated availability online. The detection and quantitation of nitrite and nitrate requires specialised, highly reliable methodology currently only available in research laboratories. Implication of sodium nitrite ingestion also relies heavily upon circumstantial evidence combined with quantification. The provision of a quantitative nitrite / nitrate analytical service greatly assists in determining the cause of death in these cases.

U.S. Blue Water Navy Veterans of the Vietnam War: Comparisons from the Vietnam Era Health Retrospective Observational Study (VE-HEROeS).

Background: US Vietnam War Blue Water Navy veterans (BWN) conducted military operations on Vietnam's offshore waters and likely experienced various war-related exposures. The overall health of the BWN has never been systematically studied. Purpose: Describe and compare BWN's health with other servicemembers and non-veterans of the Vietnam era. Materials and methods: Survey of 45 067 randomly selected US Vietnam War theatre and non-theatre veterans and 6885 non-veterans. Results: For 22 646 male respondents, self-reported health was contrasted by veteran status defined as BWN (n=985), theatre veterans (n=6717), non-theatre veterans (n=10 698) and non-veterans (n=4246). Exposure was service in the Vietnam War theatre. Collected were demographics, military service characteristics, lifestyle factors and health conditions. Adjusted odds ratios (aOR) were calculated using multivariable logistic regression. Controlling for cigarette smoking and other covariates, respiratory cancer risk was highest in BWN vs other veterans (theatre: aOR 1.65; 95% CI 1.09, 2.50; non-theatre: aOR 1.77; 1.13, 2.77) and to non-veterans (aOR 1.78; 1.15, 2.74). Other findings showed BWN's health risks between theatre and non-theatre veterans. Conclusion: There was a higher risk for respiratory cancers in BWN. Other risks were less than theatre veterans but greater than non-theatre or non-veterans, indicating a potential role of military exposures in BWN's health.

Contributions to Loss Across the Magnetopause During an Electron Dropout Event.

Dropout events are dramatic decreases in radiation belt electron populations that can occur in as little as 30 minutes. Loss to magnetopause due to a combination of magnetopause shadowing and outward radial transport plays a significant role in these events. We examine the dropout of relativistic electron populations during the October 2012 geomagnetic storm using simulated electron phase space density, evaluating the contribution of different processes to losses across the magnetopause. We compare loss contribution from outward transport calculated using a standard empirical radial diffusion model that assumes a dipolar geomagnetic field to an event-specific radial diffusion model evaluated with a non-dipolar geomagnetic field. We additionally evaluate the contribution of Shabansky type 1 particles, which bounce along magnetic field lines with local equatorial maxima, to the loss calculated during this event. We find that the empirical radial diffusion model with a dipolar background field underestimates the contribution of radial diffusion to this dropout event by up to 10% when compared to the event-specific, non-dipolar radial diffusion model. We additionally find that including Shabansky type 1 particles in the initial electron phase space density, that is, allowing some magnetic field lines distorted from the typical single-minima configuration in drift shell construction, increases the calculated loss by an average of 0.75%. This shows that the treatment of the geomagnetic field significantly impacts the calculation of electron losses to the magnetopause during dropout events, with the non-dipolar treatment of radial diffusion being essential to accurately quantify the loss of outer radiation belt populations.

Temperatures leading to heat escape responses in Antarctic marine ectotherms match acute thermal limits.

Thermal tolerance windows are key indicators of the range of temperatures tolerated by animals and therefore, a measure of resilience to climate change. In the ocean, where ectotherms are immersed, body temperatures are tightly coupled to environmental temperature and species have few options for thermoregulation. However, mobile species do have the ability to orientate towards optimal temperatures and move away from sub-optimal or dangerous temperatures. Escape responses are one such locomotory behavior, which typically manifests as a series of violent flicking movements that move individuals out of dangerous environments. We tested 11 species of Antarctic marine ectotherms, from one of the most stable shallow water marine environments, with an annual temperature range of -2°C to +2°C, that are vulnerable to small degrees of warming. Three species, the clam Laternula elliptica, the sea cucumber Cucumaria georgiana, and the brittlestar Ophionotus victoriae, showed no, or virtually no, escape response to temperature. Escape responses from a further eight species had a median response temperature of 11.2 (interquartile range, 10°C-15.7°C), which is well above current environmental temperatures but close to the range for acute lethal limits of Antarctic marine ectotherms (CTmax range, 17.2°C-26.6°C). This highlights that both acute tolerance limits and escape responses, fall outside current environmental temperatures, but also those predicted for 100s of years in the Southern Ocean. In a warmer Southern Ocean Antarctic fauna may not have the capacity to use temperature to select optimal thermal conditions, which leaves adaptation as a primary mechanism for their persistence.

Intermediate ice scour disturbance is key to maintaining a peak in biodiversity within the shallows of the Western Antarctic Peninsula.

Climate-related disturbance regimes are changing rapidly with profound consequences for ecosystems. Disturbance is often perceived as detrimental to biodiversity; however, the literature is divided on how they influence each other. Disturbance events in nature are diverse, occurring across numerous interacting trophic levels and multiple spatial and temporal scales, leading to divergence between empirical and theoretical studies. The shallow Antarctic seafloor has one of the largest disturbance gradients on earth, due to iceberg scouring. Scour rates are changing rapidly along the Western Antarctic Peninsula because of climate change and with further changes predicted, the Antarctic benthos will likely undergo dramatic shifts in diversity. We investigated benthic macro and megafaunal richness across 10-100 m depth range, much of which, 40-100 m, has rarely been sampled. Macro and megafauna species richness peaked at 50-60 m depth, a depth dominated by a diverse range of sessile suspension feeders, with an intermediate level of iceberg disturbance. Our results show that a broad range of disturbance values are required to detect the predicted peak in biodiversity that is consistent with the Intermediate Disturbance Hypothesis, suggesting ice scour is key to maintaining high biodiversity in Antarctica's shallows.

Novel Mouse Model Reveals That Serine Phosphorylation of L-Plastin Is Essential for Effective Splenic Clearance of Pneumococcus.

Asplenia imparts susceptibility to life-threatening sepsis with encapsulated bacteria, such as the pneumococcus. However, the cellular components within the splenic environment that guard against pneumococcal bacteremia have not been defined. The actin-bundling protein L-plastin (LPL) is essential for the generation of marginal zone B cells and for anti-pneumococcal host defense, as revealed by a mouse model of genetic LPL deficiency. In independent studies, serine phosphorylation of LPL at residue 5 (S5) has been described as a key "switch" in regulating LPL actin binding and subsequent cell motility, although much of the data are correlative. To test the importance of S5 phosphorylation in LPL function, and to specifically assess the requirement of LPL S5 phosphorylation in anti-pneumococcal host defense, we generated the "S5A" mouse, expressing endogenous LPL bearing a serine-to-alanine mutation at this position. S5A mice were bred to homozygosity, and LPL was expressed at levels equivalent to wild-type, but S5 phosphorylation was absent. S5A mice exhibited specific impairment in clearance of pneumococci following i.v. challenge, with 10-fold-higher bacterial bloodstream burden 24 h after challenge compared with wild-type or fully LPL-deficient animals. Defective bloodstream clearance correlated with diminished population of marginal zone macrophages and with reduced phagocytic capacity of multiple innate immune cells. Development and function of other tested leukocyte lineages, such as T and B cell motility and activation, were normal in S5A mice. The S5A mouse thus provides a novel system in which to elucidate the precise molecular control of critical immune cell functions in specific host-pathogen defense interactions.

The use of computed tomography as a first-line imaging modality in patients with primary hyperparathyroidism.

BACKGROUND: The success of minimally invasive parathyroidectomy (MIP) relies on accurate localization of the abnormal parathyroid glands. Concordant findings on ultrasound (US) and 99mTc-scintigraphy (sestamibi) are currently considered the 'gold standard'. Computed tomography (CT) has also recently been used in preoperative planning. We sought to assess the accuracy of CT for localization of abnormal parathyroid glands in such patients. METHODS: An audit of 75 patients with primary hyperparathyroidism (PHPT) who underwent neck US and CT between 2017 and 2019 at our center as their first-line imaging. RESULTS: All 75 patients underwent US and CT and 54 (72.0%) also had sestamibi. CT alone identified a potential target in all patients, of which the location was correct in 63 (84.0%). The overall combined sensitivity of US and CT was 88% (95% CI 78-94) and was higher than the combined sensitivity of US and sestamibi (65% [95% CI 53-76]; p < 0.001). Twenty-one patients (28.0%) had an ectopic gland, and the sensitivity of US and CT was 86% (95% CI 64-96) versus US and sestamibi (57% [95% CI 34-77]; p = 0.016). For adenomas < 1.0 g (n = 36; 48%), the accuracy of CT was 81% (95% CI 64-91) compared with 62% (95% CI 44-77) for US and sestamibi (p = 0.04). The correct preoperative diagnosis of multiglandular disease (n = 9; 12%) seemed to be the most difficult, with similar accuracy for US and sestamibi (40% [95% CI 14-73]) and US and CT (50% [95% CI 20-80]) (p > 0.99). CONCLUSION: The combination of US and CT was able to correctly identify the location of the abnormal parathyroid in 88% of patients and, in comparison with US and sestamibi, had better diagnostic accuracy, especially for smaller and ectopic adenomas. This finding suggests that US and CT could be considered as a first-line imaging modality in patients with PHPT considered for MIP.

Contrasting biogeographical patterns in Margarella (Gastropoda: Calliostomatidae: Margarellinae) across the Antarctic Polar Front.

Members of the trochoidean genus Margarella (Calliostomatidae) are broadly distributed across Antarctic and sub-Antarctic ecosystems. Here we used novel mitochondrial and nuclear gene sequences to clarify species boundaries and phylogenetic relationships among seven nominal species distributed on either side of the Antarctic Polar Front (APF). Molecular reconstructions and species-delimitation analyses recognized only four species: M. antarctica (the Antarctic Peninsula), M. achilles (endemic to South Georgia), M. steineni (South Georgia and Crozet Island) and the morphologically variable M. violacea (=M. expansa, M. porcellana and M. pruinosa), with populations in southern South America, the Falkland/Malvinas, Crozet and Kerguelen Islands. Margarella violacea and M. achilles are sister species, closely related to M. steineni, with M. antarctica sister to all these. This taxonomy reflects contrasting biogeographic patterns on either side of the APF in the Southern Ocean. Populations of Margarella north of the APF (M. violacea) showed significant genetic variation but with many shared haplotypes between geographically distant populations. By contrast, populations south of the APF (M. antarctica, M. steineni and M. achilles) exhibited fewer haplotypes and comprised three distinct species, each occurring across a separate geographical range. We hypothesize that the biogeographical differences may be the consequence of the presence north of the APF of buoyant kelps - potential long-distance dispersal vectors for these vetigastropods with benthic-protected development - and their near-absence to the south. Finally, we suggest that the low levels of genetic diversity within higher-latitude Margarella reflect the impact of Quaternary glacial cycles that exterminated local populations during their maxima.

The Association of Medications and Vaccination with Risk of Pneumonia in Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk for pneumonia, and corticosteroids are reported to amplify this risk. Less is known about the impact of corticosteroid-sparing IBD therapies on pneumonia risk or the efficacy of pneumococcal vaccination in reducing all-cause pneumonia in real-world IBD cohorts. METHODS: We performed a population-based study using an established Veterans Health Administration cohort of 29,957 IBD patients. We identified all patients who developed bacterial pneumonia. Cox survival analysis was used to determine the association of corticosteroids at study entry and as a time-varying covariate, corticosteroid-sparing agents (immunomodulators and antitumor necrosis-alpha [TNF] inhibitors), and pneumococcal vaccination with the development of all-cause pneumonia. RESULTS: Patients with IBD who received corticosteroids had a greater risk of pneumonia when controlling for age, gender, and comorbidities (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.90-2.57 for prior use; HR = 3.42; 95% CI, 2.92-4.01 for use during follow-up). Anti-TNF inhibitors (HR 1.52; 95% CI, 1.02-2.26), but not immunomodulators (HR 0.91; 95% CI, 0.77-1.07), were associated with a small increase in pneumonia. A history of pneumonia was strongly associated with subsequent pneumonia (HR = 4.41; 95% CI, 3.70-5.27). Less than 15% of patients were vaccinated against pneumococcus, and this was not associated with a reduced risk of pneumonia (HR = 1.02; 95% CI, 0.80-1.30) in this cohort. CONCLUSION: In a large US cohort, corticosteroids were confirmed to increase pneumonia risk. Tumor necrosis-alpha inhibitors were associated with a smaller increase in the risk of pneumonia. Surprisingly, pneumococcal vaccination did not reduce all-cause pneumonia in this population, though few patients were vaccinated.

Inhaled GM-CSF in neonatal mice provides durable protection against bacterial pneumonia.

Pneumonia poses profound health threats to preterm infants. Alveolar macrophages (AMs) eliminate inhaled pathogens while maintaining surfactant homeostasis. As AM development only occurs perinatally, therapies that accelerate AM maturation in preterms may improve outcomes. We tested therapeutic rescue of AM development in mice lacking the actin-bundling protein L-plastin (LPL), which exhibit impaired AM development and increased susceptibility to pneumococcal lung infection. Airway administration of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) to LPL-/- neonates augmented AM production. Airway administration distinguishes the delivery route from prior human infant trials. Adult LPL-/- animals that received neonatal GM-CSF were protected from experimental pneumococcal challenge. No detrimental effects on surfactant metabolism or alveolarization were observed. Airway recombinant GM-CSF administration thus shows therapeutic promise to accelerate neonatal pulmonary immunity, protecting against bacterial pneumonia.

Marine plastics threaten giant Atlantic Marine Protected Areas.

There has been a recent shift in global perception of plastics in the environment, resulting in a call for greater action. Science and the popular media have highlighted plastic as an increasing stressor [1,2]. Efforts have been made to confer protected status to some remote locations, forming some of the world's largest Marine Protected Areas, including several UK overseas territories. We assessed plastic at these remote Atlantic Marine Protected Areas, surveying the shore, sea surface, water column and seabed, and found drastic changes from 2013-2018. Working from the RRS James Clark Ross at Ascension, St. Helena, Tristan da Cunha, Gough and the Falkland Islands (Figure 1A), we showed that marine debris on beaches has increased more than 10 fold in the past decade. Sea surface plastics have also increased, with in-water plastics occurring at densities of 0.1 items m-3; plastics on seabeds were observed at ≤ 0.01 items m-2. For the first time, beach densities of plastics at remote South Atlantic sites approached those at industrialised North Atlantic sites. This increase even occurs hundreds of meters down on seamounts. We also investigated plastic incidence in 2,243 animals (comprising 26 species) across remote South Atlantic oceanic food webs, ranging from plankton to seabirds. We found that plastics had been ingested by primary consumers (zooplankton) to top predators (seabirds) at high rates. These findings suggest that MPA status will not mitigate the threat of plastic proliferation to this rich, unique and threatened biodiversity.

Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer.

Background: Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods: To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287-395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. Results: We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3' partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Conclusions: Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6-7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies.

Reproducibility of the dynamics of facial expressions in unilateral facial palsy.

The aim of this study was to assess the reproducibility of non-verbal facial expressions in unilateral facial paralysis using dynamic four-dimensional (4D) imaging. The Di4D system was used to record five facial expressions of 20 adult patients. The system captured 60 three-dimensional (3D) images per second; each facial expression took 3-4seconds which was recorded in real time. Thus a set of 180 3D facial images was generated for each expression. The procedure was repeated after 30min to assess the reproducibility of the expressions. A mathematical facial mesh consisting of thousands of quasi-point 'vertices' was conformed to the face in order to determine the morphological characteristics in a comprehensive manner. The vertices were tracked throughout the sequence of the 180 images. Five key 3D facial frames from each sequence of images were analyzed. Comparisons were made between the first and second capture of each facial expression to assess the reproducibility of facial movements. Corresponding images were aligned using partial Procrustes analysis, and the root mean square distance between them was calculated and analyzed statistically (paired Student t-test, P<0.05). Facial expressions of lip purse, cheek puff, and raising of eyebrows were reproducible. Facial expressions of maximum smile and forceful eye closure were not reproducible. The limited coordination of various groups of facial muscles contributed to the lack of reproducibility of these facial expressions. 4D imaging is a useful clinical tool for the assessment of facial expressions.

Can acclimation of thermal tolerance, in adults and across generations, act as a buffer against climate change in tropical marine ectotherms?

Thermal acclimation capacity was investigated in adults of three tropical marine invertebrates, the subtidal barnacle Striatobalanus amaryllis, the intertidal gastropod Volegalea cochlidium and the intertidal barnacle Amphibalanus amphitrite. To test the relative importance of transgenerational acclimation, the developmental acclimation capacity of A. amphitrite was investigated in F1 and F2 generations reared at a subset of the same incubation temperatures. The increase in CTmax (measured through loss of key behavioural metrics) of F0 adults across the incubation temperature range 25.4-33.4°C was low: 0.00°C (V. cochlidium), 0.05°C (S. amaryllis) and 0.06°C (A. amphitrite) per 1°C increase in incubation temperature (the acclimation response ratio; ARR). Although the effect of generation was not significant, across the incubation temperature range of 29.4-33.4°C, the increase in CTmax in the F1 (0.30°C) and F2 (0.15°C) generations of A. amphitrite was greater than in the F0 (0.10°C). These correspond to ARR's of 0.03°C (F0), 0.08°C (F1) and 0.04°C (F2), respectively. The variability in CTmax between individuals in each treatment was maintained across generations, despite the high mortality of progeny. Further research is required to investigate the potential for transgenerational acclimation to provide an extra buffer for tropical marine species facing climate warming.

Towards the prediction of flow-induced shear stress distributions experienced by breast cancer cells in the lymphatics.

Tumour metastasis in the lymphatics is a crucial step in the progression of breast cancer. The dynamics by which breast cancer cells (BCCs) travel in the lymphatics remains poorly understood. The goal of this work is to develop a model capable of predicting the shear stresses metastasising BCCs experience using numerical and experimental techniques. This paper models the fluidic transport of large particles ([Formula: see text] where [Formula: see text] is the particle diameter and W is the channel width) subjected to lymphatic flow conditions ([Formula: see text]), in a [Formula: see text] microchannel. The feasibility of using the dynamic fluid body interaction (DFBI) method to predict particle motion was assessed, and particle tracking experiments were performed. The experiments found that particle translational velocity decreased from the undisturbed fluid velocity with increasing particle size (5-14% velocity lag for [Formula: see text]). DFBI simulations were found to better predict particle behaviour than theoretical predictions; however, mesh restrictions in the near-wall region ([Formula: see text]) result in computationally expensive models. The simulations were in good agreement with the experiments ([Formula: see text] difference) across the channel ([Formula: see text]), with differences up to 25% in the near-wall region. Particles experience a range of shear stresses (0.002-0.12 Pa) and spatial shear gradients ([Formula: see text]) depending on their size and radial position. The predicted shear gradients are far in excess of values associated with BCC apoptosis ([Formula: see text]). Increasing our understanding of the shear stress magnitudes and gradients experienced by BCCs could be leveraged to elucidate whether a particular BCC size or location exists that encourages metastasis within the lymphatics.