A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform.

Pregnant women and their fetuses are often excluded from clinical trials due to missing drug-related pre-clinical trial information at the human feto-maternal interface (FMi). The two interfaces-placenta/decidua and fetal membranes/decidua are gatekeepers of drug transport; however, testing their functions is impractical during pregnancy. Limitations of current in-vivo/in-vitro models have hampered drug development and testing during pregnancy. Hence, major complications like preterm births and maternal and neonatal mortalities remain high. Advancements in organ-on-chip (OOC) platforms to test drug kinetics and efficacy and novel extracellular vesicle-based fetal drug delivery are expected to accelerate preclinical trials related to pregnancy complications. Here we report the development and testing of a humanized multi-organ fetal membrane/placenta (fetal)-decidua (maternal) interface OOC (FMi-PLA-OOC) that contains seven cell types interconnected through microchannels to maintain intercellular interactions as seen in-utero. Cytotoxicity, propagation, mechanism of action, and efficacy of engineered extracellular vesicles containing anti-inflammatory interleukin (IL)-10 (eIL-10) were evaluated to reduce FMi inflammation associated with preterm birth. A healthy and disease model (lipopolysaccharide-infectious inflammation) of the FMi-PLA-OOC was created and co-treated with eIL-10. eIL-10 propagated from the maternal to fetal side within 72-hours, localized in all cell types, showed no cytotoxicity, activated IL-10 signaling pathways, and reduced lipopolysaccharide-induced inflammation (minimized NF-kB activation and proinflammatory cytokine production). These data recapitulated eIL-10s' ability to reduce inflammation and delay infection-associated preterm birth in mouse models, suggesting FMi-PLA-OOC as an alternative approach to using animal models. Additionally, we report the utility of eIL-10 that can traverse through FMis to reduce inflammation-associated pregnancy complications.

A Dynamic Flow Fetal Membrane Organ-on-a-Chip System for Modeling the Effects of Amniotic Fluid Motion.

Fetal membrane(amniochorion), the innermost lining of the intrauterine cavity, surround the fetus and enclose amniotic fluid. Unlike unidirectional blood flow, amniotic fluid subtly rocks back and forth, and thus, the innermost amnion epithelial cells are continuously exposed to low levels of shear stress from fluid undulation. Here, we tested the impact of fluid motion on amnion epithelial cells (AECs) as a bearer of force impact and their potential vulnerability to cytopathologic changes that can destabilize fetal membrane functions. An amnion membrane (AM) organ-on-chip (OOC) was utilized to culture human fetal amnion membrane cells. The applied flow was modulated to perfuse culture media back and forth for 48 hours flow culture to mimic fluid motion. Static culture condition was used as a negative control, and oxidative stress (OS) condition was used as a positive control for pathophysiological changes. The impacts of fluidic motion were evaluated by measuring cell viability, cellular transition, and inflammation. Additionally, scanning electron microscopy (SEM) imaging was performed to observe microvilli formation. The results show that regardless of the applied flow rate, AECs and AMCs maintained their viability, morphology, innate meta-state, and low production of pro-inflammatory cytokines. E-cadherin expression and microvilli formation in the AECs were upregulated in a flow rate-dependent fashion; however, this did not impact cellular morphology or cellular transition or inflammation. OS treatment induced a mesenchymal morphology, significantly higher vimentin to CK-18 ratio, and pro-inflammatory cytokine production in AECs, whereas AMCs did not respond in any significant manner. Fluid motion and shear stress, if any, did not impact AEC cell function and did not cause inflammation. Thus, when using an amnion membrane OOC model, the inclusion of a flow culture environment is not necessary to mimic any in utero physiologic cellular conditions of fetal membrane-derived cells.

Uniform sized cancer spheroids production using hydrogel-based droplet microfluidics: a review.

Three-dimensional (3D) cell culture models have been extensively utilized in various mechanistic studies as well as for drug development studies as superior in vitro platforms than conventional two-dimensional (2D) cell culture models. This is especially the case in cancer biology, where 3D cancer models, such as spheroids or organoids, have been utilized extensively to understand the mechanisms of cancer development. Recently, many sophisticated 3D models such as organ-on-a-chip models are emerging as advanced in vitro models that can more accurately mimic the in vivo tissue functions. Despite such advancements, spheroids are still considered as a powerful 3D cancer model due to the relatively simple structure and compatibility with existing laboratory instruments, and also can provide orders of magnitude higher throughput than complex in vitro models, an extremely important aspects for drug development. However, creating well-defined spheroids remain challenging, both in terms of throughputs in generation as well as reproducibility in size and shape that can make it challenging for drug testing applications. In the past decades, droplet microfluidics utilizing hydrogels have been highlighted due to their potentials. Importantly, core-shell structured gel droplets can avoid spheroid-to-spheroid adhesion that can cause large variations in assays while also enabling long-term cultivation of spheroids with higher uniformity by protecting the core organoid area from external environment while the outer porous gel layer still allows nutrient exchange. Hence, core-shell gel droplet-based spheroid formation can improve the predictivity and reproducibility of drug screening assays. This review paper will focus on droplet microfluidics-based technologies for cancer spheroid production using various gel materials and structures. In addition, we will discuss emerging technologies that have the potential to advance the production of spheroids, prospects of such technologies, and remaining challenges.

Endocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies.

The effects of endocrine-disrupting compounds (EDCs) on the placenta, a critical gestational organ for xenobiotic protection, are well reported; however, models to determine the role of EDCs in placental disruption are limited. An advanced 2nd-trimester human placenta organ-on-chip model (2TPLA-OOC) was developed and validated, with six representative cells of the maternal and the fetal interface interconnected with microchannels. Various EDCs (150 ng mL-1 each of bisphenol A, bisphenol S, and polybrominated diphenyl ethers-47 and -99) were gradually propagated across the chip for 72 hours, and their various effects were determined. Cigarette smoke extract (CSE), an environmental risk factor, was used as a positive control. EDCs produced overall oxidative stress in the placental/decidual cells, induced cell-specific endocrine effects, caused limited (<10%) apoptosis/necrosis in trophoblasts and mesenchymal cells, induced localized inflammation but an overall anti-inflammatory shift, did not change immune cell migration from stroma to decidua, and did not affect placental nutrient transport. Overall, (1) the humanized 2TPLA-OOC recreated the placental organ and generated data distinct from the trophoblast and other cells studied in isolation, and (2) at doses associated with adverse pregnancies, EDCs produced limited and localized insults, and the whole organ compensated for the exposure.

An Instrument for High-throughput Testing of Heart Tissue In Vitro.

Cardiac trabeculae are small samples of heart muscle tissue that can be dissected and studied in vitro to better understand the underlying physiology of cardiac muscle. However, instruments for such experimentation often (1) involve delicate mounting of the muscle, (2) constrain investigations to one muscle at a time and, thus, (3) cannot retain the muscle in the same experimental configuration for post-experimental assessment including imaging analysis. Here, we present a novel device that allows trabeculae to be secured by a visible-light photo-initiated hydrogel, manipulated via a force sensor, and stimulated while being imaged. We use our robust, accurate image registration techniques to measure cantilever and gel deformation during trabecula contraction and thereby provide a measure of trabecula force production during twitches. A variety of experiments can then be conducted, with the potential for the trabecula to be fixed in place using hydrogel for further post-experiment analysis, as well as longitudinal evaluation. The device has multiple wells making it amenable to high-throughput testing.Clinical Relevance- These methods may allow longitudinal and high-throughput studies of cardiac tissue samples in health and disease.

Non-contact quantification of aortic stenosis and mitral regurgitation using carotid waveforms from skin displacements.

Objective. Early diagnosis of heart problems is essential for improving patient prognosis.Approach. We created a non-contact imaging system that calculates the vessel-induced deformation of the skin to estimate the carotid artery pressure displacement waveforms. We present a clinical study of the system in patients (n= 27) with no underlying condition, aortic stenosis (AS), or mitral regurgitation (MR).Main results. Displacement waveforms were compared to aortic catheter pressures in the same patients. The morphologies of the pressure and displacement waveforms were found to be similar, and pulse wave analysis metrics, such as our modified reflection indices (RI) and waveform duration proportions, showed no significant differences. Compared with the control group, AS patients displayed a greater proportion of time to peak (p= 0.026 andp= 0.047 for catheter and displacement, respectively), whereas augmentation index (AIx)was greater for the displacement waveform only (p= 0.030). The modified RI for MR (p= 0.047 andp= 0.004 for catheter and displacement, respectively) was lower than in the controls. AS and MR were also significantly different for the proportion of time to peak (p= 0.018 for the catheter measurements), RI (p= 0.045 andp= 0.002 for the catheter and displacement, respectively), and AIx (p= 0.005 for the displacement waveform).Significance. These findings demonstrate the ability of our system to provide insights into cardiac conditions and support further development as a diagnostic/telehealth-based screening tool.

Development of oxidative stress-associated disease models using feto-maternal interface organ-on-a-chip.

Oxidative stress (OS) and inflammation arising from cellular derangements at the fetal membrane-decidual interface (feto-maternal interface [FMi]) is a major antecedent to preterm birth (PTB). However, it is impractical to study OS-associated FMi disease state during human pregnancy, and thus it is difficult to develop strategies to reduce the incidences of PTB. A microfluidic organ-on-chip model (FMi-OOC) that mimics the in vivo structure and functions of FMi in vitro was developed to address this challenge. The FMi-OOC contained fetal (amnion epithelial, mesenchymal, and chorion) and maternal (decidua) cells cultured in four compartments interconnected by arrays of microchannels to allow independent but interconnected co-cultivation. Using this model, we tested the effects of OS and inflammation on both fetal (fetal → maternal) and maternal (maternal → fetal) sides of the FMi and determined their differential impact on PTB-associated pathways. OS was induced using cigarette smoke extract (CSE) exposure. The impacts of OS were assessed by measuring cell viability, disruption of immune homeostasis, epithelial-to-mesenchymal transition (EMT), development of senescence, and inflammation. CSE propagated (LC/MS-MS analysis for nicotine) over a 72-hour period from the maternal to fetal side, or vice versa. However, they caused two distinct pathological effects on the maternal and fetal cells. Specifically, fetal OS induced cellular pathologies and inflammation, whereas maternal OS caused immune intolerance. The pronounced impact produced by the fetus supports the hypothesis that fetal inflammatory response is a mechanistic trigger for parturition. The FMi disease-associated changes identified in the FMi-OOC suggest the unique capability of this in vitro model in testing in utero conditions.

Mediating role of self-efficacy between unmet needs and quality of life in palliative cancer caregivers.

OBJECTIVE: Although unmet support needs are associated with health-related quality of life (HRQOL) in cancer caregivers, little is known about the mechanism underlying the relationship between two variables. The self-efficacy (SE) theory and literature suggest that caregiving SE is important in the perception of and reaction to caregiving demands, which in turn affects HRQOL. The aim of this study was to examine whether caregiving SE mediates the relationship between unmet support needs and HRQOL in family caregivers of palliative cancer patients. METHODS: This secondary analysis used the data from 125 family caregivers of palliative cancer patients who were recruited from two public hospitals in Hong Kong. The caregivers completed a survey questionnaire that covered socio-demographic characteristics, unmet support needs, caregiving SE, and HRQOL. Parallel mediation analyses were conducted via SPSS PROCESS macro (Model 4) to test the hypothesized models. RESULTS: The direct effect of unmet support needs on mental HRQOL was significant (effect = -0.49, 95% CI = -0.06 to -0.92). For the indirect effect, only caregiving SE in the domain of 'care for the care recipient' mediated the relationship between unmet support needs and mental HRQOL (effect = -0.32, 95% CI = -0.08 to -0.59). CONCLUSION: The findings suggest that caregiving SE may function as a mechanism through which unmet support needs influence mental HRQOL in family caregivers of palliative cancer patients. Healthcare providers should consider developing supportive care interventions to improve caregivers' HRQOL by incorporating effective strategies to enhance SE and reduce unmet needs for this population.

Characterization of colonization kinetics and virulence potential of Salmonella Enteritidis in chickens by photonic detection.

The light emitting module lux operon (luxCDABE) of Photorhabdus luminescens can be integrated into a "dark" bacterium for expression under a suitable promoter. The technique has been used to monitor kinetics of infection, e.g., by studying gene expression in Salmonella using mouse models in vivo and ex vivo. Here, we applied the bioluminescence imaging (BLI) technique to track Salmonella Enteritidis (SEn) strains carrying the lux operon expressed under a constitutive promoter sequence (sigma 70) in chicken after oral challenge. Detectable photon signals were localized in the crop, small intestine, cecum, and yolk sac in orally gavaged birds. The level of colonization was determined by quantification of signal intensity and SEn prevalence in the cecum and yolk sac. Furthermore, an isogenic SEn mutant strain tagged with the lux operon allowed for us to assess virulence determinants regarding their role in colonization of the cecum and yolk sac. Interestingly, mutations of SPI-1(Salmonella Pathogenicity Island 1) and fur (ferric uptake regulator) showed significantly decreased colonization in yolk sac that was correlated with the BLI data. A similar trend was detected in a ΔtonB strain by analyzing enrichment culture data. The inherently low quantum yield, light scattering, and absorption by tissues did not facilitate detection of signals from live birds. However, the detection limit of lux operon has the potential to be improved by resonance energy transfer to a secondary molecule. As a proof-of-concept, we were able to show that sensitization of a fluorescent-bound molecule known as the lumazine protein (LumP) improved the limit of detection to a certain extent.

High Affinity Iron Acquisition Systems Facilitate but Are Not Essential for Colonization of Chickens by Salmonella Enteritidis.

The roles of TonB mediated Fe3+ (ferric iron) uptake via enterobactin (involving biosynthesis genes entABCDEF) and Fe2+ (ferrous iron) uptake through the FeoABC transporter are poorly defined in the context of chicken-Salmonella interactions. Both uptake systems are believed to be the major contributors of iron supply in the Salmonella life cycle. Current evidence suggests that these iron uptake systems play a major role in pathogenesis in mammals and as such, they represent promising antibacterial targets with therapeutic potential. We investigated the role of these iron uptake mechanisms regarding the ability of Salmonella Enteritidis (SEn) strains to colonize in a chicken infection model. Further we constructed a bioluminescent reporter to sense iron limitation during gastrointestinal colonization of Salmonella in chicken via ex vivo imaging. Our data indicated that there is some redundancy between the ferric and ferrous iron uptake mechanisms regarding iron acquisition during SEn pathogenesis in chicken. We believe that this redundancy of iron acquisition in the host reservoir may be the consequence of adaptation to unique avian environments, and thus warrants further investigation. To our knowledge, this the first report providing direct evidence that both enterobactin synthesis and FeoABC mediated iron uptake contribute to the virulence of SEn in chickens.

Lamina cribrosa vessel and collagen beam networks are distinct.

Our goal was to analyze the spatial interrelation between vascular and collagen networks in the lamina cribrosa (LC). Specifically, we quantified the percentages of collagen beams with/without vessels and of vessels inside/outside of collagen beams. To do this, the vasculature of six normal monkey eyes was labeled by perfusion post-mortem. After enucleation, coronal cryosections through the LC were imaged using fluorescence and polarized light microscopy to visualize the blood vessels and collagen beams, respectively. The images were registered to form 3D volumes. Beams and vessels were segmented, and their spatial interrelationship was quantified in 3D. We found that 22% of the beams contained a vessel (range 14%-32%), and 21% of vessels were outside beams (13%-36%). Stated differently, 78% of beams did not contain a vessel (68%-86%), and 79% of vessels were inside a beam (64%-87%). Individual monkeys differed significantly in the fraction of vessels outside beams (p < 0.01 by linear mixed effect analysis), but not in the fraction of beams with vessels (p > 0.05). There were no significant differences between contralateral eyes in the percent of beams with vessels and of vessels outside beams (p > 0.05). Our results show that the vascular and collagenous networks of the LC in monkey are clearly distinct, and the historical notions that each LC beam contains a vessel and all vessels are within beams are inaccurate. We postulate that vessels outside beams may be relatively more vulnerable to mechanical compression by elevated IOP than are vessels shielded inside of beams.

Reliability, validity and acceptability of the traditional Chinese version of the carer support needs assessment tool in Hong Kong palliative care settings.

BACKGROUND: Among the few existing needs assessment tools for family carers, the 14-item Carer Support Needs Assessment Tool (CSNAT) is the only brief and holistic needs screening tool designed for everyday use in palliative care practices. The aim of this study was to evaluate the reliability, validity, and acceptability of the traditional Chinese version of the CSNAT in palliative care settings in Hong Kong. METHODS: This adopted a cross-sectional and correlation design with repeated measures. The participants were 125 family carers of palliative cancer patients and 10 healthcare providers (HCPs) that were recruited from two local hospitals. The evaluation of psychometric properties included the following: (1) content validity through HCPs including frontline physicians, nurses, social workers, and clinical psychologists; (2) construct validity between the CSNAT items and those of the validated tools that measured caregiver burden, social support, and caregiving self-efficacy; and (3) one-week test-retest reliability in a sub-sample of 81 caregivers. The acceptability of the tool was assessed by the carers using several closed-ended questions. RESULTS: The content validity index of the CSNAT at the scale level was 0.98. Each item of the CSNAT was significantly and moderately correlated with caregiver burden (Spearman's r = 0.24 to 0.50) and caregiving self-efficacy (r = - 0.21 to - 0.52), but not for social support. All CSNAT items had fair to moderate test-retest reliability (weighted kappa = 0.21 to 0.48), with the exception of two items "managing your relatives' symptoms, including giving medicines" and "having time for yourself in the day". Regarding the acceptability of the CSNAT, almost all HCPs were willing to use the CSNAT for carer assessment and support. 89.6% of the carers demonstrated a comprehensibility of the CSNAT tool and 92.9% felt comfortable answering the questions. Around 90% of the carers agreed to use the tool for screening, discussing needs, and making referrals. CONCLUSION: The traditional Chinese version of the CSNAT is a tool with high validity and acceptability and adequate reliability that measures family carers' support needs, which should be considered for wide application in local palliative care practices.

Integrated palliative medicine in public oncology: a 10-year review.

OBJECTIVES: The rapid ageing population of Hong Kong has a high demand on oncology and palliative care (PC) service. This study was the first territory-wide assessment in Hong Kong to assess the palliative service coverage in patients with advanced cancer in the past decade. METHODS: Cancer deaths of all 43 public hospitals of Hong Kong were screened. Randomly selected 2800 cancer deaths formed a representative cohort in all seven service clusters of Hospital Authority at 4 time points (2006, 2009, 2012, 2015). Individual patient records were thoroughly reviewed. Predictors of PC coverage was evaluated in univariable and multivariable analyses. RESULTS: From 2006 to 2015, PC coverage improved steadily from 55.4% to 68.9% (p<0.001). Median time of referral to PC service to death was 25 days (IQR: 53). For duration of inpatient PC, the median time was 22 days (IQR: 44) and it was stable over the past 10 years. Median time of referral to outpatient service to death was 74 days (IQR: 144) and there was an improvement observed (p<0.05). The current system was highly heterogeneous that PC varied between 9.8% and 84.8% in different hospitals depending on the PC service infrastructure. Multivariable Cox model identified patients associated with lower PC coverage: male, <50, rapid disease deterioration and staying in hospitals without multidisciplinary team clinic and designated palliative bed support (all p<0.01). CONCLUSION: There was concrete achievement in palliative service development in the past decade. Heterogeneity and late service provision should be addressed in future.

Integrative Palliative Care Service Model Improved End-of-Life Care and Overall Survival of Advanced Cancer Patients in Hong Kong: A Review of Ten-Year Territory-Wide Cohort.

Background: Integrated palliative care in oncology service has been widely implemented in Hong Kong since 2006. Aim: The study aimed to review its impact on end-of-life outcomes and overall survival (OS) of cancer patients, as well as its utilization of health care resources in the past 10 years. Design: Cancer deaths of all 43 public hospitals of Hong Kong were screened. Setting/Participants: Randomly selected 2800 cancer deaths formed a representative cohort in all seven service clusters of Hospital Authority at four time points (2006, 2009, 2012, and 2015). Individual patient records were thoroughly reviewed. Propensity score-matched (PSM) analysis was employed to compare the survival of patients. Results: Palliative care provision was associated with improved palliative care outcome, including more prescription of strong opioid, fewer cardiopulmonary resuscitations and intensive care unit admissions, and less futile chemotherapy usage in the end-of-life period (all p < 0.001). In the PSM analysis, the median OS in patients with palliative service (5.10 months, 95% confidence interval [CI] 4.52-5.68 months) was significantly better than those without palliative service (1.96 months, 95% CI 1.66-2.27 months). Patients in the palliative care group had more specialist clinic visits (p < 0.001) and longer hospital stay (p < 0.001) in the last six months of life, although the duration of last admission stay at acute general ward was shortened (p < 0.001). Conclusion: Our results suggested palliative care has played a role in the remarkable improvement in end-of-life outcomes and OS. However, current palliative care model relied heavily on hospital resources. Future work is needed to strengthen community care and to build up quality monitoring systems.

Lamina Cribrosa Capillaries Straighten as Intraocular Pressure Increases.

Purpose: The purpose of this study was to visualize the lamina cribrosa (LC) capillaries and collagenous beams, measure capillary tortuosity (path length over straight end-to-end length), and determine if capillary tortuosity changes when intraocular pressure (IOP) increases. Methods: Within 8 hours of sacrifice, 3 pig heads were cannulated via the external ophthalmic artery, perfused with PBS to remove blood, and then perfused with a fluorescent dye to label the capillaries. The posterior pole of each eye was mounted in a custom-made inflation chamber for control of IOP with simultaneous imaging. Capillaries and collagen beams were visualized with structured light illumination enhanced imaging at IOPs from 5 to 50 mm Hg at each 5 mm Hg increment. Capillary tortuosity was measured from the images and paired two-sample t-tests were used to assess for significant changes in relation to changes in IOP. Results: Capillaries were highly tortuous at 15 mm Hg (up to 1.45). In all but one eye, tortuosity decreased significantly as IOP increased from 15 to 25 mm Hg (P < 0.01), and tortuosity decreased significantly in every eye as IOP increased from 15 to 40 mm Hg (P < 0.01). In only 16% of capillaries, tortuosity increased with elevated IOP. Capillaries had a surprisingly different topology from the collagen beams. Conclusions: Although high capillary tortuosity is sometimes regarded as potentially problematic because it can reduce blood flow, LC capillary tortuosity may provide slack that mitigates against reduced flow and structural damage caused by excessive stretch under elevated IOP. We speculate that low capillary tortuosity could be a risk factor for damage under high IOP.

A miniature mechanical testing device for testing hydrogel-based biomaterials in a confocal microscope.

Cardiac muscle cells are the fundamental building blocks of the heart, yet little is known about their mechanical properties in either healthy or diseased states. While many have explored unloaded myocyte behavior under a variety of interventions, methods for force measurements are limited due to cell fragility. Here, we present a custom device for manipulation and mechanical testing of hydrogels embedded with delicate cardiac muscle cells. Consisting of a custom disposable flexure, which is easily interchangeable, the device has the potential for high throughput testing of cell-gel constructs. Additionally, the mechanical testing device is the size of a microscope slide - appropriate for use in most microscopes, for simultaneous imaging of the sample. The mechanical properties of a gelatin-methacryloyl hydrogel sample were assessed, and 3D volumes of gel imaged using a confocal microscope. The Young's modulus of the gel was found to be 33kPa.Clinical Relevance- High-throughput testing provides the potential to gain insight into cardiac cell mechanics. Experimentation under the influence of a variety of pharmacological interventions could improve the rate at which treatments for cardiac disease are developed. Furthermore, methods may be extended to other embedded biological tissues.

Effects of rubble zones from oyster cultivation on habitat utilization and foraging behaviour of the endangered tri-spine horseshoe crab: An implication for intertidal oyster cultivation practices.

Estuarine structured habitats, including benthic cultivation structure, are widely cited as substantial nursery and feeding grounds for fish and macroinvertebrates. Activities such as locomotion and foraging behaviour of sediment-dwelling species, however, may be hindered in the presence of the obstacles. In this study, collected field evidence demonstrated that habitat utilization of the juvenile tri-spine horseshoe crab Tachypleus tridentatus, an iconic and endangered macroinvertebrate, was adversely affected by high-density intertidal oyster rubble zones. Despite the fact that the utilization area of individual juvenile horseshoe crabs was independent of the presence of these obstacles, the abundance and number of positional fixes of tagged juveniles in these areas were lower. The effects of these obstacles and their associated topographic changes on the movement of the juvenile horseshoe crabs was investigated in a simulated laboratory experiment. Both the simulated oyster cultches and hummocks formed between the cultches reduced the total distance and displacement of the feeding trail, and less juveniles preferred to forage on elevated, dry hummocks (dry at low tide) formed between the cultches. Our findings suggested that oyster cultches and rubbles reduced the habitat quality for juvenile horseshoe crabs. On-bottom oyster cultivation activities seeking to conserve horseshoe cabs by avoiding nursery habitats should instead consider off-bottom or offshore cultivation methods.

Comparison of the verification performance and radiation dose between ExacTrac x-ray system and On-Board Imager-A phantom study.

Recently, On-Board Imager (OBI) and ExacTrac x-ray 6 degree-of-freedom system (ExacTrac) are increasingly used verification systems in local radiotherapy centers. This study aimed to compare the differences between these two systems in terms of verification accuracy, organ doses, and verification time for head-and-neck (H&N) and pelvic cases. Rando anthropomorphic phantoms of H&N and pelvic regions were positioned with known set-up deviations from the reference position in the linear accelerator. x-Ray verification images were then acquired using both systems. Verification accuracy was evaluated based on the residual positioning error (δD) after image registration. Thermoluminescence dose meters (TLD-100s) were placed in specific locations of the phantoms for the measurement of imaging doses at the organs of interest. Besides, the verification time was also recorded for comparison. Most average detection errors for both systems were within 1 mm. The detection error of ExacTrac was significantly larger than OBI in the H&N region in all directions (p < 0.05), but was significantly lower in the pelvis (p < 0.05). The mean imaging doses to all organs of interest from ExacTrac were significantly lower than OBI (p < 0.05). The mean verification time for ExacTrac was about 10 seconds, which was significantly shorter than the 100 seconds in OBI (p < 0.001). Both verification systems achieved satisfactory performance in the H&N and pelvic regions despite ExacTrac being better in terms of verification time and organ dose. The verification accuracy of Exactrac was better in pelvic region than the H&N region when compared with OBI.

Non-contact Quantification of Jugular Venous Pulse Waveforms from Skin Displacements.

The jugular venous (JV) pressure waveform is a non-invasive, proven indicator of cardiovascular disease. Conventional clinical methods for assessing these waveforms are often overlooked because they require specialised expertise, and are invasive and expensive to implement. Recently, image-based methods have been used to quantify JV pulsation waveforms on the skin as an indirect way of estimating the pressure waveforms. However, these existing image-based methods cannot explicitly measure skin deformations and rely on the use of photoplethysmography (PPG) devices for identification of the pulsatile waveforms. As a result, they often have limited accuracy and robustness and are unsuitable in the clinical environment. Here, we propose a technique to directly measure skin deformations caused by the JV pulse using a very accurate subpixel registration algorithm. The method simply requires images obtained from the subject's neck using a commodity camera. The results show that our measured waveforms contained all of the essential features of diagnostic JV waveforms in all of 19 healthy subjects tested in this study, indicating a significantly important capability for a potential future diagnostic device. The shape of our measured JV displacement waveforms was validated using waveforms measured with a laser displacement sensor, where the average correlation score between the two waveforms was 0.93 ± 0.05. In addition, synchronously recorded ECG signals were used to verify the timings of diagnostic features of the measured waveforms. To our knowledge, this is the first use of image registration for direct measurement of JV displacement waveforms. Significant advantages of our novel method include the high precision of our measurements, and the ability to use ordinary cameras, such as those in modern mobile phones. These advantages will enable the development of affordable and accessible devices to measure JV waveforms for cardiac diagnostics in the clinical environment. Future devices based on this technology may provide viable options for telemedicine applications, point of care diagnostics, and mobile-based cardiac health monitoring systems.