In this manuscript, we discuss the development and clinical use of a thermoplastic modular microsystem for the high-throughput analysis of CTCs directly from whole blood. The modular system offers ...some innovative features that address challenges currently associated with many CTC platforms; it can exhaustively process 7.5 mL of blood in less than 45 min with recoveries >90%. In addition, the system automates the postselection CTC processing steps and thus, significantly reduces assay turnaround time (from selection to enumeration <1.5 h as compared to >8 h for many reported CTC platforms). The system is composed of 3 functional modules including (i) a thermoplastic CTC selection module composed of high aspect ratio (30 μm × 150 μm) channels containing anti-EpCAM antibodies that is scalable in terms of throughput by employing channel numbers ranging from 50 to 320; the channel number is user selected to accommodate the volume of blood that must be processed; (ii) an impedance sensor module for label-less CTC counting; and (iii) a staining and imaging module for the placement of released cells into a 2D array within a common imaging plane for phenotypic identification. To demonstrate the utility of this system, blood samples from patients with local resectable and metastatic pancreatic ductal adenocarcinoma (PDAC) were analyzed. We demonstrate the ability to select EpCAM positive CTCs from PDAC patients in high purity (>86%) and with excellent yields (mean = 53 CTCs per mL for metastatic PDAC patients) using our modular system. In addition, we demonstrate the ability to detect CTCs in PDAC patients with local resectable disease (mean = 11 CTCs per mL).
The neuropeptide oxytocin has been shown to affect social interaction. Meanwhile, the underlying mechanism remains highly debated. Using an interpersonal finger-tapping paradigm, we investigated ...whether oxytocin affects the ability to synchronise with and adapt to the behaviour of others. Dyads received either oxytocin or a non-active placebo, intranasally. We show that in conditions where one dyad-member was tapping to another unresponsive dyad-member - i.e. one was following another who was leading/self-pacing - dyads given oxytocin were more synchronised than dyads given placebo. However, there was no effect when following a regular metronome or when both tappers were mutually adapting to each other. Furthermore, relative to their self-paced tapping partners, oxytocin followers were less variable than placebo followers. Our data suggests that oxytocin improves synchronisation to an unresponsive partner's behaviour through a reduction in tapping-variability. Hence, oxytocin may facilitate social interaction by enhancing sensorimotor predictions supporting interpersonal synchronisation. The study thus provides novel perspectives on how neurobiological processes relate to socio-psychological behaviour and contributes to the growing evidence that synchronisation and prediction are central to social cognition.
SUMMARY
The amount of high-quality seismic data is expanding rapidly, and there is a need for algorithms that take advantage of classical methods to achieve high efficiency using widely available ...computing power. In this study, we develop a novel waveform inversion method to retrieve radially anisotropic Earth models that can be used to investigate deformation and flow in the mantle. Our method is comprised of two parts: (1) extraction and fitting of the fundamental mode and (2) fitting of the full synthetic waveform. The waveform inversion method results in path average model constraints with uniquely determined independent uncertainties. We demonstrate through synthetic testing that the method is able to retrieve radially anisotropic perturbations down to the mantle transition zone, and leakage effects due to ignoring P-wave anisotropy are minimal. We apply the method to ∼16 000 waveforms generated by earthquakes occurring in the East Sea (Sea of Japan) region, and we demonstrate that the subsequent linear inversion of radially anisotropic path constraints produces models that are similar to those resulting from full waveform adjoint tomography methods. We validate our model by predicting waveforms for earthquakes not included in our inversion, and we show that our method is able to extract structural information. Our results indicate low-velocity anomalies and weak radial anisotropy in NE Japan, which may be due to competing influences from ascending fluids and/or melts and horizontal flow in the lower crust and upper mantle. In the southern East Sea, we image low velocities and relatively high radial anisotropy, which may reflect high temperatures, shallow dehydration and olivine LPO in the upper mantle.
Abstract
Background
Clinical trials of extracranial-intracranial (EC-IC) bypass surgery studied patients in subacute and chronic stage after ischemic event.
OBJECTIVE
To investigate the short-term ...outcomes of EC-IC bypass in progressive acute ischemic stroke or recent transient ischemic attacks.
Methods
The study was a retrospective review at a single tertiary referral center from 2008 to 2015. Inclusion criteria consisted of EC-IC bypass within 1 yr of last ischemic symptoms ipsilateral to atherosclerotic occlusion of internal carotid or middle cerebral artery. Early bypass group who underwent surgery within 7 d of last ischemic symptoms were compared to late bypass group who underwent surgery >7 d from last ischemic symptom. The primary endpoint was perioperative ischemic or hemorrhagic stroke or intracranial hemorrhage within 7 d of surgery.
Results
Of 126 patients who underwent EC-IC bypass during the period, 81 patients met inclusion criteria, 69 (85%) persons had carotid artery occlusion, 7 (9%) had proximal MCA occlusion, and 5 (6%) had both. Early surgery had a 31% (9/29) perioperative stroke rate compared to 11.5% (6/52) of patients undergoing late bypass (P = .04). Of patients with acute stroke within 7 d of surgery, 41% (7/17) had perioperative stroke within 7 d (P = .07). Six of nine patients (67%) with blood pressure dependent fluctuation of neurologic symptoms had perioperative stroke (P = .049).
Conclusion
EC-IC bypass in setting of acute symptomatic stroke within 1 wk may confer higher risk of perioperative stroke. Patients undergoing expedited or urgent bypass for unstable or fluctuating stroke symptoms might be at highest risk for perioperative stroke.
SUMMARY
Seismic anisotropy is key to constrain mantle flow, but it is challenging to image and interpret it. Existing large-scale tomography models of seismic anisotropy typically show large ...discrepancies, which can lead to completely distinct geodynamical interpretations. To better quantify the robustness of anisotropy tomography, we create a 2-D ridge-to-slab geodynamic model and compute the associated fabrics. Using the resulting 21 elastic constants, we compute seismic full waveforms, which are inverted for isotropic and radially anisotropic structure. We test the effects of different data coverage and levels of regularization on the resulting images and on their geodynamical interpretation. Within the context of our specific imposed conditions and source–receiver configuration, the retrieved isotropic images exhibit substantial artificial slab thickening and loss of the slab’s high-velocity signature below ∼100 km depth. Our results also show that the first-order features of radial anisotropy are well retrieved despite strong azimuthal anisotropy (up to 2.7 per cent) in the input model. On the other hand, regularization and data coverage strongly control the detailed characteristics of the retrieved anisotropy, notably the depth–age dependency of anisotropy, leading to an artificial flat depth–age trend shown in existing anisotropy tomography models. Greater data coverage and additional complementary data types are needed to improve the resolution of (an)isotropic tomography models.
Activating point mutations in Anaplastic Lymphoma Kinase (ALK) have positioned ALK as the only mutated oncogene tractable for targeted therapy in neuroblastoma. Cells with these mutations respond to ...lorlatinib in pre-clinical studies, providing the rationale for a first-in-child Phase 1 trial (NCT03107988) in patients with ALK-driven neuroblastoma. To track evolutionary dynamics and heterogeneity of tumors, and to detect early emergence of lorlatinib resistance, we collected serial circulating tumor DNA samples from patients enrolled on this trial. Here we report the discovery of off-target resistance mutations in 11 patients (27%), predominantly in the RAS-MAPK pathway. We also identify newly acquired secondary compound ALK mutations in 6 (15%) patients, all acquired at disease progression. Functional cellular and biochemical assays and computational studies elucidate lorlatinib resistance mechanisms. Our results establish the clinical utility of serial circulating tumor DNA sampling to track response and progression and to discover acquired resistance mechanisms that can be leveraged to develop therapeutic strategies to overcome lorlatinib resistance.
Myrmica ants have been model species for studies in a variety of disciplines, including insect physiology, chemical communication, ant social dynamics, ant population, community ecology, and ant ...interactions with other organisms. Species belonging to the genus Myrmica can be found in virtually every habitat within the temperate regions of the northern hemisphere and their biology and systematics have been thoroughly studied. These ants serve as hosts to highly diverse parasitic organisms from socially parasitic butterfly caterpillars to microbes, and many Myrmica species even evolved into parasitizing species of their own genus. These parasites have various impacts both on the individuals and on the social structure of their hosts, ranging from morphological malformations to reduction in colony fitness. A comprehensive review of the parasitic organisms supported by Myrmica and the effects of these organisms on individuals and on whole ant colonies has not yet been compiled. Here, we provide a review of the interactions of these organisms with Myrmica ants by discussing host and parasite functional, behavioral or physiological adaptations. In addition, for all “symbiont groups” of Myrmica ants described in this paper, we examine the present limitations of the knowledge at present of their impact on individuals and host colony fitness. In conclusion, we argue that Myrmica ants serve as remarkable resource for the evolution of a wide variety of associated organisms.
The colony performance of social insects is supported by an efficient allocation of tasks among workers in the colony. The division of labor among ant workers is linked to age and caste polyethism, ...however, only a few studies have shown the relationship between workers’ behavioral variation and task performance. In this study, we investigated the task syndrome by testing the relationship between behavioral traits with task performance and
location switching
(switching the performance of tasks from inside to outside the nest) in the same-age workers of
Camponotus vagus
ants. We also investigated the division of labor in workers with and without
location switching
by checking if each caste is characterized by specific behavioral traits or tasks. Moreover, we checked whether the difference in the worker’s body size and its lifespan can influence task performance. Our results support the existence of task syndrome in ant workers by showing how individuals with specific behavioral traits are more likely to perform specific tasks within the colony. Moreover, the time of
location switching
was correlated with the tasks performed by the workers (
brood care
,
selfgrooming
and
walking
) and their behavioral traits (
aggressiveness
and
total distance
). In addition, worker size and lifespan are shown to influence task performance by the workers. Altogether, our study underpins the relationship between the behavioral traits and the task allocation and performance of workers within an ant colony.
Changes in habitat characteristics are known to have profound effects on biotic communities and their functional traits. In the context of an urban-rural gradient, urbanisation drastically alters ...abiotic characteristics, e.g., by increasing environmental temperatures and through light pollution. These abiotic changes significantly impact the functional traits of organisms, particularly insects. Furthermore, changes in habitat characteristics also drive changes in the behavioural traits of animals, allowing them to adapt and thrive in new environments. In our study, we focused on the synanthropic ant species Lasius niger as a model organism. We conducted nocturnal field observations and complemented them with laboratory experiments to investigate the influence of night warming (NW) associated with Urban Heat Islands (UHI), light pollution (ALAN), and habitat type on ant foraging behaviour. In addition, we investigated the influence of elevated temperatures on brood development and worker mortality. Our findings revealed that urban populations of L. niger were generally more active during the night compared to their rural counterparts, although the magnitude of this difference varied with specific city characteristics. In laboratory settings, higher temperatures and continuous illumination were associated with increased activity level in ants, again differing between urban and rural populations. Rural ants exhibited more locomotion compared to their urban counterparts when maintained under identical conditions, which might enable them to forage more effectively in a potentially more challenging environment. High temperatures decreased the developmental time of brood from both habitat types and increased worker mortality, although rural colonies were more strongly affected. Overall, our study provides novel insights into the influence of urban environmental stressors on the foraging activity pattern and colony development of ants. Such stressors can be important for the establishment and spread of synanthropic ant species, including invasive ones, and the biotic homogenization of anthropogenic ecosystems.
Display omitted
•Ant foraging activity was generally higher in urban areas.•In the smaller and cooler cities, ant activity was higher in rural areas.•Results of a laboratory study followed the same trend found in the field study.•Urban locomotory traits suggested adaptations to weaker competitive pressures.•In urban areas, brood developed faster but worker mortality increased.
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