Metastatic cancer cells (seeds) preferentially grow in the secondary sites with a permissive microenvironment (soil). We show that the metastatic cells can bring their own soil—stromal components ...including activated fibroblasts—from the primary site to the lungs. By analyzing the efferent blood from tumors, we found that viability of circulating metastatic cancer cells is higher if they are incorporated in heterotypic tumor-stroma cell fragments. Moreover, we show that these cotraveling stromal cells provide an early growth advantage to the accompanying metastatic cancer cells in the lungs. Consistent with this hypothesis, we demonstrate that partial depletion of the carcinoma-associated fibroblasts, which spontaneously spread to the lung tissue along with metastatic cancer cells, significantly decreases the number of metastases and extends survival after primary tumor resection. Finally, we show that the brain metastases from lung carcinoma and other carcinomas in patients contain carcinoma-associated fibroblasts, in contrast to primary brain tumors or normal brain tissue. Demonstration of the direct involvement of primary tumor stroma in metastasis has important conceptual and clinical implications for the colonization step in tumor progression.
High-resolution intravital microscopy through imaging windows has become an indispensable technique for the long-term visualization of dynamic processes in living animals. Easily accessible sites ...such as the skin, the breast and the skull can be imaged using various different imaging windows; however, long-term imaging studies on cellular processes in abdominal organs are more challenging. These processes include colonization of the liver by metastatic tumor cells and the development of an immune response in the spleen. We have recently developed an abdominal imaging window (AIW) that allows long-term imaging of the liver, the pancreas, the intestine, the kidney and the spleen. Here we describe the detailed protocol for the optimal surgical implantation of the AIW, which takes ∼1 h, and subsequent multiphoton imaging, which takes up to 1 month.
One way to achieve universal health coverage (UHC) in low- and middle-income countries (LMIC) is the implementation of health insurance schemes. A robust and up to date overview of empirical evidence ...assessing and substantiating health equity impact of health insurance schemes among specific vulnerable populations in LMICs beyond the more common parameters, such as income level, is lacking. We fill this gap by conducting a systematic review of how social inclusion affects access to equitable health financing arrangements in LMIC.
We searched 11 databases to identify peer-reviewed studies published in English between January 1995 and January 2018 that addressed the enrolment and impact of health insurance in LMIC for the following vulnerable groups: female-headed households, children with special needs, older adults, youth, ethnic minorities, migrants, and those with a disability or chronic illness. We assessed health insurance enrolment patterns of these population groups and its impact on health care utilization, financial protection, health outcomes and quality of care.
The comprehensive database search resulted in 44 studies, in which chronically ill were mostly reported (67%), followed by older adults (33%). Scarce and inconsistent evidence is available for individuals with disabilities, female-headed households, ethnic minorities and displaced populations, and no studies were yielded reporting on youth or children with special needs. Enrolment rates seemed higher among chronically ill and mixed or insufficient results are observed for the other groups. Most studies reporting on health care utilization found an increase in health care utilization for insured individuals with a disability or chronic illness and older adults. In general, health insurance schemes seemed to prevent catastrophic health expenditures to a certain extent. However, reimbursements rates were very low and vulnerable individuals had increased out of pocket payments.
Despite a sizeable literature published on health insurance, there is a dearth of good quality evidence, especially on equity and the inclusion of specific vulnerable groups in LMIC. Evidence should be strengthened within health care reform to achieve UHC, by redefining and assessing vulnerability as a multidimensional process and the investigation of mechanisms that are more context specific.
Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable ...esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen.
From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses.
The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio HR, 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (
value for interaction,
= .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38%
25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13).
The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.
Water is the dominant component of volcanic gas emissions, and water phase transformations, including the formation of ice, can be significant in the dynamics of volcanic clouds. The effectiveness of ...volcanic ash particles as ice‐forming nuclei (IN) is poorly understood and the sparse data that exist for volcanic ash IN have been interpreted in the context of meteorological, rather than volcanic clouds. In this study, single‐particle freezing experiments were carried out to investigate the effect of ash particle composition and surface area on water drop freezing temperature. Measured freezing temperatures show only weak correlations with ash IN composition and surface area. Our measurements, together with a review of previous volcanic ash IN measurements, suggest that fine‐ash particles (equivalent diameters between approximately 1 and 1000 μm) from the majority of volcanoes will exhibit an onset of freezing between ∼250–260 K. In the context of explosive eruptions where super‐micron particles are plentiful, this result implies that volcanic clouds are IN‐rich relative to meteorological clouds, which typically are IN‐limited, and therefore should exhibit distinct microphysics. We can expect that such “overseeded” volcanic clouds will exhibit enhanced ice crystal concentrations and smaller average ice crystal size, relative to dynamically similar meteorological clouds, and that glaciation will tend to occur over a relatively narrow altitude range.
The Morphometry of Impact Craters on Bennu Daly, R. T.; Bierhaus, E. B.; Barnouin, O. S. ...
Geophysical research letters,
28 December 2020, Letnik:
47, Številka:
24
Journal Article
Recenzirano
Odprti dostop
Bennu is an ~500‐m‐diameter rubble‐pile asteroid that is the target of detailed study by the Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS‐REx) ...mission. Here we use data from the OSIRIS‐REx Laser Altimeter to assess depth‐to‐diameter ratios (d/D) of 108 impact craters larger than 10 m in diameter. The d/D of craters on Bennu ranges from 0.02 to 0.19. The mean is 0.10 ± 0.03. The smallest craters show the broadest range in d/D, consistent with d/D measurements on other asteroids. A few craters have central mounds, which is interpreted as evidence that a more competent substrate lies a few meters beneath them. The range of d/D narrows as crater size increases, with craters larger than 80 m tending toward smaller d/D. At large scales, increases in target strength with depth, combined with target curvature, may affect crater morphometry.
Plain Language Summary
Between 2018 and 2020, National Aeronautics and Space Administration (NASA)'s Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS‐REx) spacecraft orbited a small asteroid called Bennu in preparation to collect a sample for return to Earth. Bennu is a “rubble‐pile” asteroid, meaning an aggregate of rock fragments that have coalesced together in space. OSIRIS‐REx observations showed that Bennu has many craters on its surface, which formed when other, smaller objects collided with it in the past. Crater depths and widths (diameters), in addition to relating to the size and speed of the impacting object, also reflect the physical characteristics of the impacted surface. Accordingly, we measured the depths and diameters of many of Bennu's craters to better understand the surface and interior properties of this rubble‐pile asteroid and how it compares to other asteroids. The smaller craters on Bennu have a variety of depths, even among similarly sized craters. The largest are so wide that they appear to be affected by the curvature of Bennu's surface and by the presence of stronger material at depth. We observe mounds inside some of the smaller craters, supporting the idea that a more competent substrate underlies the surface material.
Key Points
The depth‐to‐diameter ratio (d/D) of asteroid Bennu's craters >10 m in diameter ranges from 0.02 to 0.19 with a mean of 0.10 ± 0.03
Small craters show the greatest diversity in d/D, whereas larger craters (>80 m) span a narrower range in d/D and tend to be shallower
For craters >80 m, increases in target strength with depth, combined with target curvature, likely contribute to smaller d/D
Cell dynamics in subcutaneous and breast tumors can be studied through conventional imaging windows with intravital microscopy. By contrast, visualization of the formation of metastasis has been ...hampered by the lack of long-term imaging windows for metastasis-prone organs, such as the liver. We developed an abdominal imaging window (AIW) to visualize distinct biological processes in the spleen, kidney, small intestine, pancreas, and liver. The AIW can be used to visualize processes for up to 1 month, as we demonstrate with islet cell transplantation. Furthermore, we have used the AIW to image the single steps of metastasis formation in the liver over the course of 14 days. We observed that single extravasated tumor cells proliferated to form "pre-micrometastases," in which cells lacked contact with neighboring tumor cells and were active and motile within the confined region of the growing clone. The clones then condensed into micrometastases where cell migration was strongly diminished but proliferation continued. Moreover, the metastatic load was reduced by suppressing tumor cell migration in the pre-micrometastases. We suggest that tumor cell migration within pre-micrometastases is a contributing step that can be targeted therapeutically during liver metastasis formation.
Objective: Threat-related attention bias figures prominently in contemporary accounts of the maintenance of anxiety disorders, yet longitudinal intervention research relating attention bias to ...anxiety symptom severity is limited. Capitalizing on recent advances in the conceptualization and measurement of attention bias, we aimed to examine the relation between attention bias, indexed using trial-level bias scores (TLBSs) to quantify temporal dynamics reflecting dysregulation of attentional processing of threat (as opposed to aggregated mean bias scores) and social anxiety symptom severity over the course of cognitive-behavioral therapy (CBT) and 1-month follow-up. Method: Adults with social anxiety disorder (N = 39) assigned to either yohimbine- or placebo-augmented CBT completed measures of attention bias and social anxiety symptom severity weekly throughout CBT (5 sessions) and at 1-week and 1-month posttreatment. Results: TLBSs of attention bias temporal dynamics showed stronger psychometric properties than mean aggregated scores and were highly interrelated, in line with within-subject temporal variability fluctuating in time between attentional overengagement and strategic avoidance from threat. Attention bias toward threat and temporal variability in attention bias (i.e., attentional dysregulation), but not attention bias away from threat, significantly reduced over the course of CBT. Cross-lag analyses revealed no evidence of a causal relation between reductions in attentional dysregulation leading to symptom severity reduction, or vice versa. Observed relations did not vary as a function of time. Conclusions: We found no evidence for attentional dysregulation as a causal mechanism for symptom reduction in CBT for social anxiety disorders. Implications for future research are discussed.
What is the public health significance of this article?
This study suggests that attentional dysregulation may not be a mechanism for change in cognitive-behavioral therapy, an effective treatment for social anxiety disorder. Though data are still preliminary, our finding that cognitive-behavioral therapy did not lead to changes in attentional avoidance leaves open the possibility that targeting attentional avoidance alongside cognitive-behavioral therapy may enhance its efficacy.
Background and Objectives
It is unclear what time interval is optimal between presentation and surgical resection of left‐sided obstructive colon cancer (LSOCC). This study aims to determine whether ...a time interval beyond 4 weeks is associated with a better outcome.
Materials and Methods
Consecutive patients who underwent surgical resection of LSOCC between January 2010 and December 2019 were collected from a prospective database. Patients were divided into three groups: (1) Emergency resection (ER group), (2) surgery in less than 4 weeks (early group), and (3) surgery beyond 4 weeks (late group).
Results
The ER group consisted of 74 (44.0%), the early group of 38 (22.6%), and the late group of 56 (33.3%) patients. Ninety‐day mortality was lower in the Late group than in the ER group and the early group (1.8% vs. 12.2%, p = 0.029 vs. 15.3%, p = 0.011). In the late group 5‐year recurrence‐free survival was better than in the early group (82.1% vs. 63.2%, p = 0.039) and 5‐year overall survival (OS) was better than in the ER group (75% vs. 51.4%, p = 0.021). Definitive surgical resection beyond 4 weeks was an independent prognostic factor for OS (Hazard ratio: 0.402, 95% CI: 0.204–0.793, p = 0.009).
Conclusion
In this study surgical resection beyond 4 weeks after presentation seems to have a better short‐ and long‐term outcome for LSOCC.
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