RϠoo|ky {{ Kjh =LINK=
DOWNLOAD >> https://urlin.us/2sXz2e
Except for Peggy Gao, all the authors have received research funds from the sponsors, grants for travel to scientific meetings, and honoraria for lectures. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors.
Conceived and designed the experiments: ALD KKT JHC KJH KY SC JZ LL SY. Performed the experiments: ALD KKT JHC KJH KY SC JZ LL SY. Analyzed the data: ALD KKT PG KJH KY SC JZ LL SY. Contributed reagents/materials/analysis tools: JHC. Wrote the paper: ALD KKT PG JHC KJH KY SC JZ LL SY.
CareSource remains committed to our members and the communities we serve. In response to the growing public health concerns related to the Coronavirus (COVID-19), we have created a resource page to identify your benefit coverage and services offered during this time of need. Click below to visit our COVID-19 Member Resource Page.
The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.
The medical records of the remaining 92 were reviewed retrospectively, and constituted the study cohort. The operative methods were classified as hemihepatectomy, sectionectomy, segmentectomy (anatomical resection), and tumorectomy (non-anatomical resection). Regarding the pathologic data, the gross type was classified as described by The Korean Liver Cancer Study Group, and the differentiation was determined by the worst Edmondson-Steiner grade.9 Follow-ups were performed at 3 to 6 months intervals, unless a postoperative complication was encountered, or a recurrence was suspected. Follow-up studies and tests consisted of an alpha-fetoprotein (AFP) and a PIVKA (protein induced by vitamin K absence or antagonist), an abdominal computed tomography (CT) and/or magnetic resonance (MR) imaging, as well as a liver function test with coagulation profiles.
Intrahepatic recurrence has been reported to outnumber extrahepatic recurrence by six to seven fold and,15 thus, intrahepatic recurrence has been the subject of extensive study.5 However, the majority of studies on potential risk factors compared the treatment modalities and/or recurrence patterns, and the reported results vary considerably. Furthermore, the incongruity of the risks identified seems to be due to the different criteria applied, the discriminatory powers of the statistical methods used, and the diversity of the causative agents and patient population.16,17 This study shows that changing group criteria, even in the same patient population, results in the identification of different risk factors.4 More specifically, the risk factors of early recurrence were changed by simply modifying the RFP criterion from within 18 months to within 10 months. Likewise, when the recurrence multiplicity cutoff was altered from >1 to >3, different risk factors were identified by the univariate analysis. These results suggest that recurrence, timing, and multiplicity are driven by different factors.5
The tumor size at the initial presentation has been relatively consistently identified as a risk factor of intrahepatic recurrence,4,18 and this study confirms tumor size as a risk factor along with portal vein invasion, which together constitute the tumor (T) stage as defined by the International Union for Cancer Control (UICC).4,19,20 However, when a risk factor analysis for intrahepatic recurrence was performed versus extrahepatic recurrence, rather than non-recurrence, these significances disappeared.3,4,15 The Child-Pugh score, as an independent risk factor of intrahepatic recurrence, means that liver cirrhosis is a risk factor.4 Cumulative evidence suggests that the primary tumor burden (as indicated by the tumor size and the AFP), as well as the degree of liver cirrhosis (as indicated by the Child-Pugh score and the indocyanine green retention test) are the major conditions that provoke the intrahepatic recurrence of HCC, irrespective of the initial management modality.6,7,21,22,23 Of note, the width and involvement of the resection margins and methods (anatomical resection versus partial hepatectomy), which are long debated issues in the context of recurrence, were not identified as risk factors in this study.18,24
When HCC recurrence was subdivided into early and late recurrence, using an RFP cutoff of 18 months, the risk factors identified differed from those of recurrence per se. In this study, tumor differentiation was an independent risk factor of early recurrence for RFP cutoffs of 18 and 10 months, and tumor differentiation is known to be related to tumor invasiveness;15 however, tumor size and portal vein invasion were not found to be risk factors, even by the univariate analysis. On the other hand, Shirabe et al.8 reported that capsule invasion, a tumor location deep in the liver parenchyma, and portal vein invasion independently predicted early HCC recurrence. These discrepancies between the identified risk factors may be due to the definitions of early recurrence used, and the different study populations.25 Although the term 'early' is non-specific, discrimination is required to define the timing of recurrent HCC, because synchronous metastasis has a poorer prognosis than metachronous occurrence.26 Some authors have defined synchronous and metachronous recurrences, using modes of recurrence like intrahepatic metastasis and multicentric occurrence, respectively, and not time courses.27 We do not agree with the use of the same definitions for timing and modes of recurrence, and hope that further studies (based on tumor nucleic acid sequencing) contribute to the refining of the terminologies used.28
In our series, the serum AFP level, tumor size, tumor necrosis, and hemorrhage were significant risk factors for multiple recurrence, according to the univariate analysis. When a multiplicity cut off of >3 was used, rather than a cutoff of >1, the MELD score and the gross type replaced the tumor size and hemorrhage. Interestingly, the former factors are related to tumor mass,29 while the latter are indicative of liver cirrhosis and tumor invasiveness, respectively.12,30 Our failure to identify independent risk factors in this study may have been due to the limited number of cases, especially in the diffuse recurrence subgroup, but it might also have been due to the complex relationships between the risk factors.31 The distribution of the number of recurrent nodules among the 41 patients had two peaks at one nodule, and for diffuse recurrence throughout the remnant liver. Many authors have set the cutoff number for multiple recurrences to >3 nodules,6,10,11,29 and we found that counting more than five nodules is impractical. Whatever number criterion is used to define multiplicity, the presence of two peaks in the nodule number distribution indicates that there are distinct groups with different etiologies and prognoses.11,12,29
There were some limitations to this study. Since this was a small-volume retrospective study reported by a single center, high-volume multicenter studies need to be performed to validate our results. We presented only the recurrence-free survival results in this study, to avoid complexity of data presentation; thus, the overall patient survival results were omitted.
Sputter deposited nickel-molybdenum-tungsten (Ni-Mo-W) thin films possess a beneficial suite of properties that stem from the extremely fine growth twins that form during the deposition process. Previously these materials were only characterized in tension, however, in this study in situ micropillar compression and post-mortem microstructural analysis of nanotwinned Ni84Mo11W5 micropillars were employed to measure the compressive response and elucidate the attendant deformation mechanisms. The pillars exhibit Hookean behavior to compressive strengths of 3-3.5 GPa and the onset of non-linear plastic flow was manifest by discrete strain bursts and highly localized shear bands. Plastic deformation was concentrated at the top of the pillar, while the bulk of the micropillar was nominally unaffected. Post-mortem investigations indicate that at sufficiently high stresses shear banding is triggered, resulting in intense and highly localized plastic deformation that led to the formation of twin-free nanocrystalline grains within highly deformed shear bands. By contrast, the regions adjacent to the shear bands were unaffected. The absence of detwinning and dislocation glide mechanisms was unexpected and in direct contrast to what has been observed in nanotwinned Cu-Al. Post-mortem observations of the Ni-Mo-W micropillars suggest that the ultrafine twins create a unique form of dislocation starvation and source-limited plasticity. The ultrahigh compressive strength is governed by the triggering of shear bands rather than the activation of dislocation glide. The specialized nature of plasticity in nanotwinned Ni-Mo-W is clear, even though the precise trigger for shear band formation in nanotwinned Ni-Mo-W remains to be identified.
N1 - Funding Information:The authors GMV and KJH would like to acknowledge Prof. Jaafar El-Awady for stimulating discussions, Dr. Steven Lavenstein for his assistance in initial sample fabrication and Dr. Quan Jiao for equipment training. This work was supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under award #DE-FG02-07ER46437. WCO and GMP acknowledge support from the National Science Foundation under grant #DMR-1743343. Publisher Copyright:© 2020
N2 - Sputter deposited nickel-molybdenum-tungsten (Ni-Mo-W) thin films possess a beneficial suite of properties that stem from the extremely fine growth twins that form during the deposition process. Previously these materials were only characterized in tension, however, in this study in situ micropillar compression and post-mortem microstructural analysis of nanotwinned Ni84Mo11W5 micropillars were employed to measure the compressive response and elucidate the attendant deformation mechanisms. The pillars exhibit Hookean behavior to compressive strengths of 3-3.5 GPa and the onset of non-linear plastic flow was manifest by discrete strain bursts and highly localized shear bands. Plastic deformation was concentrated at the top of the pillar, while the bulk of the micropillar was nominally unaffected. Post-mortem investigations indicate that at sufficiently high stresses shear banding is triggered, resulting in intense and highly localized plastic deformation that led to the formation of twin-free nanocrystalline grains within highly deformed shear bands. By contrast, the regions adjacent to the shear bands were unaffected. The absence of detwinning and dislocation glide mechanisms was unexpected and in direct contrast to what has been observed in nanotwinned Cu-Al. Post-mortem observations of the Ni-Mo-W micropillars suggest that the ultrafine twins create a unique form of dislocation starvation and source-limited plasticity. The ultrahigh compressive strength is governed by the triggering of shear bands rather than the activation of dislocation glide. The specialized nature of plasticity in nanotwinned Ni-Mo-W is clear, even though the precise trigger for shear band formation in nanotwinned Ni-Mo-W remains to be identified. 2b1af7f3a8
