PD-L1, Galectin-9 and CD8+ tumor-infiltrating lymphocytes are associated with survival in hepatocellular carcinoma

Novel systemic treatments for hepatocellular carcinoma (HCC) are strongly needed. Immunotherapy is a promising strategy that can induce specific antitumor immune responses. Understanding the mechanisms of immune resistance by HCC is crucial for development of suitable immunotherapeutics. We used immunohistochemistry on tissue-microarrays to examine the co-expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM and IDO, as well as tumor CD8+ lymphocyte infiltration in HCC, in two independent cohorts of patients. We found that at least some expression in tumor cells was seen in 97% of cases for HVEM, 83% for PD-L1, 79% for Gal-9 and 66% for IDO. In the discovery cohort (n = 94), we found that lack of, or low, tumor expression of PD-L1 (p < 0.001), Galectin-9 (p < 0.001) and HVEM (p < 0.001), and low CD8+TIL count (p = 0.016), were associated with poor HCC-specific survival. PD-L1, Galectin-9 and CD8+TIL count were predictive of HCC-specific survival independent of baseline clinicopathologic characteristics and the combination of these markers was a powerful predictor of HCC-specific survival (HR 0.29; p <0.001). These results were confirmed in the validation cohort (n = 60). We show that low expression levels of PD-L1 and Gal-9 in combination with low CD8+TIL count predict extremely poor HCC-specific survival and it requires a change in two of these parameters to significantly improve prognosis. In conclusion, intra-tumoral expression of these immune inhibiting molecules was observed in the majority of HCC patients. Low expression of PD-L1 and Galectin-9 and low CD8+TIL count are associated with poor HCC-specific survival. Combining immune biomarkers leads to superior predictors of HCC mortality

Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma:a nationwide analysis

Introduction: Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). Aim: assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. Patients and methods: Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014–2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). Results: 691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89–100%), SFM-b6 was 44% (20–77%), and SFM-b5+6 was 65% (53–90%). All centers met the performance target RAS&gt;85%. Only 9 out of 17 met the performance target SFM-b5+6 &gt; 85%. Conclusion: This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated

Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma:a nationwide analysis

Introduction: Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). Aim: assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. Patients and methods: Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014–2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). Results: 691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89–100%), SFM-b6 was 44% (20–77%), and SFM-b5+6 was 65% (53–90%). All centers met the performance target RAS&gt;85%. Only 9 out of 17 met the performance target SFM-b5+6 &gt; 85%. Conclusion: This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated.</p

Reference values for body composition and associations with blood pressure in Kenyan adults aged ≥50 years old

Objectives: To develop age and sex-specific centile reference curves for fat free mass (FFM) and fat mass (FM) adjusted for height in an adult Kenyan population and to investigate the association between FM, FFM and blood pressure (BP). Methods: Measures of body composition from bioimpedance analyses and BP were collected in 1,995 participants aged ≥50y in Nakuru County, Kenya. Reference curves were produced using the LMS method. Multivariable linear regression models were used to test the cross-sectional association between body composition indexes and BP. Results: The age and sex-specific reference curves for body composition (FMI and FFMI) confirm that FFMI is lower in both men and women with increasing age. FMI declines with age in women while among men the decline starts after 70 years. FFM was higher in men (47.4 ± 7.2 kg) than in women (38.8 ± 5.5 kg), while FM was lower in men (17.3 ± 8.1 kg) than in women (24.4 ± 10.2 kg). FMI, FFMI and BMI were all positively associated with systolic and diastolic BP, and after adjusting for body weight, FFMI remained positively associated with systolic BP and the FMI remained positively associated with diastolic BP. There was no evidence to suggest that FMI and FFMI were superior to measurement of BMI alone. Conclusion: These body composition reference curves provide normative data on body composition for older adults in Kenya. Further research should consider the prospective associations with health, including frailty-related outcomes

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Testing a global standard for quantifying species recovery and assessing conservation impact.

Recognizing the imperative to evaluate species recovery and conservation impact, in 2012 the International Union for Conservation of Nature (IUCN) called for development of a "Green List of Species" (now the IUCN Green Status of Species). A draft Green Status framework for assessing species' progress toward recovery, published in 2018, proposed 2 separate but interlinked components: a standardized method (i.e., measurement against benchmarks of species' viability, functionality, and preimpact distribution) to determine current species recovery status (herein species recovery score) and application of that method to estimate past and potential future impacts of conservation based on 4 metrics (conservation legacy, conservation dependence, conservation gain, and recovery potential). We tested the framework with 181 species representing diverse taxa, life histories, biomes, and IUCN Red List categories (extinction risk). Based on the observed distribution of species' recovery scores, we propose the following species recovery categories: fully recovered, slightly depleted, moderately depleted, largely depleted, critically depleted, extinct in the wild, and indeterminate. Fifty-nine percent of tested species were considered largely or critically depleted. Although there was a negative relationship between extinction risk and species recovery score, variation was considerable. Some species in lower risk categories were assessed as farther from recovery than those at higher risk. This emphasizes that species recovery is conceptually different from extinction risk and reinforces the utility of the IUCN Green Status of Species to more fully understand species conservation status. Although extinction risk did not predict conservation legacy, conservation dependence, or conservation gain, it was positively correlated with recovery potential. Only 1.7% of tested species were categorized as zero across all 4 of these conservation impact metrics, indicating that conservation has, or will, play a role in improving or maintaining species status for the vast majority of these species. Based on our results, we devised an updated assessment framework that introduces the option of using a dynamic baseline to assess future impacts of conservation over the short term to avoid misleading results which were generated in a small number of cases, and redefines short term as 10 years to better align with conservation planning. These changes are reflected in the IUCN Green Status of Species Standard