Non-planar ABJM Theory and Integrability

Using an effective vertex method we explicitly derive the two-loop dilatation generator of ABJM theory in its SU(2)xSU(2) sector, including all non-planar corrections. Subsequently, we apply this generator to a series of finite length operators as well as to two different types of BMN operators. As in N=4 SYM, at the planar level the finite length operators are found to exhibit a degeneracy between certain pairs of operators with opposite parity - a degeneracy which can be attributed to the existence of an extra conserved charge and thus to the integrability of the planar theory. When non-planar corrections are taken into account the degeneracies between parity pairs disappear hinting the absence of higher conserved charges. The analysis of the BMN operators resembles that of N=4 SYM. Additional non-planar terms appear for BMN operators of finite length but once the strict BMN limit is taken these terms disappear.Comment: 1+26 pages, uses axodraw.sty. v2: typos fixed, references added. v3: more typos fixed, minor correction

Tsunami risk communication and management: Contemporary gaps and challenges

Very large tsunamis are associated with low probabilities of occurrence. In many parts of the world, these events have usually occurred in a distant time in the past. As a result, there is low risk perception and a lack of collective memories, making tsunami risk communication both challenging and complex. Furthermore, immense challenges lie ahead as population and risk exposure continue to increase in coastal areas. Through the last decades, tsunamis have caught coastal populations off-guard, providing evidence of lack of preparedness. Recent tsunamis, such as the Indian Ocean Tsunami in 2004, 2011 Tohoku and 2018 Palu, have shaped the way tsunami risk is perceived and acted upon. Based on lessons learned from a selection of past tsunami events, this paper aims to review the existing body of knowledge and the current challenges in tsunami risk communication, and to identify the gaps in the tsunami risk management methodologies. The important lessons provided by the past events call for strengthening community resilience and improvement in risk-informed actions and policy measures. This paper shows that research efforts related to tsunami risk communication remain fragmented. The analysis of tsunami risk together with a thorough understanding of risk communication gaps and challenges is indispensable towards developing and deploying comprehensive disaster risk reduction measures. Moving from a broad and interdisciplinary perspective, the paper suggests that probabilistic hazard and risk assessments could potentially contribute towards better science communication and improved planning and implementation of risk mitigation measures

No impact of NRAS mutation on features of primary and metastatic melanoma or on outcomes of checkpoint inhibitor immunotherapy: An italian melanoma intergroup (IMI) study

Neuroblastoma RAS Viral Oncogen Homolog (NRAS) mutant melanoma is usually considered more aggressive and more responsive to checkpoint inhibitor immunotherapy (CII) than NRAS wildtype. We retrospectively recruited 331 metastatic melanoma patients treated with CII as first line: 162 NRAS-mutant/BRAF wild-type and 169 wt/wt. No substantial differences were observed among the two cohorts regarding the melanoma onset and disease-free interval. Also, overall response to CII, progression-free survival and overall survival were similar in the two groups. Therefore, our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant melanoma. The controversy in the published data could be due to different patient characteristics and treatment heterogeneity. We believe our data adds evidence to clear up these controversial issues. Aims: It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited: 162 NRAS-mutant/BRAF wild-type (mut/wt) and 169 wt/wt. We compared the two cohorts regarding the characteristics of primary and metastatic disease, disease-free interval (DFI) and outcome to CII. No substantial differences were observed between the two groups at melanoma onset, except for a more frequent ulceration in the wt/wt group (p = 0.03). Also, the DFI was very similar in the two cohorts. In advanced disease, we only found lung and brain progression more frequent in the wt/wt group. Regarding the outcomes to CII, no significant differences were reported in overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) or overall survival (OS) (42% versus 37%, 60% versus 59%, 12 (95% CI, 7-18) versus 9 months (95% CI, 6-16) and 32 (95% CI, 23-49) versus 27 months (95% CI, 16-35), respectively). Irrespectively of mutational status, a longer OS was significantly associated with normal LDH, <3 metastatic sites, lower white blood cell and platelet count, lower neutrophil-to-lymphocyte (N/L) ratio. Our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant MM

Basal and one-month differed neutrophil, lymphocyte and platelet values and their ratios strongly predict the efficacy of checkpoint inhibitors immunotherapy in patients with advanced BRAF wild-type melanoma

Background To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to immune checkpoint inhibitors (ICI) in metastatic melanoma (MM). Methods We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Delta) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve. Results At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p < 0.001), neutrophils (p < 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Delta platelets (p = 0.039), Delta WBC (p < 0.001), and Delta neutrophils (p = 0.020), and with lower Delta lymphocytes (p < 0.001). Moreover, higher Delta NLR and Delta PLR identified patients with worse PFS, OS and DCR. In the multivariable model, only Delta NLR influenced PFS (p = 0.004), while OS resulted affected by higher Delta WBC (p < 0.001) and lower Delta lymphocytes (p = 0.038). Higher Delta WBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and Delta NLR, normal LDH/lower Delta NLR showed a higher PFS than high LDH/higher Delta NLR (20 vs 5 months). Moreover, normal LDH/higher Delta lymphocytes had a higher OS than high LDH/lower Delta lymphocytes (50 vs. 10 months). Conclusions Baseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. Our findings propose simple, inexpensive biomarkers for a better selection of patient treatments. Prospective multicenter studies are warranted to confirm these data. © 2022, The Author(s)

Anisotropy studies around the galactic centre at EeV energies with the Auger Observatory

Data from the Pierre Auger Observatory are analyzed to search for anisotropies near the direction of the Galactic Centre at EeV energies. The exposure of the surface array in this part of the sky is already significantly larger than that of the fore-runner experiments. Our results do not support previous findings of localized excesses in the AGASA and SUGAR data. We set an upper bound on a point-like flux of cosmic rays arriving from the Galactic Centre which excludes several scenarios predicting sources of EeV neutrons from Sagittarius $A$. Also the events detected simultaneously by the surface and fluorescence detectors (the `hybrid' data set), which have better pointing accuracy but are less numerous than those of the surface array alone, do not show any significant localized excess from this direction.Comment: Matches published versio

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C

Engineering reconnaissance following the August 24, 2016 M6.0 Central Italy earthquake

An earthquake with a moment magnitude reported as 6.0 from INGV (Istituto Nazionale di Geofisica e Vulcanologia); occurred at 03:36 AM (local time) on 24 August 2016 in the central part of Italy. The epicenter was located at the borders of the Lazio, Abruzzi, Marche and Umbria regions, about 2.5 km north-east of the village of Accumoli and about 100 km from Rome. The hypocentral depth was about 8 km (INGV). We summarize preliminary findings of the Italy-US GEER (Geotechnical Extreme Events Reconnaissance) team, on damage distribution, causative faults, earthquake-induced landslides and rockfalls, building and bridge performance, and ground motion characterization. Our reconnaissance team used multidisciplinary approaches, combining expertise in geology, seismology, geomatics, geotechnical engineering, and structural engineering. Our approach was to combine traditional reconnaissance activities of on-ground recording and mapping of field conditions, with advanced imaging and damage detection routines enabled by state-of-the-art geomatics technology. We anticipate that results from this study, will be useful for future post-earthquake reconnaissance efforts, and improved emergency respons

Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting

We analyzed data from 738 HER2\u2010positive metastatic breast cancer (mbc) patients treated with pertuzumab\u2010based regimens and/or T\u2010DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression free survival at first\u2010line (mPFS1) was 12 months. Pertuzumab as first\u2010line conferred longer mPFS1 compared to other first\u2010line treatments (16 vs 9 months, p=0.0001), regardless of IHC subtype. Median PFS in second\u2010line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T\u2010DM1 compared to other agents (7 vs 6 months, p=0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs) (p=0.17), while a trend emerged for tumors with one HR (p=0.05). Conversely, PFS2 gain was significant in HRs\u2010negative tumors (p=0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T\u2010DM1 in second\u2010line following pertuzumab were significantly lower compared to pertuzumab\u2010na\uefve patients(p=0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p=0.02 and p=0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment\u2010related outcomes of HER2\u2010positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor (ER) pathways in HER2\u2010positive (mbc) patients

Tsunami risk communication and management: Contemporary gaps and challenges

Supplementary data: The following is the Supplementary data to this article: Acrobat PDF file (2MB) available at: https://ars.els-cdn.com/content/image/1-s2.0-S2212420921007329-mmc1.pdfCopyright © 2022 The Authors. Very large tsunamis are associated with low probabilities of occurrence. In many parts of the world, these events have usually occurred in a distant time in the past. As a result, there is low risk perception and a lack of collective memories, making tsunami risk communication both challenging and complex. Furthermore, immense challenges lie ahead as population and risk exposure continue to increase in coastal areas. Through the last decades, tsunamis have caught coastal populations off-guard, providing evidence of lack of preparedness. Recent tsunamis, such as the Indian Ocean Tsunami in 2004, 2011 Tohoku and 2018 Palu, have shaped the way tsunami risk is perceived and acted upon. Based on lessons learned from a selection of past tsunami events, this paper aims to review the existing body of knowledge and the current challenges in tsunami risk communication, and to identify the gaps in the tsunami risk management methodologies. The important lessons provided by the past events call for strengthening community resilience and improvement in risk-informed actions and policy measures. This paper shows that research efforts related to tsunami risk communication remain fragmented. The analysis of tsunami risk together with a thorough understanding of risk communication gaps and challenges is indispensable towards developing and deploying comprehensive disaster risk reduction measures. Moving from a broad and interdisciplinary perspective, the paper suggests that probabilistic hazard and risk assessments could potentially contribute towards better science communication and improved planning and implementation of risk mitigation measures.COST (European Cooperation in Science and Technology); Royal Society, UK (grant number CHL\R1\180173); Severo Ochoa Centers of Excellence Program (CEX 2018-000797-S) funded by MCIN/ AEI /10.13039/501100011033; Lloyd's Tercentenary Research Foundation, the Lighthill Risk Network, and the Lloyd's Register Foundation-Data Centric Engineering Programme of the Alan Turing Institute