Sensitive MRD detection from lymphatic fluid after surgery in HPV-associated oropharyngeal cancer

PURPOSE: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification. EXPERIMENTAL DESIGN: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, extranodal extension (ENE), and composite definitions of high-risk pathology. We then created a machine learning model, informed by lymph MRD and clinicopathologic features, to compare with progression-free survival (PFS). RESULTS: Postoperative lymph was enriched with cf-HPV compared with plasma (P \u3c 0.0001) and correlated with pN2 stage (P = 0.003), ENE (P \u3c 0.0001), and trial-defined pathologic risk criteria (mean AUC = 0.78). In addition, the lymph mutation number and variant allele frequency were higher in pN2 ENE (+) necks than in pN1 ENE (+) (P = 0.03, P = 0.02) or pN0-N1 ENE (-) (P = 0.04, P = 0.03, respectively). The lymph MRD-informed risk model demonstrated inferior PFS in high-risk patients (AUC = 0.96, P \u3c 0.0001). CONCLUSIONS: Variant and cf-HPV quantification, performed in 24-hour postoperative lymph samples, reflects single- and multifeature high-risk pathologic criteria. Incorporating lymphatic MRD and clinicopathologic feature analysis can stratify PFS early after surgery in patients with HPV (+) head and neck cancer. See related commentary by Shannon and Iyer, p. 1223

Classification of bicovariant differential calculi on the Jordanian quantum groups GL_{g,h}(2) and SL_{h}(2) and quantum Lie algebras

We classify all 4-dimensional first order bicovariant calculi on the Jordanian quantum group GL_{h,g}(2) and all 3-dimensional first order bicovariant calculi on the Jordanian quantum group SL_{h}(2). In both cases we assume that the bicovariant bimodules are generated as left modules by the differentials of the quantum group generators. It is found that there are 3 1-parameter families of 4-dimensional bicovariant first order calculi on GL_{h,g}(2) and that there is a single, unique, 3-dimensional bicovariant calculus on SL_{h}(2). This 3-dimensional calculus may be obtained through a classical-like reduction from any one of the three families of 4-dimensional calculi on GL_{h,g}(2). Details of the higher order calculi and also the quantum Lie algebras are presented for all calculi. The quantum Lie algebra obtained from the bicovariant calculus on SL_{h}(2) is shown to be isomorphic to the quantum Lie algebra we obtain as an ad-submodule within the Jordanian universal enveloping algebra U_{h}(sl(2)) and also through a consideration of the decomposition of the tensor product of two copies of the deformed adjoint module. We also obtain the quantum Killing form for this quantum Lie algebra.Comment: 33 pages, AMSLaTeX, misleading remark remove

Effects of alcohol preload on attentional bias towards cocaine-related cues

Background Drug and alcohol users have an ‘attentional bias’ for substance-related cues, which is likely to reflect the incentive-motivational properties of those cues. Furthermore, administration of an alcohol preload increases attentional bias for alcohol and tobacco-related cues in heavy drinkers and tobacco smokers, respectively. The present study investigated attentional bias for cocaine cues in cocaine users and non-users following administration of either alcohol or placebo. Method Thirty-two regular cocaine users and 40 non-users took part. Participants were administered alcohol or placebo, and administration was double blind. After drink administration, a Visual Probe task and Modified Stroop task were used to assess attentional bias. Subjective craving and alcohol outcome expectancies were also measured. Results There was a significant interaction between group and drink type on the visual probe task indicating that cocaine users who had received alcohol had increased attentional bias for cocaine pictures compared to non-users and cocaine users who received placebo. The cocaine Stroop revealed no differences between cocaine users and non-users, and no effects of alcohol in either group. Conclusions Alcohol preload in regular cocaine users increases attentional bias for cocaine cues. However, cocaine users who received placebo did not show attentional bias for cocaine stimuli. Future research should investigate the effects of alcohol preload on attentional bias in cocaine-dependent individuals

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

In vitro expression of NGN3 identifies RAB3B as the predominant Ras-associated GTP-binding protein 3 family member in human islets

Neurogenin 3 (NGN3) commits pancreatic progenitors to an islet cell fate. We induced NGN3 expression and identified up-regulation of the gene encoding the small molecular mass GTP-binding protein, RAB3B. RAB3B localized to the cytoplasm of human beta-cells, both during the fetal period and post-natally. Genes encoding alternative RAB3 proteins and RAB27A were unaltered by NGN3 expression and in human adult islets their transcripts were many fold less prevalent than those of RAB3B. The regulation of insulin exocytosis in rodent beta-cells and responsiveness to incretins is reliant upon Rab family members, notably Rab3a and Rab27a, but not Rab3b. Our results support an important inter-species difference in regulating insulin exocytosis where RAB3B is the most expressed isoform in human beta-cell

Monetary Union, Trade Integration, and Business Cycles in 19th Century Europe

This paper studies the impact of monetary arrangements on trade integration and business cycle correlation in late 19th century Europe. We estimate a gravity model and show that tighter monetary integration was associated with substantially higher trade, as in recent studies using contemporary data. For instance, the Austro-Hungarian monetary union improved trade between member states by a factor of 3. To explain this, we build and estimate a simple model where greater monetary integration weakens the current account constraint by fostering business cycle co-movements. Copyright Springer Science + Business Media, Inc. 2005optimum currency areas, endogeneity, trade, business cycles, monetary union,