The implicit construction of multiplicity lists for classes of trees and verification of some conjectures

For the problem of understanding what multiplicities are possible for eigenvalues among real symmetric matrices with a given graph, constructing matrices with conjectured multiplicities is generally more difficult than finding constraining conditions. Here, the implicit function theorem method for constructing matrices with a given graph and given multiplicity list is refined and extended. In particular, the breadth of known circumstances in which the Jacobian is nonsingular is increased. This allows characterization of all multiplicity lists for binary, diametric, depth one trees. In addition the degree conjecture and a conjecture about the minimum number of multiplicities equal to 1 is proven for diametric trees. Finally, an intriguing conjecture about the eigenvalues of a matrix whose graph is a path and its submatrices is given, along with a discussion of some ides that would support a proof of the degree conjecture and the minimum number of 1\u27s conjecture, in general. (c) 2012 Elsevier Inc. All rights reserved

Plain language summary of the CheckMate 816 study results: nivolumab plus chemotherapy given before surgery for non–small-cell lung cancer

Immunotherapy; Neoadjuvant treatment; Presurgery treatmentImmunoteràpia; Tractament neoadjuvant; Tractament preoperatoriInmunoterapia; Tratamiento neoadyuvante; Tratamiento preoperatorioWhat is this summary about?: In this article, we summarize results from the ongoing phase 3 CheckMate 816 clinical study that were published in The New England Journal of Medicine in 2022. The goal of CheckMate 816 was to find out if nivolumab, an immunotherapy that activates a person's immune system (the body's natural defense system) to fight cancer, plus chemotherapy works better than chemotherapy alone when given before surgery in people with non-small-cell lung cancer (NSCLC) that can be removed surgically (resectable NSCLC). What happened in the study?: Adults who had not previously taken medications to treat NSCLC and whose cancer could be removed with surgery were included in CheckMate 816. During this study, a computer randomly assigned the treatment each person would receive before surgery for NSCLC. In total, 179 people were randomly assigned to receive nivolumab plus chemotherapy, and 179 people were randomly assigned to receive chemotherapy alone. The researchers assessed whether people who received nivolumab plus chemotherapy lived longer without the cancer geting worse or coming back and whether there were any cancer cells left in the tumor and lymph nodes removed by surgery. The researchers also assessed how adding nivolumab to chemotherapy affected the timing and outcomes of surgery and whether the combination of these drugs was safe. What were the results?: Researchers found that people who took nivolumab plus chemotherapy lived longer without the cancer getting worse or coming back compared with those who took chemotherapy alone. More people in the nivolumab plus chemotherapy group had no cancer cells left in the tumor and lymph nodes removed by surgery. Most people went on to have surgery in both treatment groups; the people who took nivolumab plus chemotherapy instead of chemotherapy alone had less extensive surgeries and were more likely to have good outcomes after less extensive surgeries. Adding nivolumab to chemotherapy did not lead to an increase in the rate of side effects compared with chemotherapy alone, and side effects were generally mild and manageable. What do the results of the study mean?: Results from CheckMate 816 support the benefit of using nivolumab plus chemotherapy before surgery for people with resectable NSCLC.The CheckMate 816 study was sponsored by Bristol Myers Squibb

Creativity and commerce: Michael Klinger and new film history

The crisis in film studies and history concerning their legitimacy and objectives has provoked a reinvigoration of scholarly energy in historical enquiry. 'New film history' attempts to address the concerns of historians and film scholars by working self-reflexively with an expanded range of sources and a wider conception of 'film' as a dynamic set of processes rather than a series of texts. The practice of new film history is here exemplified through a detailed case study of the independent British producer Michael Klinger (active 1961-87) with a specific focus on his unsuccessful attempt to produce a war film, Green Beach, based on a memoir of the Dieppe raid (August 1942). This case study demonstrates the importance of analysing the producer's role in understanding the complexities of film-making, the continual struggle to balance the competing demands of creativity and commerce. In addition, its subject matter - an undercover raid and a Jewish hero - disturbed the dominant myths concerning the Second World War, creating what turned out to be intractable ideological as well as financial problems. The paper concludes that the concerns of film historians need to engage with broader cultural and social histories. © 2010 Taylor & Francis

Integrating NGS-derived mutational profiling in the diagnosis of multiple lung adenocarcinomas

MICROABSTRACT: Integration of Next Generation Sequencing (NGS) information for use in distinguishing between Multiple Primary Lung Cancer and intrapulmonary metastasis was evaluated. We used a probabilistic model, comprehensive histologic assessment and NGS to classify patients. Integrating NGS data confirmed initial diagnosis (n = 41), revised the diagnosis (n = 12), while resulted in non-informative data (n = 8). Accuracy of diagnosis can be significantly improved with integration of NGS data. BACKGROUND: Distinguishing between multiple primary lung cancers (MPLC) and intrapulmonary metastases (IPM) is challenging. The goal of this study was to evaluate how Next Generation Sequencing (NGS) information may be integrated in the diagnostic strategy. PATIENTS AND METHODS: Patients with multiple lung adenocarcinomas were classified using both the comprehensive histologic assessment and NGS. We computed the joint probability of each pair having independent mutations by chance (thus being classified as MPLC). These probabilities were computed using the marginal mutation rates of each mutation, and the known negative dependencies between driver genes and different gene loci. With these NGS-driven data, cases were re-classified as MPLC or IPM. RESULTS: We analyzed 61 patients with a total of 131 tumors. The most frequent mutation was KRAS (57.3%) which occured at a rate higher than expected (p < 0.001) in lung cancer. No mutation was detected in 25/131 tumors (19.1%). Discordant molecular findings between tumor sites were found in 46 patients (75.4%); 11 patients (18.0%) had concordant molecular findings, and 4 patients (6.6%) had concordant molecular findings at 2 of the 3 sites. After integration of the NGS data, the initial diagnosis was confirmed for 41 patients (67.2%), the diagnosis was revised for 12 patients (19.7%) or was considered as non-informative for 8 patients (13.1%). CONCLUSION: Integrating the information of NGS data may significantly improve accuracy of diagnosis and staging

Exploring the relationships between psychological variables and loot box engagement, part 2: exploratory analyses of complex relationships

In a pre-registered survey linked to this paper (Exploring the relationships between psychological variables and loot box engagement, part 1: pre-registered hypotheses), we confirmed bivariate associations between engagement with loot boxes (purchasable randomized rewards in video games) and measures of problem gambling, problem video gaming, impulsivity, gambling cognitions, experiences of game-related ‘flow’, psychological distress and reduced wellbeing. However, these variables have complex relationships, so to gain further insights, we analysed the dataset (1495 gamers who purchase loot boxes and 1223 purchasers of non-randomized content) in a series of Bayesian mixed-effects multiple regressions with a zero-inflation component. The results challenge some well-established results in the literature, including associations between loot box engagement and problematic gambling measures, instead suggesting that this relationship might be underpinned by shared variance with problem video gaming and gambling-related cognitions. An entirely novel discovery revealed a complex interaction between experiences of flow and loot box engagement. Distress and wellbeing are both (somewhat contradictorily) predictive of participants engaging with loot boxes, but neither correlate with increasing loot box risky engagement/spend (among those who engage). Our findings unravel some of the nuances underpinning loot box engagement, yet remain consistent with narratives that policy action on loot boxes will have benefits for harm minimization

Exploring the relationships between psychological variables and loot box engagement, part 1: pre-registered hypotheses

Loot boxes are purchasable randomized rewards in video games that share structural and psychological similarities with gambling. Systematic review evidence has established reproducible associations between loot box purchasing and both problem gambling and problem video gaming, perhaps driven by a range of overlapping psychological processes (e.g. impulsivity, gambling-related cognitions, etc.) It has also been argued that loot box engagement may have negative influences on player financial and psychological wellbeing. We conducted a pre-registered survey of 1495 loot box purchasing gamers (LB cohort) and 1223 gamers who purchase other, non-randomized game content (nLB cohort). Our survey confirms 15 of our 23 pre-registered hypotheses against our primary outcome (risky loot box engagement), establishing associations with problem gambling, problem gaming, impulsivity, gambling cognitions, experiences of game-related ‘flow’ and specific ‘distraction and compulsion’ motivations for purchase. Results with hypotheses concerning potential harms established that risky loot box engagement was negatively correlated with wellbeing and positively correlated with distress. Overall, results indicate that any risks from loot boxes are liable to disproportionately affect various ‘at risk’ cohorts (e.g. those experiencing problem gambling or video gaming), thereby reiterating calls for policy action on loot boxes

Development and Validation of the RAFFLE: A Measure of Reasons and Facilitators for Loot Box Engagement

Qualitative studies have identified a diverse array of motivations for purchasing items within video games through chance-based mechanisms (i.e., “loot boxes”). Given that some individuals—particularly those at risk of disordered gaming and/or gambling—are prone to over-involvement with loot box purchasing, it is important to have a reliable, valid means of measuring the role of different motivations in driving purchasing behaviour. Building on prior qualitative research, this paper reports the development and validation of the “RAFFLE” scale, to measure the Reasons and Facilitators for Loot box Engagement. A 23-item, seven-factor scale was developed through cognitive interviews (n = 25) followed by two surveys of UK-based gamers who purchase loot boxes; analysed via exploratory (n = 503) and confirmatory (n = 1495) factor analysis, respectively. Subscales encompassed “enhancement’; “progression’; “social pressure’; “distraction/compulsion’; “altruism’; “fear of missing out’; and “resale”. The scale showed good criterion and construct validity (correlating well with measures of loot box engagement; the risky loot box index (r = 0.63) and monthly self-reported spend (r = 0.38)), and good internal validity (Cronbach’s alpha = 0.84). Parallels with, and divergence from, motivations for related activities of gaming and gambling, and alignment with broader theoretical models of motivation, are discussed

Bacterial Communities of Diverse Drosophila Species: Ecological Context of a Host–Microbe Model System

Drosophila melanogaster is emerging as an important model of non-pathogenic host–microbe interactions. The genetic and experimental tractability of Drosophila has led to significant gains in our understanding of animal–microbial symbiosis. However, the full implications of these results cannot be appreciated without the knowledge of the microbial communities associated with natural Drosophila populations. In particular, it is not clear whether laboratory cultures can serve as an accurate model of host–microbe interactions that occur in the wild, or those that have occurred over evolutionary time. To fill this gap, we characterized natural bacterial communities associated with 14 species of Drosophila and related genera collected from distant geographic locations. To represent the ecological diversity of Drosophilids, examined species included fruit-, flower-, mushroom-, and cactus-feeders. In parallel, wild host populations were compared to laboratory strains, and controlled experiments were performed to assess the importance of host species and diet in shaping bacterial microbiome composition. We find that Drosophilid flies have taxonomically restricted bacterial communities, with 85% of the natural bacterial microbiome composed of only four bacterial families. The dominant bacterial taxa are widespread and found in many different host species despite the taxonomic, ecological, and geographic diversity of their hosts. Both natural surveys and laboratory experiments indicate that host diet plays a major role in shaping the Drosophila bacterial microbiome. Despite this, the internal bacterial microbiome represents only a highly reduced subset of the external bacterial communities, suggesting that the host exercises some level of control over the bacteria that inhabit its digestive tract. Finally, we show that laboratory strains provide only a limited model of natural host–microbe interactions. Bacterial taxa used in experimental studies are rare or absent in wild Drosophila populations, while the most abundant associates of natural Drosophila populations are rare in the lab

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

Structure, function and diversity of the healthy human microbiome

Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMPdata was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University