bluuebunny/crossref_metadata_2025 huggingface dataset:
Wie Samaria so auch Jerusalem
Authors: Weingart Kristin
Published: July 2019

By naming Micah and citing Mi 3:12 the book of Jeremiah (Jer 26:18) provides an explicit example of the reception of older prophetic texts and traditions in later compositions. In addition, Jer 26:18f. also offer a historical setting for Micah’s activity—the time of Hezekiah and most probably the events of 701 BCE. The paper argues that the literary history of the book of Micah substantiates the assumption of an early Micah composition originating from the late 8th century BCE and discusses the extent, structure, and pragmatics of the composition which comprises Mi *1:5-3:12. Focussing on the situation of the eminent Assyrian threat, Micah uses the the fate of Samaria as a rhetorical device in order to persuade his Judean addressees of his message. In doing so, Micah not only displays a familiarity with North Israelite prophetic traditions, the composition also adopts compositional elements and rhetorical strategies found in Hosea and Amos.
Beyond UN Accountability for Human Rights Violations
Authors: Mégret Frédéric
Published: July 2019

The overarching focus on the United Nations and its agents for human rights violations and abuses they may have committed, as well as the attention to troop contributing states and even ‘victims’, has broadly shifted attention away from the role of the host state in peace operation. This article seeks to unpack that omission and suggests that it is far more problematic than commonly thought, in particular because it tends to reproduce some of the problematic features of the political economy of peacekeeping that are the background of rights abuses in the first place. Instead, as part of a tradition of thinking of human rights in terms of sovereign protection, the article makes the case for taking much more seriously the role that the host state can and should have in order to address abuses by international organizations. It emphasises how international legal discourse has tended to ‘give up’ on the host state, but also how host states have themselves been problematically quiescent about violations occurring on their territory. This has forced victims to take the improbable route of seeking to hold the UN accountable directly, bereft of the sort of legal and political mediation which one would normally expect their sovereign to provide. The article contributes some thoughts as to why host states have not taken up their citizens’ cause more forcefully with the United Nations, including governmental weakness, a domestic culture of rights neglect, but also host state dependency on peace operations. The article then suggests some leads to rethink the role of the host state in such circumstances. It points out relevant avenues under international law as well as specifically under international human rights law, drawing on the literature developed to theorise the responsibilities of states in relation to private third-party non-state actors within their jurisdiction. It argues that there is no reason why the arguments developed with private actors, notably corporations, in mind could not be applied to public actors such as the UN. Finally, the article suggests some concrete ways in which the host state could more vigorously take up the cause of rights abuses against international organizations including by requiring the setting up of standing claims commissions or making more use of its consent to peace operations, as well as ways in which it could be forced to do so through domestic law recourses. The article concludes by suggesting that reinstating the host state within what should be its natural prerogatives will not only be a better way of dealing with UN abuses, but also more conducive to the goals of peacekeeping and state construction.
Rethinking the Accountability—Immunity Axis through Remedies
Authors: E Boon Kristen
Published: July 2019

This contribution assesses compensation practices at the UN through the lens of accountability. It argues that somewhat paradoxically, some UN member states have a better track record than the UN itself where it comes to compensating third parties for harms that occur in conflict areas. The thesis of this contribution is that the UN can improve the immunity – accountability axis by drawing on the best practices of member states in the areas of compensation and victim centred remedies
The Effect of Ageing on Optimal Integration of Conflicting and Non-Conflicting Visual–Haptic Stimuli
Authors: Couth Samuel , Poole Daniel , Gowen Emma , Champion Rebecca A. , Warren Paul A. , Poliakoff Ellen
Published: July 2019

Multisensory integration typically follows the predictions of a statistically optimal model whereby the contribution of each sensory modality is weighted according to its reliability. Previous research has shown that multisensory integration is affected by ageing, however it is less certain whether older adults follow this statistically optimal model. Additionally, previous studies often present multisensory cues which are conflicting in size, shape or location, yet naturally occurring multisensory cues are usually non-conflicting. Therefore, the mechanisms of integration in older adults might differ depending on whether the multisensory cues are consistent or conflicting. In the current experiment, young () and older () adults were asked to make judgements regarding the height of wooden blocks using visual, haptic or combined visual–haptic information. Dual modality visual–haptic blocks could be presented as equal or conflicting in size. Young and older adults’ size discrimination thresholds (i.e., precision) were not significantly different for visual, haptic or visual–haptic cues. In addition, both young and older adults’ discrimination thresholds and points of subjective equality did not follow model predictions of optimal integration, for both conflicting and non-conflicting cues. Instead, there was considerable between subject variability as to how visual and haptic cues were processed when presented simultaneously. This finding has implications for the development of multisensory therapeutic aids and interventions to assist older adults with everyday activities, where these should be tailored to the needs of each individual.
Description of a novel coccoid cyanobacterial genus and species Sinocapsa zengkensis gen. nov. sp. nov. (Sinocapsaceae, incertae sedis), with taxonomic notes on genera in Chroococcidiopsidales
Authors: WANG YILANG , CAI FANGFANG , JIA NANNAN , LI RENHUI
Published: July 2019

A new terrestrial coccoid cyanobacterial strain was isolated in depression of a rough concrete surface in village Zengkeng, Fujian Province, China. This strain, named CHAB 6571, was characterized by a polyphasic approach. The strain exhibited morphological similarity to the Aliterlella species but differed in its larger cell sizes and irregular arranged thylakoids. 16S rRNA gene sequences of the strain had the maximum homology as 94.13 % to the genus Aliterella. The phylogeny based on 16S rRNA gene sequences revealed that there were four separated coccoid cyanobacterial clusters formed in the position representing Chroococcidiopsidales, at the vicinity of Nostocales and away from other coccoid cyanobacterial orders such as Chroococcales, Pleurocapsales and Synechococcales. These four main clusters as the CHAB 6571 in cluster A, genus Aliterella of the family Aliterellaceae in cluster B, Chroococcidiopsis sensu stricto of Chroococcidiopsidaceae in cluster C, and genera Chroogloeocystis and Gloeocapsopsis in cluster D, were likely to represent four different families with their 16S rRNA gene sequences similarities as 90–94%. However, the 16S rRNA phylogenetic results also revealed that the Chroococcidiopsidales were not monophyletic since the organisms belonging to Oscillatoriales such as Cephalothrix, Aerosakkonema and Microseira were phylogenetically mixed into the Chroococcidiopsidales. Combining the morphological, ecological and molecular features, CHAB 6571 as a new genus and species, as well as a novel family were therefore established, named Sinocapsa zengkensis (Sinocapsaceae, incertae sedis).
Flight density of the aquatic insect fauna over the water surface in the middle reaches of the Shinano River, Japan, mainly among caddisflies (Trichoptera)
Authors: HIRABAYASHI KIMIO , IKUTAMA ERI , OHKAWA KOUSAKU , ARAI RYOICHI , NOMURA TAKAOMI , TSUKADA MASUHIRO , ABE KOJI
Published: July 2019

We focused on the relative number of flying adult caddisflies on the river surface captured by sticky board traps with the aim of elucidating differences in the distribution pattern of caddisfly larvae along the slope in the middle reaches of the Shinano River. The individual number of adult caddisflies caught increased from April and decreased from October. Even in the same middle reaches of a river, there was a large difference geographically in the species captured. Hydroptila sp. was caught mainly downstream of the Taishyobashi Bridge, Psychomyia acutipennis (Ulmer 1908) in the vicinity of the Taishyobashi Bridge, and Stenopsyche marmorata Navás 1920 upstream of the Awasabashi Bridge. It is known that the slope of the Shinano River bed suddenly becomes less and the flow rate slower in the area from the Taishyobashi Bridge to the Awasabashi Bridge, and it was shown that the species composition and number of aquatic insects caught changes with the change in the slope of the river bed.
Biology of Anisocentropus pallidus (Martynov) (Trichoptera, Calamoceratidae): Laboratory and field observations

Authors: ITO TOMIKO
Published: July 2019

The biology of the East Asian caddisfly Anisocentropus pallidus (Martynov 1935), Calamoceratidae, was studied in both the laboratory and field in Hokkaido, northern Japan. The egg and early instar larva are newly described. The larvae are abundant in dense accumulations of plant detritus and eat the detritus in littoral areas of ponds in marshes. Their cases are flat, oval and made of two leaf pieces with anteromesal slits, posterior concavities and interior silken chambers. Just after eclosion, a temporary cylindrical tubular case is made of amorphous detritus. The pupal case is also a flattened oval with small anterior and posterior openings on dorsal valves and attached on hard leaves and stems. The prepupal + pupal stage requires 15–19 days at 15–17˚C. Adults appear from June to September with peak emergence during mid June. Females have mature ovaries at emergence. A one− or two-year life cycle is suggested by seasonal changes of instar frequency and larval weight.
Description of the larva of Cheumatopsyche lucida (Ulmer 1907) (Trichoptera: Hydropsychidae)

Authors: LAUDEE PONGSAK , PROMMI TAENG ON
Published: July 2019

Cheumatopsyche lucida (Ulmer 1907) adults, pupae and larvae were collected from Mae Tao Creek, Tak Province. The Cheumatopsyche lucida mature pupae were identified by genitalia characteristics, and the larvae were associated with the pupae.The larvae were described and illustrated. The larval morphology was compared to that of other species in Cheumatopsyche.
Index to key words, taxa, geographical distribution, and authors
Authors: MORSE JOHN C.
Published: July 2019

This index references the page numbers for the key words cited for the articles in these Proceedings, the taxonomic names and geographical names found in their titles and abstracts, and the authors by family name.
Iya Mikhailovna Levanidova, the famous Russian hydrobiologist and investigator of the East Russian Trichoptera (1 March 1914–11 November 2005)
Authors: VSHIVKOVA TATYANA S.
Published: July 2019

Iya Mikhailovna Levanidova (1914–2005) is the outstanding Russian hydrobiologist and hydroentomologist who devoted her life to study biodiversity, biogeography and ecology of the Russian Far East freshwater invertebrates. She laid the foundation of the aquatic entomology school in Eastern Russia, having continued the way of her teachers, Drs. A.V. Martynov and S.G. Lepneva. The article provides a brief description of Dr. Levanidova’s private and scientific life and her contributions to development of rhithrobiology and trichopterology in East Russia. It presents as well a list of the species described by I.M. Levanidova and patronyms described in her honor. A full list of her scientific papers, totalling 78 publications, is provided.
Effect of Tropical Nonconvective Condensation on Uncertainty in Modeled Projections of Rainfall
Authors: Stephens Benjamin A. , Jackson Charles S. , Wagman Benjamin M.
Published: July 2019

We find that part of the uncertainty in the amplitude and pattern of the modeled precipitation response to CO2 forcing traces to tropical condensation not directly involved with parameterized convection. The fraction of tropical rainfall associated with large-scale condensation can vary from a few percent to well over half depending on model details and parameter settings. In turn, because of the coupling between condensation and tropical circulation, the different ways model assumptions affect the large-scale rainfall fraction also affect the patterns of the response within individual models. In two single-model ensembles based on the National Center for Atmospheric Research (NCAR) Community Atmosphere Model (CAM), versions 3.1 and 5.3, we find strong correlations between the fraction of tropical large-scale rain and both climatological rainfall and circulation and the response to CO2 forcing. While the effects of an increasing tropical large-scale rain fraction are opposite in some ways in the two ensembles—for example, the Hadley circulation weakens with the large-scale rainfall fraction in the CAM3.1 ensemble while strengthening in the CAM5.3 ensemble—we can nonetheless understand these different effects in terms of the relationship between latent heating and circulation, and we propose explanations for each ensemble. We compare these results with data from phase 5 of the Coupled Model Intercomparison Project (CMIP5), for which some of the same patterns hold. Given the importance of this partitioning, there is a need for constraining this source of uncertainty using observations. However, since a “large-scale rainfall fraction” is a modeling construct, it is not clear how observations may be used to test various modeling assumptions determining this fraction.
Assessing Surface Heat Flux Products with In Situ Observations over the Australian Sector of the Southern Ocean
Authors: Bharti Vidhi , Schulz Eric , Fairall Christopher W. , Blomquist Byron W. , Huang Yi , Protat Alain , Siems Steven T. , Manton Michael J.
Published: July 2019

Given the large uncertainties in surface heat fluxes over the Southern Ocean, an assessment of fluxes obtained by European Centre for Medium-Range Weather Forecasts interim reanalysis (ERA-Interim) product, the Australian Integrated Marine Observing System (IMOS) routine observations, and the Objectively Analyzed Air–Sea Heat Fluxes (OAFlux) project hybrid dataset is performed. The surface fluxes are calculated using the COARE 3.5 bulk algorithm with in situ data obtained from the NOAA Physical Sciences Division flux system during the Clouds, Aerosols, Precipitation, Radiation, and Atmospheric Composition over the Southern Ocean (CAPRICORN) experiment on board the R/V Investigator during a voyage (March–April 2016) in the Australian sector of the Southern Ocean (43°–53°S). ERA-Interim and OAFlux data are further compared with the Southern Ocean Flux Station (SOFS) air–sea flux moored surface float deployed for a year (March 2015–April 2016) at ~46.7°S, 142°E. The results indicate that ERA-Interim (3 hourly at 0.25°) and OAFlux (daily at 1°) estimate sensible heat flux H s accurately to within ±5 W m−2 and latent heat flux H l to within ±10 W m−2. ERA-Interim gives a positive bias in H s at low latitudes (<47°S) and in H l at high latitudes (>47°S), and OAFlux displays consistently positive bias in H l at all latitudes. No systematic bias with respect to wind or rain conditions was observed. Although some differences in the bulk flux algorithms are noted, these biases can be largely attributed to the uncertainties in the observations used to derive the flux products.
Clarifying the Baroclinic Contribution to the Great Plains Low-Level Jet Frequency Maximum
Authors: Gebauer Joshua G. , Shapiro Alan
Published: July 2019

The frequency and intensity of the Great Plains nocturnal low-level jet (LLJ) are enhanced by baroclinicity over the sloped terrain of the region. A classical description of baroclinic-induced diurnal wind oscillations over the Great Plains considers differential heating of the slope with respect to air at the same elevation far removed from the slope, but with buoyancy constant along the slope (Holton mechanism). Baroclinicity can also occur due to differential heating of the slope itself, which creates a gradient in buoyancy along the slope. The relative prevalence of the two types of baroclinicity in this region has received scant attention in the literature. The present study uses 19 years of data from the Oklahoma Mesonet to evaluate the characteristics of along-slope buoyancy gradients over the region. A mean negative afternoon along-slope buoyancy gradient (east–west gradient) is found over Oklahoma. The sign of this afternoon buoyancy gradient is favorable for LLJ formation, as it results in the strongest southerly geostrophic wind near the ground around sunset, which is conducive to nocturnal jet formation via the inertial oscillation mechanism. The negative afternoon buoyancy gradient is at least partially created by an east–west gradient in diurnal heating and is stronger and more consistent in the summer months, which is when LLJs are most frequent. The contribution of the along-slope buoyancy gradient to the low-level geostrophic wind was found to be as important as the contribution of the Holton mechanism. Overall, these results indicate that along-slope buoyancy gradients should be accounted for in studies of LLJ dynamics over the Great Plains.
Validation of Snow Multibands in the Comma Head of an Extratropical Cyclone Using a 40-Member Ensemble
Authors: Connelly Ryan , Colle Brian A.
Published: July 2019

This paper investigates the ability of the Weather Research and Forecasting (WRF) Model in simulating multiple small-scale precipitation bands (multibands) within the extratropical cyclone comma head using four winter storm cases from 2014 to 2017. Using the model output, some physical processes are explored to investigate band prediction. A 40-member WRF ensemble was constructed down to 2-km grid spacing over the Northeast United States using different physics, stochastic physics perturbations, different initial/boundary conditions from the first five perturbed members of the Global Forecast System (GFS) Ensemble Reforecast (GEFSR), and a stochastic kinetic energy backscatter scheme (SKEBS). It was found that 2-km grid spacing is adequate to resolve most snowbands. A feature-based verification is applied to hourly WRF reflectivity fields from each ensemble member and the WSR-88D radar reflectivity at 2-km height above sea level. The Method for Object-Based Diagnostic Evaluation (MODE) tool is used for identifying multibands, which are defined as two or more bands that are 5–20 km in width and that also exhibit a >2:1 aspect ratio. The WRF underpredicts the number of multibands and has a slight eastward position bias. There is no significant difference in frontogenetical forcing, vertical stability, moisture, and vertical shear between the banded versus nonbanded members. Underpredicted band members tend to have slightly stronger frontogenesis than observed, which may be consolidating the bands, but overall there is no clear linkage in ambient condition errors and band errors, thus leaving the source for the band underprediction motivation for future work.
Role of Knowledge Networks and Boundary Organizations in Coproduction: A Short History of a Decision-Support Tool and Model for Adapting Multiuse Reservoir and Water-Energy Governance to Climate Change in California
Authors: Ziaja S.
Published: July 2019

Climate adaptation relies on theoretical frameworks of coproduced science and knowledge networks to produce acceptable outcomes for politically contentious resources. As adaptation moves from theory to implementation, there is a need for positive case studies to use as benchmarks. Building from literature on actionable science this paper presents one such positive case—the development of a hydropower and reservoir decision-support tool. The focus of this history is on the multiple phases of interaction (and noninteraction) between researchers and a semidefined community of stakeholders. The lessons presented from the Integrated Forecast and Reservoir Management (INFORM) system project stress that collaborations between managers and researchers were crucial to the success of the project by building knowledge networks, which could outlast formal processes, and by incorporating policy preferences of end users into the model. The history also provides examples of how even successful collaborative projects do not always follow the usual expectations for coproduced science and shows that, even when those guidelines are followed, external circumstances can threaten the adoption of research products. Ultimately, this paper argues for the importance of building strong knowledge networks alongside more formal processes—like those in boundary organizations—for effective collaborative engagement.
Food as a Biopower Means of Control: The Use of Food in Asylum Regimes
Authors: Amir Tally , Barak-Bianco Anda
Published: July 2019

States struggle to maintain a facade of sovereignty against the large-scale migration of immigrants and asylum seekers, who are trying to find their way into the receiving societies. Increased borders control, reinforced socio-legal boundaries and detention facilities are some of the constant efforts' states employ to quell the immigration of asylum seekers and control their presence. Disciplinary power often appears in a centralized form, such as borders and immigration systems, but also in decentralized, dispersed forms, ranging from medical practices, media and market influences, as well as many others, which were termed by Foucault as biopower. This force - which in its broad meaning describes deliberate attempts to interfere with the essential human existence and manage all spheres of life - is defined by Foucault as a ‘political power [that] had assigned itself the task of administering life’. Biopower is employed to manage, regulate and govern lives, produce obedience, and subordinate individuals and communities to disciplinary practices. The control over lives should be understood comprehensively, so that includes ‘a life of the city…political life, economic life…’ as well as ‘the management of … money … information, communication, water, sheep, grain …’. Accordingly, we argue that food is a form of biopower, an apparatus utilized to control and govern asylum-seekers. We posit that the state uses food to monitor the individuals' well-being, the community life, and affect the social existence. In this article, “food” refers to the role sustenance plays in providing nutrition and reinforcing socio-cultural values.
Emotional breakthrough and psychedelics: Validation of the Emotional Breakthrough Inventory
Authors: Roseman Leor , Haijen Eline , Idialu-Ikato Kelvin , Kaelen Mendel , Watts Rosalind , Carhart-Harris Robin
Published: July 2019

Background:

Psychedelic therapy is gaining recognition and the nature of the psychedelic experience itself has been found to mediate subsequent long-term psychological changes. Much emphasis has been placed on the occurrence of mystical-type experiences in determining long-term responses to psychedelics yet here we demonstrate the importance of another component, namely: emotional breakthrough.

Methods:

Three hundred and seventy-nine participants completed online surveys before and after a planned psychedelic experience. Items pertaining to emotional breakthrough were completed one day after the psychedelic experience, as were items comprising the already validated Mystical Experience Questionnaire and the Challenging Experience Questionnaire. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores were used to predict changes in well-being (Warwick-Edinburgh Mental Wellbeing Scale) in a subsample of 75 participants with low well-being baseline scores (⩽45).

Results:

Factor analyses revealed six emotional breakthrough items with high internal consistency (Cronbach’s alpha=0.932) and supported our prior hypothesis that emotional breakthrough is a distinct component of the psychedelic experience. Emotional breakthrough scores behaved dose-dependently, and were higher if the psychedelic was taken with therapeutic planning and intent. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores combined, significantly predicted subsequent changes in well-being ( r=0.45, p=0.0005, n=75), with each scale contributing significant predictive value. Emotional breakthrough and Mystical Experience Questionnaire scores predicted increases in well-being and Challenging Experience Questionnaire scores predicted less increases.

Conclusions:

Here we validate a six-item ‘Emotional Breakthrough Inventory’. Emotional breakthrough is an important and distinct component of the acute psychedelic experience that appears to be a key mediator of subsequent longer-term psychological changes. Implications for psychedelic therapy are discussed.
Sporting dissent: Colin Kaepernick, NFL activism, and media framing contests
Authors: Boykoff Jules , Carrington Ben
Published: July 2019

In August 2016, Colin Kaepernick, a quarterback on the San Francisco 49ers of the National Football League, sat in protest during the national anthem. He made it clear that his stance was a political statement against racialized oppression and police brutality carried out against people of color in the USA, and in doing so he became a polarizing cultural figure. This article uses content analysis to examine newspaper coverage of the emergence and evolution of Kaepernick’s political activism over a critical two-year period, from August 2016 through August 2018. First, we identify the dominant frames that media adopted when covering his protests and their aftermath. Then we examine who got to speak in the articles: which sources tended to predominate and how did this inflect the principal frames? Finally, we explore whether Kaepernick’s activism deepened discussions over police brutality against African Americans or racial inequality in the USA. We conclude that the print media’s coverage was largely favorable to Kaepernick even as much of the coverage reduced the protest from being about racial injustice in the USA to being framed, reductively, as an “anthem protest.”
Reduced percolation threshold of multi-walled carbon nanotubes/polymer composites by filling aligned ferromagnetic particles
Authors: Dong Shuai , Wu Xuan , Wang Erhua , Wang Xiaojie
Published: July 2019

Conductive polymer composites, consisting of multi-walled carbon nanotubes and a small amount of carbonyl iron particles, are fabricated under an ordinary magnetic field, to form anisotropic microstructures. The alignment of carbonyl iron particles will change the structure of a multi-walled carbon nanotube network and consequently the electrical properties of conductive polymer composites. In this research, we focus on the effect of the anisotropic microstructures on the electrical properties of the composites, especially on the percolation threshold and electrical resistivity. Monte Carlo simulations for three-dimensional stick percolation systems are performed to predict the percolation threshold of the anisotropic conductive polymer composites in terms of orientation distribution of multi-walled carbon nanotubes. In addition, an eight-chain model is proposed to investigate the influence of the anisotropic distribution of multi-walled carbon nanotubes on the electrical resistivity of the composites. It is predicted that the percolation threshold could be reduced from 0.70 vol% for the isotropic composites to 0.49 vol% for the anisotropic composites. Meanwhile, the electrical resistivity of the anisotropic composites is about 10%–20% of that of the isotropic composites when the volume fraction of multi-walled carbon nanotubes is higher than the percolation threshold. The simulation results are compared with the experimental study results that show a very similar behavior although there are some deviations in the values.
An analytical algorithm for the pylon saddle pushing stage and distance during the suspension bridge construction
Authors: Zhang Wen-ming , Qian Kai-rui , Tian Gen-min , Liu Zhao
Published: July 2019

During the construction of suspension bridges, the stress state of the pylon (tower) is improved by pushing the pylon saddle by an appropriate distance at the proper time. An analytical algorithm for the assessment of the required timing and displacements for the pylon saddle pushing at particular construction stages is proposed and verified in this study. The timing calculation is based on the assessment of current hanger tensile forces at each construction stage and the pylon stress state, while the pushing distance/displacement is derived from the conditions of elevation difference closure and the conservation of unstrained length of the main cable segments. This algorithm was successfully applied during the construction of a particular suspension bridge in China with a main span of 730 m. The results obtained strongly indicate that the bending moment in the pylon bottom is contributed by both horizontal and vertical forces of the main cable. The horizontal constituent is dominant and its share gradually increases in the bridge construction process. In a suspension bridge with side spans of various lengths, the stresses in the pylon bottom on the side with a larger side span is more likely to exceed the limit. Therefore, the respective strength criterion controls the pylon saddle-pushing schedule. The proposed analytical algorithm is quite straightforward and is recommended for wider application.
Considering Network Effects in the Design and Analysis of Field Experiments on State Legislatures
Authors: Phadke Sayali , Desmarais Bruce A.
Published: July 2019

Recent work on legislative politics has documented complex patterns of interaction and collaboration through the lens of network analysis. In a largely separate vein of research, the field experiment—with many applications in state legislatures—has emerged as an important approach in establishing causal identification in the study of legislative politics. The stable unit treatment value assumption (SUTVA)—the assumption that a unit's outcome is unaffected by other units' treatment statuses— is required in conventional approaches to causal inference with experiments. When SUTVA is violated via networked social interaction, treatment effects spread to control units through the network structure. We review recently developed methods that can be used to account for interference in the analysis of data from field experiments on state legislatures. The methods we review require the researcher to specify a spillover model, according to which legislators influence each other, and specify the network through which spillover occurs. We discuss these and other specification steps in detail. We find mixed evidence for spillover effects in data from two previously published field experiments. Our replication analyses illustrate how researchers can use recently developed methods to test for interference effects, and support the case for considering interference effects in experiments on state legislatures.
Integrative genomic analysis identifies key pathogenic mechanisms in primary mediastinal large B-cell lymphoma
Authors: Mottok Anja , Hung Stacy S. , Chavez Elizabeth A. , Woolcock Bruce , Telenius Adèle , Chong Lauren C. , Meissner Barbara , Nakamura Hisae , Rushton Christopher , Viganò Elena , Sarkozy Clementine , Gascoyne Randy D. , Connors Joseph M. , Ben-Neriah Susana , Mungall Andrew , Marra Marco A. , Siebert Reiner , Scott David W. , Savage Kerry J. , Steidl Christian
Published: July 2019

Primary mediastinal large B-cell lymphoma (PMBL) represents a clinically and pathologically distinct subtype of large B-cell lymphomas. Furthermore, molecular studies, including global gene expression profiling, have provided evidence that PMBL is more closely related to classical Hodgkin lymphoma (cHL). Although targeted sequencing studies have revealed a number of mutations involved in PMBL pathogenesis, a comprehensive description of disease-associated genetic alterations and perturbed pathways is still lacking. Here, we performed whole-exome sequencing of 95 PMBL tumors to inform on oncogenic driver genes and recurrent copy number alterations. The integration of somatic gene mutations with gene expression signatures provides further insights into genotype–phenotype interrelation in PMBL. We identified highly recurrent oncogenic mutations in the Janus kinase-signal transducer and activator of transcription and nuclear factor κB pathways, and provide additional evidence of the importance of immune evasion in PMBL (CIITA, CD58, B2M, CD274, and PDCD1LG2). Our analyses highlight the interferon response factor (IRF) pathway as a putative novel hallmark with frequent alterations in multiple pathway members (IRF2BP2, IRF4, and IRF8). In addition, our integrative analysis illustrates the importance of JAK1, RELB, and EP300 mutations driving oncogenic signaling. The identified driver genes were significantly more frequently mutated in PMBL compared with diffuse large B-cell lymphoma, whereas only a limited number of genes were significantly different between PMBL and cHL, emphasizing the close relation between these entities. Our study, performed on a large cohort of PMBL, highlights the importance of distinctive genetic alterations for disease taxonomy with relevance for diagnostic evaluation and therapeutic decision-making.
In vivo dynamics of T cells and their interactions with dendritic cells in mouse cutaneous graft-versus-host disease
Authors: Morin-Zorman Sarah , Wysocki Christian , Zhu Jieqing , Li Hongmei , Zorman Sylvain , Matte-Martone Catherine , Kisanga Edwina , McNiff Jennifer , Jain Dhanpat , Gonzalez David , Rothstein David M. , Lakkis Fadi G. , Haberman Ann , Shlomchik Warren D.
Published: July 2019

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (alloSCT). By static microscopy, cutaneous GVHD lesions contain a mix of T cells and myeloid cells. We used 2-photon intravital microscopy to investigate the dynamics of CD4+ and CD8+ T cells and donor dendritic cells (DCs) in cutaneous GVHD lesions in an MHC-matched, multiple minor histocompatibility antigen-mismatched (miHA) model. The majority of CD4 and CD8 cells were stationary, and few cells entered and stopped or were stopped and left the imaged volumes. CD8 cells made TCR:MHCI-dependent interactions with CD11c+ cells, as measured by the durations that CD8 cells contacted MHCI+ vs MHCI− DCs. The acute deletion of Langerin+CD103+ DCs, which were relatively rare, did not affect CD8 cell motility and DC contact times, indicating that Langerin−CD103− DCs provide stop signals to CD8 cells. CD4 cells, in contrast, had similar contact durations with MHCII+ and MHCII− DCs. However, CD4 motility rapidly increased after the infusion of an MHCII-blocking antibody, indicating that TCR signaling actively suppressed CD4 movements. Many CD4 cells still were stationary after anti-MHCII antibody infusion, suggesting CD4 cell heterogeneity within the lesion. These data support a model of local GVHD maintenance within target tissues.
Analysis of loss to follow-up in 4099 multidrug-resistant pulmonary tuberculosis patients
Authors: Walker Ian F. , Shi Oumin , Hicks Joseph P. , Elsey Helen , Wei Xiaolin , Menzies Dick , Lan Zhiyi , Falzon Dennis , Migliori Giovanni Battista , Pérez-Guzmán Carlos , Vargas Mario H. , García-García Lourdes , Sifuentes Osornio José , Ponce-De-León Alfredo , van der Walt Martie , Newell James N.
Published: July 2019

Loss to follow-up (LFU) of ≥2 consecutive months contributes to the poor levels of treatment success in multidrug-resistant tuberculosis (MDR-TB) reported by TB programmes. We explored the timing of when LFU occurs by month of MDR-TB treatment and identified patient-level risk factors associated with LFU.

We analysed a dataset of individual MDR-TB patient data (4099 patients from 22 countries). We used Kaplan–Meier survival curves to plot time to LFU and a Cox proportional hazards model to explore the association of potential risk factors with LFU.

Around one-sixth (n=702) of patients were recorded as LFU. Median (interquartile range) time to LFU was 7 (3–11) months. The majority of LFU occurred in the initial phase of treatment (75% in the first 11 months). Major risk factors associated with LFU were: age 36–50 years (HR 1.3, 95% CI 1.0–1.6; p=0.04) compared with age 0–25 years, being HIV positive (HR 1.8, 95% CI 1.2–2.7; p<0.01) compared with HIV negative, on an individualised treatment regimen (HR 0.7, 95% CI 0.6–1.0; p=0.03) compared with a standardised regimen and a recorded serious adverse event (HR 0.5, 95% CI 0.4–0.6; p<0.01) compared with no serious adverse event.

Both patient- and regimen-related factors were associated with LFU, which may guide interventions to improve treatment adherence, particularly in the first 11 months.
High therapeutic efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated falciparum malaria in Somalia
Authors: Warsame Marian , Hassan Abdillahi Mohamed , Hassan Abdikarim Hussein , Jibril Ali Mohamed , Khim Nimol , Arale Abdulkadir Mohamed , Gomey Ahamed Hassan , Nur Zainab Said , Osman Said Mohamed , Mohamed Marian Said , Abdulrahman Ali , Yusuf Fahmi Essa , Amran Jamal Ghilan Hefzullah , Witkowski Benoit , Ringwald Pascal
Published: July 2019

Background

Artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DHA/PPQ) are the recommended first- and second-line treatments, respectively, for uncomplicated falciparum malaria in Somalia. The studies reported here were conducted to assess the efficacy of these artemisinin-based combinations and the mutations in Plasmodium falciparum K13-propeller (Pfk13) domain and amplification in Pfplasmepsin 2 (Pfpm2) gene in Somalia.

Methods

One-arm prospective studies were conducted to assess the clinical and parasitological responses to DHA/PPQ and AL at two sites in 2016 and 2017, respectively, using the standard WHO protocol. The patterns of molecular markers associated with artemisinin and PPQ resistance were investigated for the first time in Somalia.

Results

A total of 339 patients were enrolled with 139 for AL and 200 for DHA/PPQ. With AL, no parasite recurrence was observed among patients treated at either site, corresponding to 100% clinical and parasitological responses. For DHA–PPQ, an adequate clinical and parasitological response rate > 97% was observed. All study patients on both treatments at both sites were parasite-free on day 3. Of the 138 samples with interpretable results for the polymorphism in Pfk13, only one (0.7%), from Bosaso, contained a non-synonymous mutation (R622I), which is not one of the known markers of artemisinin resistance. No Pfpm2 amplification was observed among the 135 samples with interpretable results.

Conclusions

AL and DHA/PPQ were highly effective in the treatment of uncomplicated falciparum malaria, and there was no evidence of resistance to artemisinin or PPQ. These two combinations are thus relevant in the chemotherapeutic strategy for malaria control in Somalia.

Trial registration ACTRN12616001005448 (Jowhar DP study), ACTRN12616000553471 (Bosaso DP study), ACTRN12617001055392 (AL study in Bosaso and Jowhar)
Stigma in psychiatry seen through the lens of sexuality and gender
Authors: King Michael
Published: July 2019

The history of psychiatry and homosexuality illuminates how stigma develops in the professions, how it is linked to cultural values and religious attitudes and how it affects patients. Homosexuality was medicalised as a disorder in the late 19th century and this led to treatments to change it. Same-gender contacts between men were decriminalised in many countries in the 1960s and 1970s, but – as recently as the 1980s – 30% of doctors in the USA did not think that gay students should be admitted to medical school and 40% would not allow gay doctors to specialise in paediatrics or psychiatry. Lesbians and gay men were effectively debarred from training in the main psychoanalytical schools in the USA and the UK. Although mainstream psychological treatments to make gay and bisexual people heterosexual fell into disrepute in the 1980s, so-called conversion or reparative treatments took their place and are still practised today. Transgender people have been the target of similar disapproval and attitudes towards them have been even slower to change than those towards lesbians and gay men. This stigma had consequences on the health, well-being and social inclusion of those who were lesbian, gay, bisexual and transgender (LGBT). This history suggests we need to examine where psychiatry and psychology are making similar mistakes today.
Early shifts in immune cell subsets to predict response to immune checkpoint blockade in non-small cell lung cancer (NSCLC).
Authors: Rosner Samuel , Forde Patrick M. , Naidoo Jarushka , Marrone Kristen , Reuss Joshua E. , Feliciano Josephine Louella , Levy Benjamin Philip , Hann Christine L. , Velculescu Victor E. , Brahmer Julie R. , Anagnostou Valsamo
Published: July 2019

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Background: The use of immune targeted agents for NSCLC has improved outcomes for patients (pts) with metastatic disease. Biomarkers such as the neutrophil-to-lymphocyte ratio (NLR) prior to therapy have been shown to predict outcomes however little is known about dynamic changes in immune subset composition during therapy. Methods: A single institution, retrospective review was performed of 88 NSCLC pts who received anti-PD1 therapy. NLR and relative lymphocyte count (RLC) were recorded at baseline, 4 weeks after treatment initiation, and at every subsequent computed tomography scan until time of progression. Endpoints included overall survival (OS) and durable clinical benefit (DCB), defined as stable disease or response at 6 months after therapy. Non parametric tests were used to compare NLR and RLC between responders and non-responders, cox-proportional hazards regression analysis was used for univariate associations with OS and Kaplan-Meier survival curves were compared by the log-rank test. Results: Our cohort comprised of 60 male pts with a median age of 63 years and a median OS of 38.5 months. Baseline NLR and RLC were not associated with response to therapy (Mann Whitney p=0.25 and p=0.23, respectively). We identified a statistically significant higher RLC and lower NLR at week 4 in pts with DCB (Mann Whitney p=0.001). Continuous NLR and RLC values at 4 weeks were statistically significantly correlated with OS (HR=1.008, 95% CI 1.001-1.015, p=0.03 and HR=0.939, 95% CI 0.9-0.98, p=0.004 respectively). Using median RLC at 4 weeks as a threshold, pts with high RLC at 4 weeks had significantly favorable survival (log-rank p<0.0001). Using the previously reported cut-off point of NLR=4, pts with NLR>4 had significantly worse OS (log-rank p<0.0001). For pts with acquired resistance to therapy, RLC increased early during treatment followed by a decrease at the time of progression. Conclusions: Our findings suggest early immune cell subset dynamics are associated with clinical outcomes for NSCLC pts treated with anti-PD1 therapy. Our observations reflect the differential immune repertoire shifts and if prospectively validated may be used to stratify pts receiving immune targeted agents.
Serum NY-ESO-1 and XAGE1 antibodies as predictive biomarkers in anti-PD-1 therapy for non-small-cell lung cancer.
Authors: Oka Mikio , Ohue Yoshihiro , Kurose Koji , Karasaki Takahiro , Masuda Takeshi , Fukuda Masaaki , Kinoshita Akitoshi , Shimizu Katsuhiko , Nakata Masao , Hattori Noboru , Kakimi Kazuhiro , Yamaguchi Hiroyuki , Fukuda Minoru
Published: July 2019

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Background: Programmed death-1 (PD-1) inhibitors effectively treat non-small-cell lung cancer (NSCLC) and prolong survival, but the clinical benefits are limited in a small population. However, robust biomarkers for predicting clinical benefits with anti-PD-1 therapy have yet to be identified, therefore, predictive biomarkers are needed to select patients with benefits. On the other hand, NSCLC expresses NY-ESO-1 and XAGE1 cancer-testis antigens, which elicit spontaneous immune responses in NSCLC patients. Methods: We conducted a prospective multicenter study to investigate whether serum antibody against NY-ESO-1 and/or XAGE1 antigens was a predictive biomarker in anti-PD-1 therapy for NSCLC. Serum antibody was serially detected by ELISA, and antibody titers were monitored during anti-PD-1 therapy. Tumor tissues were analyzed by immunohistochemistry and whole exome sequencing. Objective response rate (ORR) and survival were the primary and secondary endpoint, respectively. Results: In the discovery cohort (n = 13), six antibody-positive NSCLC responded to anti-PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC did not. Antibody positivity was associated with good response and survival, regardless of tumor PD-ligand1 expression, mutation burden, and CD8 T-cell infiltration. In the independent validation cohort (n = 40), ten antibody-positive NSCLC obtained the significant clinical benefits with anti-PD-1 therapy as compared with 30 negative NSCLC (ORR 50% vs 6.7%, P = 0.006). In the multivariate analysis, only antibody positivity was a significantly better predictive biomarker of progression free survival (HR 0.04, 95% CI 0.0 to 0.3) and overall survival (HR 0.2, 95% CI 0.0 to 0.9) after anti-PD-1 therapy. Antibody titers in responders transiently increased with spikes and gradually decreased with tumor shrinkage after anti-PD-1 therapy, and strongly correlated with tumor reduction rates and tumor burden. Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits and monitoring tumor burden in anti-PD-1 therapy for NSCLC.