bluuebunny/crossref_metadata_2025 huggingface dataset:
Verteilungspolitische Interventionen
Authors: Krämer Hagen
Published: October 2020

Der Beitrag beschäftigt sich mit der Frage, auf welche Art und Weise die Verteilungspolitik in der heutigen Zeit ausgestaltet werden kann. Welches sind denkbare Ziele, welches mögliche Instrumente von verteilungspolitischen Interventionen in einer marktwirtschaftlichen Ordnung? Sind weitgehende Eingriffe in Marktprozesse unvermeidbar, wenn die Ungleichheit der Einkommensverteilung reduziert werden soll? Oder sollten diese weitgehend vermieden werden?

Zur Beantwortung dieser Fragen wird zunächst ein kurzer Überblick über wesentliche Denkrichtungen in den Wirtschaftswissenschaften gegeben, die sich damit beschäftigt haben, ob und wie stark der Staat die Einkommensverteilung beeinflussen sollte. Danach werden verschiedene Kriterien für distributive Gerechtigkeit besprochen. Anschließend wird ein vereinfachtes Schema für verschiedene Verteilungstypologien entwickelt, das unterschiedliche Vorstellungen von distributiver Gerechtigkeit abbilden kann. Abschließend wird der Versuch einer neuen Systematisierung der Distributionspolitik vorgestellt, mit der eine Erweiterung des üblichen Schemas „Primär- versus Sekundärverteilung“ vorgenommen wird.
Authority, Gender and Space in the Anglo-Norman World, 900–1200
Authors: Weikert Katherine
Published: October 2020

Ground-breaking interdisciplinary approach to the medieval manor pre- and post-Conquest.
Pre-hospital hypothermia is associated with transfusion risk after traumatic injury
Authors: Jivraj Naheed K. , Kaustov Lilia , Hao Kennedy Ning , Strauss Rachel , Callum Jeannie , Tien Homer , Alam Asim Q.
Published: October 2020

Objectives

In traumatically injured patients, excessive blood loss necessitating the transfusion of red blood cell (RBC) units is common. Indicators of early RBC transfusion in the pre-hospital setting are needed. This study aims to evaluate the association between hypothermia (<36°C) and transfusion risk within the first 24 hours after arrival to hospital for a traumatic injury.

Methods

We completed an audit of all traumatically injured patients who had emergent surgery at a single tertiary care center between 2010 and 2014. Using multivariable logistic regression analysis, we evaluated the association between pre-hospital hypothermia and transfusion of ≥1 unit of RBC within 24 hours of arrival to the trauma bay.

Results

Of the 703 patients included to evaluate the association between hypothermia and RBC transfusion, 203 patients (29%) required a transfusion within 24 hours. After controlling for important confounding variables, including age, sex, coagulopathy (platelets and INR), hemoglobin, and vital signs (blood pressure and heart rate), hypothermia was associated with a 68% increased odds of transfusion in multivariable analysis (OR: 1.68; 95% CI: 1.11-2.56).

Conclusions

Hypothermia is strongly associated with RBC transfusion in a cohort of trauma patients requiring emergent surgery. This finding highlights the importance of early measures of temperature after traumatic injury and the need for intervention trials to determine if strategies to mitigate the risk of hypothermia will decrease the risk of transfusion and other morbidities.
Can a screening tool safely identify low risk cardiac patients to be transported with primary care flight paramedics?
Authors: Godbout Justin , Moore Sean W. , Sawadsky Bruce , Pan Andy , Vaillancourt Christian
Published: October 2020

Objectives

We aimed to determine the rate of adverse events during interfacility transport of cardiac patients identified as low risk by a consensus-derived screening tool and transported by primary care flight paramedics (PCP(f)).

Methods

We conducted a health records review of adult patients diagnosed with a cardiac condition who were identified as low risk by the screening tool and transported by PCP(f). We excluded patients transported by an advanced care crew, those accompanied by a clinical escort from hospital, and those transported from a scene call, by rotary wing or ground vehicle. We recorded patient and transportation parameters using a piloted-standardized collection tool. We defined adverse events during transport a priori. We report descriptive statistics using mean (standard deviation), [range], (percentage).

Results

We included 400 patients: mean age 66.9 years old, 66.5% male. Mean transport duration was 136.2 (74.9) minutes. Most common comorbidities were hypertension (50.3%) and coronary artery disease (39.5%). Most transports originated out of Northern Ontario and were for cardiac catheterization (61.8%) or coronary artery bypass grafting (26.8%). Overall, the adverse event rate was low (0.3%), with no serious event such as cardiac arrest, death, or airway intervention.

Conclusions

A screening tool can identify cardiac patients at low risk for clinical deterioration during air-medical transport. We believe patients screened with this tool can be transported safely by a PCP(f) crew, leading to potentially significant resource savings.
Abdominal ultrasound image acquisition and interpretation by novice practitioners after minimal training on a simulated patient model
Authors: Waterman Bradley , Van Aarsen Kristine , Lewell Michael , Tien Homer , Myslik Frank , Peddle Michael , Doran Sean
Published: October 2020

Background

The Focused Assessment with Sonography in Trauma (FAST) exam is a rapid ultrasound test to identify evidence of hemorrhage within the abdomen. Few studies examine the accuracy of paramedic performed FAST examinations. The duration of an ultrasound training program remains controversial. This study's purpose was to assess the accuracy of paramedic FAST exam interpretation following a one hour didactic training session.

Methods

The interpretation of paramedic performed FAST exams was compared to the interpretation of physician performed FAST examinations on a mannequin model containing 300ml of free fluid following a one hour didactic training course. Results were compared using the Chi-square test. Differences in accuracy rate were deemed significant if p < 0.05.

Results

Fourteen critical care flight paramedics and four emergency physicians were voluntarily recruited. The critical care paramedics were mostly ultrasound-naive whereas the emergency physicians all had ultrasound training. The correct interpretation of FAST scans was comparable between the two groups with accuracy of 85.6% and 87.5% (∆1.79 95%CI -33.85 to 21.82, p = 0.90) for paramedics and emergency physicians respectively.

Conclusions

This study determined that critical care paramedics were able to use ultrasound to detect free fluid on a simulated mannequin model and interpret the FAST exam with a similar accuracy as experienced emergency physicians following a one hour training course. This suggests the potential use of prehospital ultrasound to aid in the triage and transport decisions of trauma patients while limiting the financial and logistical burden of ultrasound training.
Blood product transfusion during air medical transport: A needs assessment
Authors: MacDonald Russell D. , Ramjaun Aliya
Published: October 2020

Objectives

Early administration of blood products to patients with hemorrhagic shock has a positive impact on morbidity and mortality. Smaller hospitals may have limited supply of blood, and air medical systems may not carry blood. The primary outcome is to quantify the number of patients meeting established physiologic criteria for blood product administration and to identify which patients receive and which ones do not receive it due to lack of availability locally.

Methods

Electronic patient care records were used to identify a retrospective cohort of patients undergoing emergent air medical transport in Ontario, Canada, who are likely to require blood. Presenting problems for blood product administration were identified. Physiologic data were extracted with criteria for transfusion used to identify patients where blood product administration is indicated.

Results

There were 11,520 emergent patient transports during the study period, with 842 (7.3%) where blood product administration was considered. Of these, 290 met established physiologic criteria for blood products, with 167 receiving blood, of which 57 received it at a hospital with a limited supply. The mean number of units administered per patient was 3.5. The remaining 123 patients meeting criteria did not receive product because none was unavailable.

Conclusion

Indications for blood product administration are present in 2.5% of patients undergoing time-sensitive air medical transport. Air medical services can enhance access to potentially lifesaving therapy in patients with hemorrhagic shock by carrying blood products, as blood may be unavailable or in limited supply locally in the majority of patients where it is indicated.
Health Union and Bioethical Union: Does Hippocrates Require Socrates?
Authors: COGHLAN Niall
Published: October 2020

Health Union raises bioethical questions ranging from resource allocation and risk balancing to respect for specific bioethical prohibitions, as an analysis of the European Parliament’s proposal for such a union shows. To date, European Union (EU) health law has succeeded in avoiding or circumscribing such questions, leading to the limited and inconsistent patchwork of EU bioethical provisions we currently have. Can this continue with a Health Union? This article argues that whilst full harmonisation is neither possible nor desirable, Health Union should entail a deepening of bioethical integration. This should occur via a robust legislative process involving citizen panels and ethical advisory group input; if Treaty change occurs, this process could be included in primary law. This is so for three reasons. First, addressing Health Union’s unavoidable bioethical questions coherently and openly reduces the risk of inadequate protection and, conversely, of interest groups “smuggling in” unsupported answers. Second, this will ensure respect for primary law, including Article 2 TEU and Article 3 CFR. Third, EU biolaw offers a middle ground between limited national and weak international human rights law on bioethics, whilst also consolidating European identity.
SUITABILITY OF ACID-SOLUBLE AND ACID-INSOLUBLE LEATHER FRACTIONS IN RADIOCARBON DATING
Authors: Tate Alyssa M , Hundman Brittany , Heile Jonathan
Published: October 2020

Leather has been produced by a variety of methods throughout human history, providing researchers unique insight into multiple facets of social and economic life in the past. Archaeologically recovered leather is often fragile and poorly preserved, leading to the use of various conservation and restoration efforts that may include the application of fats, oils, or waxes. Such additives introduce exogenous carbon to the leather, contaminating the specimen. These contaminants, in addition to those accumulated during interment, must be removed through chemical pretreatment prior to radiocarbon (14C) dating to ensure accurate dating. DirectAMS utilizes organic solvents, acid-base-acid (ABA) and gelatinization for all leather samples. Collagen yield from leather samples is variable due to the method of production and the quality of preservation. However, evaluating the acid-soluble collagen fraction, when available, provides the most accurate 14C dates for leather samples. In instances where gelatinization does not yield sufficient material, the resulting acid-insoluble fraction may be dated. Here we examine the effectiveness of the combined organic solvent and ABA pretreatment with gelatinization for leather samples, as well as the suitability of the acid-insoluble fraction for 14C dating.
Bridging the Gap between Expectation and Reality: Urban Planning and the Public Bus System in Abu Dhabi
Authors: Ryu Seunga Iris
Published: October 2020

In urban planning, governments usually hold the decision-making power to shape not only city landscapes but also people's lives with the promoted goals of social welfare. Although states expect their own version of ideal scenarios in mind when carrying out infrastructural developments, after competition, people in reality have their own ways of perceiving and utilizing state-made infrastructures and urban transportation, sometimes in alignment with government plan, and sometimes at odds with it. Abu Dhabi is one of the cities in the world in which the government planned out the whole city and created urban infrastructure from scratch, including the city bus system. Although the Abu Dhabi public buses started operating in 2008, car dependency is still high and many residents consider public buses to be inefficient and time consuming and only used by certain immigrant working population.
Contesting Labels: Revisiting old Questionnaires
Authors: Yücel Şebnem , Ada Serhan
Published: October 2020

As a response to several questionnaires, manifestos, interviews, and letters that were included in the book Modern Art in the Arab World: Primary Documents, this article carries out a new questionnaire with seven artists form various backgrounds and geographies, in an attempt to update and re-question some of the issues that were highlighted in the collected essays. The questionnaire includes three questions, each focusing on a different issue. The first issue considers the validity of the term “Arab Art,” the second tries to identify the main dynamics of contemporary artistic production, and the last one questions the relation of contemporary production of arts to geography and history. The following interviews have been edited for consistency and clarity.
LOOK, KNAVE
Authors: MORRILL THOMAS
Published: October 2020

We examine a recursive sequence in which

$s_n$
is a literal description of what the binary expansion of the previous term

$s_{n-1}$
is not. By adapting a technique of Conway, we determine the limiting behaviour of

$\{s_n\}$
and dynamics of a related self-map of

$2^{\mathbb {N}}$
. Our main result is the existence and uniqueness of a pair of binary sequences, each the complement-description of the other. We also take every opportunity to make puns.
Prospective associations between vitamin D and depression in middle-aged adults: findings from the UK Biobank cohort
Authors: Ronaldson Amy , Arias de la Torre Jorge , Gaughran Fiona , Bakolis Ioannis , Hatch Stephani L. , Hotopf Matthew , Dregan Alexandru
Published: October 2020

Background

A possible role of vitamin D in the pathophysiology of depression is currently speculative, with more rigorous research needed to assess this association in large adult populations. The current study assesses prospective associations between vitamin D status and depression in middle-aged adults enrolled in the UK Biobank.

Methods

We assessed prospective associations between vitamin D status at the baseline assessment (2006–2010) and depression measured at the follow-up assessment (2016) in 139 128 adults registered with the UK Biobank.

Results

Amongst participants with no depression at baseline (n= 127 244), logistic regression revealed that those with vitamin D insufficiency [adjusted odds ratio (aOR) = 1.14, 95% confidence interval (CI) = 1.07–1.22] and those with vitamin D deficiency (aOR = 1.24, 95% CI 1.13–1.36) were more likely to develop new-onset depression at follow-up compared with those with optimal vitamin D levels after adjustment for a wide range of relevant covariates. Similar prospective associations were reported for those with depression at baseline (n= 11 884) (insufficiency: aOR = 1.11, 95% CI 1.00–1.23; deficiency: aOR = 1.30, 95% CI 1.13–1.50).

Conclusions

The prospective associations found between vitamin D status and depression suggest that both vitamin D deficiency and insufficiency might be risk factors for the development of new-onset depression in middle-aged adults. Moreover, vitamin D deficiency (and to a lesser extent insufficiency) might be a predictor of sustained depressive symptoms in those who are already depressed. Vitamin D deficiency and insufficiency is very common, meaning that these findings have significant implications for public health.
Information specialist collaboration in Europe: collaborative methods, processes, and infrastructure through EUnetHTA
Authors: Waffenschmidt Siw , van Amsterdam-Lunze Marli , Gomez Rebeca Isabel , Rehrmann Maike , Harboe Ingrid , Hausner Elke
Published: October 2020

The history of European health technology assessment (HTA) goes back more than 30 years. Almost as old as HTA agencies themselves is the desire to achieve European collaboration. This gained further impetus with the establishment of the European Network of Health Technology Assessment (EUnetHTA) in 2006. In this context, the field of information management faced specific challenges. Although these services are an integral part of HTA and information specialists play a key role here, this field is often not adequately represented in the HTA agencies within EUnetHTA. Furthermore, the organization of HTA production, including the types of HTAs produced, as well as funding, varies considerably. In order to meet these different conditions, information specialists have created various products and defined processes. With the EUnetHTA guideline, a common methodological understanding for the production of rapid Relative Effectiveness Assessments now exists. Furthermore, the Standard Operating Procedures map the complex information retrieval processes within EUnetHTA in a hands-on manner. The newly established Information Specialist Network (ISN) will in future ensure that information specialists are involved in all EUnetHTA assessments and that the methods are applied consistently in all assessments. In addition, the steering committee of the ISN manages enquiries and can be contacted to discuss methodological issues. Major barriers such as heterogeneity in the daily work of the EUnetHTA members can only be overcome through more collaboration and training.
Bidirectional pathways between psychosocial risk factors and paranoid ideation in a general nonclinical population
Authors: Saarinen Aino , Granö Niklas , Hintsanen Mirka , Lehtimäki Terho , Cloninger C. Robert , Keltikangas-Järvinen Liisa
Published: October 2020

We investigated (a) whether psychosocial factors (experienced stress, anticipatory worry, social detachment, sleeping disturbances, alcohol use) predict the course of paranoid ideation between the ages of 24 to 50 years and (b) whether the predictive relationships are more likely to proceed from the psychosocial factors to paranoid ideation, or vice versa. The participants (N = 1534–1553) came from the population-based Young Finns study. Paranoid ideation and psychosocial factors were assessed by reliable self-report questionnaires in 2001, 2007, and 2011/2012. The data were analyzed using growth curve and structural equation models. High experienced stress, anticipatory worry, social detachment, frequent sleeping disturbances, and frequent alcohol use predicted more paranoid ideation. More risk factors predicted increasing paranoid ideation. There were bidirectional predictive relationships of paranoid ideation with experienced stress, anticipatory worry, social detachment, and sleeping disturbances. The link between alcohol use and paranoid ideation was only correlative. In conclusion, paranoid ideation increases by reciprocal interactions with stress, worry, social detachment, and sleeping disturbances. The findings support the threat–anticipation model of paranoid ideation, providing important implications for treatment of paranoia.
Dosimetric analysis and comparison of volumetric-modulated arc therapy versus intensity-modulated radiation therapy for liver carcinoma
Authors: Chiang Bing-Hao , Schnell Erich , Hibbitts Kerry , Herman Terence , Ahmad Salahuddin
Published: October 2020

Aim:

This study dosimetrically compared volumetric-modulated arc therapy (VMAT) to intensity-modulated arc therapy (IMRT) for patients with liver carcinoma.

Materials and methods:

Ten patients with liver carcinoma previously treated with IMRT or VMAT were retrospectively selected for this study. Each patient received a total dose of 54 Gy in 1·8 Gy fractions. Dosimetric evaluations for each patient were performed using the dose–volume histograms (DVHs) for planning target volumes (PTVs) and organs at risk (OAR). All dosimetric parameters were statistically analysed using mean values, standard deviations and p-values for determining the significance. The conformality index (CI) and homogeneity index (HI) were calculated and compared. For efficiency evaluation, monitor units (MUs) and beam on times (BOT) were recorded.

Results:

Compared to IMRT, VMAT plans showed significant differences in the heterogeneity with p < 0·01 and insignificant differences in both conformality and normal tissue sparing. VMAT required marginally fewer mean MU and shorter BOT when compared to IMRT with insignificant differences.

Conclusions:

For radiation therapy treatment of liver carcinoma, IMRT and VMAT can achieve similar PTV coverage and normal tissue sparing. Treatment time is only marginally shorter with VMAT versus IMRT with insignificant differences.
Saint-Saëns and Sophocles
Authors: Huebner Steven
Published: October 2020

Saint-Saëns's incidental music for Sophocles’ Antigone (Comédie-Française, 1893, trans. Meurice and Vacquerie) gives witness both to his engagement with culture classique and an experimental orientation in the context of fin-de-siècle music theatre. This essay situates Saint-Saëns's highly idiosyncratic score within the frame of late nineteenth-century research into ancient Greek music by François-Auguste Gevaert and Louis-Albert Bourgault-Ducoudray. It documents how Saint-Saëns aimed to participate in the creation of an authentic experience of ancient Greek theatre, one enhanced by the initiative of the Comédie-Française to stage its production at the open air Théâtre d'Orange in southern France. The article also shows the limitations of authenticity resulting from the nature of the translation as well as from Saint-Saëns's own compositional instincts.
SEMANTICS FOR PURE THEORIES OF CONNEXIVE IMPLICATION
Authors: WEISS YALE
Published: October 2020

In this article, I provide Urquhart-style semilattice semantics for three connexive logics in an implication-negation language (I call these “pure theories of connexive implication”). The systems semantically characterized include the implication-negation fragment of a connexive logic of Wansing, a relevant connexive logic recently developed proof-theoretically by Francez, and an intermediate system that is novel to this article. Simple proofs of soundness and completeness are given and the semantics is used to establish various facts about the systems (e.g., that two of the systems have the variable sharing property). I emphasize the intuitive content of the semantics and discuss how natural informational considerations underly each of the examined systems.
PROBABILISTIC STABILITY, AGM REVISION OPERATORS AND MAXIMUM ENTROPY
Authors: MIERZEWSKI KRZYSZTOF
Published: October 2020

Several authors have investigated the question of whether canonical logic-based accounts of belief revision, and especially the theory of AGM revision operators, are compatible with the dynamics of Bayesian conditioning. Here we show that Leitgeb’s stability rule for acceptance, which has been offered as a possible solution to the Lottery paradox, allows to bridge AGM revision and Bayesian update: using the stability rule, we prove that AGM revision operators emerge from Bayesian conditioning by an application of the principle of maximum entropy. In situations of information loss, or whenever the agent relies on a qualitative description of her information state—such as a plausibility ranking over hypotheses, or a belief set—the dynamics of AGM belief revision are compatible with Bayesian conditioning; indeed, through the maximum entropy principle, conditioning naturally generates AGM revision operators. This mitigates an impossibility theorem of Lin and Kelly for tracking Bayesian conditioning with AGM revision, and suggests an approach to the compatibility problem that highlights the information loss incurred by acceptance rules in passing from probabilistic to qualitative representations of belief.
SUPPORT FOR GEOMETRIC POOLING
Authors: BACCELLI JEAN , STEWART RUSH T.
Published: October 2020

Supra-Bayesianism is the Bayesian response to learning the opinions of others. Probability pooling constitutes an alternative response. One natural question is whether there are cases where probability pooling gives the supra-Bayesian result. This has been called the problem of Bayes-compatibility for pooling functions. It is known that in a common prior setting, under standard assumptions, linear pooling cannot be nontrivially Bayes-compatible. We show by contrast that geometric pooling can be nontrivially Bayes-compatible. Indeed, we show that, under certain assumptions, geometric and Bayes-compatible pooling are equivalent. Granting supra-Bayesianism its usual normative status, one upshot of our study is thus that, in a certain class of epistemic contexts, geometric pooling enjoys a normative advantage over linear pooling as a social learning mechanism. We discuss the philosophical ramifications of this advantage, which we show to be robust to variations in our statement of the Bayes-compatibility problem.
Traces ofAztecCulturalMemory inSixteenth-CenturySongs andChronicles:The Case of Tlacahuepan
Authors: Szoblik Katarzyna
Published: October 2020

This article aims to analyze traces of Aztec cultural memory recorded in sixteenth-century cultural sources of Central Mexico. It is a study of the particular case of an Aztec hero named Tlacahuepan, whose glorious death was commemorated in many songs and chronicles. The texts in question reveal highly symbolic language, as well as clearly established narrative patterns. The study of their discursive tools can cast considerable light on the ideological background that underlies the oral tradition on which these stories have been based. It can also contribute to a better understanding of the methods and strategies employed by the Aztecs to memorize the past and explain the present.
“Vivir Mejor”:Radio Education in Rural Colombia (1960–80)
Authors: Cant Anna
Published: October 2020

Founded in 1947 by a Catholic priest, Acción Cultural Popular (ACPO) was a pioneer in radio education. Offering a radio station (Radio Sutatenza), study manuals, and a newspaper, ACPO provided basic education and encouraged campesinos to seek personal development and to “vivir mejor”--to live better. From 1947 to 1994, it attracted over four million subscribers and became a model in 13 Latin American countries. In this article I show how ACPO's approach to rural development and communication style evolved between 1960 and 1980. As a consequence of technological, economic, and cultural developments, Radio Sutatenza, a station with a more or less captive audience of illiterate peasants, changed as it was forced to respond to rural Colombians’ shifting aspirations and competition from commercial radio. While the organization's founding principles remained constant throughout this period, its articulation of what it meant to “live better” changed over time, reflecting the struggles of a religious organization to remain relevant in a rapidly changing world. While ACPO saw itself as the bearer of modernity, it was often confronted by independent processes of change already occurring in rural communities.
Simulation of Central Indian Ocean Mode in S2S Models
Authors: Qin Jianhuang , Zhou Lei , Li Baosheng , Murtugudde Raghu
Published: October 2020

Simulation of monsoon intraseasonal oscillations (MISO) during the Indian summer monsoon (ISM) is a grand scientific challenge. The Subseasonal‐to‐Seasonal (S2S) prediction project provides a unique way to examine the key dynamics of MISO. Recently, a Central Indian Ocean (CIO) mode was proposed as an intrinsic climate mode over the Indian Ocean, and it has a close relation with MISO during the ISM. In this study, the simulations of the CIO mode events in S2S models are examined. The results confirm that a better rendition of the CIO mode in S2S models tends to result in a better simulation of northward propagating MISO and leads to stronger subseasonal rainfall during the ISM. The positive CIO mode cases are classified into well‐simulated and poorly simulated groups. It is shown that the barotropic energy conversion due to the meridional shear of background zonal winds (
) enhances the kinetic energy at subseasonal timescales during the CIO mode in the well‐simulated group, which also agrees with observations. As a result, the enhanced meridional wind anomalies transport moisture from the tropics to the subtropics and reinforce midtropospheric moisture loading in the subtropics, which nourishes the northward propagating MISO. Therefore, a better simulation of
and moisture transport by subseasonal meridional wind anomalies are required to improve the CIO mode simulation, which is expected to benefit the simulation and prediction of MISO during the ISM.
Mucin-derived O-glycans supplemented to diet mitigate diverse microbiota perturbations
Authors: Pruss K M , Marcobal A , Southwick A M , Dahan D , Smits S A , Ferreyra J A , Higginbottom S K , Sonnenburg E D , Kashyap P C , Choudhury B , Bode L , Sonnenburg J L
Published: October 2020

Microbiota-accessible carbohydrates (MACs) are powerful modulators of microbiota composition and function. These substrates are often derived from diet, such as complex polysaccharides from plants or human milk oligosaccharides (HMOs) during breastfeeding. Host-derived mucus glycans on gut-secreted mucin proteins serve as a continuous endogenous source of MACs for resident microbes; here we investigate the potential role of purified, orally administered mucus glycans in maintaining a healthy microbial community. In this study, we liberated and purified O-linked glycans from porcine gastric mucin and assessed their efficacy in shaping the recovery of a perturbed microbiota in a mouse model. We found that porcine mucin glycans (PMGs) and HMOs enrich for taxonomically similar resident microbes. We demonstrate that PMGs aid recovery of the microbiota after antibiotic treatment, suppress Clostridium difficile abundance, delay the onset of diet-induced obesity, and increase the relative abundance of resident Akkermansia muciniphila. In silico analysis revealed that genes associated with mucus utilization are abundant and diverse in prevalent gut commensals and rare in enteric pathogens, consistent with these glycan-degrading capabilities being selected for during host development and throughout the evolution of the host–microbe relationship. Importantly, we identify mucus glycans as a novel class of prebiotic compounds that can be used to mitigate perturbations to the microbiota and provide benefits to host physiology.
Keap1 inhibition sensitizes head and neck squamous cell carcinoma cells to ionizing radiation via impaired non-homologous end joining and induced autophagy
Authors: Deville Sara Sofia , Luft Susanne , Kaufmann Maria , Cordes Nils
Published: October 2020

The function of Keap1 (Kelch-like ECH-associated protein 1), a sensor of oxidative and electrophilic stress, in the radiosensitivity of cancer cells remains elusive. Here, we investigated the effects of pharmacological inhibition of Keap1 with ML344 on radiosensitivity, DNA double-strand break (DSB) repair and autophagy in head and neck squamous cell carcinoma (HNSCC) cell lines. Our data demonstrate that Keap1 inhibition enhances HNSCC cell radiosensitivity. Despite elevated, Nrf2-dependent activity of non-homologous end joining (NHEJ)-related DNA repair, Keap1 inhibition seems to impair DSB repair through delayed phosphorylation of DNA-PKcs. Moreover, Keap1 inhibition elicited autophagy and increased p62 levels when combined with X-ray irradiation. Our findings suggest HNSCC cell radiosensitivity, NHEJ-mediated DSB repair, and autophagy to be co-regulated by Keap1.
Early-onset autoimmunity associated with SOCS1 haploinsufficiency
Authors: Hadjadj Jérôme , Castro Carla Noemi , Tusseau Maud , Stolzenberg Marie-Claude , Mazerolles Fabienne , Aladjidi Nathalie , Armstrong Martin , Ashrafian Houman , Cutcutache Ioana , Ebetsberger-Dachs Georg , Elliott Katherine S. , Durieu Isabelle , Fabien Nicole , Fusaro Mathieu , Heeg Maximilian , Schmitt Yohan , Bras Marc , Knight Julian C. , Lega Jean-Christophe , Lesca Gaetan , Mathieu Anne-Laure , Moreews Marion , Moreira Baptiste , Nosbaum Audrey , Page Matthew , Picard Cécile , Ronan Leahy T. , Rouvet Isabelle , Ryan Ethel , Sanlaville Damien , Schwarz Klaus , Skelton Andrew , Viallard Jean-Francois , Viel Sebastien , Villard Marine , Callebaut Isabelle , Picard Capucine , Walzer Thierry , Ehl Stephan , Fischer Alain , Neven Bénédicte , Belot Alexandre , Rieux-Laucat Frédéric
Published: October 2020

Autoimmunity can occur when a checkpoint of self-tolerance fails. The study of familial autoimmune diseases can reveal pathophysiological mechanisms involved in more common autoimmune diseases. Here, by whole-exome/genome sequencing we identify heterozygous, autosomal-dominant, germline loss-of-function mutations in the SOCS1 gene in ten patients from five unrelated families with early onset autoimmune manifestations. The intracellular protein SOCS1 is known to downregulate cytokine signaling by inhibiting the JAK-STAT pathway. Accordingly, patient-derived lymphocytes exhibit increased STAT activation in vitro in response to interferon-γ, IL-2 and IL-4 that is reverted by the JAK1/JAK2 inhibitor ruxolitinib. This effect is associated with a series of in vitro and in vivo immune abnormalities consistent with lymphocyte hyperactivity. Hence, SOCS1 haploinsufficiency causes a dominantly inherited predisposition to early onset autoimmune diseases related to cytokine hypersensitivity of immune cells.
Vestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers
Authors: Bradley Sherille D. , Talukder Amjad H. , Lai Ivy , Davis Rebecca , Alvarez Hector , Tiriac Herve , Zhang Minying , Chiu Yulun , Melendez Brenda , Jackson Kyle R. , Katailiha Arjun , Sonnemann Heather M. , Li Fenge , Kang Yaan , Qiao Na , Pan Bih-Fang , Lorenzi Philip L. , Hurd Mark , Mittendorf Elizabeth A. , Peterson Christine B. , Javle Milind , Bristow Christopher , Kim Michael , Tuveson David A. , Hawke David , Kopetz Scott , Wolff Robert A. , Hwu Patrick , Maitra Anirban , Roszik Jason , Yee Cassian , Lizée Gregory
Published: October 2020

Cytotoxic T lymphocyte (CTL)-based cancer immunotherapies have shown great promise for inducing clinical regressions by targeting tumor-associated antigens (TAA). To expand the TAA landscape of pancreatic ductal adenocarcinoma (PDAC), we performed tandem mass spectrometry analysis of HLA class I-bound peptides from 35 PDAC patient tumors. This identified a shared HLA-A*0101 restricted peptide derived from co-transcriptional activator Vestigial-like 1 (VGLL1) as a putative TAA demonstrating overexpression in multiple tumor types and low or absent expression in essential normal tissues. Here we show that VGLL1-specific CTLs expanded from the blood of a PDAC patient could recognize and kill in an antigen-specific manner a majority of HLA-A*0101 allogeneic tumor cell lines derived not only from PDAC, but also bladder, ovarian, gastric, lung, and basal-like breast cancers. Gene expression profiling reveals VGLL1 as a member of a unique group of cancer-placenta antigens (CPA) that may constitute immunotherapeutic targets for patients with multiple cancer types.
Neonicotinoids disrupt circadian rhythms and sleep in honey bees
Authors: Tackenberg Michael C. , Giannoni-Guzmán Manuel A. , Sanchez-Perez Erik , Doll Caleb A. , Agosto-Rivera José L. , Broadie Kendal , Moore Darrell , McMahon Douglas G.
Published: October 2020

Honey bees are critical pollinators in ecosystems and agriculture, but their numbers have significantly declined. Declines in pollinator populations are thought to be due to multiple factors including habitat loss, climate change, increased vulnerability to disease and parasites, and pesticide use. Neonicotinoid pesticides are agonists of insect nicotinic cholinergic receptors, and sub-lethal exposures are linked to reduced honey bee hive survival. Honey bees are highly dependent on circadian clocks to regulate critical behaviors, such as foraging orientation and navigation, time-memory for food sources, sleep, and learning/memory processes. Because circadian clock neurons in insects receive light input through cholinergic signaling we tested for effects of neonicotinoids on honey bee circadian rhythms and sleep. Neonicotinoid ingestion by feeding over several days results in neonicotinoid accumulation in the bee brain, disrupts circadian rhythmicity in many individual bees, shifts the timing of behavioral circadian rhythms in bees that remain rhythmic, and impairs sleep. Neonicotinoids and light input act synergistically to disrupt bee circadian behavior, and neonicotinoids directly stimulate wake-promoting clock neurons in the fruit fly brain. Neonicotinoids disrupt honey bee circadian rhythms and sleep, likely by aberrant stimulation of clock neurons, to potentially impair honey bee navigation, time-memory, and social communication.
Blumgart anastomosis reduces the incidence of pancreatic fistula after pancreaticoduodenectomy: a systematic review and meta-analysis
Authors: Li Zhenlu , Wei Ailin , Xia Ning , Zheng Liangxia , Yang Dujiang , Ye Jun , Xiong Junjie , Hu Weiming
Published: October 2020

Postoperative pancreatic fistula (POPF) is the most serious complication after pancreaticoduodenectomy (PD). Recently, Blumgart anastomosis (BA) has been found to have some advantages in terms of decreasing POPF compared with other pancreaticojejunostomy (PJ) using either the duct-to-mucosa or invagination approach. Therefore, the aim of this study was to examine the safety and effectiveness of BA versus non-Blumgart anastomosis after PD. The PubMed, EMBASE, Web of Science and the Cochrane Central Library were systematically searched for studies published from January 2000 to March 2020. One RCT and ten retrospective comparative studies were included with 2412 patients, of whom 1155 (47.9%) underwent BA and 1257 (52.1%) underwent non-Blumgart anastomosis. BA was associated with significantly lower rates of grade B/C POPF (OR 0.38, 0.22 to 0.65; P = 0.004) than non-Blumgart anastomosis. Additionally, in the subgroup analysis, the grade B/C POPF was also reduced in BA group than the Kakita anastomosis group. There was no significant difference regarding grade B/C POPF in terms of soft pancreatic texture between the BA and non-Blumgart anastomosis groups. In conclusion, BA after PD was associated with a decreased risk of grade B/C POPF. Therefore, BA seems to be a valuable PJ to reduce POPF comparing with non-Blumgart anastomosis.
Quantitative PCR methodology with a volume-based unit for the sophisticated cellular kinetic evaluation of chimeric antigen receptor T cells
Authors: Yamamoto Syunsuke , Matsumoto Shin-ichi , Goto Akihiko , Ugajin Miyuki , Nakayama Miyu , Moriya Yuu , Hirabayashi Hideki
Published: October 2020

Although the cellular kinetics of chimeric antigen receptor T (CAR T) cells are expressed in units of copies/μg gDNA, this notation carries the risk of misrepresentation owing to dramatic changes in blood gDNA levels after lymphocyte-depleting chemotherapy and rapid expansion of CAR T cells. Therefore, we aimed to establish a novel qPCR methodology incorporating a spike-in calibration curve that expresses cellular kinetics in units of copies/μL blood, as is the case for conventional pharmacokinetic studies of small molecules and other biologics. Dog gDNA was used as an external control gene. Our methodology enables more accurate evaluation of in vivo CAR T-cell expansion than the conventional approach; the unit “copies/μL blood” is therefore more appropriate for evaluating cellular kinetics than the unit “copies/μg gDNA.” The results of the present study provide new insights into the relationship between cellular kinetics and treatment efficacy, thereby greatly benefiting patients undergoing CAR T-cell therapy.
Comparative morphological and transcriptomic analyses reveal chemosensory genes in the poultry red mite, Dermanyssus gallinae
Authors: Bhowmick Biswajit , Tang Yu , Lin Fang , Øines Øivind , Zhao Jianguo , Liao Chenghong , Ignell Rickard , Hansson Bill S. , Han Qian
Published: October 2020

Detection of chemical cues via chemosensory receptor proteins are essential for most animals, and underlies critical behaviors, including location and discrimination of food resources, identification of sexual partners and avoidance of predators. The current knowledge of how chemical cues are detected is based primarily on data acquired from studies on insects, while our understanding of the molecular basis for chemoreception in acari, mites in particular, remains limited. The poultry red mite (PRM), Dermanyssus gallinae, is one of the most important blood-feeding ectoparasites of poultry. PRM are active at night which suck the birds' blood during periods of darkness and hide themselves in all kinds of gaps and cracks during the daytime. The diversity in habitat usage, as well as the demonstrated host finding and avoidance behaviors suggest that PRM relies on their sense of smell to orchestrate complex behavioral decisions. Comparative transcriptome analyses revealed the presence of candidate variant ionotropic receptors, odorant binding proteins, niemann-pick proteins type C2 and sensory neuron membrane proteins. Some of these proteins were highly and differentially expressed in the forelegs of PRM. Rhodopsin-like G protein-coupled receptors were also identified, while insect-specific odorant receptors and odorant co-receptors were not detected. Furthermore, using scanning electron microscopy, the tarsomeres of all leg pairs were shown to be equipped with sensilla chaetica with or without tip pores, while wall-pored olfactory sensilla chaetica were restricted to the distal-most tarsomeres of the forelegs. This study is the first to describe the presence of chemosensory genes in any Dermanyssidae family. Our findings make a significant step forward in understanding the chemosensory abilities of D. gallinae.
Evaluating the seasonality of growth in infants using a mobile phone application
Authors: Narumi Satoshi , Ohnuma Tetsu , Takehara Kenji , Morisaki Naho , Urayama Kevin Y. , Hattori Tomoyuki
Published: October 2020

It has been observed that growth velocity of toddlers and school children shows seasonal variation, while such seasonality is unknown in infants. The aim of this study was to examine whether growth velocity (length and weight) of infants differs by seasons. We assessed longitudinal measurement data obtained for 9,409 Japanese infants whose parents used the mobile phone application, “Papatto Ikuji”, during the period from January 2014 to October 2017. On average, each infant had 4.8 entries for length and 5.4 entries for weight. The mean daily change in sex- and age-adjusted z-scores between two time points was estimated as the growth velocity during that period: ΔLAZ/day and ΔWAZ/day for length and weight, respectively. We analyzed 20,007 ΔLAZ/day (mean, −0.0022) and 33,236 ΔWAZ/day (mean, 0.0005) measurements, and found that ΔLAZ/day showed seasonal differences with increases during summer. We conducted a multilevel linear regression analysis, in which effects of age, sex, nutrition and season of birth were adjusted, showing significant difference in ΔLAZ/day between winter and summer with a mean ΔLAZ/day difference of 0.0026 (95%CI 0.0015 to 0.0036; P < 0.001). This seasonal difference corresponded to 13% of the average linear growth velocity in 6-month-old infants. A modest effect of nutrition on linear growth was observed with a mean ΔLAZ/day difference of 0.0015 (95%CI 0.0006 to 0.0025; P < 0.001) between predominantly formula-fed infants and breastfed infants. In conclusion, we observed that linear growth, but not weight gain, of Japanese infants showed significant seasonality effects represented by increases in summer and decreases in winter.
Phosphodiesterase 2A2 regulates mitochondria clearance through Parkin-dependent mitophagy
Authors: Lobo Miguel J. , Reverte-Salisa Laia , Chao Ying-Chi , Koschinski Andreas , Gesellchen Frank , Subramaniam Gunasekaran , Jiang He , Pace Samuel , Larcom Natasha , Paolocci Ester , Pfeifer Alexander , Zanivan Sara , Zaccolo Manuela
Published: October 2020

Programmed degradation of mitochondria by mitophagy, an essential process to maintain mitochondrial homeostasis, is not completely understood. Here we uncover a regulatory process that controls mitophagy and involves the cAMP-degrading enzyme phosphodiesterase 2A2 (PDE2A2). We find that PDE2A2 is part of a mitochondrial signalosome at the mitochondrial inner membrane where it interacts with the mitochondrial contact site and organizing system (MICOS). As part of this compartmentalised signalling system PDE2A2 regulates PKA-mediated phosphorylation of the MICOS component MIC60, resulting in modulation of Parkin recruitment to the mitochondria and mitophagy. Inhibition of PDE2A2 is sufficient to regulate mitophagy in the absence of other triggers, highlighting the physiological relevance of PDE2A2 in this process. Pharmacological inhibition of PDE2 promotes a ‘fat-burning’ phenotype to retain thermogenic beige adipocytes, indicating that PDE2A2 may serve as a novel target with potential for developing therapies for metabolic disorders.
IM30 IDPs form a membrane-protective carpet upon super-complex disassembly
Authors: Junglas Benedikt , Orru Roberto , Axt Amelie , Siebenaller Carmen , Steinchen Wieland , Heidrich Jennifer , Hellmich Ute A. , Hellmann Nadja , Wolf Eva , Weber Stefan A. L. , Schneider Dirk
Published: October 2020

Members of the phage shock protein A (PspA) family, including the inner membrane-associated protein of 30 kDa (IM30), are suggested to stabilize stressed cellular membranes. Furthermore, IM30 is essential in thylakoid membrane-containing chloroplasts and cyanobacteria, where it is involved in membrane biogenesis and/or remodeling. While it is well known that PspA and IM30 bind to membranes, the mechanism of membrane stabilization is still enigmatic. Here we report that ring-shaped IM30 super-complexes disassemble on membranes, resulting in formation of a membrane-protecting protein carpet. Upon ring dissociation, the C-terminal domain of IM30 unfolds, and the protomers self-assemble on membranes. IM30 assemblies at membranes have been observed before in vivo and were associated with stress response in cyanobacteria and chloroplasts. These assemblies likely correspond to the here identified carpet structures. Our study defines the thus far enigmatic structural basis for the physiological function of IM30 and related proteins, including PspA, and highlights a hitherto unrecognized concept of membrane stabilization by intrinsically disordered proteins.
Reward uncertainty asymmetrically affects information transmission within the monkey fronto-parietal network
Authors: Taghizadeh Bahareh , Foley Nicholas C. , Karimimehr Saeed , Cohanpour Michael , Semework Mulugeta , Sheth Sameer A. , Lashgari Reza , Gottlieb Jacqueline
Published: October 2020

A central hypothesis in research on executive function is that controlled information processing is costly and is allocated according to the behavioral benefits it brings. However, while computational theories predict that the benefits of new information depend on prior uncertainty, the cellular effects of uncertainty on the executive network are incompletely understood. Using simultaneous recordings in monkeys, we describe several mechanisms by which the fronto-parietal network reacts to uncertainty. We show that the variance of expected rewards, independently of the value of the rewards, was encoded in single neuron and population spiking activity and local field potential (LFP) oscillations, and, importantly, asymmetrically affected fronto-parietal information transmission (measured through the coherence between spikes and LFPs). Higher uncertainty selectively enhanced information transmission from the parietal to the frontal lobe and suppressed it in the opposite direction, consistent with Bayesian principles that prioritize sensory information according to a decision maker’s prior uncertainty.