bluuebunny/crossref_metadata_2025 huggingface dataset:
Indígena or Não‐Indígena? The Gendered Politics of Assimilation in Colonial Mozambique, 1917–61
Authors: Havstad Lilly
Published: July 2021

This article examines the intersections of race, sex and gender that shaped the legal system of assimilation in colonial Mozambique. Between 1917 and 1961, Africans could apply for assimilated (assimilado/a) status, granting them limited rights of Portuguese citizenship. Analysis of assimilation case files, administrative reports and public debates in local newspapers reveals that assimilation was an ambiguous, changing and gendered system shaped not only by its Portuguese legislative architects, but also by the African men and women who navigated the law, and encouraged its reforms, over time. Using a feminist historical approach to challenge entrenched scholarly interpretations of the system as uniformly male gendered, this article reveals that marriage, miscegenation and women were at the centre of the assimilation system as a contested site of the politics of ‘civilisation’ in the colonial capital of Lourenço Marques.
Connecting resilience concepts to operational behaviour: A disaster exercise case study
Authors: Pettersson Jenny , Jonson Carl‐Oscar , Berggren Peter , Hermelin Jonas , Trnka Jiri , Woltjer Rogier , Prytz Erik
Published: July 2021

Contemporary crisis management studies often make use of the concept of resilience. However, resilience as a term has a wide variety of meanings and has been criticized as lacking operationalization and empirical validation. The current study aimed to link resilience concepts to observable behaviour within a disaster medicine management system. Resilience concepts, captured in so‐called capability cards and further operationalized into six resilience prerequisites, were used in the study. An experienced crisis management team participated in a large‐scale crisis management exercise and behaviours were captured through observations, video and audio recordings. Using a markers and strategies analytical framework, two blinded raters classified observable behaviours that exemplified resilient practice. The analysis showed a high degree of agreement (79%) between the combined operationalized capability cards and resilience prerequisites and the empirical classification of behaviours. The current study shows an empirical link from resilience concepts to observable behaviours during an exercise. Observed episodic narratives exemplify empirically connected specific strategies to specific resilience markers. These results demonstrate a method with observed narratives for analyzing resilience in crisis management teams using a markers and strategies approach. Future studies can use the results to create structured observation protocols to evaluate resilient behaviours in crisis management teams.
Progress in micellar casein concentrate: Production and applications
Authors: Hammam Ahmed R. A. , Martínez‐Monteagudo Sergio I. , Metzger Lloyd E.
Published: July 2021

Micellar casein concentrate (MCC) is a novel ingredient with high casein content. Over the past decade, MCC has emerged as one of the most promising dairy ingredients having applications in beverages, yogurt, cheese, and process cheese products. Industrially, MCC is manufactured by microfiltration (MF) of skim milk and is commercially available as a liquid, concentrated, or dried containing ≥9, ≥22, and ≥80% total protein, respectively. As an ingredient, MCC not only imparts a bland flavor but also offers unique functionalities such as foaming, emulsifying, wetting, dispersibility, heat stability, and water‐binding ability. The high protein content of MCC represents a valuable source of fortification in a number of food formulations. For the last 20 years, MCC is utilized in many applications due to the unique physiochemical and functional characteristics. It also has promising applications to eliminate the cost of drying by producing concentrated MCC. This work aims at providing a succinct overview of the historical progress of the MCC, a review on the manufacturing methods, a discussion of MCC properties, varieties, and applications.
Nanocarrier‐delivered dsRNA suppresses wing development of green peach aphids
Authors: Zhang Yun‐Hui , Ma Zhong‐Zheng , Zhou Hang , Chao Zi‐Jian , Yan Shuo , Shen Jie
Published: July 2021

RNA interference (RNAi) has developed rapidly as a potential “green” pest management strategy. At present, most studies have focused on the screening of aphid lethal genes, whereas only a few studies have been conducted on wing development, which is crucial for aphid migration and plant‐virus dissemination. Here, the Myzus persicae genes vestigial (vg) and Ultrabithorax (Ubx) related to wing development, were cloned. These two genes were expressed in various tissues of 3rd‐instar winged aphids. The mRNA level of vg was high in 3rd‐instar nymphs, whereas the expression level of Ubx was high in adults. The nanocarrier‐mediated delivery system delivered double‐stranded RNAs for aphid RNAi using topical and root applications. The expression levels of vg and Ubx were downregulated by 44.0% and 36.5%, respectively, using the topical application. The simultaneous RNAi of the two target genes caused 63.3% and 32.2% wing aberration rates using topical and root applications, respectively. The current study provided a promising method for controlling aphid migration to alleviate the spread of insect transmitted plant diseases.
Olfactory impact of guaiacol, ortho‐vanillin, 5‐methyl, and 5‐formyl‐vanillin as byproducts in synthetic vanillin
Authors: Yu Hai‐Yan , Shi Qi‐Xuan , Mao Hai‐Fang , Chen Chen , Tian Huai‐Xiang
Published: July 2021

To better control the quality of synthetic vanillin obtained by using the guaiacol synthesis method, the olfactory impacts of byproducts on the aroma of the synthetic vanillin samples were evaluated and their optimum concentration ranges were determined. Four byproducts (guaiacol, ortho‐vanillin, 5‐methyl‐vanillin, and 5‐formyl‐vanillin) were identified by gas chromatography–mass spectrometry (GC–MS) and quantified by gas chromatography–flame ionization detection (GC–FID) in the synthetic vanillin samples with different degrees of purity. The aroma intensities (AIs) of the four byproducts obtained by gas chromatography–olfactometry (GC–O) were: guaiacol (AI: 3.5–4.0, smoke), ortho‐vanillin (AI: 1.6–2.5, almond), 5‐methyl‐vanillin (AI: 2.5–3.3, aldehyde), and 5‐formyl‐vanillin (AI: 3.2–3.8, green). The aroma perceptual interactions of the four byproducts and the vanillin in the synthetic vanillin samples were determined by S‐curve analysis. Guaiacol and 5‐methyl‐vanillin showed synergistic effects by Feller's additive model. Combined with the results of an addition experiment, when the contents of guaiacol, ortho‐vanillin, 5‐methyl‐vanillin, and 5‐formyl‐vanillin were within 50, 10, 400, and 1,000 mg/kg respectively, the byproducts had no effects on the aroma quality of the synthetic vanillin samples.

Practical Application

Synthetic vanillin is one of the most commonly used food additives. Currently, the purity of synthetic vanillin can reach 99.9%, but trace byproducts are still present. Continuing to improve the purity of synthetic vanillin will significantly increase its production costs. Therefore, it is necessary to determine whether the presence of these byproducts affects the aroma quality of the synthetic vanillin samples or not. If they have a negative effect on its aroma, it will be important to reduce their content. If they have no influence or positive role, there is no need to control the content of these byproducts to very low levels. This study determined the content of the byproducts produced during the synthesis of vanillin by guaiacol glyoxylic acid method, judged the perceptual interaction between the byproducts and the vanillin in the synthetic vanillin samples, and determined the optimum range within which the byproducts had no effects on the aroma quality. This study provides a theoretical basis for improving the aroma quality of synthetic vanillin while controlling the production costs.
Penicillin biosensor based on rhombus‐shaped porous carbon/hematoxylin/penicillinase
Authors: Wang Hongsu , Wang Li , Xiu Yi , Zhang Shaoqi , Wang Song , Niu Xiaodi
Published: July 2021

In this experiment, we designed an electrochemical sensor using penicillinase (Pen X)‐rhombus porous carbon (RPC) as the detection element and hematoxylin as the indicator to detect low concentrations of penicillin sodium (Pen G). A differential pulse voltammetry (DPV) method was used to detect Pen G in the concentration range of 10–8–10–5 mg·mL–1 under optimal experimental conditions. The results showed that the peak current value and the logarithm of Pen G concentration showed a good linear relationship (R2 = 0.9915), and the LOD was 2.68 × 10–7 mg·mL–1 (S/N = 3). The actual milk samples were detected by the addition method and compared with the high‐performance liquid phase method; no significant difference was found in the detection results. The working electrode prepared by cross‐linking method not only extends the service life of the sensor, but also improves the sensitivity and reproducibility of the sensor. It can also be used to detect the Pen G residue in the actual milk samples repeatedly.

Practical Application

In this study, an electrochemical sensor for the rapid detection of penicillin sodium in milk was prepared, which has good sensitivity and fast detection speed.
A review of artificial intelligence applications for motion tracking in radiotherapy
Authors: Mylonas Adam , Booth Jeremy , Nguyen Doan Trang
Published: July 2021

During radiotherapy, the organs and tumour move as a result of the dynamic nature of the body; this is known as intrafraction motion. Intrafraction motion can result in tumour underdose and healthy tissue overdose, thereby reducing the effectiveness of the treatment while increasing toxicity to the patients. There is a growing appreciation of intrafraction target motion management by the radiation oncology community. Real‐time image‐guided radiation therapy (IGRT) can track the target and account for the motion, improving the radiation dose to the tumour and reducing the dose to healthy tissue. Recently, artificial intelligence (AI)‐based approaches have been applied to motion management and have shown great potential. In this review, four main categories of motion management using AI are summarised: marker‐based tracking, markerless tracking, full anatomy monitoring and motion prediction. Marker‐based and markerless tracking approaches focus on tracking the individual target throughout the treatment. Full anatomy algorithms monitor for intrafraction changes in the full anatomy within the field of view. Motion prediction algorithms can be used to account for the latencies due to the time for the system to localise, process and act.
SPART: A versatile and standardized data exchange format for species partition information
Authors: Miralles Aurélien , Ducasse Jacques , Brouillet Sophie , Flouri Tomas , Fujisawa Tomochika , Kapli Paschalia , Knowles L. Lacey , Kumari Sangeeta , Stamatakis Alexandros , Sukumaran Jeet , Lutteropp Sarah , Vences Miguel , Puillandre Nicolas
Published: July 2021

A wide range of data types can be used to delimit species and various computer‐based tools dedicated to this task are now available. Although these formalized approaches have significantly contributed to increase the objectivity of species delimitation (SD) under different assumptions, they are not routinely used by alpha‐taxonomists. One obvious shortcoming is the lack of interoperability among the various independently developed SD programs. Given the frequent incongruences between species partitions inferred by different SD approaches, researchers applying these methods often seek to compare these alternative species partitions to evaluate the robustness of the species boundaries. This procedure is excessively time consuming at present, and the lack of a standard format for species partitions is a major obstacle. Here, we propose a standardized format, SPART, to enable compatibility between different SD tools exporting or importing partitions. This format reports the partitions and describes, for each of them, the assignment of individuals to the “inferred species”. The syntax also allows support values to be optionally reported, as well as original trees and the full command lines used in the respective SD analyses. Two variants of this format are proposed, overall using the same terminology but presenting the data either optimized for human readability (matricial SPART) or in a format in which each partition forms a separate block (SPART.XML). ABGD, DELINEATE, GMYC, PTP and TR2 have already been adapted to output SPART files and a new version of LIMES has been developed to import, export, merge and split them.
Chromosome‐level genome assembly of Welwitschia mirabilis, a unique Namib Desert species
Authors: Han Yuwei , Zhang Weixiong , Zhou Botong , Zeng Peng , Tian Zunzhe , Cai Jing
Published: July 2021

Welwitschia mirabilis, which is endemic to the Namib Desert, is the only living species within the family Welwitschiaceae. This species has an extremely long lifespan of up to 2,000 years and bears a single pair of opposite leaves that persist whilst alive. However, the underlying genetic mechanisms and evolution of the species remain poorly elucidated. Here, we report on a chromosome‐level genome assembly for W. mirabilis, with a 6.30‐Gb genome sequence and contig N50 of 27.50 Mb. In total, 39,019 protein‐coding genes were predicted from the genome. Two brassinosteroid‐related genes (BRI1 and CYCD3), key regulators of cell division and elongation, were strongly selected in W. mirabilis and may contribute to their long ever‐growing leaves. Furthermore, 29 gene families in the mitogen‐activated protein kinase signalling pathway showed significant expansion, which may contribute to the desert adaptations of the plant. Three positively selected genes (EHMT1, EIF4E, SOD2) may be involved in the mechanisms leading to long lifespan. Based on molecular clock dating and fossil calibrations, the divergence time of W. mirabilis and Gnetum montanum was estimated at ~123.5 million years ago. Reconstruction of population dynamics from genome data coincided well with the aridification of the Namib Desert. The genome sequence detailed in the current study provides insight into the evolution of W. mirabilis and should be an important resource for further study on gnetophyte and gymnosperm evolution.
Development and validation of a Behçet's Disease Damage Index for adults with BD: An Explicit, Composite and Rated (ECR) tool
Authors: Gheita Tamer A. , Hammam Nevin , Fawzy Samar M. , Abd El‐Latif Eiman , El‐Gazzar Iman I. , Samy Nermeen , El‐Hammady Dina H. , Abdel Noor Rasha , El‐Shebini Emad , El‐Najjar Amany R. , Eesa Nahla N. , Salem Mohamed N. , Ibrahim Soha E. , El‐Essawi Dina F. , Elsaman Ahmed M. , Senara Soha , Fathi Hanan M. , Sallam Rehab A. , El Shereef Rawhya R. , Abd Elazeem Mervat I. , Fawzy Rasha M. , Khalil Noha M. , Shahin Dina , El‐Saadany Hanan M. , ElKhalifa Marwa , Nasef Samah I. , Abdalla Ahmed M. , Noshy Nermeen , Said Emtethal A. , Saad Ehab , Moshrif Abdel Hafeez , El‐Shanawany Amira T. , Abdel‐Fattah Yousra H. , Raafat Hala A. , Khalil Hossam M. ,   the Egyptian College of Rheumatology‐Behçet's Disease Study Group (ECR‐BDSG)
Published: July 2021

Background

Behçet's disease (BD) is a chronic multisystem variable vessel vasculitis. Disease damage is irreversible and permanent. Validated tools evaluating damage are limited. Enhancements in the clinical treatment of vasculitis will take place from the development of refined and exclusive indices for individual vasculitic syndromes including BD and attempting their international validation.

Objectives

This aim was to develop and validate a simple BD Damage Index (BDI).

Methods

This was a nationwide study including 1252 BD patients. The work consisted of 3 stages. Stage 1: items generation for score content. Stage 2: items selection for the draft score was performed by an expert rheumatologist. Stage 3: the content validity of the draft score was assessed and BDI, Vasculitis Damage Index (VDI), Antineutrophil cytoplasmic antibody‐associated Vasculitis Index of Damage (AVID) and Combined Damage Assessment Index (CDAI) were calculated and compared.

Results

The mean age of the BD patients was 36.1 ± 9.9 years. Stages 1 and 2 resulted in a BDI instrument containing 73 items with a maximum score of 100. Stage 3, the VDI, CDAI, AVID, and BDI were 2.9 ± 2.2, 3.1 ± 2.3, 3.1 ± 2.3 and 5.1 ± 2.9, respectively. High correlations (r = .9) between comparable damage scores assured acceptable concurrent validity.

Conclusion

The proposed BDI represents a new robust and potentially useful tool when dealing with BD chronic status.
Epicardial carvernous hemangioma: The diagnostic challenge of a middle mediastinal mass
Authors: Drevet Gabrielle , Chalabreysse Lara , Gamondes Delphine , Tronc François , Maury Jean‐Michel
Published: July 2021

Primary tumors in the middle mediastinum are rare and pose diagnostic challenges. Lymphomas, mediastinal cysts and thymomas most frequently affect this anatomic area. Primary cardiac tumors are rare and constitute a differential diagnosis for the inferior middle mediastinum. Surgical exploration and resection is often mandatory in order to make a definitive diagnosis. Here, we report the case of a 69 year‐old women who presented with persistent dyspnea. A complete preoperative workup revealed a large tissular mass adjacent to the right atrium. A diagnosis of a typical epicardial cavernous hemangioma was made following surgical resection.
Trajectories of alcohol misuse among the UK Armed Forces over a 12‐year period
Authors: Palmer Laura , Norton Sam , Jones Margaret , Rona Roberto J. , Goodwin Laura , Fear Nicola T.
Published: July 2021

Aim

To identify the main trajectories of alcohol misuse among UK military personnel from 12 years after the start of the Iraq war (2003) and the factors associated with each trajectory.

Design

Longitudinal cohort study with three phases of data collection (2004–06, 2007–09 and 2014–16).

Setting

United Kingdom.

Participants

Serving and ex‐serving personnel of the UK Armed Forces (n = 7111) participating at Phase 1 and at least one follow‐up phase of the King's Centre for Military Health Research (KCMHR) cohort study.

Measurements

Trajectories of alcohol misuse were derived from scores using the Alcohol Use Disorders Identification Test (AUDIT‐10) over three data collection phases. Demographic and military characteristics were collected and, among the key covariates, post‐traumatic stress disorder (PTSD) was measured using the PTSD checklist (PCL‐C) and childhood interpersonal stress and violence was measured using items from the Adverse Childhood Experiences questionnaire.

Findings

Five trajectories of alcohol misuse were identified, including ‘no misuse’ (n = 2249, 31.6%) and ‘hazardous’ (n = 3398, 47.8%), ‘harmful’ (n = 832, 11.7%), ‘severe‐to‐hazardous’ (n = 258, 5.3%) and ‘severe’ (n = 374, 3.6%) drinking. Substantial changes were evident only among severe drinkers, where more than half reduced over the study period. The factors most strongly associated with belonging to harmful/severe drinking classes were young age, male gender and childhood adversities and antisocial behaviour. Severe drinkers at Phase 1 were more likely to report probable PTSD and shorter military careers and were less likely to serve as Officers. Persistent severe drinkers were less likely to serve in the RAF compared to the Army and were more likely to be reserves. Not misusing alcohol was also associated with reserve status and having left service.

Conclusions

In a cohort of approximately 7000 UK military personnel, trajectories of alcohol misuse appeared stable between 2004 and 2016. More than half of severe drinkers made substantial improvements over the period, but 68% of the cohort continued to drink hazardously or harmfully. Lack of change for the majority of the sample signals the need for strategies to address alcohol misuse and its cultural and psychosocial drivers.
Comparison of the effects from coronal pre‐flaring and glide‐path preparation on torque generation during root canal shaping procedure
Authors: Kwak Sang Won , Ha Jung‐Hong , Shen Ya , Haapasalo Markus , Kim Hyeon‐Cheol
Published: July 2021

This study aimed to evaluate the effect of glide‐path preparation and coronal pre‐flaring on torque generation of rotary nickel–titanium files. Sixty mesiobuccal root canals of 3D printed resin teeth (Dentalike) were randomly divided into 4 groups (n = 15) according to the preparation method; Group 1: OneCurve only; Group 2: OneG and OneCurve; Group 3: OneFlare and OneCurve; Group 4: OneFlare, OneG, and OneCurve. During the final canal preparation procedure, the torque generated was recorded. The sum of generated torque and maximum torque were calculated. Statistical analysis was performed with one‐way ANOVA and Duncan’s post hoc comparison. The summed torque was reduced by glide‐path preparation and coronal pre‐flaring (P < 0.05), whereas the maximum torque was not reduced by the glide‐path preparation (P > 0.05). It will be advantageous to create a glide‐path with coronal pre‐flaring to reduce the stress and reactive forces to the NiTi file and root dentin.
Forest insects and the binary power law
Authors: Taylor R. A. J.
Published: July 2021

Hughes and Madden's binary power law was used to analyse sample data of three life stages of gypsy moth (Lymantria dispar) and adult emerald ash borer (Agrilus planipennis), both important invasive forest pests in North America.

Tally thresholds were used to convert quantitative gypsy moth data to binomial, presence–absence data for binary power law analysis.

Presence–absence data from two emerald ash borer surveys were analysed, an initial highly intensive and expensive survey expanding out from the point of introduction in Michigan and a second extensive survey designed to detect and track the leading edge of the beetle's expanding range.

Emerald ash borer was found to be moderately aggregated in the initial survey data, but very near to random in the leading edge survey. The latter result is consistent with other findings that spatial distribution is less aggregated at range edges than near the centre of the range.

Estimates of the proportion of positive observations in the initial intensive survey were found to be more precise than those obtained in the leading edge survey.

Comparisons of binomial power law estimates and Taylor's power law estimates of the gypsy moth data suggest the possibility of a fundamental connection between the two power laws. A possible connection, the effect of tally thresholds and their relationship with sampling efficiency are discussed.
Evolution and long‐term outcomes of combined immunodeficiency due to CARMIL2 deficiency
Authors: Kolukisa Burcu , Baser Dilek , Akcam Bengu , Danielson Jeffrey , Bilgic Eltan Sevgi , Haliloglu Yesim , Sefer Asena Pinar , Babayeva Royale , Akgun Gamze , Charbonnier Louis‐Marie , Schmitz‐Abe Klaus , Kendir Demirkol Yasemin , Zhang Yu , Gonzaga‐Jauregui Claudia , Jimenez Heredia Raul , Kasap Nurhan , Kiykim Ayca , Ozek Yucel Esra , Gok Veysel , Unal Ekrem , Pac Kisaarslan Aysenur , Nepesov Serdar , Baysoy Gokhan , Onal Zerrin , Yesil Gozde , Celkan Tulin Tiraje , Cokugras Haluk , Camcioglu Yildiz , Eken Ahmet , Boztug Kaan , Lo Bernice , Karakoc‐Aydiner Elif , Su Helen C. , Ozen Ahmet , Chatila Talal A. , Baris Safa
Published: July 2021

Background

Biallelic loss‐of‐function mutations in CARMIL2 cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV‐related smooth muscle tumors. Clinical and immunological characterizations of the disease with long‐term follow‐up and treatment options have not been previously reported in large cohorts. We sought to determine the clinical and immunological features of CARMIL2 deficiency and long‐term efficacy of treatment in controlling different disease manifestations.

Methods

The presenting phenotypes, long‐term outcomes, and treatment responses were evaluated prospectively in 15 CARMIL2‐deficient patients, including 13 novel cases. Lymphocyte subpopulations, protein expression, regulatory T (Treg), and circulating T follicular helper (cTFH) cells were analyzed. Three‐dimensional (3D) migration assay was performed to determine T‐cell shape.

Results

Mean age at disease onset was 38 ± 23 months. Main clinical features were skin manifestations (n = 14, 93%), failure to thrive (n = 10, 67%), recurrent infections (n = 10, 67%), allergic symptoms (n = 8, 53%), chronic diarrhea (n = 4, 27%), and EBV‐related leiomyoma (n = 2, 13%). Skin manifestations ranged from atopic and seborrheic dermatitis to psoriasiform rash. Patients had reduced proportions of memory CD4+ T cells, Treg, and cTFH cells. Memory B and NK cells were also decreased. CARMIL2‐deficient T cells exhibited reduced T‐cell proliferation and cytokine production following CD28 co‐stimulation and normal morphology when migrating in a high‐density 3D collagen gel matrix. IBD was the most severe clinical manifestation, leading to growth retardation, requiring multiple interventional treatments. All patients were alive with a median follow‐up of 10.8 years (range: 3–17 years).

Conclusion

This cohort provides clinical and immunological features and long‐term follow‐up of different manifestations of CARMIL2 deficiency.
Immunological effects of adjuvanted low‐dose allergoid allergen‐specific immunotherapy in experimental murine house dust mite allergy
Authors: Heldner Alexander , Alessandrini Francesca , Russkamp Dennis , Heine Sonja , Schnautz Benjamin , Chaker Adam , Mwange Juliet , Carreno Velazquez Thalia L. , Heath Matthew D. , Skinner Murray A. , Kramer Matthias F. , Zissler Ulrich M. , Schmidt‐Weber Carsten B. , Blank Simon
Published: July 2021

Background

Native allergen extracts or chemically modified allergoids are routinely used to induce allergen tolerance in allergen‐specific immunotherapy (AIT), although mechanistic side‐by‐side studies are rare. It is paramount to balance optimal dose and allergenicity to achieve efficacy warranting safety. AIT safety and efficacy could be addressed by allergen dose reduction and/or use of allergoids and immunostimulatory adjuvants, respectively. In this study, immunological effects of experimental house dust mite (HDM) AIT were investigated applying high‐dose HDM extract and low‐dose HDM allergoids with and without the adjuvants microcrystalline tyrosine (MCT) and monophosphoryl lipid A (MPL) in a murine model of HDM allergy.

Methods

Cellular, humoral, and clinical effects of the different AIT strategies were assessed applying a new experimental AIT model of murine allergic asthma based on physiological, adjuvant‐free intranasal sensitization followed by subcutaneous AIT.

Results

While low‐dose allergoid and high‐dose extract AIT demonstrated comparable potency to suppress allergic airway inflammation and Th2‐type cytokine secretion of lung‐resident lymphocytes and draining lymph node cells, low‐dose allergoid AIT was less effective in inducing a potentially protective IgG1 response. Combining low‐dose allergoid AIT with MCT or MCT and dose‐adjusted MPL promoted Th1‐inducing mechanisms and robust B‐cell activation counterbalancing the allergic Th2 immune response.

Conclusion

Low allergen doses induce cellular and humoral mechanisms counteracting Th2‐driven inflammation by using allergoids and dose‐adjusted adjuvants. In light of safety and efficacy improvement, future therapeutic approaches may use low‐dose allergoid strategies to drive cellular tolerance and adjuvants to modulate humoral responses.
Identification of novel biomarkers to distinguish bradykinin‐mediated angioedema from mast cell‐/histamine‐mediated angioedema
Authors: Bindke Gesa , Gehring Manuela , Wieczorek Dorothea , Kapp Alexander , Buhl Timo , Wedi Bettina
Published: July 2021

Background

The pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood.

Methods

To identify clinical and laboratory parameters specific for a certain AE subtype, 40 AE patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE‐inhibitor induced (ACE‐AE), and 12 mast cell‐mediated without wheals in chronic spontaneous urticaria (CSU‐AE). Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin‐lectin pathway, of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme‐linked immunosorbent assay.

Results

New routine clinical diagnostic criteria could not be identified, not even for distinguishing bradykinin‐mediated (BK‐) AE (ie, HAE and ACE‐AE) from mast cell‐/histamine‐mediated CSU‐AE. However, FAP‐α and tPA were significantly increased in all AE compared to controls. In HAE, FAP‐ α, tPA, uPAR, pentraxin‐3, Tie‐2, sE‐selectin, and VE‐cadherin were significantly increased compared to controls. In HAE compared to CSU‐AE and ACE‐AE, sE‐Selectin, Tie‐2, and VE‐Cadherin were significantly increased, whereas for Ang‐2 the difference was significant compared to CSU‐AE only. Tie‐2 correlated strongly negatively with C4, C1‐INH activity, and C1‐INH function.

Conclusions

This study is the first to compare HAE, ACE‐AE, and CSU‐AE. Although significance is limited by small sample size, Tie‐2 was identified as a new promising biomarker candidate for HAE. FAP‐ α and tPA might serve as a marker for AE in general, whereas sE‐selectin and Ang‐2 were increased in BK‐AE only. Our results add information to the role of endothelial dysfunction and serine proteases in different AE subtypes.
A Heuristic Model for Designing Interventions in Multicultural Mental Health Encounters: The Case of a Community Mental Health Center among the Mapuche of Chile
Authors: Wiencke Markus
Published: July 2021

In this paper, I develop the integrative concept of “shared experience of sense” as a heuristic model to design interventions in multicultural health encounters in the field of mental health promotion. For this purpose, I use extensive ethnographic material from the Mapuche’s territory in Chile, analyzing the interactions between an outpatient community mental health center and deinstitutionalized patients in their home settings. The patients and their families navigate the medical pluralism of their domestic settings and make varying use of each of the different therapeutic options that are available to them, offered by the outpatient community mental health center, Indigenous healers, and Pentecostalism.

The concept of “shared experience of sense” characterizes a specific form of meaning‐making that may be beneficial to health in mental illness. This “positive” meaning making is made possible by a person's emotional and physical participation in the social events of therapeutic settings. In this regard, I highlight the bridges that the community mental health center builds to the everyday lives of patients and their families. Because of the support and access to resources provided by such therapeutic settings, persons are able to cope with their illness in everyday life, which can mean different things depending on the context. This is what I mean when I refer to “health promotion” in this article.
The Sensory Deprivation Tank – A Time Machine
Authors: Phillips Matthew T
Published: July 2021

This paper explores Henri Bergson’s understanding of time in relation to the experience of the sensory deprivation tank. In this exploration, the tank is presented as a time machine: a machine that separates time from space and takes the floater into an experience of what Bergson describes as pure time. At the same time, the tank acts as a kind of phenomenological epoché that, through the disabling of the floater’s sensory‐motor schema, literally suspends the human being outside of the world and forces them to reconsider their previous judgements and understandings of consciousness and time. The tank is tied in with contemporary scientific and philosophical discourses on consciousness, such as those of David Chalmers and what he has described as the hard problem of consciousness. As Chalmers discusses, the hard problem requires a radically new type of thinking beyond contemporary science and its inherent materialistic and mechanistic worldview. The tank is presented as a machine that could play a part in this radical rethinking of consciousness—a literal black box working through the black box problems of consciousness.
Synthesis of coagulation factors during long‐term ex situ liver perfusion
Authors: Eshmuminov Dilmurodjon , Hefti Max , Mueller Matteo , Schuler Martin J. , Bautista Borrego Lucia , Schneider Marcel André , Koch Karin , Weisskopf Miriam , Tibbitt Mark W. , Dutkowski Philipp , Rudolf von Rohr Philipp , Studt Jan‐Dirk , Becker Dustin , Clavien Pierre‐Alain
Published: July 2021

Robust viability assessment of grafts during normothermic liver perfusion is a prerequisite for organ use. Coagulation parameters are used commonly for liver assessment in patients. However, they are not yet included in viability assessment during ex situ perfusion. In this study, we analysed coagulation parameters during one week ex situ perfusion at 34℃. Eight discarded human livers were perfused with blood‐based, heparinised perfusate for one week; perfusions in a further four livers were terminated on day 4 due to massive ongoing cell death. Coagulation parameters were well below the physiologic range at perfusion start. Physiologic levels were achieved within the first two perfusion days for factor V (68.5 ± 35.5%), factor VII (83.5 ± 26.2%), fibrinogen (2.1 ± 0.4 g/L) and antithrombin (107 ± 26.5%) in the livers perfused for one week. Despite the increased production of coagulation factors, INR was detectable only at 24h of perfusion (2.1 ± 0.3) and prolonged thereafter (INR > 9). The prolongation of INR was related to the high heparin level in the perfusate (anti‐FXa > 3 U/mL). Intriguingly, livers with ongoing massive cell death also disclosed synthesis of factor V and improved INR. In summary, perfused livers were able to produce coagulation factors at a physiological level ex situ. We propose that single coagulation factor analysis is more reliable for assessing the synthetic function of perfused livers as compared to INR when using a heparinised perfusate.
Acute gastrointestinal bleeding: proposed study outcomes for new randomised controlled trials
Authors: Jensen Dennis M. , Barkun Alan , Cave David , Gralnek Ian M. , Jutabha Rome , Laine Loren , Lau James Y. W. , Saltzman John R. , Soetikno Roy , Sung Joseph J. Y.
Published: July 2021

Background

Acute gastrointestinal bleeding (GIB) remains a common cause of hospitalisation. However, interpretation and comparisons of published studies in GIB have been hampered by disparate study methodology.

Aims

To make recommendations about outcome measures to be used in future randomised controlled trials (RCTs) of patients with acute bleeding from any GI source (nonvariceal UGI, variceal, small bowel, or colon) and suggest new RCTs in acute GIB for future peer‐reviewed funding.

Methods

As part of a National Institutes of Health conference entitled “Hemostatic Outcomes in Clinical Trials”, a group of GIB experts performed targeted critical reviews of available evidence with the goal of proposing a bleeding outcome that could potentially be applied to different disciplines. In addition, the panel sought to develop a clinically meaningful primary endpoint specifically for acute GIB, potentially allowing a more contemporary regrouping of clinically relevant outcomes.

Results

The primary endpoint proposed was a composite outcome of further bleeding within 30 days after randomisation leading to red blood cell transfusion, urgent intervention (repeat endoscopy; interventional radiology or surgery), or death. Secondary outcomes may include the individual components of the primary outcome, length of hospitalisation, serious adverse events, and health care resource utilisation.

Conclusion

The proposed endpoint may help move the GIB field forward by focusing on the most clinically relevant outcomes for patients with acute GIB of all types and informing study design and importance of sample size determination for future RCTs in GIB.
Personality as a moderator of immediate and delayed ostracism distress
Authors: Yaakobi Erez
Published: July 2021

Although ostracism is known to have negative consequences, individuals are affected to differing extents and show different patterns of recovery. To better understand these differences, the Big Five personality model was used to examine the moderating role of personality on immediate and delayed ostracism distress. In this laboratory study, 408 participants played Cyberball and completed batteries on needs satisfaction and mood distress. The results show that more Agreeable or Conscientious individuals experienced greater distress on the immediate and the delayed distress measures (needs satisfaction and mood). Greater Openness to experience was related to greater effects of Agreeableness or Conscientious on distress experienced after being ostracized than when included. The discussion centres on the steps that can be taken to achieve greater relief after ostracism. This research contributes new theoretical insights and presents practical implications leading to a better understanding of those individuals who are at greater risk of being affected by ostracism, the personality characteristics that moderate ostracism distress, and when.
Transplantation of kidneys after normothermic perfusion: A single center experience
Authors: Pearson Robert , Geddes Colin , Mark Patrick , Clancy Marc , Asher John
Published: July 2021

Background

In order to expand the pool of usable donors from circulatory death (DCD) there is increasing interest in normothermic regional perfusion (NRP) to assess and improve liver viability.1,2 NRP may also improve outcomes in kidney transplantation.We present our single center experience of outcomes in imported kidneys following NRP.

Methods

Data was obtained from a prospectively maintained database between December 2012 and September 2018. Primary endpoints were incidence of delayed graft function (DGF) and estimated glomerular filtration rate (eGFR).

Results

Six‐hundred and thirty‐two decease donor kidneys were transplanted, 229 from DCD donors, 29 of which had NRP. The DGF rate was lower for NRP versus DCD (six of 29, 20.7% vs. 70 of 200, 35.0%) with reduced duration of DGF. Multivariate analysis demonstrated transplant type to be a statistically significant independent predictor of eGFR at 7 and 14 days. Early transplant function in NRP kidneys was comparable to DBD. There were no graft losses within 30 days in the NRP group. One‐year graft loss rate was 3.4% for NRP and 6.0% for standard DCD.

Conclusion

This data suggests NRP is safe, and reduces rates of DGF and improves early renal transplant function.
Doing violence to evidence on violence? How the alcohol industry created doubt in order to influence policy
Authors: Bartlett Andrew , McCambridge Jim
Published: July 2021

Introduction

In 2015/2016 controversy followed the publication of a report on an anthropological study of Australian and New Zealand night‐time economies funded by a major alcohol producer. This paper explores the background, moments of public controversy and political uses of the report.

Methods

Informed by the sociology of scientific controversies, we review the available relevant work of the author of the report, associated material such as press releases, newspaper articles (n = 18) and industry submissions to government (n = 12). Attention was paid to the ways in which claims were made about the relationship between alcohol and violence, and the ways in which credibility and legitimacy were constructed.

Results

The author of the report has longstanding associations with alcohol industry organisations. Claims made regarding alcohol and violence have remained highly consistent over time, and appear oblivious to developments in the evidence. In the media, the story was largely framed as a contest of credibility between compromised parties. The report continues to be used in alcohol industry submissions to government.

Discussion and Conclusions

This analysis suggests that this is a ‘counterfeit scientific controversy’; in our assessment, the report has had value not as a contribution to the scientific literature, but as a resource in the claims‐making practices of the alcohol industry. Studies of the ways in which industry actors foster science‐related content conducted at significant social and conceptual distance from the core of the relevant research community will enhance understandings of the ways in which industry actors engage with science and policy.
Genetic and environmental influences on executive functions and intelligence in middle childhood
Authors: Freis Samantha M. , Morrison Claire L. , Lessem Jeffrey M. , Hewitt John K. , Friedman Naomi P.
Published: July 2021

Executive functions (EFs) and intelligence (IQ) are phenotypically correlated. In twin studies, latent variables for EFs and IQ display moderate to high heritability estimates; however, they show variable genetic correlations in twin studies spanning childhood to middle age. We analyzed data from over 11,000 children (9‐ to 10‐year‐olds, including 749 twin pairs) in the Adolescent Brain Cognitive Development (ABCD) Study to examine the phenotypic and genetic relations between EFs and IQ in childhood. We identified two EF factors—Common EF and Updating‐Specific—which were both related to IQ (rs = 0.64–0.81). Common EF and IQ were heritable (53%–67%), and their genetic correlation (rG = 0.86) was not significantly different than 1. These results suggest that EFs and IQ are phenotypically but not genetically separable in middle childhood, meaning that this phenotypic separability may be influenced by environmental factors.
The brain basis of handwriting deficits in Chinese children with developmental dyslexia
Authors: Yang Yang , Zuo Zhentao , Tam Fred , Graham Simon J. , Li Junjun , Ji Yuzhu , Meng Zelong , Gu Chanyuan , Bi Hong‐Yan , Ou Jian , Xu Min
Published: July 2021

Abundant behavioral studies have demonstrated high comorbidity of reading and handwriting difficulties in developmental dyslexia (DD), a neurological condition characterized by unexpectedly low reading ability despite adequate nonverbal intelligence and typical schooling. The neural correlates of handwriting deficits remain largely unknown; however, as well as the extent that handwriting deficits share common neural bases with reading deficits in DD. The present work used functional magnetic resonance imaging to examine brain activity during handwriting and reading tasks in Chinese dyslexic children (n = 18) and age‐matched controls (n = 23). Compared to controls, dyslexic children exhibited reduced activation during handwriting tasks in brain regions supporting sensory‐motor processing (including supplementary motor area and postcentral gyrus) and visual‐orthography processing (including bilateral precuneus and right cuneus). Among these regions, the left supplementary motor area and the right precuneus also showed a trend of reduced activation during reading tasks in dyslexics. Moreover, increased activation was found in the left inferior frontal gyrus and anterior cingulate cortex in dyslexics, which may reflect more efforts of executive control to compensate for the impairments of motor and visual‐orthographic processing. Finally, dyslexic children exhibited aberrant functional connectivity among brain areas for cognitive control and sensory‐motor processes during handwriting tasks. Together, these findings suggest that handwriting deficits in DD are associated with functional abnormalities of multiple brain regions implicated in motor execution, visual‐orthographic processing, and cognitive control, providing important implications for the diagnosis and treatment of dyslexia.
Long‐term outcome in patients with follicular lymphoma following high‐dose therapy and autologous stem cell transplantation
Authors: Metzner Bernd , Pott Christiane , Müller Thomas H. , Casper Jochen , Kimmich Christoph , Petershofen Eduard K. , Renzelmann Andrea , Rosien Bernd , Thole Ruth , Voß Andreas , Köhne Claus Henning , Wellnitz Dominique
Published: July 2021

Objective

To contribute data on long‐term outcome and potential curative impact of ASCT in FL, especially following HDT with the BEAM protocol (BCNU, etoposide, cytarabine and melphalan), given very limited data on this topic in the literature.

Patients and methods

Patients with FL (n = 76) were treated in our institution with HDT and ASCT. In the case of long‐term remission (≥8 years), peripheral blood was tested for minimal residual disease by t(14;18)‐ and IGH‐PCR, including the last follow‐up.

Results

10‐year overall survival, progression‐free survival, and freedom from progression (FFP) after first‐line ASCT (n = 20) were 80%, 60%, and 69%, after second‐line ASCT (n = 48, following BEAM) 66%, 38%, and 41%, after third/fourth‐line ASCT (n = 8) 33%, 25%, and 25%, respectively. Prognostic factors for FFP were treatment line and FLIPI (Follicular Lymphoma International Prognostic Index). 10‐year FFP for second‐line ASCT and low‐risk FLIPI at relapse was 69%, intermediate‐risk 28%, and high‐risk 25% (P < .05). 26 patients developed sustained long‐term clinical and molecular remissions of up to 27 years.

Conclusions

Sustained long‐term clinical and molecular complete remissions up to 27 years can be achieved following ASCT (including HDT with BEAM in second treatment line), indicating a potential curative impact of ASCT in FL.
Post‐transplant maintenance therapy in patients with FLT3‐mutated acute myeloid leukemia: Real‐world treatment patterns and outcomes
Authors: Griffin James D. , Song Yan , Yang Hongbo , Freimark Jonathan , Shah Manasee V.
Published: July 2021

Objectives

Maintenance therapy is one strategy to prolong survival in patients with acute myeloid leukemia (AML) following hematopoietic stem cell transplantation (HSCT). We evaluated real‐world treatment patterns and outcomes in patients with newly diagnosed FLT3‐mutated AML receiving HSCT after complete remission with first‐line chemotherapy.

Methods

A global, retrospective chart review to evaluate maintenance therapy and outcomes in patients with FLT3‐mutated AML after HSCT.

Results

Data from 1208 charts from eight countries showed that most patients (n = 765 [63.3%]) received no maintenance therapy after HSCT, 219 (18.1%) received FLT3 inhibitor maintenance therapy, and 224 (18.5%) received other types of maintenance therapy. No systematic differences were observed in healthcare resource utilization across the three groups. Clinical benefit was observed with FLT3 inhibitor maintenance over no maintenance therapy with relapse‐free survival (adjusted hazard ratio [HR] 0.57 [95% CI 0.34‐0.94], P < .05). FLT3 inhibitor and other maintenance also demonstrated overall survival benefit over no maintenance (adjusted HR 0.50 [95% CI 0.28‐0.89] and 0.46 [95% CI 0.23‐0.91], respectively; both P < .05).

Conclusions

Real‐world maintenance therapies after HSCT in patients with FLT3‐mutated AML were heterogeneous. While overall use of healthcare resources was not significantly increased in patients receiving maintenance therapy versus those who did not, clinical outcomes were improved.