bluuebunny/crossref_metadata_2025 huggingface dataset:
Women as interpreters in colonial New Netherland
Authors: Kolb Waltraud , Pöllabauer Sonja
Published: February 2023

This contribution presents a case study of Sara Kierstede (aka Roelof, Van Borsum, Stouthoff), a Dutch-speaking New Netherland settler and 17th-century interpreter who was proficient in Dutch and Native American languages and served as interpreter in a male-dominated colonial environment in settings that today would be labeled as public service interpreting (PSI) or, in some instances, diplomatic interpreting. Following a microhistorical approach, rooted in Translator Studies, we discuss the agency and positioning of Kierstede as one of the few female interpreters in a multilingual colonial contact zone. We use different historical and secondary sources and reinterpret them from a translatological perspective to explore Kierstede’s interactions and relations with other stakeholders as linguistic go-between and official provincial interpreter in Dutch colonial encounters and her role as an influential woman and cultural mediator in the self-contained network of relationships that characterised Dutch colonial society in New Amsterdam.
Systemic modelling
Authors: Behr Martina
Published: February 2023

This article explains how systems theory can be used for a profound understanding of the phenomenon of interpreting. An online tool based on systems theory for the analysis and simulation of complex situations and processes was used in class for training students on how to do research in Interpreting Studies. It was found that such an approach helps to better understand and reflect the complexity of interpreting and to familiarise the students with research on interpreting. Moreover, this approach seems to be promising for interpreting research as a whole. Such a tool could be beneficial for structuring, fostering and performing interpreting research if an online model of interpreting is created jointly by the interpreting research community.
Interpreting for access
Authors: Romero-Fresco Pablo
Published: February 2023

Whereas prototypical conceptions of translation and interpreting as two separate and distinct entities are still being upheld in different contexts, the professional reality shows a less clear-cut picture, where the boundaries between translation, interpreting and accessibility are increasingly blurring. A case in point is Speech-To-Text Interpreting (STTI), which allows the production of written access to live events or programmes for people with and without hearing loss. This paper introduces STTI for readers who may not be familiar with it and addresses the quality of its final product and its recognition at the European Union and the ISO normalisation committees. The article ends on a personal note dedicated to Franz Pöchhacker, whose work is fundamental to support STTI as a new form of communication that can help bring down barriers.
Are interpreters and interpreting technology ready for the post-Covid era?
Authors: Salaets Heidi , Balogh Katalin
Published: February 2023

From its onset in early 2020, the Covid-19 (hereafter Covid) crisis has uncovered both the insecurity about new technologies and their flexibility. In this chapter, we will attempt to provide a non-exhaustive map of the field of interpreting technology in different settings, of research on these new technologies and research using them. Tools and resources that enhance an interpreter’s performance will also be discussed as part of technological evolution, while the final question to be answered is whether “interpreters [can] survive in an AI-dominated world” (Downie 2020). This contribution wants to be a call to do more large-scale research and to inform future interpreters better about technological development and opportunities in the classroom.
Basic translation competence
Authors: Nord Christiane
Published: February 2023

Students often decide to take up translator training despite having little or no proficiency in the foreign language they wish to choose for translation.1 There are two ways to tackle this problem: either by offering integrated preparatory language courses (INT) as part of a “translation” or “translation studies (TS)” programme, which is basically intended to train students for the profession in four or five years, or by requiring a satisfactory degree of language proficiency (e.g., minimum B2 or C1 according to the Common European Framework, CEFR), which may be acquired anywhere outside the programme (EXT), possibly even in the country where the language is used. The latter choice would entail taking an exam to ensure that the level of competence was sufficient to act as an entrance qualification for translator training. The INT model can be organised in two possible forms: either as a separate preparatory language tuition phase before the start of the actual translation or TS programme (INT-SEP), or a mixture of language tuition and translation teaching (INT-MIX). In this chapter, I will discuss the pros and cons of these forms. I will try to show how language teaching in translator training programmes can be geared towards translation competence without using translation as a tool for language acquisition (translation-oriented language teaching, TOLT).
Foreign language teaching in translator and interpreter training
Authors: Seidl Eva
Published: February 2023

This chapter explores language education in translation and interpreting (TI) programs through the lens of linguistic multi-competence. In doing so, language learning and teaching in the multilingual foreign language classroom are considered as a multisensory, multimodal, multidirectional, and multidimensional adaptation process and an acculturation process with emphasis on the students’ agency. The purpose of this chapter is to stress the importance of addressing and pedagogically adopting new linguistic concepts such as translanguaging or translinguistics in translator and interpreter training. New developments in the discipline of modern translation studies (TS) which reconfigure and redefine the field by adopting a cross-disciplinary perspective lend themselves well to blending with critical, empowering plurilingual pedagogies in higher education.
Free voluntary reading as a language and knowledge enhancement tool and its impact on interpreting students’ self-perceived B language fluency
Authors: Aguirre Fernández Bravo Elena , Guindal Pintado María Dolores
Published: February 2023

The present proposal argues that it is relevant to design, implement and test more practical strategies to help Interpreting students enhance their second active working language to meet market requirements. Within the framework of a dialogue interpreting B.A. course, a free voluntary reading (FVR) experiment was conducted, based on the extensive literature proving that self-selected reading contributes to improving second language acquisition. The aim was to explore its potential as a Language and Knowledge Enhancement tool in improving native Spanish Interpreting students’ self-perceived fluency in English, and to analyze whether introducing FVR transversally as a horizontal activity in different B.A. in TI courses can help students build more robust active core competences in this foreign language.
Teaching contrastive legal grammar for translators
Authors: Klabal Ondrej
Published: February 2023

This chapter instrumentalises an area of foreign language teaching that is often neglected in translation programmes’ curricula, namely the contrastive grammar of specialised languages. More specifically, this chapter addresses the incorporation of the contrastive grammar of legal English and Czech into an English grammar classroom. First, the rationale behind such an approach is presented with reference to the existing legal translation competence models and curricular design. Second, a number of linguistic phenomena encountered in English legal texts, and possibly neglected in English language classes for translators, are discussed from a socio-constructivist training perspective, and a series of exercises is presented that may be used, or adapted for use, by the instructors of such courses to help them cover these specific aspects of English grammar.
Task-based L2 skill development for TI trainees
Authors: Marín García Álvaro , Pérez Fernández Tamara
Published: February 2023

The present chapter reports on the design and implementation of a C2-level English course for TI trainees in an attempt to move away from the more traditional instruction based on linguistic competence. We intend to bring the classroom closer to industry demands by facilitating the students’ language skill development in context-relevant tasks. The course presents students with an expertise-oriented, task-based learning experience that is structured in a portfolio aiming at the development of skills identified as needs in the industry. This shift in focus – from competence to its subsumed skills – allows for more flexibility in addressing identified needs from an L2 training perspective (communication skills, general knowledge, information gathering and processing) in graduates entering the job market.
Do translators need a different knowledge of their target language?
Authors: Schulte Kim
Published: February 2023

This chapter aims to identify areas in which students of translation can benefit from specific language teaching geared towards their needs as future translators who will normally be expected to translate from as well as into their second language. Drawing on data from translations by several hundred students at a Spanish university, it is shown that general English teaching as it is currently conceived is not sufficient to prepare these students for the job, mainly because they require specific knowledge and contrastive awareness to be able to produce linguistically, stylistically and formally correct translations of the written texts they will be confronted with as professional translators. The data allows us to distinguish several types of frequent mistakes caused by linguistic interference, providing insights into the specific language teaching needs of translation students and setting a starting point for establishing a cross-linguistically valid inventory of the most common types of interference-based errors in translation.
Using action-oriented methods in foreign language classes to enhance translation competence
Authors: Siever Holger , Wehberg Anne Simone
Published: February 2023

This chapter presents an empirical study conducted in foreign language classes and in translator training classes (Spanish–German). The main aim of the study was twofold: (1) to show whether methods used in translation classes could be used in foreign language classes to enhance foreign language competence; and (2) to show whether, and if so how, translation competence could be enhanced by using action-oriented methods in translator training classes. So, instead of beginning class by analysing the source text’s features and then translating the source text right away, students first discussed the topics and culture-specific items mentioned in the source text. The resulting translations based on the respective action-oriented translator training classes were also better than those of students who attended “traditional” translation classes.
Developing translation sub-competences by implementing Content and Language Integrated Learning (CLIL)
Authors: Singer Néstor , Velozo Carlos , Poblete José Luis
Published: February 2023

Translator training in Chile faces the challenge of developing the students’ linguistic competence and translator competence (TC). This chapter explores the use of Content and Language Integrated Learning (CLIL) as a means to thematically articulate a language and a translation course in an undergraduate translation program. Three CLIL-based thematic units are delivered in an English language course. The academic results of the fifteen students suggest an academic improvement in the translation course in comparison to previous cohorts. Nine of those participants and the translation lecturer engage in semi-structured interviews to explore their perceptions of the approach. The findings indicate that CLIL performs an enabling function in fostering the development of TC in the translation course.
Altered temporal connectivity and reduced meta-state dynamism in adolescents born very preterm
Authors: Lahti Katri , Setänen Sirkku , Vorobyev Victor , Nyman Anna , Haataja Leena , Parkkola Riitta
Published: February 2023

Adolescents born very preterm have an increased risk for anxiety, social difficulties and inattentiveness, i.e. the ‘preterm behavioural phenotype’. The extreme end of these traits comprises the core diagnostic features of attention and hyperactivity disorders and autism spectrum disorder, which have been reported to show aberrant dynamic resting-state functional network connectivity. This study aimed to compare this dynamism between adolescents born very preterm and controls. A resting-state functional magnetic resonance imaging was performed on 24 adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) and 32 controls born full term (≥37 weeks of gestation) at 13 years of age. Group-wise comparisons of dynamic connectivity between the resting-state networks were performed using both hard clustering and meta-state analysis of functional network connectivity. The very preterm group yielded a higher fraction of time spent in the least active connectivity state in hard clustering state functional network connectivity, even though no group differences in pairwise connectivity patterns were discovered. The meta-state analysis showed a decreased fluidity and dynamic range in the very preterm group compared with controls. Our results suggest that the 13-year-old adolescents born very preterm differ from controls in the temporal characteristics of functional connectivity. The findings may reflect the long-lasting effects of prematurity and the clinically acknowledged ‘preterm behavioural phenotype’.
Nation-destroying, emigration and Iraqi nationhood after the 2003 intervention
Authors: Kadhum Oula
Published: February 2023

While emigration and population displacements have long been a feature of Iraqi history, this article argues that the 2003 Anglo-American intervention in Iraq and its legacy has contributed to the gradual disappearance of many non-Muslim Iraqi minorities from Iraq. Though the legacy of 2003 can be attributed to a confluence of domestic and geopolitical factors, it is argued here that the 2003 intervention set in motion a process of nation-destroying instead of nation-building, as Iraqi nationhood was divided along primordial lines. Caught between competing ethnic and sectarian nationalisms, Iraqi non-Muslim minorities became targets in the quest for territorial gain and political power heralding an unprecedented and steady level of emigration. This has changed the ethnic and religious demographic of Iraq, the identity of the Iraqi nation-state, as well as fragmented Iraq's multiple ethnic and religious nations both inside and outside the country. Indeed, the effects of nation-destroying have also been transported to the diaspora, strengthening communal identities, altering attachments and creating distance between Iraqi communities abroad. This has led to distanced transnational ethnic and religious Iraqi nations in diaspora who must now also contend with assimilation, a loss of culture and language in the absence of physical links to Iraq. The article offers the first comprehensive and scholarly treatment of the effects of emigration of Iraq's non-Muslim minorities on Iraqi nationhood within the new Iraqi nation-state. It therefore contributes conceptually and empirically to advancing our understanding of the role of nation-destroying and emigration in nationalizing processes, a neglected area in current migration and nationalism scholarship.
Low-carbon warfare: climate change, net zero and military operations
Authors: Depledge Duncan
Published: February 2023

Defence has a carbon problem. The strengthening of net-zero emissions targets in response to the deepening climate crisis is forcing militaries to find answers to the question of how to wield force effectively within the constraints of a net-zero world. This article introduces the concept of ‘low-carbon warfare’ as a means of capturing recent developments, the extent to which they dovetail with existing concerns regarding the business of war in the twenty-first century, and the prospect of significant changes to how militaries operate in the years ahead as the global energy transition unfolds. The article demonstrates that the pursuit of low-carbon warfare will not be easy owing to the practical challenges of transitioning militaries away from fossil fuels. Moreover, low-carbon warfare will not mitigate all the ethical and environmental concerns associated with military deployments up to and including war. It does nevertheless offer a valuable starting point for conceptualizing how militaries are beginning to address their ‘carbon bootprints’ and what this will mean for future operations.
Halting genocide in a post-liberal international order: intervention, institutions and norms
Authors: Peak Thomas
Published: February 2023

Drawing on history and International Relations, this article considers how states might respond to genocide in a more realist, post-liberal international order (LIO). It argues that even within an emergent realist international order (RIO) that downgrades normative commitments to fundamental human rights, unchecked genocide will continue to pose a threat to international peace and security and states will be interested in halting it. Within an emergent RIO, many of the non-coercive tools for halting genocide made available by liberal order will be constrained. Yet, scholars have in any case found that where genocidal-type violence has already begun, non-coercive tools are rarely effective (Bellamy and McLoughlin, 2022; Broache and Cronin-Furman, 2021). This article suggests that within an RIO which encourages greater amounts of self-help, regional and local actors will have realpolitik motivations for undertaking military interventions which halt genocides occurring in their neighbourhood. While such dynamics are observable during earlier period of international history, an emergent RIO will also benefit from the persistence of fundamental norms such as the prohibition on genocide. Given these factors, and while it will be highly non-ideal, an emerging RIO might retain the possibility of effectively responding to some genocides.
Deal-making, diplomacy and transactional forced migration
Authors: Adamson Fiona B , Greenhill Kelly M
Published: February 2023

Former US President Donald J. Trump was infamous for his nakedly transactional approach to politics. However, as we demonstrate in this article through the lens of migration politics, this kind of unabashedly transactional approach is less an outlier than a common feature of contemporary international politics. Drawing in part upon initial findings from our ongoing Diplomacy of Forced Migration Dataset Project, we explore historical and contemporary cases to illustrate how transactional migration management ‘deals’ such as the 2022 UK–Rwanda Migration and Economic Development Partnership are not particularly new, unusual, or revolutionary. In this exploration of the long history of deal-making in the realm of forced migration management, we first define the phenomenon—which we term transactional forced migration (TFM)—and situate it within the growing literature on migration diplomacy, externalization and what is known as the instrumentalization and/or weaponization of migration. We then highlight illustrative historical precedents that presage what we are witnessing today. We additionally identify and unpack several of the under-appreciated connections between TFM schemes and other dimensions of diplomacy and international politics. We conclude with a summary of our argument, its implications for contemporary policy and a few thoughts about what current trends suggest the future is likely to hold.
Respiratory depression driven by membrane damage as a mechanism for linalool to inhibitPseudomonas lundensisand its preservation potential for beef
Authors: He Rongrong , Chen Haiming , Chen Weijun , Zhang Ming , Pei Jianfei , Chen Wenxue , Zhong Qiuping
Published: February 2023

Aims

This study aimed to investigate the mechanism of linalool against Pseudomonas lundensis and its application on beef.

Methods and Results

Field emission scanning electron microscopy found that linalool exerted antibacterial activity with a minimum inhibitory concentration (MIC) of 1.5 ml l−1 by disrupting cell structure. Loss of cell membrane integrity was monitored due to leakage of nucleic acids and K+. In addition, respiratory depression appeared in Ps. lundensis based on inhibition of enzyme activities including hexokinase (HK), glucose 6-phosphate dehydrogenase (G6PDH), phosphofructokinase (PFK), pyruvate kinase (PK), pyruvate dehydrogenase (PDH), citrate synthase (CS), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH). Subsequently, energy limitation also occurred according to the decrease in ATP content and ATPase activity. Molecular docking confirmed that linalool can combine with enzymes in cell wall (ddlB) and energy synthesis (AtpD) pathways to exert antibacterial effect. Of note, linalool has advantages for beef preservation by delaying quality changes including pH, total volatile basic nitrogen (TVB-N) and total viable count (TVC).

Conclusions

Linalool has significant inhibitory effect on Ps. lundensis, and respiratory depression driven by membrane damage is the main inhibitory mechanism.
Differentiation of benign nevoid rests and metastatic melanoma in sentinel lymph node biopsy
Authors: Phillipos Joseph , Khan Afaq , Jayasuriya Neil
Published: February 2023

Patients with cutaneous melanoma routinely undergo sentinel lymph node (SLN) biopsy. If this first lymph node is clear, the entire lymph node basin is very likely to be free from the metastatic disease. Lymph node analysis is therefore of great importance with respect to prognostication and further management. Various cell types, including benign nevoid rests, can mimic metastatic melanomatous cells in the SLN. There is no standardized method to differentiate naevoid rests from metastatic melanoma. Diagnosis is based on cell location, morphology and multiple immunohistochemical techniques, with no single test being completely diagnostic. We present a patient with Lentigo Maligna melanoma, who was found to have benign nevoid rests on SLN biopsy, and discuss the diagnostic tests and considerations in differentiating benign nevoid rests from metastatic melanoma.
Pneumatosis cystoides coli in a patient with stage IV diffuse large B-cell lymphoma
Authors: Sanchez Gabriel Atan , Thompson Andrew Michael
Published: February 2023

A 49-year-old female with a background of stage IV diffuse large B-cell lymphoma and subsequent graft-versus-host disease from a bone marrow transplant presented to a rural hospital in New South Wales, Australia with 12-h history of painless per rectal bleeding and fever. On examination she had a soft, but distended abdomen. Laboratory investigations revealed thrombocytopenia and hypokalaemia. Computed tomography of the abdomen and pelvis had a bizarre appearance due to pneumatosis cystoides coli extending from the ileocaecal junction to the mid-transverse colon. Given her benign abdominal examination, her management was initially supportive with intravenous antibiotics, intravenous fluid resuscitation and correction of electrolyte abnormalities.
Massive effects on chromatin after ploidy rearrangement in doubled haploids
Authors: Mateo-Bonmatí Eduardo
Published: February 2023

This article comments on:

Piskorz EW, Xu L, Ma Y, Jiang H. 2023. Doubled-haploid induction generates extensive differential DNA methylation in Arabidopsis. Journal of Experimental Botany 74, 835–847
A herbaceous species provides insights into drought-driven plant adaptation
Authors: Johnson Kate M , Fletcher Leila R
Published: February 2023

This article comments on:

Thonglim A, Bortolami G, Delzon S, Larter M, Offringa R, Keurentjes JJB, Smets E, Balazadeh S, Lens F. 2023. Drought response in Arabidopsis displays synergistic coordination between stems and leaves. Journal of Experimental Botany 74, 1004–1021
Risk Factors for Cage Migration Following Lateral Lumbar Interbody Fusion Combined with Posterior Instrumentation: A Multicenter Retrospective Study of 983 Cases
Authors: Kimura Hiroaki , Fujibayashi Shunsuke , Otsuki Bungo , Shimizu Takayoshi , Murata Koichi , Takemoto Mitsuru , Odate Seiichi , Shikata Jitsuhiko , Sakamoto Takeshi , Tsutsumi Ryosuke , Ota Masato , Kitaori Toshiyuki , Matsuda Shuichi
Published: February 2023

Study Design.

A multicenter retrospective study.

Objective.

This study aimed to elucidate the incidence and risk factors of lateral cage migration (LCM) after lateral lumbar interbody fusion (LLIF) combined with posterior instrumentation.

Summary of Background Data.

LLIF has recently become a widely accepted procedure for the treatment of lumbar degenerative diseases. Although LLIF complications include vascular, nerve, and abdominal organ injuries, few studies have identified specific risk factors for LCM after LLIF.

Methods.

Between January 2015 and December 2020, 983 patients with lumbar degenerative diseases or osteoporotic vertebral fractures underwent LLIF combined with posterior instrumentation. The fusion sites were located within the lumbosacral lesions. LCM was defined as a change of >3 mm in the movement of the radiopaque marker on radiographs. Patients were classified into LCM and non-LCM groups. The medical records and preoperative radiographs were also reviewed. The 1:5 nearest-neighbor propensity score matching technique was used to compare both groups, and radiological parameters, including preoperative disc height (DH), preoperative sagittal disc angle (SDA), disc geometry, height variance (cage height minus DH), and endplate injury, were analyzed to identify the factors influencing LCM incidence.

Results.

There were 16 patients (1.6%) with LCM (10 men and 6 women; mean age 70.1 y). The Cochran–Armitage trend test showed a linear trend toward an increased rating of LCM with an increasing number of fused segments (P=0.003), and LCM occurred at the terminal cage-inserted disc level in all patients in the LCM group. After propensity-matched analysis, we identified high DH (P<0.001), large SDA (P=0.009), round-type disc (P=0.008), and undersized cage selection (P<0.001) as risk factors for LCM.

Conclusion.

We identified risk factors for LCM after LLIF combined with posterior instrumentation. To avoid this complication, it is important to select the appropriate cage sizes and enhance posterior fixation for at-risk patients.
Combined nutritional and frailty screening improves assessment of short-term prognosis in older adults following percutaneous coronary intervention
Authors: Mangalesh Sridhar , Daniel Kevin Varughese , Dudani Sharmila , Joshi Ajay
Published: February 2023

Background

Frailty and malnutrition are well-known factors influencing outcomes of myocardial infarction (MI) in older adults. Due to considerable overlap between both entities, whether the simultaneous assessment of frailty and nutrition adds nonredundant value to risk assessment is unknown.

Methods

We performed a prospective cohort study on 402 patients aged at least 65 years diagnosed with ST-elevation MI that underwent percutaneous coronary intervention. Nutritional status was assessed by Controlling Nutritional Status score (CONUT), Prognostic Nutritional Index, and Geriatric Nutritional Response Index. Frailty was assessed by Clinical Frailty Scale (CFS), Derby frailty index, and acute frailty network. Primary outcome was major adverse cardiac events (MACE), comprising all-cause mortality, non-fatal MI, and unplanned repeat revascularization during 28-day follow-up. Increment in Global Registry of Acute Coronary Events (GRACE) score performance following the addition of nutrition and frailty was assessed.

Results

The incidence of MACE was 8.02 (6.38–9.95) per 1000 person-days. The CONUT score and CFS were the best predictors of MACE and independent predictors in the multivariate Cox-regression models [hazard ratios, 2.80 (1.54–5.09) and 2.54 (1.50–4.29)]. CONUT score classified 151 (37.6%) patients as malnourished, and CFS classified 131 (32.6%) as frail. The addition of both CONUT and CFS to the GRACE score led to better model discrimination and calibration through improved c-statistic (+0.165) (P< 0.0001) and Akaike and Bayesian information criteria.

Conclusion

Combining CONUT and CFS provides nonredundant prognostic value despite their overlapping nature. Combined nutritional and frailty screening may improve risk prognostication in older adults following MI.
Recent advances in epilepsy surgery
Authors: Medina-Pizarro Mauricio , Spencer Dennis D. , Damisah Eyiyemisi C.
Published: February 2023

Purpose of review

Technological innovations in the preoperative evaluation, surgical techniques and outcome prediction in epilepsy surgery have grown exponentially over the last decade. This review highlights and emphasizes relevant updates in techniques and diagnostic tools, discussing their context within standard practice at comprehensive epilepsy centres.

Recent findings

High-resolution structural imaging has set an unprecedented opportunity to detect previously unrecognized subtle abnormalities. Machine learning and computer science are impacting the methodologies to analyse presurgical and surgical outcome data, building more accurate prediction models to tailor treatment strategies. Robotic-assisted placement of depth electrodes has increased the safety and ability to sample epileptogenic nodes within deep structures, improving our understanding of the seizure networks in drug-resistant epilepsy. The current available minimally invasive techniques are reasonable surgical alternatives to ablate or disrupt epileptogenic regions, although their sustained efficacy is still an active area of research.

Epilepsy surgery is still underutilized worldwide. Every patient who continues with seizures despite adequate trials of two well selected and tolerated antiseizure medications should be evaluated for surgical candidacy. Collaboration between academic epilepsy centres is of paramount importance to answer long-standing questions in epilepsy surgery regarding the understanding of spatio-temporal dynamics in epileptogenic networks and its impact on surgical outcomes.
Brain oscillatory modes as a proxy of stroke recovery
Authors: harquel syvain , Hummel Friedhelm
Published: February 2023

Background: Stroke is the leading cause of long-term disability, making the search for successful rehabilitation treatment one of the most important public health issues. A better understanding of the neural mechanisms underlying impairment and recovery, and the development of associated biomarkers is critical for tailoring treatments with the ultimate goal of maximizing therapeutic outcomes. Here, we studied the longitudinal changes in brain oscillatory modes, linked to GABAergic system activity, and determined their importance for residual upper-limb motor functions and recovery. Methods: Transcranial Magnetic Stimulation (TMS) was combined with multichannel Electroencephalography (EEG) to analyze TMS-induced brain oscillations in a cohort of 66 stroke patients from the acute to the late subacute phase after a stroke. Results: A data-driven parallel factor analysis (PARAFAC) approach to tensor decomposition allowed to detect brain oscillatory modes notably driven by the α frequency band, which evolved longitudinally across stroke stages. Notably, the observed modulations of the α-mode, which is known to be linked with GABAergic system activity, were associated to the extent of motor recovery. Conclusions: Overall, longitudinal evaluation of brain modes provides novel insights into the functional reorganization of brain networks after a stroke and its underlying mechanisms. Notably, we propose that the observed α-mode decrease corresponds to a beneficial disinhibition phase between the early and late subacute stages that fosters structural and functional plasticity and facilitates recovery. Monitoring this phenomenon at the individual patient level will provide critical information for phenotyping patients, developing electrophysiological biomarkers and refining therapies based on personalized excitatory/inhibitory neuromodulation using noninvasive or invasive brain stimulation techniques.
South Africa’s male homicide epidemic hiding in plain sight: exploring sex differences and patterns in homicide risk in a retrospective descriptive study of postmortem investigations
Authors: Matzopoulos R , Prinsloo M , Mhlongo S , Marineau L , Cornell M , Bowman B , Mamashela TA , Gwebushe N , Ketelo A , Martin LJ , Dekel B , Lombard C , Jewkes R , Abrahams N
Published: February 2023

Background

South Africa has homicide rates six times the global average, predominantly among men, but little is known about male victims. As part of the country’s first ever study of male homicide we compared 2017 male and female victim profiles for selected covariates, against global averages and previous estimates for 2009.

Methods

We conducted a retrospective descriptive study of routine data collected through postmortem investigations, calculating age-standardised mortality rates for manner of death by age, sex and province and male-to-female incidence rate ratios with 95% confidence intervals. We then used generalised linear models and linear regression models to assess the association between sex and victim characteristics including age and mechanism of injury (guns, stabs and blunt force) within and between years.

Findings

87% of 19,477 homicides in 2017 were males, equating to seven male deaths for every female, with sharp force and firearm discharge the most common external causes. Rates were higher among males than females at all ages, and up to eight times higher among males aged 15-44 years. Provincial rates varied overall and by sex, with the highest comparative risk for men vs. women in the Western Cape Province (11.4 males for every 1 female). Male homicides peaked during December and were highest on weekends, underscoring the prominent role of alcohol as a risk factor. Significantly more males tested positive for alcohol than females.

Interpretation

The massive, disproportionate and enduring homicide risk borne by adult South African men highlights the negligible prevention response. Only through challenging the normative perception of male invulnerability can we begin to address the enormous burden of violence impacting men. There is an urgent need to address the insidious effect of such societal norms alongside implementing structural interventions to overcome the root causes of poverty and inequality and better control alcohol and firearms.

Funding

South African Medical Research Council and Ford Foundation.
Optimized testing strategy for the diagnosis of GAA-FGF14ataxia
Authors: Bonnet Céline , Pellerin David , Roth Virginie , Clément Guillemette , Wandzel Marion , Lambert Laëtitia , Frismand Solène , Douarinou Marian , Grosset Anais , Bekkour Ines , Weber Frédéric , Girardier Florent , Robin Clément , Cacciatore Stéphanie , Bronner Myriam , Pourié Carine , Dreumont Natacha , Puisieux Salomé , Dicaire Marie-Josée , Evoy François , Rioux Marie-France , Hocquel Armand , La Piana Roberta , Synofzik Matthis , Houlden Henry , Danzi Matt C. , Zuchner Stephan , Brais Bernard , Renaud Mathilde
Published: February 2023

Background

Dominantly inherited GAA repeat expansions inFGF14are a common cause of spinocerebellar ataxia (GAA-FGF14ataxia; SCA27B, late-onset). Molecular confirmation ofFGF14GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories.

Methods

We developed and validated a strategy to detectFGF14GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing. We compared this strategy to targeted nanopore sequencing in a cohort of 22 French Canadian patients and next validated it in a cohort of 53 French index patients with unsolved ataxia.

Results

Diagnosis was accurately confirmed for all 22 French Canadian patients using this strategy. Method comparison showed that capillary electrophoresis of long-range PCR products significantly underestimated expansion sizes compared to nanopore sequencing (slope, 0.87 [95% CI, 0.81 to 0.93]; intercept, 14.58 [95% CI, -2.48 to 31.12]) and gel electrophoresis (slope, 0.84 [95% CI, 0.78 to 0.97]; intercept, 21.34 [95% CI, -27.66 to 40.22]). The latter techniques yielded similar size estimates. Following calibration with internal controls, expansion size estimates were similar between capillary electrophoresis and nanopore sequencing (slope: 0.98 [95% CI, 0.92 to 1.04]; intercept: 10.62 [95% CI, -7.49 to 27.71]), and gel electrophoresis (slope: 0.94 [95% CI, 0.88 to 1.09]; intercept: 18.81 [95% CI, -41.93 to 39.15]). We identified 9 French patients (9/53; 17%) and 2 of their relatives who carried anFGF14(GAA)≥250expansion.

Conclusion

This novel strategy reliably detected and sizedFGF14GAA expansions. It compared favorably to long-read sequencing and can readily be implemented in clinical laboratories.
Machine learning assisted discovery of synergistic interactions between environmental pesticides, phthalates, phenols, and trace elements in child neurodevelopment
Authors: Midya Vishal , Alcala Cecilia Sara , Rechtman Elza , Hertz-Picciotto Irva , Gennings Chris , Rosa Maria , Valvi Damaskini
Published: February 2023

A growing body of literature suggests that higher developmental exposure to individual or mixtures of environmental chemicals (ECs) is associated with autism spectrum disorder (ASD). However, the effect of interactions among these ECs is challenging to study. We introduced a composition of the classical exposure-mixture Weighted Quantile Sum (WQS) regression, and a machine-learning method called signed iterative random forest (SiRF) to discover synergistic interactions between ECs that are (1) associated with higher odds of ASD diagnosis, (2) mimic toxicological interactions, and (3) are present only in a subset of the sample whose chemical concentrations are higher than certain thresholds. In the case-control Childhood Autism Risks from Genetics and Environment study, we evaluated multi-ordered synergistic interactions among 62 ECs measured in the urine samples of 479 children in association with increased odds for ASD diagnosis (yes vs. no). WQS-SiRF discovered two synergistic two-ordered interactions between (1) trace-element cadmium(Cd) and alkyl-phosphate pesticide - diethyl-phosphate(DEP); and (2) 2,4,6-trichlorophenol(TCP-246) and DEP metabolites. Both interactions were suggestively associated with increased odds of ASD diagnosis in a subset of children with urinary concentrations of Cd, DEP, and TCP-246 above the 75thpercentile. This study demonstrates a novel method that combines the inferential power of WQS and the predictive accuracy of machine-learning algorithms to discover interpretable EC interactions associated with ASD.

Synopsis

The effect of interactions among environmental chemicals on autism spectrum disorder (ASD) diagnosis is challenging to study. We used a combination of Weighted Quantile Sum regression and machine-learning tools to study multi-ordered synergistic interactions between environmental chemicals associated with higher odds of ASD diagnosis.

Graphical Abstract
Subnational HIV incidence trends in Malawi: large, heterogeneous declines across space
Authors: Wolock Timothy M , Flaxman Seth , Chimpandule Tiwonge , Mbiriyawanda Stone , Jahn Andreas , Nyirenda Rose , Eaton Jeffrey W
Published: February 2023

The rate of new HIV infections globally has decreased substantially from its peak in the late 1990s, but the epidemic persists and remains highest in many countries in eastern and southern Africa. Previous research hypothesised that, as the epidemic recedes, it will become increasingly concentrated among sub-populations and geographic areas where transmission is the highest and that are least effectively reached by treatment and prevention services. However, empirical data on subnational HIV incidence trends is sparse, and the local transmission rates in the context of effective treatment scale-up are unknown. In this work, we developed a novel Bayesian spatio-temporal epidemic model to estimate adult HIV prevalence, incidence and treatment coverage at the district level in Malawi from 2010 through the end of 2021. We found that HIV incidence decreased in every district of Malawi between 2010 and 2021 but the rate of decline varied by area. National-level treatment coverage more than tripled between 2010 and 2021 and more than doubled in every district. Large increases in treatment coverage were associated with declines in HIV transmission, with 12 districts having incidence-prevalence ratios of 0.03 or less (a previously suggested threshold for epidemic control). Across districts, incidence varied more than HIV prevalence and ART coverage, suggesting that the epidemic is becoming increasingly spatially concentrated. Our results highlight the success of the Malawi HIV treatment programme over the past decade, with large improvements in treatment coverage leading to commensurate declines in incidence. More broadly, we demonstrate the utility of spatially resolved HIV modelling in generalized epidemic settings. By estimating temporal changes in key epidemic indicators at a relatively fine spatial resolution, we were able to directly assess, for the first time, whether the ART scaleup in Malawi resulted in spatial gaps or hotspots. Regular use of this type of analysis will allow HIV program managers to monitor the equity of their treatment and prevention programmes and their subnational progress towards epidemic control.
Pre-existing autoimmunity is associated with increased severity of COVID-19: A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C)
Authors: Yadaw Arjun S. , Afzali Behdad , Hotaling Nathan , Sidky Hythem , Pfaff Emily R , Sahner David K. , Mathé Ewy A.
Published: February 2023

Importance

Identifying individuals with a higher risk of developing severe COVID-19 outcomes will inform targeted or more intensive clinical monitoring and management.

Objective

To examine, using data from the National COVID Cohort Collaborative (N3C), whether patients with pre-existing autoimmune disease (AID) diagnosis and/or immunosuppressant (IS) exposure are at a higher risk of developing severe COVID-19 outcomes.

Design, setting and participants

A retrospective cohort of 2,453,799 individuals diagnosed with COVID-19 between January 1st, 2020, and June 30th, 2022, was created from the N3C data enclave, which comprises data of 15,231,849 patients from 75 USA data partners. Patients were stratified as those with/without a pre-existing diagnosis of AID and/or those with/without exposure to IS prior to COVID-19.

Main outcomes and measures

Two outcomes of COVID-19 severity, derived from the World Health Organization severity score, were defined, namely life-threatening disease and hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression models with and without adjustment for demographics (age, BMI, gender, race, ethnicity, smoking status), and comorbidities (cardiovascular disease, dementia, pulmonary disease, liver disease, type 2 diabetes mellitus, kidney disease, cancer, and HIV infection).

Results

In total, 2,453,799 (16.11% of the N3C cohort) adults (age> 18 years) were diagnosed with COVID-19, of which 191,520 (7.81%) had a prior AID diagnosis, and 278,095 (11.33%) had a prior IS exposure. Logistic regression models adjusted for demographic factors and comorbidities demonstrated that individuals with a prior AID (OR = 1.13, 95% CI 1.09 - 1.17;p=2.43E-13), prior exposure to IS (OR= 1.27, 95% CI 1.24 - 1.30;p=3.66E-74), or both (OR= 1.35, 95% CI 1.29 - 1.40;p=7.50E-49) were more likely to have a life-threatening COVID-19 disease. These results were confirmed after adjusting for exposure to antivirals and vaccination in a cohort subset with COVID-19 diagnosis dates after December 2021 (AID OR = 1.18, 95% CI 1.02 - 1.36;p=2.46E-02; IS OR= 1.60, 95% CI 1.41 - 1.80;p=5.11E-14; AID+IS OR= 1.93, 95% CI 1.62 - 2.30;p=1.68E-13). These results were consistent when evaluating hospitalization as the outcome and also when stratifying by race and sex. Finally, a sensitivity analysis evaluating specific IS revealed that TNF inhibitors were protective against life-threatening disease (OR = 0.80, 95% CI 0.66-0.96;p=1.66E-2) and hospitalization (OR = 0.80, 95% CI 0.73 - 0.89;p=1.06E-05).

Conclusions and Relevance

Patients with pre-existing AID, exposure to IS, or both are more likely to have a life-threatening disease or hospitalization. These patients may thus require tailored monitoring and preventative measures to minimize negative consequences of COVID-19.
Membranous Nephropathy in the UK Biobank
Authors: Hamilton Patrick , Blaikie Kieran , Roberts Stephen A. , Gittins Matthew , Downie Mallory L. , Gupta Sanjana , Voinescu Catalin , Kanigicherla Durga , Stanescu Horia , Kleta Robert , Brenchley Paul
Published: February 2023

Background

Despite MN being one of the most common causes of nephrotic syndrome worldwide, its biological and environmental determinants are poorly understood in large-part due to it being a rare disease. Making use of the UK Biobank, a unique resource holding a clinical dataset and stored DNA, serum and urine for ∼500,000 participants, this study aims to address this gap in understanding.

Methods

The primary outcome was putative MN as defined by ICD-10 codes occurring in the UK Biobank. Univariate relative risk regression modelling was used to assess the associations between the incidence of MN and related phenotypes with sociodemographic, environmental exposures, and previously described increased-risk SNPs.

Results

502,507 patients were included in the study of whom 100 were found to have a putative diagnosis of MN; 36 at baseline and 64 during the follow-up. Prevalence at baseline and last follow-up were 72 and 199 cases/million respectively. At baseline, as expected, the majority of those previously diagnosed with MN had proteinuria, and there was already evidence of proteinuria in patients diagnosed within the first 5 years of follow-up. The highest incidence rate for MN in patients was seen in those homozygous for the high-risk alleles (9.9/100,000 person-years).

Conclusion

It is feasible to putatively identify patients with MN in the UK Biobank and cases are still accumulating. This study shows the chronicity of disease with proteinuria present years before diagnosis. Genetics plays an important role in disease pathogenesis, with the at-risk group providing a potential population for recall.