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Plyometric training is one commonly used method of improving jump performance through improving explosive power generation. Research has also demonstrated that whole body vibration (WBV) can improve jumping and enhance explosive strength especially when supplementing resistance and plyometric training programs. With the drop jump being a common training skill, proper lower extremity landing mechanics are important to consider. Limited evidence suggests that WBV may reduce ground reaction forces and improve knee stability however, its influence on knee loading have not been reported. This study sought to examine the effects of WBV on ground reaction forces and knee valgus during a drop jump. 19 participants (10 female) completed drop jumps pre, immediately post, 10 & 20 minutes post WBV. Results were analyzed by repeated measures ANOVA. Main findings indicated that valgus knee angle increased significantly (p=0.011) post vibration and remained elevated across the 10 & 20 minute post vibration time intervals. Significant differences between sexes revealed that females demonstrated greater internal knee abduction moments (p=0.038). Findings that WBV increases knee valgus angle, a position linked to anterior cruciate ligament injury, suggest further investigation understand the effects of WBV on neuromuscular control and eccentric loading. Strength and conditioning professionals should exercise caution when incorporating WBV into plyometric protocols.

BackgroundIn low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can characterise the scale and determinants of the pandemic, as well as elucidate protection conferred by prior exposure.MethodsWe conducted repeated cross-sectional serosurveys (July 2020 – November 2021) using residual plasma from routine convenient blood samples from patients with non-COVID-19 conditions from Cape Town, South Africa. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses, to estimate variant disease severity.FindingsAmong the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2% in July 2020 to 67.8% in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35).InterpretationThe high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19.FundingWellcome Trust, National Health Laboratory Service, the Division of Intramural Research, NIAID, NIH (ADR) and Western Cape Government Health.Research in contextEvidence before this studyIn low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can help describe the true extent of the pandemic.Infection from Omicron was associated with less severe disease in South Africa, but it is unclear whether this was due to a decrease in virulence of the variant or if prior infection provided protection.Added value of this studyThe seroprevalence data nested within a population cohort enabled us to assess differential case ascertainment rates, as well as to examine the contribution of both natural and vaccine-induced immunity in protecting communities against infections and severe disease with different SARS-CoV-2 variants.Implications of the available evidenceInequality and differential access to resources resulted in poorer communities having higher seroprevalence and COVID-19 death rates, with lower case ascertainment rates. Antibody positivity provided strong protection against an immune escape variant like Omicron but came at a high mortality cost.

The worldwide introduction of English as a medium of instruction (EMI) programmes has stimulated numerous reflections within and outside academia. These reflections find their expression in both scholarly studies into EMI and public debates about its impact. In this article we argue that one can distinguish two types of reflections about EMI. The first type focuses on improving EMI. The second type focuses on the legitimation of EMI, that is whether EMI programmes are justified in view of their assumptions and consequences. We investigate the genesis and the differences between two separate discourses that express the different types of reflections. We unfold a history that shows that roughly three phases can be distinguished in the development of EMI: the incubation of EMI, its consolidation and its politicisation. We argue that the heuristic value of the two types of reflection is that they are conducive to comprehending this development of EMI and look at it with critical eyes. In addition, we suggest that politicised issues like the impact of Englishization on the cultural identity, language hierarchies, top-down implementations of language policies and the inequalities regarding the access to EMI programmes might be fruitfully addressed in terms of linguistic justice and democracy. By distinguishing two types of reflection, blind spots in EMI research can be revealed.

BackgroundSingle-cell sequencing studies have elucidated some of the underlying mechanisms responsible for immune checkpoint inhibitor (ICI) response, but are difficult to implement as a general strategy or in a clinical diagnostic setting. In contrast, bulk RNAseq is now routine for both research and clinical applications. Therefore, our analysis extracts small transcription factor-directed co-expression networks (regulons) from single-cell RNA-seq data and uses them to deconvolute immune functional states from bulk RNA-seq data to characterize patient responses.MethodsRegulons were inferred in pre-treatment CD45+ cells from metastatic melanoma samples (n=19) treated with first-line ICI therapy (discovery dataset). A logistic regression-based classifier identified immune cell states associated with response, which were characterized according to differentially active, cell-state specific regulons. The complexity of these regulons was reduced and scored in bulk RNAseq melanoma samples from four independent studies (n=209, validation dataset). Patients were clustered according to their regulon scores, and the associations between cluster assignment, response, and survival were determined. Intercellular communication analysis of cell states was performed, and the resulting effector genes were analyzed by trajectory inference.ResultsRegulons preserved the information of gene expression data and accurately delineated immune cell phenotypes, despite reducing dimensionality by > 100-fold. Four cell states, termed exhausted T cells, monocyte lineage cells, memory T cells, and B cells, were associated with therapeutic responses in the discovery dataset. The cell states were characterized by seven differentially active and specific regulons that showed low specificity in non-immune cells. Four clusters with significantly different response outcomes (P ConclusionsRegulon-based characterization of cell states provides robust and functionally informative markers that can deconvolve bulk RNA-seq data to identify ICI responders.

ObjectivesTuberculosis (TB) remains prevalent despite the availability of effective anti-TB medications, and accumulating evidence suggests a high rate of mental disorders in people with TB. This is because TB and psychiatric disorders share several risk factors, such as poverty, homelessness and substance use disorder. Moreover, psychiatric comorbidities in patients with TB are associated with poor treatment outcomes. This study explored the psychiatric comorbidity and clinical correlates in individuals receiving TB treatment.DesignA cross-sectional survey over 10 months.SettingTwo primary care clinics at King Sabata Dalindyebo district, Mthatha, Eastern Cape, South Africa.ParticipantPatients receiving TB treatment in the two clinics.InterventionThe Mini-International Neuropsychiatric Interview was used to screen for psychiatric disorders.Primary and secondary outcome measuresRates of mental disorders in patients with TB over a 10-month period. Variation in rates by sex, employment status and HIV comorbidity.ResultsIn a sample of 197 participants, most patients were men (62%) and screened positive for a mental disorder (82%) with anxiety (48%), depression (38%) and substance use disorders (43%) being the most common psychiatric conditions. On average, individuals had 4 (SD 2) mental disorders. Females had higher rates of depression (p=0.005) and non-adherence to TB treatment (p=0.003), and alcohol use disorder was more common in males (pConclusionsMental disorders are common in patients with TB, and mental health services need to be integrated into the management of patients with TB. Factors linked to mental disorders in this cohort, such as low education, gender and unemployment, may be useful for compiling a risk profile to help identify those with TB who may require more intensive support for their mental health.

Objective The aims of this study were to describe pediatric emergency department (ED) referrals from urgent care centers and to determine the percentage of referrals considered essential and serious. Methods A prospective study was conducted between April 2013 and April 2015 on patients younger than 21 years referred directly to an ED in central Pennsylvania from surrounding urgent care centers. Referrals were considered essential or serious based on investigations/procedures performed or medications/consultations received in the ED. Results Analysis was performed on 455 patient encounters (mean age, 8.7 y), with 347 (76%) considered essential and 40 (9%) considered serious. The most common chief complaints were abdominal pain (83 encounters), extremity injury (76), fever (39), cough/cold (29), and head/neck injury (29). Thirty-three percent of the patients received laboratory diagnostic investigations (74% serum, 56% urine), and 52% received radiologic investigations (67% x-ray, 17% computed tomography scan, 13% ultrasound, 11% magnetic resonance imaging). Forty-four percent of the patients received a procedure, with the most common being intravenous (IV) placement (66%); reduction, casting, or splinting of extremity fracture/dislocation (18%); and laceration repair (14%). The most common medications administered were IV fluids (33%), oral analgesics (30%), and IV analgesics (26%). Eighty-three percent of the patients were discharged home, 12% were hospitalized, and 4% had emergent surgical intervention. The most common primary diagnoses were closed extremity fracture (60 encounters), gastroenteritis (42), brain concussion (28), upper respiratory infection (24), and nonsurgical, unspecified abdominal pain (24). Conclusions Many ED referrals directed from urgent care centers in our sample were considered essential, and few were considered serious. Urgent care centers should develop educational and preparedness strategies based on the epidemiology of emergencies that may occur.

We present a case of cytokine release syndrome (CRS) that occurred five days after vaccination with BTN162b2 (tozinameran), an mRNA COVID-19 vaccine, in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-y/IL-2R/IL-18/IL-16/IL-10), and steroid responsiveness.

The introduction of English as a medium of instruction (EMI) has changed higher education enormously in many European countries. This development is increasingly encapsulated under the term Englishization, that is, the increasing dispersion of English as a means of communication in non-Anglophone contexts. Englishization is not undisputed: legal challenges have arisen in several countries. Nor is it uniform; universities across Europe embrace Englishization, but they do so in their own way. In this volume, authors from 15 European countries present analyses from a range of perspectives coalescing around core concerns: the quality of education, cultural identity, inequality of opportunities and access, questions of justice and democracy, and internationalization and language policy. This book will appeal to researchers in applied linguistics, sociolinguistics, educational sciences, and political science, as well as policy makers and people with a concern about the direction of higher education.

The tension between monolingualism and multilingualism has left its mark on the cultural history of Europe. Current public and academic debates about the Englishization of higher education pitch proponents of the monolingual ideal of a common language that promotes communication against advocates of the maintenance of linguistic diversity that does more justice to the multicultural reality and enriches life. Notwithstanding the differences between European countries, the switch from an initially monolingual curriculum to a bilingual and sometimes multilingual curriculum in higher education has led to debates about the consequences of the Englishization for the quality of higher education, cultural identity, inequality between stakeholders and the opportunities to express concern about this process.

Centre for Infectious Diseases Research in Africa;4UCT Medical Imaging Research Unit, Division of Bio- medical Engineering, UCT, RSA;5Cape Universities Body Imaging Centre, UCT and Neuroscience Institute, University of Cape Town, RSA;6Department of Medicine, Imperial College London1H-Magnetic Resonance Spectroscopy (MRS) allows non-invasive quantification of the biochemical com- position of imaged tissue in a single voxel within the brain; including concentrations of the neuroinhibitory and neuroexcitatory metabolites, GABA and glutamate. Excessive glutamate and neuro-excitotoxicity contribute to pathogenesis in tuberculous meningitis (TBM)[1], and like in other neurological conditions[2] may lead to cell death and brain injury. We hypothesised that glutamate would be raised and GABA decreased, in TBM vs healthy controls (HC). 11 patients with TBM, and 8 HC underwent 3-T MRI imaging at the University of Cape Town, South Africa, at two timepoints (baseline, day-56). We used MEGA-PRESS spectroscopy and GANNET software[3] to estimate metabolite concentrations in a voxel placed within the ‘tubercular zone’. Glutamate at baseline was significantly higher in TBM vs HC (15.9 vs 12.2 IU, p=0.042). This decreased by day-56, although did not return to levels seen in HC, suggesting ongoing neuro-excitation in the post-acute phase. By contrast, at baseline GABA was non-significantly decreased in TBM vs HC (3.79 vs4.02 IU, p=0.5). These findings provide further rationale for the investigation of glutamate/GABA as brain injury pathways and potential drug targets in TBM.1. Rohlwink, U.K., et al., Nat Commun, 2019. 10(1): p. 3767 2. Meldrum, B.S., J Nutr, 2000. 130(4S Suppl): p. 1007S-15S. 3. Edden, R.A., et al., J Magn Reson Imaging, 2014. 40(6): p. 1445–52.angharadgracedavis@gmail.com

As the capacity for generating large scale data continues to grow the ability to extract meaningful biological knowledge from it remains a limitation. Here we describe the development of a new fixed repertoire of transcriptional modules. It is meant to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome profiling data. It is supported by customized resources, which include analysis workflows, fingerprint grid plots data visualizations, interactive web applications. These provide access to a vast number of module-specific functional profiling reports, reference transcriptional profiles, and give users the ability to visualize changes in transcript abundance across the modular repertoire at different granularity levels. A use case focusing on a set of six modules comprising interferon-inducible genes is also provided. Taken together, this well-characterized set of modules may be employed for the interpretation and benchmarking of blood transcriptome profiles obtained within and across patient cohorts.

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), accounting for around 1-5% of the global TB caseload, with mortality of approximately 20% in children and up to 60% in persons co-infected with human immunodeficiency virus even in those treated. Relatively few centres of excellence in TBM research exist and the field would therefore benefit from greater co-ordination, advocacy, collaboration and early data sharing. To this end, in 2009, 2015 and 2019 we convened the TBM International Research Consortium, bringing together approximately 50 researchers from five continents. The most recent meeting took place on 1stand 2ndMarch 2019 in Lucknow, India. During the meeting, researchers and clinicians presented updates in their areas of expertise, and additionally presented on the knowledge gaps and research priorities in that field. Discussion during the meeting was followed by the development, by a core writing group, of a synthesis of knowledge gaps and research priorities within seven domains, namely epidemiology, pathogenesis, diagnosis, antimicrobial therapy, host-directed therapy, critical care and implementation science. These were circulated to the whole consortium for written input and feedback. Further cycles of discussion between the writing group took place to arrive at a consensus series of priorities. This article summarises the consensus reached by the consortium concerning the unmet needs and priorities for future research for this neglected and often fatal disease.

Tuberculous meningitis is the most severe form of tuberculosis and causes widespread mortality and morbidity. Understanding of the epidemiology and pathogenesis is incomplete, and the optimal diagnosis and treatment are poorly defined. To generate research collaboration and coordination, as well as to promote sharing of ideas and advocacy efforts, the International Tuberculous Meningitis Research Consortium was formed in 2009. During the most recent meeting of this group in Lucknow, India, in March 2019, the Consortium decided to bring together key articles on tuberculous meningitis in one supplement. The supplement covers recent scientific updates, expert perspectives on specific clinical challenges, consensus statements on how to conduct research, and a set of priorities for future investigation.

The delayed diagnosis of tuberculous meningitis (TBM) leads to poor outcomes, yet the current diagnostic methods for identifying Mycobacterium tuberculosis in cerebrospinal fluid (CSF) are inadequate. The first comparative study of the new GeneXpert MTB/RIF Ultra (Xpert Ultra) for TBM diagnosis suggested increased sensitivity of Xpert Ultra. Two subsequent studies have shown Xpert Ultra has improved sensitivity, but has insufficient negative predictive value to exclude TBM. Collecting and processing large volumes of CSF for mycobacterial testing are important for optimal diagnostic test performance. But clinical, radiological, and laboratory parameters remain essential for TBM diagnosis and empiric therapy is often needed. We therefore caution against the use of Xpert Ultra as a single diagnostic test for TBM; it cannot be used to “rule out” TBM., Xpert Ultra may be superior to Xpert for detecting Mycobacterium tuberculosis in cerebrospinal fluid. However, Xpert Ultra has insufficient negative predictive value to exclude Tuberculous Meningitis (TBM). We caution against using Xpert Ultra as a single diagnostic test for TBM.

This chapter investigates plurilingual students’ perceptions in English-medium instruction (EMI) programmes. It reports a study into the language perceptions of plurilingual students (n = 140) from different bachelor’s degree programmes at a Dutch university which is officially bilingual. The quantitative questionnaire (valid response 105) probed the students’ perceptions of educational democracy and linguistic justice, according to gender, plurilingualism and their degree programme. Little research has been done into how students perceive issues related to these two constructs. The research results reveal scarcely no effect of plurilingualism, but there are some significant gender and degree programme effects. The discussion suggests that not only may the university and the degree programmes be neglecting the students’ linguistic repertoires, but that plurilingual students may also be discounting their own plurilingual competences.

This paper reflects on the contributions to this special issue, which offers a timely insight into research trends on the integration of content and language in higher education. The principle focus of the papers lies on the effects of English as the instructional language, in line with the professional activity of the authors. The papers amplify several trends in English-medium instruction (EMI) research: collaboration, identity, and teacher training. In a world where both students and teachers are increasingly transient, the studies serve to identify ways of promoting effective learning among students with differential language constellations, including language minority students, so that speakers from specific language groups are not marginalized or excluded.

Despite the enormous expansion of EMI research, the potential of students' multilingualism remains unacknowledged. The challenge is not to neglect this multilingualism that includes the different languages students master and their access to language-related knowledge resources. Therefore, this study aimed to unravel students' multilingualism as a resource. It explores the range of language competences in three consecutive cohorts of EMI students at a Dutch university (total 342). Using a questionnaire and focus groups, the study reveals respondents speaking at least two or three additional languages. Reported competence is high in L1 and L2, but declines sharply in L3, L4 and L5. Results suggest scope for additional language learning and sufficient potential for expanding additional language use in EMI programmes. The challenge is to incorporate multilingualism in EMI. Students’ linguistic repertoires have the potential to convey knowledge to speakers of a specific language and elaborate nuances that many English L2 speakers report missing in English-only programmes. This might improve the quality of education. However, the multilingual challenge in EMI confronts the paradox that the more a cohort becomes linguistically and culturally diverse, the greater the pressures to converge on a single medium of communication.