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Neonatal patients with melioidosis: a systematic review
Get PDFBackground: Melioidosis is a neglected, but increasingly prevalent, tropical disease. Whilst rare in neonates, it has been associated with high mortality in this population. Despite this, little work focusing on neonatal melioidosis has been undertaken. Here, we report the first PRISMA-compliant systematic review exploring the clinical characteristics of culture- confirmed melioidosis in neonates. Method: We searched several databases, including Web of Science, WHO Global Index, Scopus and Ovid, for primary studies reporting a case of neonatal melioidosis. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) tool and the Oxford Levels of Evidence. 50 neonatal cases were identified across 24 publications. Of these, 26 cases from 19 papers were reported in sufficient detail to enable analysis. Results: All studies identified were of poor quality, and largely consisted of case reports, with little uniformity in study reporting. However, the cases typically occurred in the early neonatal period, presented with symptoms atypical of melioidosis in other populations and showed a high mortality rate of over 65%. Importantly, instances of vertical transmission were identified, which is likely under-recognized and under-reported. Conclusions: This review demonstrates substantial need for further work to build the evidence base surrounding this neglected pathology. Despite this, we identified a number of features of the disease in this population that may inform diagnosis and management. We also note several common barriers preventing effective treatment, including lack of a rapid diagnostic testing, lack of clinician awareness and high levels of antibiotic resistance
Non-commutative L p spaces and Grassmann stochastic analysis: Non-commutative L p spaces..
Get PDFWe introduce a theory of non-commutative Lp spaces suitable for non-commutative probability in a non-tracial setting and use it to develop stochastic analysis of Grassmann-valued processes, including martingale inequalities, stochastic integrals with respect to Itô–Grassmann processes, Girsanov’s formula and a weak formulation of Grassmann SDEs. We apply this new setting to the construction of several unbounded random variables including a Grassmann analog of the Φ24 Euclidean QFT in a bounded region and weak solution to singular SPDEs in the spirit of the early work of Jona-Lasinio and Mitter on the stochastic quantisation of Φ24
Measurements of WH and ZH production with Higgs boson decays into bottom quarks and direct constraints on the charm Yukawa coupling in 13 TeV pp collisions with the ATLAS detector
Get PDFA study of the Higgs boson decaying into bottom quarks (H → bb¯) and charm quarks (H → cc¯) is performed, in the associated production channel of the Higgs boson with a W or Z boson, using 140 fb−1 of proton-proton collision data at s = 13 TeV collected by the ATLAS detector. The individual production of WH and ZH with H → bb¯ is established with observed (expected) significances of 5.3 (5.5) and 4.9 (5.6) standard deviations, respectively. Differential cross-section measurements of the gauge boson transverse momentum within the simplified template cross-section framework are performed in a total of 13 kinematical fiducial regions. The search for the H → cc¯ decay yields an observed (expected) upper limit at 95% confidence level of 11.5 (10.6) times the Standard Model prediction. The results are also used to set constraints on the charm coupling modifier, resulting in |κc| < 4.2 at 95% confidence level. Combining the H → bb¯ and H → cc¯ measurements constrains the absolute value of the ratio of Higgs-charm and Higgs-bottom coupling modifiers (|κc/κb|) to be less than 3.6 at 95% confidence level
Inequality Measurement for Bounded Variables
Get PDFMany health indicators are bounded, that is, their values lie between a lower and an upper bound. Inequality measurement with bounded variables faces two normative challenges well‐known in the health inequality literature. One is that inequality rankings may or may not be consistent across admissible attainment and shortfall representations of the variable. The other is that the set of maximum‐inequality distributions for bounded variables is different from the respective set for variables with no upper bound. Therefore, the ethical criteria for ranking maximum‐inequality distributions with unbounded variables may not be appropriate for bounded variables. In a novel proposal, we justify an axiom requiring maximum‐inequality distributions of bounded variables to be ranked equally, irrespective of their means. Then, our axiomatic characterization naturally leads to indices that measure inequality as an increasing function of the observed proportion of maximum attainable inequality for a given mean. Additionally, our inequality indices rank distributions consistently when switching between attainment and shortfall representations. In our empirical illustration with three health indicators, a starkly different picture of cross‐country inter‐temporal inequality emerges when traditional inequality indices give way to our proposed normalized inequality indices
Plasmodium falciparum infection induces T cell tolerance that is associated with decreased disease severity upon re-infection
Get PDFImmunity to severe malaria is acquired quickly, operates independently of pathogen load, and represents a highly effective form of disease tolerance. The mechanism that underpins tolerance remains unknown. We used a human rechallenge model of falciparum malaria in which healthy adult volunteers were infected three times over a 12 mo period to track the development of disease tolerance in real-time. We found that parasitemia triggered a hardwired innate immune response that led to systemic inflammation, pyrexia, and hallmark symptoms of clinical malaria across the first three infections of life. In contrast, a single infection was sufficient to reprogram T cell activation and reduce the number and diversity of effector cells upon rechallenge. Crucially, this did not silence stem-like memory cells but instead prevented the generation of cytotoxic effectors associated with autoinflammatory disease. Tolerized hosts were thus able to prevent collateral tissue damage in the absence of antiparasite immunity
Astrocytic RNA editing regulates the host immune response to alpha-synuclein
Get PDFRNA editing is a posttranscriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte-specific, ADAR1-mediated RNA editing in neuroinflammation in Parkinson's disease (PD). We generated human induced pluripotent stem cell-derived astrocytes, neurons and cocultures and exposed them to small soluble alpha-synuclein aggregates. Oligomeric alpha-synuclein triggered an inflammatory glial state associated with Toll-like receptor activation, viral responses, and cytokine secretion. This reactive state resulted in loss of neurosupportive functions and the induction of neuronal toxicity. Notably, interferon response pathways were activated leading to up-regulation and isoform switching of the RNA deaminase enzyme, ADAR1. ADAR1 mediates A-to-I RNA editing, and increases in RNA editing were observed in inflammatory pathways in cells, as well as in postmortem human PD brain. Aberrant, or dysregulated, ADAR1 responses and RNA editing may lead to sustained inflammatory reactive states in astrocytes triggered by alpha-synuclein aggregation, and this may drive the neuroinflammatory cascade in Parkinson's
Emerging forms of life from muddy ruins: an ethnography about care and violence: Emerging forms of life from muddy ruins
Get PDFThis thesis discusses emerging forms of life in Petrópolis, Brazil. In specific, this study delves on how people care for life amidst recurring socioenvironmental disasters, and the processes of 'becoming-with' through which embodied subjectivities, more-than-human socialities, and landscapes take shape. Through ten weeks of ethnographic fieldwork, I engaged with activists, governmental workers, dwellers, and policymakers, tracing the emerging forms of life in its shifting landscapes, seasonally trespassed by floods and landslides. I paid particular attention to the diversity of care work practices that unfold in this context, recognizing that these extend beyond formal institutions and may become embedded in people's daily lives, as part of their ongoing struggles to survive. I approach these practices as situated efforts that often have to grapple with moral dilemmas, navigate conflicting temporal-spatialities, and work within systems that are themselves sources of exclusion and harm. This study is situated within the broader framework of more-than-human anthropology and critical place inquiry, and aims to contribute to understanding how violence reverberates across time, space and matter, producing material and immaterial traces in people's lives and landscapes. In order to break away from a 'damage-centered' perspective, that tends to depict certain groups as being solely defined by subjection to injustice and marginalization, this study undertakes a temporal reorientation of knowledge, paying attention to how pain and desire might become intertwined. Through a life-affirming writing, this research seeks to apprehend the processes through which people grapple with destruction, uncertainty and precarity, reconfiguring their relationships with the world and with one another
Translating historical trans life-writing: Aleksandr Aleksandrov (1783-1866)
Get PDFThis essay presents our reflections on translating historical trans life-writing into English as collaborative work. It is based on our conversations over the last three years, comparing our positionalities and skill sets as educators, activists (Cheryl) and scholars (Margarita). Specifically, it discusses our work on translating biographical narratives by and about a Russian-Ukrainian hero of the Napoleonic wars and celebrated trans author Aleksandr Aleksandrov (Nadezhda Durova) (1783-1866). In contrast to the emancipatory theoretical impetus of Anglophone trans studies, translation into English is invariably constrained by the language's grammatical limitations in expressing gender. As a result, translating trans biographies into English, creates specific challenges when working with texts originally written in more gendered languages. In this essay, we argue that Aleksandrov's transmasculine self-presentation, obvious in the original Russian, was erased in previous English translations that have embedded him in the canon of nineteenth-century women writers. Below, we reflect on the challenges associated with reclaiming Aleksandrov's gender identity in the process of collaborative translation of secondary sources
Measurement properties of the Edmonton Frail Scale in older adults: a systematic review and meta-analysis
Get PDFBackground: Frailty is a clinical condition characterised by heightened vulnerabilities to stressors and negative health consequences. The Edmonton Frail Scale is a prominent multidimensional tool for assessing frailty across various settings.
Objectives: This review aimed to synthesise and evaluate the certainty of evidence and the quality of Edmonton Frail Scale in older adults aged 60 and above with respect to its reliability (test–retest, inter-rater) and construct validity (convergent, known-group).
Design: Systematic review and meta-analysis.
Setting and participants: Older adults across clinical and community settings.
Methods: A comprehensive search was conducted across eight databases from inception to 29 January 2024. An updated search in MEDLINE (PubMed) on 10 April 2025 identified no additional eligible articles. COSMIN risk-of-bias checklist was used for quality appraisal, and evidence synthesis followed COSMIN guidelines. Random-effects meta-analysis and univariate logistic regression was used to quantitatively synthesise evidence for reliability and construct validity, respectively.
Results: Twenty studies involving 3852 older adults were included. The original Edmonton Frail Scale demonstrated sufficient construct validity across most populations, supported by high certainty of evidence. However, construct validity was inconsistent in acute care populations and in studies using modified Edmonton Frail Scale versions, where content adaptations (e.g., omission of performance-based items) may have affected psychometric performance. Meta-regression revealed that modified versions were significantly less likely to yield positive validity ratings compared to the original Edmonton Frail Scale (OR = 0.29; 95 % CI: 0.09–0.95; p = 0.042). Test–retest and inter-rater reliability were sufficient, though heterogeneity was considerable, and certainty of evidence remained moderate.
Conclusion: The Edmonton Frail Scale shows good overall reliability and validity in assessing frailty among older adults, particularly in stable clinical or community settings. However, caution is warranted when using modified versions or applying the tool in acutely ill populations. Future studies should validate Edmonton Frail Scale adaptations and enhance the precision of reliability estimates, especially in underrepresented regions and high-risk subgroups.
Registration: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42024504735)
Integrating alternative fragmentation techniques into standard LC-MS workflows using a single deep learning model enhances proteome coverage
Get PDFWe built and characterised a mass spectrometer capable of performing CID (both beam type and resonant type), UVPD, EID and ECD in an automated fashion during an LCMS type experiment. We exploited this ability to generate large datasets through multienzyme deep proteomics experiments for characterisation of these activation techniques. As a further step, motivated by the complexity generated by these dissociation techniques, we developed a single Prosit deep learning model for fragment ion intensity prediction covering all of these techniques. The generated model has been made publicly available and has been utilised in FragPipe within its MSBooster module. Rescoring allowed both data-dependent acquisition (DDA) and data-independent acquisition (DIA) to achieve on average more than 10% increase in protein identifications across all dissociation techniques and enzymatic digestions. We demonstrate that these alternative fragmentation approaches can now be used within standard data analysis pipelines and can produce data competitive to CID in terms of eficiency, but in the cases of EID and UVPD with far richer and more comprehensive spectra