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Epidemiologic and genomic characterization of an outbreak of Rift Valley fever among humans and dairy cattle in northern Tanzania
No full textBackground:
A periurban outbreak of Rift Valley fever virus (RVFV) among dairy cattle from May through August 2018 in northern Tanzania was detected through testing samples from prospective livestock abortion surveillance. We sought to identify concurrent human infections, their phylogeny, and epidemiologic characteristics in a cohort of febrile patients enrolled from 2016 to 2019 at hospitals serving the epizootic area.
Methods:
From September 2016 through May 2019, we conducted a prospective cohort study that enrolled febrile patients hospitalized at 2 hospitals in Moshi, Tanzania. Archived serum, plasma, or whole blood samples were retrospectively tested for RVFV by PCR. Human samples positive for RVFV were sequenced and compared to RVFV sequences obtained from cattle through a prospective livestock abortion study. Phylogenetic analysis was performed on complete RVFV genomes.
Results:
Among 656 human participants, we detected RVFV RNA in 4 (0.6%), including 1 death with hepatic necrosis and other end-organ damage at autopsy. Humans infected with RVFV were enrolled from June through August 2018, and all resided in or near urban areas. Phylogenetic analysis of human and cattle RVFV sequences demonstrated that most clustered to lineage B, a lineage previously described in East Africa. A lineage E strain clustering with lineages in Angola was also identified in cattle.
Conclusions:
We provide evidence that an apparently small RVFV outbreak among dairy cattle in northern Tanzania was associated with concurrent severe and fatal infections among humans. Our findings highlight the unidentified scale and diversity of interepizootic RVFV transmission, including near and within an urban area
Uptitration of Sacubitril/Valsartan and outcomes in patients with heart failure ― insight from the REVIEW-HF Registry ―
Get PDFBackground: Guideline-directed medical therapy has become an important component of heart failure (HF) therapy, with sacubitril/valsartan as one of the recommended drugs; however, the real-world prognostic implications of sacubitril/valsartan uptitration are unclear.
Methods and Results: Patients with HF newly initiated on sacubitril/valsartan were registered in a retrospective multicenter study (REVIEW-HF). In all, 995 patients were divided into 3 groups according to the maximum dose achieved: high dose, sacubitril/valsartan 400 mg; intermediate dose, sacubitril/valsartan 200–<400 mg; and low dose, sacubitril/valsartan <200 mg. A total of 397 (39.9%) patients received high-dose sacubitril/valsartan; they had a significantly lower risk of mortality or HF hospitalization than patients in the low-dose (hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.29–0.53; P<0.001) and intermediate-dose (HR 0.64; 95% CI 0.45–0.94; P=0.03) groups. In the multivariable Cox regression model, higher systolic blood pressure and maintained geriatric nutritional risk index were significantly associated with a higher incidence of achieving a high dose of sacubitril/valsartan. Patients who did not receive high-dose sacubitril/valsartan experienced more hypotension during the follow-up period, whereas hyperkalemia, severe renal events, and angioedema did not differ across the achieved dose classifications.
Conclusions: Patients who achieved sacubitril/valsartan uptitration had a better prognosis than those who did not. Before sacubitril/valsartan uptitration, patients need to monitor blood pressure closely to prevent worsening events
Upregulation of haematopoetic cell kinase (Hck) activity by a secreted parasite effector protein (Ta9) drives proliferation of Theileria annulata-transformed leukocytes.
Get PDFReversible transformation of bovine leukocytes by the intracellular parasites Theileria annulata and Theileria parva is central to pathogenesis of the diseases they cause, tropical theileriosis and East Coast Fever, respectively. Parasite-dependent constitutive activation of major host transcription factors such as AP-1 (Activating Protein 1) and NF-κB (Nuclear Factor-Kappa B) sustains the transformed state. Although parasite interaction with host cell signaling pathways upstream of AP-1 have been studied, the precise contribution of Theileria encoded factors capable of modulating AP-1 transcriptional activity, and other infection-altered signaling pathways is not fully understood. We previously showed that the Ta9 protein from T. annulata (TA15705) is secreted into the host cell cytoplasm and contributes to infection-induced AP-1 transcriptional activity. The current study employed RNA-seq to investigate the ability of ectopically expressed Ta9 to modulate the gene transcription profile of a bovine macrophage cell line, BoMac. RNA-seq identified 560 (400 upregulated and 160 downregulated) differentially expressed genes. KEGG analysis predicted a high number of upregulated genes associated with carcinogenesis such as CCND1, CDKN1A, ETV4, ETV5, FLI1, FRA1, GLI2, GRO1, HCK, IL7R, MYBL1, MYCN, PIM1 and TAL1. Ta9 introduction also affected genes associated with proinflammatory processes such as cytokines, chemokines, growth factors and metalloproteinases. Enrichment analysis of differentially expressed genes revealed that Ta9 is potentially involved in activating other host cell signaling pathways in addition to those that lead to induction of AP-1. Comparing our data with data on differentially expressed BoMac genes modulated by the secreted TashAT2 factor of T. annulata identified the gene encoding the tyrosine protein kinase hematopoietic cell kinase (HCK) as common to both data sets. HCK is essential for the proliferation of T. parva-transformed B cells and herein, we demonstrate that enzymatic activity of HCK is also essential for T. annulata- and T. lestoquardi-transformed macrophage proliferation
Protocol to assess changes in brain network resistance to perturbation during offline processing using TMS-EEG
Get PDFSummary:
Transcranial magnetic stimulation (TMS) perturbs specific brain regions and, combined with electroencephalography (EEG), enables the assessment of activity within their connected networks. We present a resting-state TMS-EEG protocol, combined with a controlled experimental design, to assess changes in brain network activity during offline processing, following a behavioral task. We describe steps for experimental design planning, setup preparation, data collection, and analysis. This approach minimizes biases inherent to TMS-EEG, ensuring an accurate assessment of changes within the network
Canine oncology: investigating 3D technology as a visual preoperative and clinical aid for veterinary surgeons treating dogs with hepatocellular carcinoma
No full textHepatocellular carcinoma (HCC) is a primary liver tumor in dogs, typically occurring around nine years of age and accounting for over 50% of hepatic tumors.
Veterinary oncologists must have a deep understanding of hepatic anatomy to assess liver tumor resectability, acquired through various educational resources. Successful liver cancer treatment, including surgery, relies on precise knowledge of the liver’s multi-lobular structure and its vascular complexity. This includes understanding the hepatic artery, vein, and the portal vein tributaries’ branching patterns, which can vary between patients. Surgeons need to determine blood supply routes, assess tumor heterogeneity, and understand the local environment before surgery.
Current computed tomography (CT) technology has limitations in anatomical perception, hindering surgical planning for liver tumor surgery. In veterinary oncology, unlike human medicine, 3D technology is still emerging. This research explores the feasibility of creating 3D models of canine liver anatomy from CT datasets, including HCC cases, and integrating them with digital sculpting and game engine software to build interactive user interfaces.
The resulting application enables veterinary surgeons and students to visualize the normal liver and liver with HCC in 3D. Users can also simulate the placement, size, and severity of HCC tumors within the liver, aiding communication with dog owners.
The evaluation process received highly positive feedback, highlighting the value of interacting with 3D models for context, visual accuracy, perceptual learning, and improving client-vet communication
Dietary micronutrient intake during pregnancy is suboptimal in a group of healthy Scottish women, irrespective of maternal body mass index
Get PDFBackground/Objectives: A balanced nutritious diet is vital during pregnancy for both the mother and the baby. The aims of this longitudinal study were to (1) determine any differences in macro- and micronutrient intakes in a group of UK women during pregnancy (and in the post-partum period) who were overweight or obese (BMI mean (SD) 31.1 (2.9)) at antenatal booking appointment compared with women who were within the ideal BMI range (BMI mean (SD) 22.1 (1.9)) and (2) determine the proportion of women who met the Harmonized Average Requirements (H-AR) during pregnancy. Methods: Forty-two participants attended four clinic visits: three during pregnancy, one in each trimester (V1, V2, and V3), and one 12 weeks post-partum (V4). Dietary intake was assessed by 24 h diet recall and analysed using DietPlan6. Results: There were no differences in energy and macronutrient intakes between overweight/obese and lean women. During pregnancy, the overweight/obese women consumed a mean (SD) of 3238 (941) sodium (mg per day), which was approximately 10% higher compared to 2934 (732) sodium (mg per day) in the lean group (p = 0.015). Dietary and supplemental intakes of the sodium to potassium ratio was 21% higher in overweight/obese women compared to the lean women, p = 0.0031 (mean (SD) of 1.17 (0.35) versus 0.93 (0.28), respectively). Virtually all women did not meet the H-AR for niacin, folate, and vitamin D through dietary intake alone. Conclusions: The ‘eat better and not more’ message during pregnancy is supported
1-bit Phase Reconfigurable Unit Cell for X-band Intelligent Reflective Surface
Get PDFIn this study, a 1-bit phase reconfigurable unit cell
(UC) is proposed for an X-band intelligent reflective surface
(IRS). The UC is designed by integrating a PIN diode into a
slotted copper patch. The maximum phase shift occurs at the
design frequency of 9.5 GHz and the phase difference varies
within 180° ± 20° from 9 to 10 GHz in the X-band. A 16 × 16
IRS is designed and simulated using the proposed UC to verify
gain and beam steering performance. The IRS has a gain of 20.5
dBi at θ = 0◦
. At θ = ±40◦
the gain is 18.6 dBi which validates
good beam steering performance
Comparison of quantitative Krenning Scores with visual assessment in ⁹⁹ᵐTc-EDDA/HYNIC-TOC SPECT-CT
No full textPurpose:
The aim of this study is to assess inter-observer variability of the Krenning Score for ⁹⁹ᵐTc-EDDA/HYNIC-TOC single photon emission computed tomography (SPECT)-computed tomography (CT) images and compare against quantitative metrics obtained from tumour and physiological uptake measurements.
Methods:
Thirty-two patients with 117 lesions visible on ⁹⁹ᵐTc-EDDA/HYNIC-TOC SPECT-CT were scored by two expert observers using the Krenning Score. Five observers with less extensive experience also scored the lesions on visual assessment. Inter-observer agreement and comparison to the expert consensus was tested. Three observers made quantitative measurements of the lesions and physiological uptake, with intra-observer and inter-observer variation investigated. Assessment of agreement between quantitative metrics and the expert visual consensus was also made.
Results:
Inter-observer agreement for visual assessment was 44.3% for proportions of agreement and 0.576 for Fleiss’ Kappa, whilst for the best-performing quantitative metric the inter-observer Fleiss’ Kappa was equal to 1. The agreement with expert consensus for the best-performing visual observer was 89.8% for percentage of agreement and 0.914 for Cohen’s Kappa, similar to the best-performing quantitative metric (a derived quantitative Krenning Score) at 86.4% and κ = 0.877. Standardised uptake value maximum (SUVmax) also showed similar levels of agreement at 85.1% and κ = 0.871.
Conclusion:
A derived quantitative Krenning Score, or alternatively SUVmax, can provide similar levels of agreement with an expert consensus Krenning Score as visual assessment, with reduced inter-observer variability. Quantification can deliver greater consistency in scoring of ⁹⁹ᵐTc-EDDA/HYNIC-TOC images over visual assessment, an important factor when imaging is used to determine patient eligibility for peptide receptor radiotherapy
Bordering, de-bordering and re-bordering comparative and international pedagogy
Get PDFTwo polarised logics co-exist in international research and programming on quality teaching and learning. One logic understands pedagogy as embedded in its cultural, structural, political and historical contexts. In contrast, an interventionist agenda seeks solutions to the improvement of teaching practice, and isolates it and its influences in order to understand what works to improve learning outcomes. The borders between these two epistemic communities have hardened in the post-COVID, mid-SDG period. In the current quest for ready solutions, our field has never felt so divided. This article is based on the 2024 BAICE Presidential Address. After mapping these borders, it suggests strategies for de-bordering and re-bordering this field. De-bordering means overcoming epistemic hubris and acknowledging the strengths and the weaknesses of these approaches. Re-bordering means thinking differently about how pedagogical researchers, policymakers and programmers work together; it also means thinking differently about scale, community, and what is important
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