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Fasciolosis, a parasitic disease of ruminants, poses significant economic and animal-health challenges in Algeria. This study aimed to assess spatial, temporal, and species-specific patterns of fasciolosis prevalence across diverse agro-climatic zones and to estimate associated economic losses. Between 2013 and 2023, eight wilayas El-Tarf, Skikda, Jijel (Region I), Blida, Mila (Region II), and M’Sila, Medea, Laghouat (Region III) were surveyed. Systematic postmortem inspections of 1,569,392 animals (349,176 cattle; 982,669 sheep; 235,639 goats; 1,882 camels; 26 horses) were performed by qualified veterinarians, with liver and bile-duct examination for Fasciola. Data on region, species, year, and season were analyzed in R 4.4.0 using ANOVA, Kruskal–Wallis, Tukey’s post hoc tests, and principal component analysis (PCA). Economic losses were calculated from condemned liver weights in Blida, Laghouat, and Jijel, converted to USD. PCA distinguished three regional prevalence profiles, with PC1 (77.7% variance) separating overall prevalence levels. Region I exhibited the highest mean prevalence (2.47%), peaking at 3.54% in 2018 – significantly greater than Region II (1.39%) and Region III (1.96%) (p < 0.01). Cattle showed the greatest infection rate (mean 4.14%), significantly higher than sheep (1.32%; p < 0.001) and goats (0.25%; p < 0.001), while horses and camels remained uninfected. Seasonal analysis revealed highest prevalence in autumn and winter (≈2.1%) versus spring (≈1.5%). Economic losses totaled USD 10.6 million in Blida, USD 1.0 million in Laghouat, and USD 142.2 million in Jijel over the study period. Targeted control strategies, adapted to regional and seasonal risk patterns, are essential. Future work should investigate environmental and management factors driving regional differences and evaluate cost-effective interventions to mitigate fasciolosis impact in Algerian livestock.
Background: Antibodies directed against acetylcholine receptor (AChR) are absent in approximately 15% of patients with gMG. Approved treatment options represent an unmet need in the AChR-antibody (Ab)- gMG population. Efgartigimod is an immunoglobulin G1 (IgG1) antibody Fc fragment that selectively reduces IgG levels by blocking neonatal Fc receptor (FcRn)-mediated IgG recycling. Here, we describe efgartigimod efficacy in AChR-Ab- participants with gMG receiving either efgartigimod IV or subcutaneous (SC) efgartigimod PH20 (coformulated with recombinant human hyaluronidase PH20) across clinical studies. Methods: Post hoc analyses were conducted to examine efficacy and safety of efgartigimod IV and/or efgartigimod PH20 SC in AChR-Ab- participants in ADAPT/ADAPT+ and ADAPT-SC/ADAPT-SC+ trials. Results: Among pooled AChR-Ab- participants (n=56), mean (SE) MG-ADL total score improvement from baseline to Week 3 was -3.7 (Cycle 1: 0.44 [n=55]). Consistent MG-ADL improvements occurred with repeated cycles. Clinically meaningful improvements (CMI; ≥2-point MG-ADL decrease) occurred in 76.4% (n=42/55) of participants (Cycle 1, Week 3). In Cycle 1, 23.2% (n=13/56) of participants achieved minimal symptom expression (MG-ADL 0-1). Similar efficacy results occurred across all cycles. Overall safety profile was similar between AChR-Ab+ and AChR-Ab- participants. Conclusions: Both efgartigimod IV and efgartigimod PH20 SC were well tolerated and led to CMI in participants with AChR-Ab- gMG.
Background: RAISE-XT (NCT04225871; Phase 3 study) showed clinically meaningful and sustained improvements in myasthenia gravis (MG)-specific outcomes with zilucoplan, a macrocyclic peptide complement component 5 inhibitor, in patients with acetylcholine receptor autoantibody-positive generalised MG. Methods: Adults self-administered once-daily subcutaneous zilucoplan 0.3mg/kg. This post hoc analysis assessed durability of response to Week 120 in MG-Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) responders at Week 1 of two double-blind studies (NCT03315130, NCT04115293). Responder definitions: improvements of ≥3-points (MG-ADL) or ≥5-points (QMG) (interim data cut: 11 November 2023). Results: 93 patients were randomised to zilucoplan 0.3mg/kg in the double-blind studies; 43.0% (n=40/93) and 33.3% (n=31/93) were MG-ADL and QMG responders, respectively, at Week 1. Week 1 responders spent a median #of 98.9% (5.8–99.2) and 99.0% (2.5–99.2) time in response up to Week 120 for MG-ADL and QMG. Week 1 non-responders spent# a median #of 84.6% (0.0–98.3) and 66.7% (0.0–98.9) time in response up to Week 120 for MG-ADL and QMG, with most responding later in the study. Conclusions: Among early (Week 1) zilucoplan responders, time in response remained high (99%) up to Week 120. These data demonstrate rapid and sustained efficacy with long-term zilucoplan treatment.#
Background: The efficacy and safety of lecanemab have previously been evaluated in the Phase 3 randomized clinical trial, Clarity AD (NCT03887455). Methods: A Markov cohort model was developed to estimate the cost-effectiveness of lecanemab versus standard of care (SoC) in patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD), with confirmed beta-amyloid (Aβ) pathology, from a Canadian societal perspective. Health states were determined by Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. Transitions between health states during month 0-18 were estimated from Clarity AD. Beyond month 18, relative efficacy for lecanemab in the form of the hazard ratio for time-to-worsening of CDR-SB was applied to literature-based transition probabilities. The model included the effects of lost productivity and impact on carer health-related quality of life. Results: The incremental cost-effectiveness ratio (ICER) for lecanemab vs SoC was estimated to be CAD 62,751 per QALY gained. The probability that lecanemab was cost-effective at a threshold of CAD 100,000 was estimated to be 88.5%. Conclusions: Lecanemab represents a cost-effective option for the treatment for early AD from the Canadian societal perspective. The results of this analysis can be used to inform clinical and economic decision making.
Background: Generalized myasthenia gravis (gMG) is a rare, chronic, autoimmune disease characterized by muscle weakness and fatigue. This study aims to describe the natural history, disease burden and treatment patterns of gMG patients in Canada. Methods: Data was analyzed from the Adelphi MG II DSP™, a gMG patient-level cross-sectional database, collected through surveys between February-June 2024. Neurologists provided sociodemographic, symptomatology, and treatments data. Results: Fifteen neurologists provided data for 46 gMG patients. The cohort’s mean (SD) age was 58.1 (14.7) years, 52.2% male, 82.6% White/Caucasian and 89.1% were anti-AChR Ab positive. Mean time since diagnosis was 3.4 (3.1) years, 22% reported a change in employment status due to gMG. Most had public insurance (68.9%). Disease severity was mostly MGFA class II (78.2%) patients. Common symptoms included eyelid ptosis (76.1%), dysarthria (50.0%), and dyspnea (54.3%) – mean MG-ADL was 5.6 (5.1). During their disease course, 34.9% experienced ≥1 myasthenic crisis, while 25.6% reported symptom exacerbation. At time of survey, patients had used 1.8 (0.9) lines of maintenance treatment. Most prescribed treatments (alone or in combinations) were pyridostigmine (95.6%), corticosteroids (48.9%), non-steroidal immunosuppressants (42.2%), Immunoglobulins (31.1%), and biologics (22.2%). Conclusions: gMG patients continue to experience symptoms burden and crisis/exacerbations. These findings highlight an unmet need for new, safe and effective therapeutics that are publicly covered to manage gMG-related clinical manifestations.
Background: Transcranial doppler ultrasound (TCD) in a pediatric neurocritical setting can determine cerebral hemodynamics by assessing the blood flow velocity in main cerebral arteries. In large vessel occlusions (LVO) that require endovascular thrombectomy (EVT), TCD can monitor recanalization and arterial re-occlusion. We describe one case in a previously healthy 13-year-old girl with a right M1 middle cerebral artery occlusion. Methods: Analysis was done via a retrospective case review. Results: Our patient underwent a successful endovascular thrombectomy (EVT) six hours after symptom onset. Follow up TCDs done at 4, 8, and 24 hours showed stable peak systolic velocities (PSV) on the narrowing of right M1 ranging from 245 to 270 cm/s with stable pre-stenotic PSV around 110 cm/s, indicating focal and stable narrowing of M1 without reocclusion. No high transient signals (HITS) were identified on sub 10 minute TCDs. An urgent echocardiogram revealed a bicuspid aortic valve with vegetations, with later confirmation of infective endocarditis. The patient made an impressive recovery with only mild deficits. Conclusions: TCD can be an effective tool in a pediatric neurocritical setting in guiding initial recanalization after EVT and monitoring for arterial re-occlusion, HITS and hyperperfusion. TCD monitoring also decreases the amount of radiation exposure via CTA.
Evidence indicates hypervitaminosis A may be attributed to overconsumption of natural preformed vitamin A (VA) and overlapping VA intervention strategies. Hypervitaminosis A can disrupt metabolic processes; however, the extent and mechanisms of these impacts are not well understood. This study aims to assess metabolic differences related to hypervitaminosis A and VA supplementation by performing metabolomics analysis. A subsample of South African preschoolers participating in the country’s VA supplementation programme was selected. Participants were divided into two groups: adequate VA (n 15; 0·59–0·99 µmol/g total liver reserve and high VA (n 15; ≥ 1·0 µmol/g total liver reserve). Serum samples were collected at baseline and 28 d after consuming a 200 000 IU VA supplement. Lipidomics and oxylipins assays were conducted using ultraperformance LC-MS. At baseline, unsaturated lysophosphatidylcholines and unsaturated phosphatidylcholines were significantly lower in the high VA group (P < 0·05). A group-by-time interaction with VA supplementation was observed for polyunsaturated lysophosphatidylcholines and polyunsaturated phosphatidylcholines (P < 0·05). Additionally, a group effect was noted for oxylipins, and a time effect in response to VA supplementation was seen with decreased arachidonic acid and lipoxygenase- and non-enzymatically derived oxylipins (P < 0·05). Hypervitaminosis A is associated with modifications in lipids involved in cell structure and signalling, particularly unsaturated lysophosphatidylcholines and phosphatidylcholines. Further research is needed to identify the mechanisms behind these modifications, their physiological effects and their potential as biomarkers of elevated vitamin A status.
The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
This study from a South Indian tertiary care hospital found a 41% peri-rectal Carbapenem-resistant Enterobacterales colonization prevalence at intensive care unit admission, with New Delhi metallo-β-lactamase as the predominant carbapenemase. It underscores the need for contextually appropriate, cost-effective infection prevention strategies to mitigate the spread of resistant organisms in Indian healthcare settings.
We present the Evolutionary Map of the Universe (EMU) survey conducted with the Australian Square Kilometre Array Pathfinder (ASKAP). EMU aims to deliver the touchstone radio atlas of the southern hemisphere. We introduce EMU and review its science drivers and key science goals, updated and tailored to the current ASKAP five-year survey plan. The development of the survey strategy and planned sky coverage is presented, along with the operational aspects of the survey and associated data analysis, together with a selection of diagnostics demonstrating the imaging quality and data characteristics. We give a general description of the value-added data pipeline and data products before concluding with a discussion of links to other surveys and projects and an outline of EMU’s legacy value.
Low vegetable intake is a key contributor to the health burden experienced by young adults in rural communities(1). Digital interventions provide an accessible delivery model that can be personalised to meet the diverse preferences of young adults(2). This study aimed to determine the feasibility, acceptability and efficacy of a personalised digital intervention to increase vegetable intake (Veg4Me), co-designed to meet the needs of young adults living in rural Australian communities(3). A 12-week assessor-blinded, two-arm, parallel randomised controlled trial was undertaken from August 2023 until April 2024. Young adults (18–35 years; consuming < 5 serves of vegetables/day; with an internet-connected device) living in Loddon Campaspe or Colac Otway Shire in Victoria, Australia, were recruited via social media and local government networks. Participants were randomised to receive 12 weeks of personalised (intervention) or non-personalised (control) support via a free web application (app; Veg4Me). Key features included 1) recipes personalised to users’ dietary and cooking preferences, 2) geo-located food environment map, 3) healthy eating resources, 4) goal-setting portal and 5) personalised e-newsletters. The primary outcome was feasibility: recruitment, participation and retention rate. Secondary outcomes were usability and user experience, perceived changed in vegetable intake, self-reported vegetable intake, and confidence to cook fresh green and root vegetables. Regression analyses (adjusted for baseline) were used to test for significant differences between groups. A total of n = 536 individuals registered on the Veg4Me website. After excluding fraudulent and duplicate responses (n = 289), n = 124 were eligible and provided consent to participate, n = 116 were randomised and n = 83 completed postintervention data collection. The recruitment rate was 47%, participation rate was 93% and retention rate was 72%. Compared to the control, more intervention participants were satisfied with Veg4Me (76% vs 52%). Most intervention participants reported that access to personalised recipes gave them confidence to eat a wider variety of vegetables (83%), while 76% accessed the food environment map, 63% accessed the healthy eating resources, 78% accessed the goal-setting function and 90% reported that the e-newsletters prompted them to access Veg4Me. Compared to the control, more intervention participants perceived that their vegetable intake had changed in the last 12 weeks (85% vs 57%; p = 0.013). Mean vegetable intake at 12 weeks in intervention and control participants was 2.7 (SD 1.0) and 2.7 (SD 1.4) serves/day, respectively (p = 0.67). Confidence to cook fresh green vegetables at 12 weeks in intervention and control participants was 93% and 91%, respectively (p = 0.24), while for root vegetables this was 88% and 81%, respectively (p = 0.11). Findings demonstrate the feasibility and acceptability of the Veg4Me intervention, and some evidence of efficacy. This study introduces a new strategy that has promise for addressing diet and health inequities experienced by young adults living in rural communities.
Approximately half of Australian universities offer a degree in nutrition, nutrition science, human nutrition or nutrition combined with another discipline. In the absence of any formal accreditation requirements, the design of nutrition undergraduate courses is guided by national nutrition science competencies(1). Degrees might also include specialisations such as in public health, food industry or animal nutrition, and a range of special interest topics included to enhance the graduate skillset for the workforce. This diversity in degrees develops graduates with broad and transferrable skills, thought to be desirable to industry employers. In an earlier study by the authors(2), it was identified that graduates placed high value on nutrition science theory and practical content, but there was an expressed desire for more work-integrated-learning opportunities and professional skill development for work in private practice. To triangulate the perspectives of students and graduates, there is a need for universities to understand how nutrition graduates are received by employers. This paper will present preliminary findings from the Working in Nutrition Employer (WIN-E) study. The aims of this study were to build on findings from the WIN-G study(2) and explore the perceptions of nutrition graduate employers in Australia regarding aspects of the graduate skillset that were highly valued, and identify training gaps. After being tested for face validity, the purpose-built WIN-E survey was delivered online via Qualtrics between June–December 2022. The survey included a mix of 32 closed- and open-ended questions about employer characteristics, additional education, employment and professional experience, and employers perceived graduate preparedness for the workforce. An interim analysis revealed that 110 participants had given informed consent; of these, 41 completed 75% of the questions, with 32 having relevance to nutrition graduate employment, and were included in the current analyses. Most respondents were female (n = 25, 78%) aged 25–34 years (n = 13, 52%). Respondents predominantly identified as working in education (n = 8), research (n = 5) or in ‘other settings’ (n = 5) such as community aged care, digital media/coaching, food preparation, agriculture or homelessness project work. To a lesser extent domains in retail/hospitality (n = 4), food industry (n = 3), public health/not for profit (n = 2), clinical (n = 2) and sport and fitness (n = 1) were represented. Fifteen (47%) employers felt nutrition graduates had all, or some of the expected skills and attributes at time of employment. More development of skills in written health translation (n = 2), data analysis (n = 1), working collaboratively in health systems (e.g., aged care) (n = 2), marketing (n = 1), and understanding transferable skillsets with the motivation for ongoing professional development were also valued (n = 2). Further data analysis will provide more context around the roles and responsibilities employers typically assign to nutrition graduates, highlighting potential training gaps and opportunities for universities to better prepare graduates for the workforce.
Despite advances in antiretroviral treatment (ART), human immunodeficiency virus (HIV) can detrimentally affect everyday functioning. Neurocognitive impairment (NCI) and current depression are common in people with HIV (PWH) and can contribute to poor functional outcomes, but potential synergies between the two conditions are less understood. Thus, the present study aimed to compare the independent and combined effects of NCI and depression on everyday functioning in PWH. We predicted worse functional outcomes with comorbid NCI and depression than either condition alone.
Methods:
PWH enrolled at the UCSD HIV Neurobehavioral Research Program were assessed for neuropsychological performance, depression severity (≤minimal, mild, moderate, or severe; Beck Depression Inventory-II), and self-reported everyday functioning.
Results:
Participants were 1,973 PWH (79% male; 66% racial/ethnic minority; Age: M = 48.6; Education: M = 13.0, 66% AIDS; 82% on ART; 42% with NCI; 35% BDI>13). ANCOVA models found effects of NCI and depression symptom severity on all functional outcomes (ps < .0001). With NCI and depression severity included in the same model, both remained significant (ps < .0001), although the effects of each were attenuated, and yielded better model fit parameters (i.e., lower AIC values) than models with only NCI or only depression.
Conclusions:
Consistent with prior literature, NCI and depression had independent effects on everyday functioning in PWH. There was also evidence for combined effects of NCI and depression, such that their comorbidity had a greater impact on functioning than either alone. Our results have implications for informing future interventions to target common, comorbid NCI and depressed mood in PWH and thus reduce HIV-related health disparities.
Objectives/Goals: Ischemic stroke treatments assist in restoring blood flow, but do not guarantee good outcomes. Since extracellular vesicles (EVs) able to cross the blood brain barrier, total (nonspecific) and astrocyte enriched EVs (TEVs, AEVs, respectively) from plasma may emerge as plasma biomarkers for prognostication and targeted therapeutics. Methods/Study Population: “Blood and Clot Thrombectomy Registry and Collaboration” (BACTRAC; NCT03153683) is a human stroke biobank at the University of Kentucky that collects samples at the time of mechanical thrombectomy during emergent large vessel occlusions (ELVO; ischemic stroke). EVs were isolated, via size exclusion chromatography, from unbanked plasma and concentrated resulting in TEVs. AEVs were immunoprecipitated with anti-EAAT1 (GLAST), an astrocyte-specific transmembrane glycoprotein. Isolated protein was sent to Olink and ran on their metabolic panel. Demographics and medical histories of the subjects were exported from REDcap and investigators were blinded during EV analysis. Results/Anticipated Results: ELVO subjects (8 females/ 5 males) were an average age of 71.1 ± 11.7 years. Lower TEV enolase 2, a neuronal glycolysis enzyme, associated with increased stroke severity (NIHSS; rs = -0.7819, p = 0.0476). Higher systemically TEV quinoid dihydropteridine reductase (QDPR), essential co-factor enzyme, was associated with more severe strokes (NIHSS; rs = 0.8486, p = 0.0123) and lower cognition (MoCA; r2 = 0.7515, p = 0.0254). Interestingly, higher intracranial AEVs QDPR was associated with lower infarct volumes (rs = -0.7333, p = 0.0202), less severe strokes (NIHSS; rs = -0.6095, p = 0.0388), and better cognition (MoCA; r2 = 0.6095, p = 0.0388). Increased AEV nicotinamide adenine dinucleotide kinase another essential co-factor enzyme, intracranially also correlated to higher cognition (MoCA; rs = 0.8356, p = 0.0298). Discussion/Significance of Impact: Plasma TEV and AEV metabolic proteins correlate with the progression of stroke outcomes and should be investigated as target therapies during MT to improve outcomes.
This report explores key considerations in relation to adopting a dynamic discount rate funding approach and the impacts of doing so in a range of areas, including funding volatility, investment strategy and end game objectives. It considers the advantages and disadvantages of this approach from the perspective of a range of stakeholders and the challenges that need overcoming in order to fully implement and support the approach, for example data challenges and the new skills required in the industry. The report includes sample modelling to highlight the practical issues that arise when adopting this approach. It describes a step-by-step approach for assessing the risks to be considered when determining an appropriate level of assets to provide funding for a sample set of pension scheme cash flows, as summarised in the table below.
Steps involved in determining the funding buffer and discount rate
Step 1
Create an asset portfolio based on best estimate liability cash flows
Step 2
Adjustment for investment costs
Step 3
Buffer: allowance for asset-side risks
Step 4
Buffer: allowance for asset-liability mismatch risk (reinvestment and disinvestment risk)
Step 5
Buffer: allowance for liability-side risks
Step 6
Buffer: consideration of risk diversification when determining the buffer
It also considers how a dynamic discount rate approach fits within the proposed future funding regulations. Finally, the report puts forward recommendations for the IFoA, Scheme Actuaries and TPR.
Consequences of schemes adopting a dynamic discount rate approach could include very different investment strategies with investment in a wider pool of assets, less use of leveraged Liability Driven Investment, fewer schemes targeting buy-out as their end game strategy and an increase in technical work for actuaries in advising on the optimisation of asset and liability cash flows.
Integral to the fabric of human technology, knots have shaped survival strategies since their first invention. As the ties that bind, their evolution and diversity have afforded human cultural change and expression. This study examines knotting traditions over time and space. We analyse a sample of 338 knots from 86 ethnographically or archaeologically documented societies over 12 millennia. Utilizing a novel approach that combines knot theory with computational string matching, we show that knotted structures can be precisely represented and compared across cultures. This methodology reveals a staple set of knots that occur cross-culturally, and our analysis offers insights into their cultural transmission and the reasons behind their ubiquity. We discuss knots in the context of cultural evolution, illustrating how the ethnographic and archaeological records suggest considerable know-how in knot-tying across societies spanning from the deep past to contemporary times. The study also highlights the potential of this methodology to extend beyond knots, proposing its applicability to a broader range of string and fibre technologies.
Iceland is an isolated, sub-Arctic, oceanic island of volcanic origin in the northern North Atlantic. With a limited faunal diversity and being the most northern point in the distributional range for some species, it is an intriguing model region to study parasite biodiversity and biogeography. Since 2006, there has been a history of intense biodiversity discoveries of freshwater trematodes (Trematoda, Digenea), thanks to the use of integrative taxonomic methods. The majority of digeneans (28 out of 41 known) were characterised with molecular genetic methods and morphological analyses, with some of their life-cycle stages and geographical distribution assessed. A surprising diversity has been discovered, comprising species of the families Allocreadiidae, Cyclocoeliidae, Diplostomidae, Echinostomatidae, Gorgoderidae, Plagiorchiidae, Notocotylidae, Schistosomatidae, and Strigeidae. Many of the recorded species complete their life cycles within Iceland, with three snail species (Ampullaceana balthica, Gyraulus parvus, Physa acuta) known as intermediate hosts. No trematodes endemic for Iceland were found; they appear to be generalists with wide geographical ranges dispersed mainly by migratory birds. Interestingly, fish trematodes recorded in Iceland were found in mainland Europe, indicating that they might be dispersed by anadromous fishes, by human activity, or by migratory birds carrying intermediate hosts. The trematode fauna is mainly Palaearctic, with few species recorded in North America. We highlight the ongoing need for precise species identification via integrative taxonomic methods, which is a baseline for any further ecological studies and adequate epidemiological and conservation measures. Also, there is still a need of obtaining well-preserved vouchers of adults for definite species delimitation.
Fasciolosis, caused by the liver flukes Fasciola hepatica and Fasciola gigantica, is a zoonotic parasitic disease associated with substantial economic losses in livestock. The transforming growth factor-beta signalling pathway is implicated in developmental processes and biological functions throughout the animal kingdom, including the Fasciola spp. It may also mediate host–helminth interactions during infection. In this work, we present an exploration of FgSmad4, the sole member of the Co-Smad protein family in F. gigantica. The isolated FgSmad4 cDNA was 4,014 bp in length encoding for a protein comprising 771 amino acids. FgSmad4 exhibited typical Co-Smad protein features, including Mad Homology 1 (MH1) and Mad Homology 2 (MH2) domains, a Nuclear Localisation Signal, a DNA-Binding Motif, and a Nuclear Export Signal. Sequence and phylogenetic analyses of FgSmad4 revealed that its MH1 and MH2 sequences are most similar to those of other trematode species. The MH1 domain, in particular, closely resembles the Co-Smad protein in mammalian hosts more than those in cestodes and nematodes. The expression patterns of FgSmad4 during the liver fluke’s developmental stages showed significant variation. Transcript levels were highest at the newly excysted juvenile stage, followed by unembryonated egg, redia, and metacercaria, with the lowest expression in the adult fluke, embryonated egg, and cercaria stages. Our results underscore the conservation and suggest the potential role of FgSmad4, a key transforming growth factor-beta signalling molecule within the liver fluke F. gigantica. As Co-Smad is typically involved in several biological pathways, the precise functions and mechanisms of this identified FgSmad4 necessitate further exploration.
Estimates of test size (probability of Type I error) were obtained for several specific repeated measures designs. Estimates were presented for configurations where the underlying covariance matrices exhibited varying degrees of heterogeneity. Conventional variance ratios were employed as basic statistics in order to produce estimates of size for a conventional test, an ∊-adjusted test, and ∊-adjusted test and a conservative test. Indices for empirical distributions of two estimators of ∊j, a measure of covariance heterogeneity, were also provided.