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The complete mitochondrial genome of Dama dama , and their phylogenetic relationships to other Cervidae
This publication presents the complete mitochondrial genome of Dama dama along with in depth phylogenetic relationship and species divergence analysis in respect to other Cervidae. The mitochondrial genome presented here is 16,332 bp which is comprised of 13 genes, 2 rRNAs and 22 tRNAs. The mitochondrial genome for Dama dama is the smallest, compared to other Cervidae. Transfer RNA genes have a specific secondary structure, resembling a clover leaf, however, tRNASer (Serine 1) in Dama dama has been found to only have 3 arms, it is missing the dihydrouridine arm. The phylogenetic analysis conducted in this study compared the mitochondrial sequences from 25 different Cervidae species. Findings suggest that Dama dama, compared to other Cervidae, is most closely related to Dama mesopotamica and Megaloceros giganteus. With regards to Dama dama, the species divergence time from Dama mesopotamica and Megaloceros giganteus is 5.68 mya. Whereas the divergence time between Dama mesopotamica and Megaloceros giganteus is 5.35 mya. Our findings provide strong support for the distinction between Dama dama and Dama mesopotamica as a sub-species and a close evolutionary relationship between Dama mesopotamica and Megaloceros giganteus. Supporting previous reports of a sister-group relationship with a shared common ancestor. This study has provided a new perspective on the ancestral origin of the Dama genus, which can be further investigated using the Dama dama mitochondrial genome presented in this report. Understanding the evolution of Dama dama may help to better understand the lack of genetic diversity within the species and advance future management strategies to resolve this
BIOM-10. CLINICAL PERFORMANCE EVALUATION OF A BRAIN CANCER LIQUID BIOPSY
Diagnostic delays impact the quality of life and survival of patients with brain cancer. Currently, with no blood test to assist them, clinicians must make their referral decision based on symptoms. Existing symptom-based referral guidelines inadequately stratify patients for brain imaging based on suspicion of cancer. A simple, rapid liquid biopsy placed in a primary care setting would enable more efficient triage of patients with non-specific symptoms related to brain cancer. The Dxcover® Liquid Biopsy is a rapid multi-omic liquid biopsy that interrogates a blood sample with infrared radiation and produces a distinctive signature that represents the whole biomolecular profile of the sample, and is sensitive to the hallmarks of brain cancer. The nature of the technology also allows for the diagnostic models to be tailored towards higher sensitivity (or specificity) depending on clinical priorities and international healthcare markets. In initial feasibility studies, we recruited 988 patients prospectively with non-specific symptoms associated with a brain tumor, and the algorithm detected 96% of the patients with brain tumors and 100% of glioblastomas (GBM), when tuned for greater sensitivity. EMBRACE is a prospective, observational, multicenter study, currently recruiting patients across seven sites in the United Kingdom, Belgium, Sweden and Switzerland. The study duration is 24 months and will recruit a minimum of 2200 participants. The target population is comprised of patients presenting to primary care with non-specific symptoms that are associated with brain cancer, such as headache and new onset neurological defect. The primary objective is to determine the clinical performance of the liquid biopsy for patients with brain cancer, in terms of diagnostic sensitivity and specificity. The test performance will be determined by comparing the liquid biopsy result to diagnostic imaging. Earlier and expeditious diagnoses in these patients are crucial to reduce the morbidities and mortalities associated with brain cancer. This simple, non-invasive liquid biopsy would facilitate the triage of brain tumor patients for rapid imaging
The persistent shadow of the supermassive black hole of M 87
In April 2019, the Event Horizon Telescope (EHT) Collaboration reported the first-ever event-horizon-scale images of a black hole, resolving the central compact radio source in the giant elliptical galaxy M 87. These images reveal a ring with a southerly brightness distribution and a diameter of ∼42 μas, consistent with the predicted size and shape of a shadow produced by the gravitationally lensed emission around a supermassive black hole. These results were obtained as part of the April 2017 EHT observation campaign, using a global very long baseline interferometric radio array operating at a wavelength of 1.3 mm. Here, we present results based on the second EHT observing campaign, taking place in April 2018 with an improved array, wider frequency coverage, and increased bandwidth. In particular, the additional baselines provided by the Greenland telescope improved the coverage of the array. Multiyear EHT observations provide independent snapshots of the horizon-scale emission, allowing us to confirm the persistence, size, and shape of the black hole shadow, and constrain the intrinsic structural variability of the accretion flow. We have confirmed the presence of an asymmetric ring structure, brighter in the southwest, with a median diameter of 43.3−3.1+1.5 μas. The diameter of the 2018 ring is remarkably consistent with the diameter obtained from the previous 2017 observations. On the other hand, the position angle of the brightness asymmetry in 2018 is shifted by about 30° relative to 2017. The perennial persistence of the ring and its diameter robustly support the interpretation that the ring is formed by lensed emission surrounding a Kerr black hole with a mass ∼6.5 × 109 M⊙. The significant change in the ring brightness asymmetry implies a spin axis that is more consistent with the position angle of the large-scale jet
Infliximab for maintenance of medically-induced remission in Crohn's disease
Background
Infliximab is a monoclonal antibody that binds and neutralises tumour necrosis factor‐alpha (TNF‐α) which is present in high levels in the blood serum, mucosa and stool of patients with Crohn's disease.
Objectives
To determine the efficacy and safety of infliximab for maintaining remission in patients with Crohn's disease.
Search methods
On 31 August, 2021 and 23 June, 2023, we searched CENTRAL, Embase, MEDLINE, ClinicalTrials.gov, and WHO ICTRP.
Selection criteria
Randomised controlled trials (RCTs) in which infliximab was compared to placebo or another active comparator for maintenance, remission, or response in patients with Crohn's disease.
Data collection and analysis
Pairs of review authors independently selected studies and conducted data extraction and risk of bias assessment. We expressed outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using GRADE.
Our primary outcome was clinical relapse. Secondary outcomes were loss of clinical response, endoscopic relapse, and withdrawal due to serious and adverse events.
Main results
Nine RCTs with 1257 participants were included. They were conducted between 1999 and 2022; seven RCTs included biologically‐naive patients, and the remaining two included a mix of naive/not naive patients. Three studies included patients in clinical remission, five included patients with a mix of activity scores, and one study included biologic responders with active disease at baseline. All studies allowed some form of concomitant medication during their duration. One study exclusively included patients with fistulating disease. The age of the participants ranged from 18 to 69 years old.
All but one single‐centre RCT were multicentre RCTs. Four studies were funded by pharmaceutical companies, two had a mix of commercial and public funding, and two had public funding.
Infliximab is probably superior to placebo in preventing clinical relapse in patients who have mixed levels of clinical disease activity at baseline, and are not naive to biologics (56% vs 75%, RR 0.73, 95% CI 0.63 to 0.84, NNTB = 5, moderate‐certainty evidence). We cannot draw any conclusions on loss of clinical response (RR 0.59, 95% CI 0.37 to 0.96), withdrawals due to adverse events (RR 0.66, 95% CI 0.37 to 1.19), or serious adverse events (RR 0.60, 95% CI 0.36 to 1.00) because the evidence is very low certainty.
Infliximab combined with purine analogues is probably superior to purine analogues for clinical relapse (12% vs 59%, RR 0.20, 95% CI 0.10 to 0.42, NNTB = 2, moderate‐certainty evidence), for patients in remission, and who are not naive to biologics. We cannot draw any conclusions on withdrawals due to adverse events (RR 0.47, 95% CI 0.15 to 1.49), and serious adverse events (RR 1.19, 95% CI 0.54 to 2.64) because the evidence is very low certainty.
We cannot draw any conclusions about the effects of infliximab on serious adverse events compared to purine analogues (RR 0.79, 95% CI 0.37 to 1.68) for a population in remission at baseline because the evidence is very low certainty. There was no evidence available for the outcomes of clinical relapse, loss of clinical response, and withdrawal due to adverse events.
Infliximab may be equivalent to biosimilar for clinical relapse (47% vs 40% RR 1.18, 95% CI 0.82 to 1.69), and it may be slightly less effective in averting loss of clinical response (49% vs 32%, RR 1.50, 95% CI 1.01 to 2.23, low‐certainty evidence), for a population with mixed/low disease activity at baseline. Infliximab may be less effective than biosimilar in averting withdrawals due to adverse events (27% vs 0%, RR 20.73, 95% CI 2.86 to 150.33, low‐certainty evidence). Infliximab may be equivalent to biosimilar for serious adverse events (10% vs 10%, RR 0.99, 95% CI 0.39 to 2.50, low‐certainty evidence).
We cannot draw any conclusions on the effects of subcutaneous biosimilar compared with intravenous biosimilar on clinical relapse (RR 1.01, 95% CI 0.65 to 1.57), loss of clinical response (RR 0.94, 95% CI 0.70 to 1.25), and withdrawals due to adverse events (RR 0.77, 95% CI 0.30 to 1.97) for an active disease population with clinical response at baseline because the evidence is of very low certainty.
We cannot draw any conclusions on the effects of infliximab compared to adalimumab on loss of clinical response (RR 0.68, 95% CI 0.29 to 1.59), withdrawals due to adverse events (RR 0.10, 95% CI 0.01 to 0.72), serious adverse events (RR 0.09, 95% CI 0.01 to 1.54) for an active disease population with clinical response at baseline because the evidence is of very low certainty. There was no evidence available for the outcome of clinical relapse.
Authors' conclusions
Infliximab is probably more effective in preventing clinical relapse than placebo (moderate‐certainty evidence). Infliximab in combination with purine analogues is probably more effective in preventing clinical and endoscopic relapse than purine analogues alone (moderate‐certainty evidence). No conclusions can be drawn regarding prevention of loss of clinical response, occurrence of withdrawals due to adverse events, or total adverse events due to very low‐certainty evidence for both of these comparisons.
There may be little or no difference in prevention of clinical relapse, withdrawal due to adverse events or total adverse events between infliximab and a biosimilar (low‐certainty evidence). Infliximab may lead to more loss of clinical response than a biosimilar (low‐certainty evidence).
We were unable to draw meaningful conclusions about other comparisons and outcomes related to missing data or very low‐certainty evidence due to serious concerns about imprecision and risk of bias. Further research should focus on comparisons with other active therapies for maintaining remission, as well as ensuring adequate power calculations and reporting of methods
Dark tourism acceptance and peacebuilding in troubled destinations
Dark tourism represents an established area of research and has a world-leading academic center for dark tourism scholarship, research and teaching. Extended body of research proved that troubled destinations need to acknowledge their pasts. This acknowledgement is absolutely necessary for the construction of identity but also peacebuilding; while moving forward without talking about the past increases trauma within a destination. However, a debate still exists on how dark tourism places and spaces are interpreted. Reflecting on the timeline of historical past events, the Greek Cypriot and Turkish Cypriot authorities have different representations of collective memories. This chapter discusses and debates how tourism can support peacebuilding activities through the acknowledgement of all dark sites within the island of Cyprus and include them in specialized tours, where the tourists personally can acknowledge the island’s dark and turbulent past. Acknowledgement rather than dismissiveness can pave the path towards peacebuilding
Preventing and Controlling Zinc Deficiency Across the Life Course: A Call to Action
Through diverse roles, zinc determines a greater number of critical life functions than any other single micronutrient. Beyond the well-recognized importance of zinc for child growth and resistance to infections, zinc has numerous specific roles covering the regulation of glucose metabolism, and growing evidence links zinc deficiency with increased risk of diabetes and cardiometabolic disorders. Zinc nutriture is thus vitally important to health across the life course. Zinc deficiency is also one of the most common forms of micronutrient malnutrition globally. A clearer estimate of the burden of health disparity attributable to zinc deficiency in adulthood and later life emerges when accounting for its contribution to global elevated fasting blood glucose and related non-communicable diseases (NCDs). Yet progress attenuating its prevalence has been limited due, in part, to the lack of sensitive and specific methods to assess human zinc status. This narrative review covers recent developments in our understanding of zinc's role in health; the impact of the changing climate and global context on zinc intake; novel functional biomarkers showing promise for monitoring population-level interventions; and solutions for improving population zinc intake. It aims to spur on implementation of evidence-based interventions for preventing and controlling zinc deficiency across the life course. Increasing zinc intake and combatting global zinc deficiency requires context-specific strategies and a combination of complementary, evidence-based interventions including supplementation, food fortification, and food and agricultural solutions such as biofortification, alongside efforts to improve zinc bioavailability. Enhancing dietary zinc content and bioavailability through zinc biofortification is an inclusive nutrition solution that can benefit the most vulnerable individuals and populations affected by inadequate diets to the greatest extent
Hands-On Youth Citizen Social Science Meta Report of the YouCount Experiences with Case Study Implementation
This D2.3 Meta Report of the YouCount Experiences with Case Study Implementation is rooted in WP2 and the implementation of hands-on youth citizen social science (Y-CSS). In particular it addresses the work of Tasks 2.1 to 2.10 which include laying the foundations and planning multidisciplinary research teams that include professional researchers, students and young people as Youth Citizen Scientists (YCS), recruiting and engaging YCS, students and stakeholders, developing and refining research methods to explore social inclusion with YCS and conducting co-creative research with young people. The primary focus is on case experiences with implementing the social inclusion sub study. It therefore provides details of the 10 local cases in nine countries in a multiple case study of co-creative Y-CSS in Europe and their experiences. The cross case thematic analysis builds on the individual case reports, extracts from the evaluation self-reports and notes from consortium or WP2 discussions.
This Report comprises six parts: (1) background and contextual overview of YouCount’s aims and intentions in implementing the multiple case study of hands-on Y-CSS; (2) planning and establishing Y-CSS; (3) recruitment, training and support of YCS; (4) methodologies adopted by the local cases including the designs, methods and data analysis conducted; (5) what co-creation meant in practice; (6) summary and conclusions.
The main target groups for this Deliverable are those interested in how Y-CSS can be conducted in practice, either as practitioner, scientists or evaluator of best practices
Translation in Transition: The Cabinet of Curiosities
Working collaboratively: digital and analogue, artist and machine, artist and artist is a constant activity of negotiation and translation – between code, language, process, matrix material and metaphor. The CFPR’s Artist in Residence programme aims to explore methods of translating between craft and the multiple, interactive fundamentals of ink on paper, digital modelling and 3D printing. The result is The Cabinet of Curiosities - a bespoke multifaceted, self-contained and portable travelling exhibition that, when unfolded, can be transformed into a wall-free exhibition space. The bespoke wooden Cabinet showcases a range of original multiples made using cutting-edge technologies. The following case studies are some examples of novel and unique artworks that span a range of digital and analogue tools as a transition and translation between artist and audience and a means to explore and discuss themes around digital, technology and creativity
Are microcycles with different training session numbers providing sufficient load for male soccer players? Load, wellness and training/match ratios analysis of a professional team
Professional soccer involves varying numbers of training sessions and matches each week, which can influence load distribution. Understanding the exact distribution may allow appropriate load periodisation and planning for players. Thus, this study aimed to (i) compare accumulated load and wellness between weeks with different numbers of training sessions and (ii) compare the training/match ratio (TMr) of external and internal load between weeks with different numbers of training sessions. Ten players with a minimum of 45 minutes of weekly match-play participation were analysed over 16 weeks. The microcycle structures consisted of three (3dW), four (4dW), five (5dW) and six (6dW) training sessions plus match-day per week. The following measures were used for analysis: duration, fatigue, quality of sleep, muscle soreness, stress, mood, rating of perceived exertion (RPE), session-RPE (s-RPE), high-speed running distance (HSR), sprint distance (SPD), number of accelerations (ACC) and number of decelerations (DEC). Accumulated wellness/load were calculated by adding all training and match sessions, while TMr was calculated by dividing the accumulated load by match data. The main results showed that accumulated wellness and load were significantly different, with moderate to very large effect sizes, except regarding mood, duration, s-RPE, SPD during 5dW vs 6dW and s-RPE, HSR, SPD, ACC and DEC during 3dW vs 4dW (all p > 0.05). Moreover, 6dW was significantly higher than 4dW regarding TMr of duration (p < 0.05, moderate effect size), RPE, HSR and SPD (all p < 0.05 with very large effect sizes) and for 3dW of HSR and ACC (p < 0.05 with very large effect sizes). This study showed that 5dW and 6dW had higher training measures than 3dW or 4dW. Additionally, higher wellness was presented in the microcycles with higher training frequencies. These findings suggest that physical load and wellness were not adjusted according to the number of training sessions within a microcycle