JURNAL AGROTEKNOLOGI
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Radioimmunotherapy for brain metastases: The potential for inflammation as a target of choice
No full textBrain metastases (BM) are frequently detected during the follow-up of patients with malignant tumors, particularly in those with advanced disease. Despite a major progress in systemic anti-cancer treatments, the average overall survival of these patients remains limited (6 months from diagnosis). Also, cognitive decline is regularly reported especially in patients treated with whole brain external beam radiotherapy (WBRT), due to the absorbed radiation dose in healthy brain tissue. New targeted therapies, for an earlier and/or more specific treatment of the tumor and its microenvironment, are needed. Radioimmunotherapy (RIT), a combination of a radionuclide to a specific antibody, appears to be a promising tool. Inflammation, which is involved in multiple steps, including the early phase, of BM development is attractive as a relevant target for RIT. This review will focus on the (1) early biomarkers of inflammation in BM pertinent for RIT, (2) state of the art studies on RIT for BM, and (3) the importance of dosimetry to RIT in BM. These two last points will be addressed in comparison to the conventional EBRT treatment, particularly with respect to the balance between tumor control and healthy tissue complications. Finally, because new diagnostic imaging techniques show a potential for the detection of BM at an early stage of the disease, we focus particularly on this therapeutic window
High-dose ion irradiation damage in Fe28Ni28Mn26Cr18 characterised by TEM and depth-sensing nanoindentation
No full textOne of the key challenges for the development of high-performance fusion materials is to design materials capable of maintaining mechanical and structural integrity under the extreme levels of displacement damage, high temperature and transmutation rates. High-entropy alloys (HEAs) and other concentrated alloys have attracted attention with regards to their performance under fusion conditions. In recent years, a number of investigations of the irradiation responses of HEAs have peaked the community’s interest in them, such as the work of Kumar et al. (2016), who examined Fe27Ni28Mn27Cr18 at doses as high as 10 dpa. In this work, we study Fe28Ni28Mn26Cr18 concentrated multicomponent alloy with irradiation doses as high as 20 dpa. We find the presence of Cr rich bcc precipitates in both the un-irradiated and in the irradiated condition, and the presence of dislocation loops only in the irradiated state. We correlate the features found with irradiation hardening by the continuous stiffness method (CSM) depth-sensing nanoindentation technique and see that the change in the bulk hardness increases significantly at 20 dpa for temperatures 450 °C. These results indicate that the alloy is neither stable as a single phase after annealing at 900 °C, nor particularly resistant to irradiation hardening
Modern Siberian dog ancestry was shaped by several thousand years of Eurasian-wide trade and human dispersal
No full textDogs have been essential to life in the Siberian Arctic for over 9,500 y, and this tight link between people and dogs continues in Siberian communities. Although Arctic Siberian groups such as the Nenets received limited gene flow from neighboring groups, archaeological evidence suggests that metallurgy and new subsistence strategies emerged in Northwest Siberia around 2,000 y ago. It is unclear if the Siberian Arctic dog population was as continuous as the people of the region or if instead admixture occurred, possibly in relation to the influx of material culture from other parts of Eurasia. To address this question, we sequenced and analyzed the genomes of 20 ancient and historical Siberian and Eurasian Steppe dogs. Our analyses indicate that while Siberian dogs were genetically homogenous between 9,500 to 7,000 y ago, later introduction of dogs from the Eurasian Steppe and Europe led to substantial admixture. This is clearly the case in the Iamal-Nenets region (Northwestern Siberia) where dogs from the Iron Age period (∼2,000 y ago) possess substantially less ancestry related to European and Steppe dogs than dogs from the medieval period (∼1,000 y ago). Combined with findings of nonlocal materials recovered from these archaeological sites, including glass beads and metal items, these results indicate that Northwest Siberian communities were connected to a larger trade network through which they acquired genetically distinctive dogs from other regions. These exchanges were part of a series of major societal changes, including the rise of large-scale reindeer pastoralism ∼800 y ago
Statin prescription in patients with chronic obstructive pulmonary disease and risk of exacerbations: a retrospective cohort study in the Clinical Practice Research Datalink
No full textObjective Observational studies have suggested a beneficial effect of taking statins on frequency of chronic obstructive pulmonary disease (COPD) exacerbations. However, clinical trials of statins in people with COPD did not confirm those results. This study aimed to investigate this association using a methodological approach, which reduces the biases associated with some previous observational study designs.
Design Retrospective cohort study comparing new-users of statins with non-users.
Setting General practices in England contributing to the Clinical Practice Research Datalink in 2007–2017, with linkage to data on Hospital Episode Statistics inpatient episodes.
Participants 48 124 people with COPD, aged over 40 years, who had not been prescribed statin in the previous year.
Exposure Participants became new-users of statins at their first prescription for a statin during follow-up. They were then assumed to remain statin users. Statin users were compared with non-users.
Outcomes Primary outcomes were COPD exacerbation, or severe exacerbation requiring hospitalisation. Secondary outcomes were death from any cause (for comparison with other studies) and urinary tract infection (negative-control). Maximum follow-up was 3 years. Adjusted HR were calculated using time-dependent Cox regression. The Andersen-Gill model was used for recurrent exacerbations. Covariates included demographic variables, variables related to COPD severity, cardiovascular comorbidities as time-dependent variables, and other comorbidities at baseline.
Results 7266 participants became new-users of statins over an average 2.5 years of follow-up. In total, 30 961 people developed an exacerbation, 8110 severe exacerbation, 3650 urinary tract infection and 5355 died. Adjusted HR (95% CI) in statin users compared with non-users were first exacerbation 1.01 (0.96–1.06), severe exacerbation 0.92 (0.84–0.99), number of exacerbations 1.00 (0.97–1.04), urinary tract infection 1.10 (0.98–1.23) and death 0.63 (0.57–0.70).
Conclusions In this study of health records from a Primary Care database, statin use in people with COPD was not associated with a lower risk of COPD exacerbation
Understanding the benefits and burdens associated with a malaria human infection study in Kenya: experiences of study volunteers and other stakeholders
No full textBackground
Human infection studies (HIS) that involve deliberately infecting healthy volunteers with a pathogen raise important ethical issues, including the need to ensure that benefits and burdens are understood and appropriately accounted for. Building on earlier work, we embedded social science research within an ongoing malaria human infection study in coastal Kenya to understand the study benefits and burdens experienced by study stakeholders in this low-resource setting and assess the wider implications for future research planning and policy.
Methods
Data were collected using qualitative research methods, including in-depth interviews (44), focus group discussions (10) and non-participation observation. Study participants were purposively selected (key informant or maximal diversity sampling), including volunteers in the human infection study, study staff, community representatives and local administrative authorities. Data were collected during and up to 18 months following study residency, from sites in Coastal and Western Kenya. Voice recordings of interviews and discussions were transcribed, translated, and analysed using framework analysis, combining data- and theory-driven perspectives.
Findings
Physical, psychological, economic and social forms of benefits and burdens were experienced across study stages. Important benefits for volunteers included the study compensation, access to health checks, good residential living conditions, new learning opportunities, developing friendships and satisfaction at contributing towards a new malaria vaccine. Burdens primarily affected study volunteers, including experiences of discomfort and ill health; fear and anxiety around aspects of the trial process, particularly deliberate infection and the implications of prolonged residency; anxieties about early residency exit; and interpersonal conflict. These issues had important implications for volunteers’ families, study staff and the research institution’s reputation more widely.
Conclusion
Developing ethically and scientifically strong HIS relies on grounded accounts of volunteers, study staff and the wider community, understood in the socioeconomic, political and cultural context where studies are implemented. Recognition of the diverse, and sometimes perverse, nature of potential benefits and burdens in a given context, and who this might implicate, is critical to this process. Prior and ongoing stakeholder engagement is core to developing these insights
Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance
No full textOf the 10 million people estimated to have fallen ill with tuberculosis (TB) in 2019, nearly half million developed TB resistant to rifampicin (RIF), and over one million developed TB susceptible to RIF but resistant to isoniazid (INH). Drug resistance must be detected rapidly and accurately to initiate appropriate and effective treatment.
The detection of RIF resistance has improved significantly in the past decade with the introduction of rapid diagnostic tools based on DNA detection. The introduction of these tests has dramatically increased the number of TB patients tested for RIF resistance, leading to a 129% increase of individuals started on second-line TB treatment between 2012 and 2019.
The majority of patients with RIF-resistant TB can be detected by analysing the 81-base pair fragment of the rpoB gene region. However, the situation is not that clear for other anti-TB drugs due to the lack of knowledge of how phenotypic resistance is associated with mutations in the Mycobacterium tuberculosis (Mtb) genome.
In response to this issue the WHO has developed a catalogue of Mtb mutations in the and their association with phenotypic drug resistance. The catalogue provides a reference standard for the interpretation of mutations conferring resistance to all first-line and a variety of second-line drugs. The report summarises the analysis of over 38,000 isolates with matched data on whole genome sequencing and phenotypic drug susceptibility testing from over 40 countries for 13 anti-TB medicines. It lists over 17,000 mutations, their frequency and association with or not with resistance and includes methods used, mutations identified and summaries of important findings for each drug.
Tuberculosis laboratories around the world can use the catalogue as a support in the interpretation of genome sequencing results. The catalogue can also guide the development of new molecular drug susceptibility tests, including next-generation sequencing
Institutionalizing ethics in AI through broader impact requirements
No full textTurning principles into practice is one of the most pressing challenges of artificial intelligence (AI) governance. In this Perspective, we reflect on a governance initiative by one of the world’s largest AI conferences. In 2020, the Conference on Neural Information Processing Systems (NeurIPS) introduced a requirement for submitting authors to include a statement on the broader societal impacts of their research. Drawing insights from similar governance initiatives, including institutional review boards (IRBs) and impact requirements for funding applications, we investigate the risks, challenges and potential benefits of such an initiative. Among the challenges, we list a lack of recognized best practice and procedural transparency, researcher opportunity costs, institutional and social pressures, cognitive biases and the inherently difficult nature of the task. The potential benefits, on the other hand, include improved anticipation and identification of impacts, better communication with policy and governance experts, and a general strengthening of the norms around responsible research. To maximize the chance of success, we recommend measures to increase transparency, improve guidance, create incentives to engage earnestly with the process, and facilitate public deliberation on the requirement’s merits and future. Perhaps the most important contribution from this analysis are the insights we can gain regarding effective community-based governance and the role and responsibility of the AI research community more broadly
Estimating ocean wave directional spreading using wave following buoys: a comparison of experimental buoy and gauge data
No full textDirectional spreading of ocean waves plays an important role in various aspects of ocean engineering, such as wave-induced loads, nonlinear wave evolution, and wave breaking. Wave following buoys, which are widely deployed across the oceans, offer the potential to measure directional wave properties. To assess the accuracy of directional spreading estimates made using buoy measurements, we compared estimates based on experimentally obtained buoy and wave gauge measurements, first presented in McAllister and van den Bremer (J Phys Oceanogr 50:399–414, 2020) Buoy and gauge measurements were recorded at the same locations and in identical sea states, allowing for a like-for-like comparison. We examine experiments with both following (unimodal in direction) and crossing (bimodal in direction) sea states. In addition to this, we use synthetic wave data to investigate the effects of wave generation and nonlinearity on spreading estimates. Our results show that while directional estimates produced using buoy measurements are reasonably accurate in following sea states, they struggle to identify distinct directional peaks in crossing sea states. We find that spreading estimates made using buoy measurements tend to underestimate the degree of directional spreading by approximately 9−14% in following sea states, which is most apparent in narrowly spread conditions
Expanded host and geographic range of tadpole associations with the Severe Perkinsea Infection group
No full textSevere Perkinsea infection is an emerging disease of amphibians, specifically tadpoles. Disease presentation correlates with liver infections of a subclade of Perkinsea (Alveolata) protists, named Pathogenic Perkinsea Clade (PPC). Tadpole mortality events associated with PPC infections have been reported across North America, from Alaska to Florida. Here, we investigate the geographic and host range of PPC associations in seemingly healthy tadpoles sampled from Panama, a biogeographic provenance critically affected by amphibian decline. To complement this work, we also investigate a mortality event among Hyla arborea tadpoles in captive-bred UK specimens. PPC SSU rDNA was detected in 10 of 81 Panama tadpoles tested, and H. arborea tadpoles from the UK. Phylogenies of the Perkinsea SSU rDNA sequences demonstrate they are highly similar to PPC sequences sampled from mortality events in the USA, and phylogenetic analysis of tadpole mitochondrial SSU rDNA demonstrates, for the first time, PPC associations in diverse hylids. These data provide further understanding of the biogeography and host range of this putative pathogenic group, factors likely to be important for conservation planning
Carers’ experiences of assistive technology use in dementia care: a cross sectional survey
No full textBackground:
Assistive Technology (AT) supports persons with dementia and their carers (family, friends and neighbours), yet little is known about experiences and the impact of AT on carers. We report on an exploratory survey that examined the types, uses, costs and impact of AT on carers as well as their quality of life.
Methods:
A cross-sectional survey using the Carers Assistive Technology Experience Questionnaire collected data from carers in the UK, who used at least one AT in the previous year and provided more than 10 hours of care for a person with dementia, living at home. Carers completed the questionnaire online or on paper and information on AT, socio-demographic details, and Short-Form Health Survey (SF-12) data were collected. Descriptive and inferential statistics were used to report results and draw conclusions.
Results:
Data from 201 carers was analysed. Smartphones and tablet computers were the most frequently used AT. AT were used predominantly for safety, communication, and reminders. Carers usually make decisions on buying and continued use of AT. Multiple AT devices were used in the care of persons with dementia and number of AT used was associated with perceived satisfaction. Satisfaction with AT was not related to age, living arrangements and relationship of carers. From the SF-12, Mean Physical Component Score was 49.19 (95%CI- 47.75 to 50.63) and Mental Component Score was 45.37 (95%CI- 43.93 to 46.80). Women, carers in the 46-65 age group and carers who were not extremely satisfied with AT had lower MCS scores. Carers who lived with the person with dementia and older carers had lower PCS scores.
Conclusions:
Carers report that AT has a beneficial impact. Carers use multiple ATs, perceive AT to be satisfactory and recommend AT use to others. To support carers, we recommend establishment of centrally funded information sources and a loan store for AT. Further research on incremental addition of AT and changes to formal/paid care because of using AT should be undertaken. Practitioners, academics, manufactures and policy makers should consider the experiences of carers in research, development and use of AT to facilitate improved community living of people with dementia