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28 result(s) for "Fortin, Elizabeth"
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‘New agriculture’ for sustainable development? Biofuels and agrarian change in post-war Sierra Leone
In sub-Saharan Africa, commercial bioenergy production has been hailed as a new form of ‘green capitalism’ that will deliver ‘win-win’ outcomes and ‘pro poor’ development. Yet in an era of global economic recession and soaring food prices, biofuel ‘sustainability’ has been at the centre of controversy. This paper focuses on the case of post-war Sierra Leone, a country that has over the last decade been consistently ranked as one of the poorest in the world, facing food insecurity, high unemployment and entrenched poverty. Following a recent government strategy to secure foreign direct investment in biofuels production in agriculturally rich regions of the country, the largest foreign investment in Sierra Leone since the end of its civil war has been secured: a Swiss company is to invest US$368 million into a large-scale biofuels project over the course of 3 years, and promises to simultaneously stimulate an enabling environment for investment, provide job opportunities for youth and increase food production. For multiple actors involved in the project, the concept of ‘sustainability’ is crucial but accordingly there are varying interpretations of its meaning. Such differences in interpretation and the complex contradictions within discourses of sustainability are in turn framed by the various scales within which these actors are situated. While attempts have been made to manage these contradictions through global sustainability standards, the unequal power relations between different actors will ultimately determine the ways in which they are likely to be resolved. The paper concludes by reflecting on how these processes may be contributing to a changing governance landscape and wider global political economy within which bioenergy is being produced, processed and consumed.
Struggles with activism: NGO engagements with land tenure reform in post-apartheid South Africa
In 2004, a long-awaited piece of post-apartheid legislation, the Communal Land Rights Act – to reform the land tenure of those living in the former ‘homelands’ of South Africa – was passed into law unanimously by parliament. This unanimity, however, conceals the extent to which the process towards this moment was deeply contested. Exploring the efforts by land sector NGOs to secure legitimacy in their engagements with this process reveals the extent to which wider power relations and contestations have determined their positioning. Those within the non-governmental land sector who opposed the legislation pitted themselves against African National Congress politicians and high-profile traditional leaders. However, the adoption of a Mamdani-inspired discourse to contest such politics and oppose the proposed legislation contributed to reinscribing narrow readings of knowledge considered to be legitimate. Their engagements were also shaped by changes in the NGO sector. Reduced funding for land sector NGOs and an increasingly ambivalent relationship between them and government contributed to contestations between NGOs and among people working within them. Their strategic engagements in such wider and internal politics influenced both the frames within which such policy change could be debated and the ways in which individuals working for NGOs consequently positioned themselves in relation to their constituents.
Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g>A/ND4-LHON
ObjectiveREFLECT is the first randomised, double-masked, placebo-controlled multicentre phase 3 clinical trial that evaluated the efficacy and safety of bilateral intravitreal (IVT) injection of lenadogene nolparvovec in subjects with Leber hereditary optic neuropathy carrying the m.11778G>A mutation.Methods and analysisA total of 98 subjects were enrolled with vision loss of ≤12 months. The subjects were randomised to one of two treatment arms with all subjects receiving an intravitreal (IVT) injection of lenadogene nolparvovec in their first affected eye and the second-affected eye randomised to receive IVT of either lenadogene nolparvovec or placebo.ResultsThe majority of subjects were male with a mean duration of vision loss of 8.3 months. All but one subject experienced bilateral loss of vision at the time of injection. The mean best-corrected visual acuity of first-affected eyes was worse compared with second/not-yet-affected eyes. Analysis of retinal anatomical parameters showed increased thinning in the first-affected eyes when compared with the second/not-yet-affected eyes with both treatment arms showing significant changes compared with unaffected individuals.ConclusionThe REFLECT trial is the third and the largest phase 3 clinical study evaluating lenadogene nolparvovec in m.11778G>A Leber hereditary optic neuropathy (LHON) subjects. The observed demographics in REFLECT are consistent with previous reports in LHON subjects in the acute and dynamic phases of LHON disease. Combined with the visual function and anatomical parameters obtained in the previous RESCUE and REVERSE trials, REFLECT has provided a uniformly collected data set that should help direct future LHON clinical trials.
Removing inter-subject technical variability in magnetic resonance imaging studies
Magnetic resonance imaging (MRI) intensities are acquired in arbitrary units, making scans non-comparable across sites and between subjects. Intensity normalization is a first step for the improvement of comparability of the images across subjects. However, we show that unwanted inter-scan variability associated with imaging site, scanner effect, and other technical artifacts is still present after standard intensity normalization in large multi-site neuroimaging studies. We propose RAVEL (Removal of Artificial Voxel Effect by Linear regression), a tool to remove residual technical variability after intensity normalization. As proposed by SVA and RUV [Leek and Storey, 2007, 2008, Gagnon-Bartsch and Speed, 2012], two batch effect correction tools largely used in genomics, we decompose the voxel intensities of images registered to a template into a biological component and an unwanted variation component. The unwanted variation component is estimated from a control region obtained from the cerebrospinal fluid (CSF), where intensities are known to be unassociated with disease status and other clinical covariates. We perform a singular value decomposition (SVD) of the control voxels to estimate factors of unwanted variation. We then estimate the unwanted factors using linear regression for every voxel of the brain and take the residuals as the RAVEL-corrected intensities. We assess the performance of RAVEL using T1-weighted (T1-w) images from more than 900 subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI), as well as healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We compare RAVEL to two intensity-normalization-only methods: histogram matching and White Stripe. We show that RAVEL performs best at improving the replicability of the brain regions that are empirically found to be most associated with AD, and that these regions are significantly more present in structures impacted by AD (hippocampus, amygdala, parahippocampal gyrus, enthorinal area, and fornix stria terminals). In addition, we show that the RAVEL-corrected intensities have the best performance in distinguishing between MCI subjects and healthy subjects using the mean hippocampal intensity (AUC=67%), a marked improvement compared to results from intensity normalization alone (AUC=63% and 59% for histogram matching and White Stripe, respectively). RAVEL is promising for many other imaging modalities. •Between-scan unwanted variation is still present after intensity normalization.•We propose a scan-effect removal tool for removing post-normalization artifacts.•We model the unwanted variability between MRI T1-w scans using CSF region.•We use a large subset of the ADNI database to showcase our method.•We show that our method improves replicability of the voxels associated with AD.•MRI intensities corrected by our method improves prediction of AD and MCI.
Leveraging Open‐Source Geographic Databases to Enhance the Representation of Landscape Heterogeneity in Ecological Models
Wildlife abundance and movement are strongly impacted by landscape heterogeneity, especially in cities which are among the world's most heterogeneous landscapes. Nonetheless, current global land cover maps, which are used as a basis for large‐scale spatial ecological modeling, represent urban areas as a single, homogeneous, class. This often requires urban ecologists to rely on geographic resources from local governments, which are not comparable between cities and are not available in underserved countries, limiting the spatial scale at which urban conservation issues can be tackled. The recent expansion of community‐based geographic databases, for example, OpenStreetMap (OSM), represents an opportunity for ecologists to generate large‐scale maps geared toward their specific research needs. However, computational differences in language and format, and the high diversity of information within, limit the access to these data. We provide a framework, using R, to extract geographic features from the OSM database, classify, and integrate them into global land cover maps. The framework includes an exhaustive list of OSM features describing urban and peri‐urban landscapes and is validated by quantifying the completeness of the OSM features characterized, and the accuracy of its final output in 34 cities in North America. We portray its application as the basis for generating landscape variables for ecological analysis by using the OSM‐enhanced map to generate an urbanization index, and subsequently analyze the spatial occupancy of six mammals throughout Chicago, Illinois, USA. The OSM features characterized had high completeness values for impervious land cover classes (50%–100%). The final output, the OSM‐enhance map, provided an 89% accurate representation of the landscape at 30m resolution. The OSM‐derived urbanization index outperformed other global spatial data layers in the spatial occupancy analysis and concurred with previously seen local response trends, whereby lagomorphs and squirrels responded positively to urbanization, while skunks, raccoons, opossums, and deer responded negatively. This study provides a roadmap for ecologists to leverage the fine resolution of open‐source geographic databases and apply it to spatial modeling by generating research‐specific landscape variables. As our occupancy results show, using context‐specific maps can improve modeling outputs and reduce uncertainty, especially when trying to understand anthropogenic impacts on wildlife populations. We leverage the resolution power of OpenStreetMap to improve the representation of landscapeheterogeneity in urban areas within LULC maps. To assess the information extracted with our framework, we conducted extensive testing in 34 North American cities, comparing our output to spatial data commonly used as landscape variables for ecological studies worldwide. The results demonstrated a ~90% accuracy in representing landscape heterogeneity, reinforcing the practicality and reliability of our approach. We included a case study to demonstrate the framework's applicability in ecological research where we developed a wildlife‐specific urbanization index representing habitat and shelter availability, vicinity to water resources, and road presence to analyze spatial occupancy of urban mammals. We predicted the spatial distribution of six mammal species across 93 camera trap sites in Chicago. We compared the predictions against using the “human influence index” as a landscape variable. The results from our case study demonstrated our framework strongly improved the model outputs, as it allows for higher resolution and context‐specific spatial variables.
Liver stage malaria infection is controlled by host regulators of lipid peroxidation
The facets of host control during Plasmodium liver infection remain largely unknown. We find that the SLC7a11-GPX4 pathway, which has been associated with the production of reactive oxygen species, lipid peroxidation, and a form of cell death called ferroptosis, plays a critical role in control of Plasmodium liver stage infection. Specifically, blocking GPX4 or SLC7a11 dramatically reduces Plasmodium liver stage parasite infection. In contrast, blocking negative regulators of this pathway, NOX1 and TFR1, leads to an increase in liver stage infection. We have shown previously that increased levels of P53 reduces Plasmodium LS burden in an apoptosis-independent manner. Here, we demonstrate that increased P53 is unable to control parasite burden during NOX1 or TFR1 knockdown, or in the presence of ROS scavenging or when lipid peroxidation is blocked. Additionally, SLC7a11 inhibitors Erastin and Sorafenib reduce infection. Thus, blocking the host SLC7a11-GPX4 pathway serves to selectively elevate lipid peroxides in infected cells, which localize within the parasite and lead to the elimination of liver stage parasites.
External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial
Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov, NCT00282035. Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p<0·0001). Late radiation toxicity (grade ≥2, later than 3 months) was more common in patients treated with APBI (346 [32%] of 1070 patients) than whole breast irradiation (142 [13%] of 1065 patients; p<0·0001). Adverse cosmesis (defined as fair or poor) was more common in patients treated with APBI than in those treated by whole breast irradiation at 3 years (absolute difference, 11·3%, 95% CI 7·5–15·0), 5 years (16·5%, 12·5–20·4), and 7 years (17·7%, 12·9–22·3). External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.
Changes to Parental Consent Requirements for Abortion in Massachusetts and Impact on Timeliness of Care for Adolescents Aged 16 to 17 Years
Objectives. To measure the effect of the ROE Act, which eliminated parental consent requirements for abortion for individuals ages 16 to 17 years, on abortion timing for adolescents in this age group in Massachusetts. Methods. The primary outcome was gestational duration at abortion for individuals aged 16 to 19 years at Planned Parenthood League of Massachusetts from 2017 to 2022. Our control group included abortions among those aged 18 to 19 years. In our primary analysis, we used a comparative interrupted time series with a linear model to capture temporal trends, seasonality, whether an abortion was undergone during the acute phase of the COVID-19 pandemic, previous abortion, and race/ethnicity categories. Results. Minors aged 16 to 17 years underwent 749 abortions during the study. Individuals aged 18 to 19 years underwent 2773 abortions. The ROE Act resulted in a 5.46-day decrease in gestational duration at abortion among minors (95% confidence interval = −11.82, 0.91). Conclusions. Removal of the parental involvement requirement for adolescents aged 16 to 17 years in Massachusetts led to minors undergoing abortions at earlier gestational durations, highlighting the importance of potential impacts of similar legislation to decrease barriers to abortion access for minors. ( Am J Public Health. 2025;115(3):397–402. https://doi.org/10.2105/AJPH.2024.307918 )
COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series
ObjectiveTo assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease.MethodsWe conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed.ResultsFrequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2–53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection.ConclusionIn COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection.
KEeP ACTIVe Club Study: Kidney Transplant Recipients’ Experiences of a Physical Activity and Social Interaction Virtual Group
Background: It can be difficult for kidney transplant recipients (KTRs) to be physically active after their transplantation. Physical inactivity is a risk factor for cardiovascular disease, one of the leading cause of death among KTRs. To help KTRs start and maintain a physical activity routine, we developed the KEeP ACTIVe Club, a 6-month online intervention with access to a kinesiologist, a patient partner, and a private support group with an online platform (Facebook). Objective: The objective of this study was to capture the participants’ experiences of the KEeP ACTIVe Club. Design: Individual interviews. Setting: The Center hospitalier de l’Université de Montréal (CHUM) and the McGill University Health Center (MUHC) kidney transplant programs. Participants: Kidney transplant recipients who participated in the KEeP ACTIVe Club. Methods: Between October and December 2021, we conducted 11 individual semi-directed interviews with KTRs from 2 urban kidney transplant programs who participated in the KEeP ACTIVe Club. The interviews were digitally recorded and transcribed. Thematic analysis was conducted. Results: Participants’ principal motivation to participate in the KEeP ACTIVe Club was to improve their physical fitness following their transplant in a pandemic period. One of the main benefits of the KEeP ACTIVe Club was the improvement of participant’s self-confidence and the knowledge gained regarding exercises adapted to their reality as KTRs. However, the small number of participants and the schedules of classes offered were viewed as a pitfall of the current intervention. Finally, the peer mentoring and support gained by other participants were important and viewed as highly impactful aspects of the KEeP ACTIVe Club. Limitations: Only 11 of the 18 patients who participated in the KEeP ACTIVe Club took part in the interviews. Conclusion: Participants reported a positive experience with the KEeP ACTIVe Club. Peer mentoring and support gained from other participants seem to be essential aspects of the experience within the KEeP ACTIVe Club. This program is a good avenue to offer in post-transplant care to help KTRs to be more active and to connect with other patients.