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Abstract Introduction High-quality evidence is crucial for guiding effective humanitarian responses, yet conducting rigorous research, particularly randomised controlled trials, in humanitarian crises remains challenging. The TISA (“traitement intégré de la sous-nutrition aiguë”) trial aimed to evaluate the impact of a Water, Sanitation and Hygiene (WASH) intervention on the standard national treatment of uncomplicated Severe Acute Malnutrition (SAM) in children aged 6–59 months. Implemented in two northern Senegalese regions from December 22, 2021, to February 20, 2023, the trial faced numerous challenges, which this paper explores along with the lessons learned. Methods The study utilised trial documentation, including field reports, meeting minutes, training plans, operational monitoring data and funding proposals, to retrace the trial timeline, identify challenges and outline implemented solutions. Contributions from all TISA key staff—current and former, field-based and headquarters—were essential for collecting and interpreting information. Challenges were categorised as internal (within the TISA consortium) or external (broader contextual issues). Results The TISA trial, executed by a consortium of academic, operational, and community stakeholders, enrolled over 2000 children with uncomplicated SAM across 86 treatment posts in a 28,000 km2 area. The control group received standard outpatient SAM care, while the intervention group also received a WASH kit and hygiene promotion. Initially planned to start in April 2019 for 12 months, the trial faced a 30-month delay and was extended to 27 months due to challenges like the COVID-19 pandemic, national strikes, health system integration issues and weather-related disruptions. Internal challenges included logistics, staffing, data management, funding and aligning diverse stakeholder priorities. Discussion and conclusion Despite these obstacles, the trial concluded successfully, underscoring the importance of tailored monitoring, open communication, transparency and community involvement. Producing high-quality evidence in humanitarian contexts demands extensive preparation and strong coordination among local and international researchers, practitioners, communities, decision-makers and funders from the study’s inception. Trial registration Clinicaltrials.gov NCT04667767 .

Abstract Background Colon capsule endoscopy (CCE) is a non-invasive alternative to colonoscopy. The reported sensitivity and specificity of CCE for the detection of clinically significant colonic neoplasia is high. To date, there have been no reported cases of colorectal cancer (CRC) missed by CCE which were located in segments adequately visualised by the capsule. Case presentation We present the case of a 71-year-old female, who underwent CCE for new lower gastrointestinal symptoms. The CCE reported 17 polyps (largest size 10 mm) and angiodysplasia. A 40 mm caecal pole tumour, not detected by the CCE, was identified at follow up colonoscopy. Surgical resection was performed, and the pathology sample was reported as moderately differentiated adenocarcinoma, pT2 pN0 (0/19) M0, with no evidence of EMVI. The patient made an uneventful recovery. The caecal pole tumour was not definitively identified on retrospective review of the CCE images. Conclusion To date, this is the first published case of a CRC missed entirely by CCE. Further research is required to allow calculation of the post CCE interval CRC rate to allow comparison with colonoscopy and CT colonogram.

Seaweed cultivation is gaining interest world-wide for both food and non-food applications. Global seaweed aquaculture production currently exceeds 32 Mt WW per annum but is dominated (86% of total) by Asian countries. To meet future demand for seaweed products, regions beyond Asia with aquaculture production potential are being explored. The goal of this study was to assess the suitability of the native kelp Macrocystis pyrifera (Phaeophyceae, Laminariales), for aquaculture in Tasmania, south-eastern Australia. M. pyrifera was cultivated on seeded twine on loops (1 – 5 m depth) along 100-m longlines at two sites (Okehampton Bay and Great Taylor Bay) from April-November 2020. Temporal and spatial variability in (1) yield (kg m-1, WW), (2) biofouling (% coverage), and (3) biochemical composition (including proximate composition, fatty acids, dietary minerals, heavy metal profiling, C, N, H, S concentrations and C:N ratio, antioxidants (phenolic compounds), and pigments (Chl-a, Chl-c, fucoxanthin)) was compared amongst the two cultivation sites, at two depths (1 and 5 m) from harvests between July – November 2020. Yield (kg m-1, WW) did not significantly change across harvest times, but was greater at a depth of 1 m compared to 5 m. Biofouling on the kelp blades increased significantly in early spring (September). The biochemical composition of the cultured biomass varied over time, between sites and with depth for most of the compounds analysed. Higher lipid, protein and ash content was reported for cultures cultivated at Okehampton Bay compared to Great Taylor Bay and at 5 m compared to 1 m depth, and levels of these macronutrients decreased during the harvest period. The iodine content was slightly above the tolerable content for dried seaweed products in Australia and New Zealand. The combined results of yield, biofouling, and biochemical composition suggest that, for an April deployment at the sites investigated, M. pyrifera should be harvested in July-August (mid to late winter) to optimise yield and quality of the cultured kelp biomass. These findings provide a better understanding of the variation in growth and quality of cultivated M. pyrifera biomass in the region, and inform future management and development of kelp aquaculture in south-eastern Australia and in a global context.

The water–energy–food (WEF) nexus has been promoted in recent years as an intersectional concept designed to improve planning and regulatory decision-making across the three sectors. The production and consumption of water, energy and food resources are inextricably linked across multiple spatial scales (from the global to the local), but a common feature is competition for land which through different land management practices mediates provisioning ecosystem services. The nexus perspective seeks to understand the interlinkages and use systems-based thinking to frame management options for the present and the future. It aims to highlight advantage and minimise damaging and unsustainable outcomes through informed decisions regarding trade-offs inclusive of economic, ecological and equity considerations. Operationalizing the WEF approach is difficult because of the lack of complete data, knowledge and observability – and the nature of the challenge also depends on the scale of the investigation. Transboundary river basins are particularly challenging because whilst the basin unit defines the hydrological system this is not necessarily coincident with flows of food and energy. There are multiple national jurisdictions and geopolitical relations to consider. Land use changes have a profound influence on hydrological, agricultural, energy provisioning and regulating ecosystem services. Future policy decisions in the water, energy and food sectors could have profound effects, with different demands for land and water resources, intensifying competition for these resources in the future. In this study, we used Google Earth Engine (GEE) to analyse the land cover changes in the Zambezi river basin (1.4 million km2) from 1992 to 2015 using the European Space Agency annual global land cover dataset. Early results indicate transformative processes are underway with significant shifts from tree cover to cropland, with a 4.6 % loss in tree cover and a 16 % gain in cropland during the study period. The changes were found to be occurring mainly in the eastern (Malawi and Mozambique) and southern (Zimbabwe and southern Zambia) parts of the basin. The area under urban land uses was found to have more than doubled during the study period gearing urban centres increasingly as the foci for resource consumption. These preliminary findings are the first step in understanding the spatial and temporal interlinkages of water, energy and food by providing reliable and consistent evidence spanning the local, regional, national and whole transboundary basin scale.

No abstract available. doi:10.2204/iodp.sd.15.10.2013

This paper raises some issues for discussion and debate concerning the nature of research within a mental health setting. Research, no matter what form it takes, is always an intervention. Sensitivity to various concerns surrounding research is required of the mental health worker. Participatory research, which is seen as empowering participants, has become popular in mental health programmes. Attention needs to be paid however, to the meaning of participation and the process of decision-making. Researchers are often uncomfortable with shedding their “objective informer” stance and adopting a position that requires social action. Some of this has to do with the epistemological view taken by the researcher. This paper suggests that the knowledge produced in research is a social construction created in interaction between the researcher and participants and has a multiplicity of potential meanings. The instrumental, conceptual and persuasive uses of research are discussed, and two intervention-type research procedures (needs assessment and evaluation) are critically reviewed It is concluded that research, as with all other interventions, should be carefully planned, implemented, monitored and evaluated.

ABSTRACT We report the first abundance and density estimates for American black bears (Ursus americanus) in Glacier National Park (NP), Montana, USA. We used data from 2 independent and concurrent noninvasive genetic sampling methods—hair traps and bear rubs—collected during 2004 to generate individual black bear encounter histories for use in closed population mark–recapture models. We improved the precision of our abundance estimate by using noninvasive genetic detection events to develop individual‐level covariates of sampling effort within the full and one‐half mean maximum distance moved (MMDM) from each bear's estimated activity center to explain capture probability heterogeneity and inform our estimate of the effective sampling area. Models including the one‐half MMDM covariate received overwhelming Akaike's Information Criterion support suggesting that buffering our study area by this distance would be more appropriate than no buffer or the full MMDM buffer for estimating the effectively sampled area and thereby density. Our model‐averaged super‐population abundance estimate was 603 (95% CI = 522–684) black bears for Glacier NP. Our black bear density estimate (11.4 bears/100 km2, 95% CI = 9.9–13.0) was consistent with published estimates for populations that are sympatric with grizzly bears (U. arctos) and without access to spawning salmonids. Published 2013. This article is a U.S. Government work and is in the public domain in the USA

The film Sunset Limited is an HBO adaptation of Cormac McCarthy’s play of the same name, and it is an in-depth character study of two individuals: Black (played by Samuel L. Jackson) and White (played by Tommy Lee Jones). In the beginning of the film, Black has already saved White from committing suicide and they are sitting together at a small, round kitchen table; viewers learn that Black was going to work when he saw White on the train platform about ready to jump in front of the Sunset Limited. Black is a religious Christian and White is an outright atheist; one believes in Jesus Christ and one believes in nothing; one has faith and one has no faith in anything. These ideological standpoints (the lack of an ideology is still an ideology) are the foundation of this text. The focus of Suset Limited is the push and pull between religious belief (Black) and philosophical thought (White), which ultimately will determine whether White stays and decides to live, or goes and decides to take his life. In essence, Sunset Limited is an exercise in rhetoric, in the art of persuasion, and how this artform can be used in both religious and secular conversation. This study of Sunset Limited will devote time to Cormac McCarthy’s connections to religion and philosophy using research about his work; then, there will be an in-depth textual analysis of the film, which will speak to not only who these characters are but also what they want to relay to one another about what they know (rather than what they believe) about the world. Black and White are polar opposites of each other (black and white); what this essay intends to prove is that there are similarities to their thought processes, even if they may not recognize it.

Epilepsy affects all ages, races, genders, and socioeconomic groups. In about one third of patients, epilepsy is uncontrolled with current medications, leaving a vast need for improved therapies. The causes of epilepsy are diverse and not always known but one gene mutated in a small subpopulation of patients is phosphatase and tensin homolog (PTEN). Moreover, focal cortical dysplasia, which constitutes a large fraction of refractory epilepsies, has been associated with signaling defects downstream of PTEN. So far, most preclinical attempts to reverse PTEN deficiency-associated neurological deficits have focused on mTOR, a signaling hub several steps downstream of PTEN. Phosphoinositide 3-kinases (PI3Ks), by contrast, are the direct enzymatic counteractors of PTEN, and thus may be alternative treatment targets. PI3K activity is mediated by four different PI3K catalytic isoforms. Studies in cancer, where PTEN is commonly mutated, have demonstrated that inhibition of only one isoform, p110β, reduces progression of PTEN-deficient tumors. Importantly, inhibition of a single PI3K isoform leaves critical functions of general PI3K signaling throughout the body intact. Here, we show that this disease mechanism-targeted strategy borrowed from cancer research rescues or ameliorates neuronal phenotypes in male and female mice with neuron-specific PTEN deficiency. These phenotypes include cell signaling defects, protein synthesis aberrations, seizures, and cortical dysplasia. Of note, p110β is also dysregulated and a promising treatment target in the intellectual disability Fragile X syndrome, pointing towards a shared biological mechanism that is therapeutically targetable in neurodevelopmental disorders of different etiologies. Overall, this work advocates for further assessment of p110β inhibition not only in PTEN deficiency-associated neurodevelopmental diseases but also other brain disorders characterized by defects in the PI3K/mTOR pathway.

Streptococcus sanguinis is an early colonizer of tooth surfaces and a key player in plaque biofilm development. However, the mechanism of biofilm formation of S. sanguinis is still unclear. Here, we showed that deletion of a transcription factor, brpL, promotes cell aggregation and biofilm formation in S. sanguinis SK36. Glucan, a polysaccharide synthesized from sucrose, was over-produced and aggregated in the biofilm of ΔbrpL, which was necessary for better biofilm formation ability of ΔbrpL. Quantitative RT-PCR demonstrated that gtfP was significantly up-regulated in ΔbrpL, which increased the productions of water-insoluble and water-soluble glucans. The ΔbrpLΔgtfP double mutant decreased biofilm formation ability of ΔbrpL to a level similar like that of ΔgtfP. Interestingly, the biofilm of ΔbrpL had an increased tolerance to ampicillin treatment, which might be due to better biofilm formation ability through the mechanisms of cellular and glucan aggregation. RNA sequencing and quantitative RT-PCR revealed the modulation of a group of genes in ΔbrpL was mediated by activating the expression of ciaR, another gtfP-related biofilm formation regulator. Double deletion of brpL and ciaR decreased biofilm formation ability to the phenotype of a ΔciaR mutant. Additionally, RNA sequencing elucidated a broad range of genes, related to carbohydrate metabolism and uptake, were activated in ΔbrpL. SSA_0222, a gene involved in the phosphotransferase system, was dramatically up-regulated in ΔbrpL and essential for S. sanguinis survival under our experimental conditions. In summary, brpL modulates glucan production, cell aggregation and biofilm formation by regulating the expression of ciaR in S. sanguinis SK36.

Using multiple detection methods can increase the number, kind, and distribution of individuals sampled, which may increase accuracy and precision and reduce cost of population abundance estimates. However, when variables influencing abundance are of interest, if individuals detected via different methods are influenced by the landscape differently, separate analysis of multiple detection methods may be more appropriate. We evaluated the effects of combining two detection methods on the identification of variables important to local abundance using detections of grizzly bears with hair traps (systematic) and bear rubs (opportunistic). We used hierarchical abundance models (N-mixture models) with separate model components for each detection method. If both methods sample the same population, the use of either data set alone should (1) lead to the selection of the same variables as important and (2) provide similar estimates of relative local abundance. We hypothesized that the inclusion of 2 detection methods versus either method alone should (3) yield more support for variables identified in single method analyses (i.e. fewer variables and models with greater weight), and (4) improve precision of covariate estimates for variables selected in both separate and combined analyses because sample size is larger. As expected, joint analysis of both methods increased precision as well as certainty in variable and model selection. However, the single-method analyses identified different variables and the resulting predicted abundances had different spatial distributions. We recommend comparing single-method and jointly modeled results to identify the presence of individual heterogeneity between detection methods in N-mixture models, along with consideration of detection probabilities, correlations among variables, and tolerance to risk of failing to identify variables important to a subset of the population. The benefits of increased precision should be weighed against those risks. The analysis framework presented here will be useful for other species exhibiting heterogeneity by detection method.

Interannual changes in the occurrence of Bryde’s whale (Balaenoptera edeni) have been observed in La Paz Bay (southwestern Gulf of California, Mexico) over the last 20 years. We suggest that these changes could be driven by natural fluctuations in food resources that are related to climate variability. We compared monthly Bryde’s whale occurrence in La Paz Bay from 1988 to 2006 to climate variability at seasonal and interannual time scales and its effect on prey availability. The results showed that Bryde’s whales do not have a well-defined pattern of seasonal occurrence; however, large numbers of whales were consistently recorded during La Niña conditions when the Gulf of California sardine population is distributed further south within the gulf. In contrast, fewer whales were recorded during El Niño and neutral conditions. This indicates that changes in the occurrence of Bryde’s whales at La Paz Bay are driven by the El Niño-Southern Oscillation interannual variability and are probably mediated by their prey availability.

Female transgenic mice that constitutively overexpress the transcription factor ATF3 in the basal epithelium of the mammary gland develop mammary carcinomas with high frequency, but only if allowed to mate and raise pups early in life. This transgenic mouse model system reproduces some features of human breast cancer in that about 20% of human breast tumor specimens exhibit overexpression of ATF3 in the tumor cells. The ATF3-induced mouse tumors are phenotypically similar to mammary tumors induced by overexpression of activating Wnt/β-catenin pathway genes. We now show that the Wnt/β-catenin pathway is indeed activated in ATF3-induced tumors. β-catenin is transcriptionally up-regulated in the tumors, and high levels of nuclear β-catenin are seen in tumor cells. A reporter gene for Wnt/β-catenin pathway activity, TOPGAL, is up-regulated in the tumors and several downstream targets of Wnt signaling, including Ccnd1, Jun, Axin2 and Dkk4, are also expressed at higher levels in ATF3-induced tumors compared to mammary glands of transgenic females. Several positive-acting ligands for this pathway, including Wnt3, Wnt3a, Wnt7b, and Wnt5a, are significantly overexpressed in tumor tissue, and mRNA for Wnt3 is about 5-fold more abundant in transgenic mammary tissue than in non-transgenic mammary tissue. Two known transcriptional targets of ATF3, Snai1 and Snai2, are also overexpressed in the tumors, and Snail and Slug proteins are found to be located primarily in the nuclei of tumor cells. In vitro knockdown of Atf3 expression results in significant decreases in expression of Wnt7b, Tcf7, Snai2 and Jun, suggesting that these genes may be direct transcriptional targets of ATF3 protein. By chromatin immunoprecipitation analysis, both ATF3 and JUN proteins appear to bind to a particular subclass of AP-1 sites upstream of the transcriptional start sites of each of these genes.