Global phylogenomic assessment of Leptoseris and Agaricia reveals substantial undescribed diversity at mesophotic depths.

BACKGROUND: Mesophotic coral communities are increasingly gaining attention for the unique biological diversity they host, exemplified by the numerous mesophotic fish species that continue to be discovered. In contrast, many of the photosynthetic scleractinian corals observed at mesophotic depths are assumed to be depth-generalists, with very few species characterised as mesophotic-specialists. This presumed lack of a specialised community remains largely untested, as phylogenetic studies on corals have rarely included mesophotic samples and have long suffered from resolution issues associated with traditional sequence markers. RESULTS: Here, we used reduced-representation genome sequencing to conduct a phylogenomic assessment of the two dominant mesophotic genera of plating corals in the Indo-Pacific and Western Atlantic, respectively, Leptoseris and Agaricia. While these genome-wide phylogenies broadly corroborated the morphological taxonomy, they also exposed deep divergences within the two genera and undescribed diversity across the current taxonomic species. Five of the eight focal species consisted of at least two sympatric and genetically distinct lineages, which were consistently detected across different methods. CONCLUSIONS: The repeated observation of genetically divergent lineages associated with mesophotic depths highlights that there may be many more mesophotic-specialist coral species than currently acknowledged and that an urgent assessment of this largely unstudied biological diversity is warranted.

Children´s priorities to improve the acceptability of MDR-TB treatment: qualitative data from South Africa.

BACKGROUND: Multidrug-resistant TB (MDR-TB) treatment for children frequently includes unpalatable drugs with low overall acceptability. This can negatively impact children and their caregivers´ treatment experiences and is an important contributor to poor adherence, and potentially, poor treatment outcomes. Children and their caregivers´ preferences for MDR-TB treatment are not well documented. We describe children and caregivers´ priorities to inform future MDR-TB treatment regimens.METHODS: We conducted a cross-sectional qualitative study at a TB hospital in South Africa using semi-structured interviews and participatory research activities with caregivers and children routinely diagnosed and treated for MDR-TB between June and August 2018.RESULTS: We conducted 15 interviews with children and their caregivers. Children ranged from 2 to 17 years of age (median age: 8.3 years). Children and caregivers had an overall negative experience of MDR-TB treatment. Children and caregivers described how future MDR-TB drugs and regimens should prioritise sweeter flavours, fewer pills, brighter colours, and formulations that are easy to prepare and administer and dispensed in colourful, small and discrete packaging.CONCLUSIONS: MDR-TB treatment acceptability remains low, and negatively impacts children and their caregivers´ treatment experiences. Improving the overall acceptability of MDR-TB treatment requires engaging with children and their caregivers to better understand their priorities for new treatment regimens and child-friendly formulations.

Implementation of behaviour change training in practice amongst pharmacy professionals in primary care settings: Analysis using the COM-B model.

BACKGROUND: The Pharmacy Integration Fund (PhIF) was established in England in 2016, with funded learning programmes or 'pathways' designed to support the development of clinical pharmacy practice in a range of settings. Despite pharmacy staff being well positioned to provide more clinical work, limited research has investigated behaviour change training targeted at widespread practice transformation. OBJECTIVE(S): To investigate implementation of PhIF learning in practice, using the COM-B model of behaviour change. METHODS: An online survey distributed in February and October 2020 included questions on motivations for learning, confidence in target behaviours and impact of PhIF training on behaviour. The October 2020 survey also included questions exploring the effect of the COVID-19 pandemic. Quantitative data were analysed in SPSS. v.27 (IBM). Inferential statistics were used to compare between the pathways (Primary care pathways [PCP], Post-registration pathway [PRP] and Accuracy Checking Pharmacy Technician [ACPT] pathway). Free text comments were categorised and themed. RESULTS: Three-hundred and eighty-three responses were received (49% PRP learners, 39% PCP learners and 12% ACPT learners). Learners generally had the capacity and opportunities to apply learning, and were strongly motivated to implement behaviours in practice, although learners based in community pharmacy (those on the PRP) were less likely to report receiving employer support. Enhanced knowledge/skills (capacity) were more commonly reported than change to patient-facing activities, leading clinical services and conducting medication reviews with patients with complex needs (clinical practice behaviours targeted by the pathways). The COVID-19 pandemic heightened barriers to implementing practice change. CONCLUSIONS: Implementation of a range of clinical practice behaviours following at scale training appears to have been largely successful. Despite this, the community pharmacy context, where funded service opportunities may be lacking, continues to present challenges to workforce transformation plans. More work is needed to understand how training can be implemented to promote practice change for pharmacy professionals in all settings.

A flexible proton beam imaging energy spectrometer (PROBIES) for high repetition rate or single-shot high energy density (HED) experiments (invited).

The PROBIES diagnostic is a new, highly flexible, imaging and energy spectrometer designed for laser-accelerated protons. The diagnostic can detect low-mode spatial variations in the proton beam profile while resolving multiple energies on a single detector or more. When a radiochromic film stack is employed for "single-shot mode," the energy resolution of the stack can be greatly increased while reducing the need for large numbers of films; for example, a recently deployed version allowed for 180 unique energy measurements spanning ∼3 to 75 MeV with <0.4 MeV resolution using just 20 films vs 180 for a comparable traditional film and filter stack. When utilized with a scintillator, the diagnostic can be run in high-rep-rate (>Hz rate) mode to recover nine proton energy bins. We also demonstrate a deep learning-based method to analyze data from synthetic PROBIES images with greater than 95% accuracy on sub-millisecond timescales and retrained with experimental data to analyze real-world images on sub-millisecond time-scales with comparable accuracy.

Title: Obesogenic microbial signatures and the development of obesity in childhood acute lymphoblastic leukemia.

Childhood acute lymphoblastic leukemia (ALL) is the most common childhood cancer with survival exceeding 90% for standard-risk groups. A debilitating side-effect of treatment is the development of overweight/obesity (OW/OB), which develops in approximately 40% of children by the end of treatment. The microbiome has been associated with the development of OW/OB. We examined fluctuations in the microbiome with the development of OW/OB during the first six months of treatment at diagnosis, and two subsequent timepoints (N = 62). Shotgun metagenomic sequencing was performed on Illumina Nextseq system, and taxa and functional pathways were extracted from sequences using kraken2 and humann2, respectively. An association of increased presence of several species (e.g., Klebsiella pneumoniae, Escherichia coli) was observed in children with OW/OB, while lean-promoting species (Veillonella, Haemophilus, and Akkermansia) were increased in children who maintained a normal weight. Pathway analysis revealed purine nucleotide biosynthesis, sugar nucleotide biosynthesis, and enzyme cofactor biosynthesis were positively correlated with Bacteroides spp. among children with OW/OB. We identified several taxa and functional pathways that may confer increased risk for the development of OW/OB. The associations observed in this pilot are preliminary and warrant further research in the microbiome and the development of OW/OB in childhood ALL.

PRECISION: the Belgian molecular profiling program of metastatic cancer for clinical decision and treatment assignment.

PRECISION is an initiative from the Belgian Society of Medical Oncology (BSMO) in collaboration with several stakeholders, encompassing four programs that aim to boost genomic and clinical knowledge with the ultimate goal to offer patients with metastatic solid tumors molecularly guided treatments. The PRECISION 1 study has led to the creation of a clinico-genomic database. The Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT) and GeNeo studies will increase the number of patients with advanced cancer that have comprehensive genotyping of their cancer. The PRECISION 2 project consists of investigator-initiated phase II studies aiming to provide access to a targeted drug for patients whose tumors harbor actionable mutations in case the matched drug is not available through reimbursement or clinical trials in Belgium.

Defibrillator generator replacements in patients with left ventricular assist device support: The risks of hematoma and infection.

BACKGROUND: The majority (89%) of left ventricular assist device (LVAD) patients have an implantable cardioverter-defibrillator (ICD) in place. Due to the advances of modern-day LVAD therapy, more patients are on support for longer. This inevitably leads to more LVAD patients facing ICD generator battery depletion. Until now, there are insufficient data regarding periprocedural risks of generator replacements in a high-risk group like the LVAD cohort. METHODS: A retrospective, single-center analysis of pocket-related outcomes of all ICD generator replacements in LVAD and Non-LVAD patients between January 2014 and December 2018. The primary outcome was the combined endpoint of clinically significant pocket hematoma and/or cardiac implantable electronic device (CIED) infection in the first 6 months after ICD generator exchange. The clinically significant hematoma was defined as hematoma requiring reoperation, prolongation of hospitalization, or interruption of anticoagulation. The cumulative incidence function was calculated for the primary endpoint. RESULTS: Two hundred seventy-seven patients underwent ICD generator exchange in our clinic in this time. Of these, 251 patients had a complete 6-month follow-up regarding clinically significant pocket hematomas and pocket infections. One hundred ninety patients had no LVAD, and 61 patients were on LVAD support. The rate of the primary combined endpoint clinically significant pocket hematoma and/or CIED infection was 3.5 times higher in LVAD patients compared to the non-LVAD cohort (event rate 39.14 vs 11.07 per 100 patient-years, p = 0.048). Clinically significant pocket hematomas necessitating revision occurred nearly 4 times more often in the LVAD group (p = 0.042). Pocket device infection rates were around 16 times higher in LVAD patients compared to non-LVAD patients (p = 0.002). CONCLUSIONS: Compared to Non-LVAD patients, LVAD patients exhibit a relevant higher rate of clinically significant pocket hematoma and CIED infection after ICD generator exchange. This information should additionally be considered in the decision-making process regarding the indication for ICD generator exchange.

Evaluating the implementation of a multi-level mHealth study to improve hydroxyurea utilization in sickle cell disease.

Background: Sickle Cell Disease (SCD) is a progressive genetic disease that causes organ damage and reduces longevity. Hydroxyurea is an underutilized evidence-based medication that reduces complications and improves survival in SCD. In a multi-site clinical trial, part of the NIH-funded Sickle Cell Disease Implementation Consortium (SCDIC), we evaluate the implementation of a multi-level and multi-component mobile health (mHealth) patient and provider intervention to target the determinants and context of low hydroxyurea use. Given the complexity of the intervention and contextual variability in its implementation, we combined different behavioral and implementation theories, models, and frameworks to facilitate the evaluation of the intervention implementation. In this report, we describe engagement with stakeholders, planning of the implementation process, and final analytical plan to evaluate the implementation outcomes. Methods: During 19 meetings, a 16-member multidisciplinary SCDIC implementation team created, conceived, and implemented a project that utilized Intervention Mapping to guide designing an intervention and its evaluation plan. The process included five steps: (1) needs assessment of low hydroxyurea utilization, (2) conceptual framework development, (3) intervention design process, (4) selection of models and frameworks, and (5) designing evaluation of the intervention implementation. Results: Behavioral theories guided the needs assessment and the design of the multi-level mHealth intervention. In designing the evaluation approach, we combined two implementation frameworks to best account for the contextual complexity at the organizational, provider, and patient levels: (1) the Consolidated Framework for Implementation Research (CFIR) that details barriers and facilitators to implementing the mHealth intervention at multiple levels (users, organization, intervention characteristics, broader community), and (2) the Technology Acceptance Model (TAM), a conceptual model specific for explaining the intent to use new information technology (including mHealth). The Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM) framework was used to measure the outcomes. Discussion: Our research project can serve as a case study of a potential approach to combining different models/frameworks to help organize and plan the evaluation of interventions to increase medication adherence. The description of our process may serve as a blueprint for future studies developing and testing new strategies to foster evidence-based treatments for individuals living with SCD.

Urban stormwater nutrient and metal removal in small-scale green infrastructure: exploring engineered plant biofilter media optimisation.

The present study evaluated engineered media for plant biofilter optimisation in an unvegetated column experiment to assess the performance of loamy sand, perlite, vermiculite, zeolite and attapulgite media under stormwater conditions enriched with varying nutrients and metals reflecting urban pollutant loads. Sixty columns, 30 unvegetated and 30 Juncus effusus vegetated, were used to test: pollutant removal, infiltration rate, particulate discharge, effluent clarity and plant functional response, over six sampling rounds. All engineered media outperformed conventional loamy sand across criteria, with engineered attapulgite consistently among the best performers. No reportable difference existed in vegetation exposed to different material combinations. For all media, the results show a net removal of NH3-N, PO43--P, Cd, Cu, Pb and Zn and an increase of NO3--N, emphasizing the importance of vegetation in biofilters. Growth media supporting increased rate of infiltration whilst maintaining effective remediation performance offers the potential for reducing the area required by biofilters, currently recommended at 2% of its catchment area, encouraging the use of small-scale green infrastructure in the urban area. Further research is required to assess the carrying capacity of engineered media in laboratory and field settings, particularly during seasonal change, gauging the substrate's potential moisture availability for root uptake.

An unanticipated tumor-suppressive role of the SUMO pathway in the intestine unveiled by Ubc9 haploinsufficiency.

Sumoylation is an essential posttranslational modification in eukaryotes that has emerged as an important pathway in oncogenic processes. Most human cancers display hyperactivated sumoylation and many cancer cells are remarkably sensitive to its inhibition, thus supporting application of chemical sumoylation inhibitors in cancer treatment. Here we show, first, that transformed embryonic fibroblasts derived from mice haploinsufficient for Ubc9, the essential and unique gene encoding the SUMO E2 conjugating enzyme, exhibit enhanced proliferation and transformed phenotypes in vitro and as xenografts ex vivo. To then evaluate the possible impact of loss of one Ubc9 allele in vivo, we used a mouse model of intestinal tumorigenesis. We crossed Ubc9+/- mice with mice harboring a conditional ablation of Apc either all along the crypt-villus axis or only in Lgr5+ crypt-based columnar (CBC) cells, the cell compartment that includes the intestinal stem cells proposed as cells-of-origin of intestinal cancer. While Ubc9+/- mice display no overt phenotypes and no globally visible hyposumoylation in cells of the small intestine, we found, strikingly, that, upon loss of Apc in both models, Ubc9+/- mice develop more (>2-fold) intestinal adenomas and show significantly shortened survival. This is accompanied by reduced global sumoylation levels in the polyps, indicating that Ubc9 levels become critical upon oncogenic stress. Moreover, we found that, in normal conditions, Ubc9+/- mice show a moderate but robust (15%) increase in the number of Lgr5+ CBC cells when compared to their wild-type littermates, and further, that these cells display higher degree of stemness and cancer-related and inflammatory gene expression signatures that, altogether, may contribute to enhanced intestinal tumorigenesis. The phenotypes of Ubc9 haploinsufficiency discovered here indicate an unanticipated tumor-suppressive role of sumoylation, one that may have important implications for optimal use of sumoylation inhibitors in the clinic.

Bayesian strategy selection identifies optimal solutions to complex problems using an example from GP prescribing.

Complex health problems require multi-strategy, multi-target interventions. We present a method that uses machine learning techniques to choose optimal interventions from a set of possible interventions within a case study aiming to increase General Practitioner (GP) discussions of physical activity (PA) with their patients. Interventions were developed based on a causal loop diagram with 26 GPs across 13 clinics in Geelong, Australia. GPs prioritised eight from more than 80 potential interventions to increase GP discussion of PA with patients. Following a 2-week baseline, a multi-arm bandit algorithm was used to assign optimal strategies to GP clinics with the target outcome being GP PA discussion rates. The algorithm was updated weekly and the process iterated until the more promising strategies emerged (a duration of seven weeks). The top three performing strategies were continued for 3 weeks to improve the power of the hypothesis test of effectiveness for each strategy compared to baseline. GPs recorded a total of 11,176 conversations about PA. GPs identified 15 factors affecting GP PA discussion rates with patients including GP skills and awareness, fragmentation of care and fear of adverse outcomes. The two most effective strategies were correctly identified within seven weeks of the algorithm-based assignment of strategies. These were clinic reception staff providing PA information to patients at check in and PA screening questionnaires completed in the waiting room. This study demonstrates an efficient way to test and identify optimal strategies from multiple possible solutions.

Citizen science in hydrological monitoring and ecosystem services management: State of the art and future prospects.

Hydrological monitoring is essential to guide evidence-based decision making necessary for sustainable water resource management and governance. Limited hydrometric datasets and the pressure on long-term hydrological monitoring networks make it paramount to explore alternative methods for data collection. This is particularly the case for low-income countries, where data scarcity is more pronounced, and where conventional monitoring methods are expensive and logistically challenging. Citizen science in hydrological research has recently gained popularity and crowdsourced monitoring is a promising cost-effective approach for data collection. Citizen science also has the potential to enhance knowledge co-creation and science-based evidence that underpins the governance and management of water resources. This paper provides a comprehensive review on citizen science and crowdsourced data collection within the context of hydrology, based on a synthesis of 71 articles from 2001 to 2018. Application of citizen science in hydrology is increasing in number and breadth, generating a plethora of scientific data. Citizen science approaches differ in scale, scope and degree of citizen involvement. Most of the programs are found in North America and Europe. Participation mostly comprises a contributory citizen science model, which engages citizens in data collection. In order to leverage the full potential of citizen science in knowledge co-generation, future citizen science projects in hydrology could benefit from more co-created types of projects that establish strong ties between research and public engagement, thereby enhancing the long-term sustainability of monitoring networks.

SUMOylation by SUMO2 is implicated in the degradation of misfolded ataxin-7 via RNF4 in SCA7 models.

Perturbation of protein homeostasis and aggregation of misfolded proteins is a major cause of many human diseases. A hallmark of the neurodegenerative disease spinocerebellar ataxia type 7 (SCA7) is the intranuclear accumulation of mutant, misfolded ataxin-7 (polyQ-ATXN7). Here, we show that endogenous ATXN7 is modified by SUMO proteins, thus also suggesting a physiological role for this modification under conditions of proteotoxic stress caused by the accumulation of polyQ-ATXN7. Co-immunoprecipitation experiments, immunofluorescence microscopy and proximity ligation assays confirmed the colocalization and interaction of polyQ-ATXN7 with SUMO2 in cells. Moreover, upon inhibition of the proteasome, both endogenous SUMO2/3 and the RNF4 ubiquitin ligase surround large polyQ-ATXN7 intranuclear inclusions. Overexpression of RNF4 and/or SUMO2 significantly decreased levels of polyQ-ATXN7 and, upon proteasomal inhibition, led to a marked increase in the polyubiquitination of polyQ-ATXN7. This provides a mechanism for the clearance of polyQ-ATXN7 from affected cells that involves the recruitment of RNF4 by SUMO2/3-modified polyQ-ATXN7, thus leading to its ubiquitination and proteasomal degradation. In a SCA7 knock-in mouse model, we similarly observed colocalization of SUMO2/3 with polyQ-ATXN7 inclusions in the cerebellum and retina. Furthermore, we detected accumulation of SUMO2/3 high-molecular-mass species in the cerebellum of SCA7 knock-in mice, compared with their wild-type littermates, and changes in SUMO-related transcripts. Immunohistochemical analysis showed the accumulation of SUMO proteins and RNF4 in the cerebellum of SCA7 patients. Taken together, our results show that the SUMO pathway contributes to the clearance of aggregated ATXN7 and suggest that its deregulation might be associated with SCA7 disease progression.

Citizen science pioneers in Kenya - A crowdsourced approach for hydrological monitoring.

Although water is involved in many ecosystem services, the absence of monitoring data restricts the development of effective water management strategies especially in remote regions. Traditional monitoring networks can be expensive, with unaffordable costs in many low-income countries. Involving citizens in monitoring through crowdsourcing has the potential to reduce these costs but remains uncommon in hydrology. This study evaluates the quality and quantity of data generated by citizens in a remote Kenyan basin and assesses whether crowdsourcing is a suitable method to overcome data scarcity. We installed thirteen water level gauges equipped with signboards explaining the monitoring process to passers-by. Results were sent via a text-message-based data collection framework that included an immediate feedback to citizens. A public web interface was used to visualize the data. Within the first year, 124 citizens reported 1175 valid measurements. We identified thirteen citizens as active observers providing more than ten measurements, whereas 57% only sent one record. A comparison between the crowdsourced water level data and an automatic gauging station revealed high data quality. The results of this study indicate that citizens can provide water level data of sufficient quality and with high temporal resolution.

Forest cover correlates with good biological water quality. Insights from a regional study (Wallonia, Belgium).

Forested catchments are generally assumed to provide higher quality water in opposition to agricultural and urban catchments. However, this should be tested in various ecological contexts and through the study of multiple variables describing water quality. Indeed, interactions between ecological variables, multiple land use and land cover (LULC) types, and water quality variables render the relationship between forest cover and water quality highly complex. Furthermore, the question of the scale at which land use within stream catchments most influences stream water quality and ecosystem health remains only partially answered. This paper quantifies, at the regional scale and across five natural ecoregions of Wallonia (Belgium), the forest cover effect on biological water quality indices (based on diatoms and macroinvertebrates) at the riparian and catchment scales. Main results show that forest cover - considered alone - explains around one third of the biological water quality at the regional scale and from 15 to 70% depending on the ecoregion studied. Forest cover is systematically positively correlated with higher biological water quality. When removing spatial, local morphological variations, or population density effect, forest cover still accounts for over 10% of the total biological water quality variation. Partitioning variance shows that physico-chemical water quality is one of the main drivers of biological water quality and that anthropogenic pressures often explain an important part of it (shared or not with forest cover). The proportion of forest cover in each catchment at the regional scale and across all ecoregions but the Loam region is more positively correlated with high water quality than when considering the proportion of forest cover in the riparian zones only. This suggests that catchment-wide impacts and a fortiori catchment-wide protection measures are the main drivers of river ecological water quality. However, distinctive results from the agricultural and highly human impacted Loam region show that riparian forests are positively linked to water quality and should therefore be preserved.