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Inadequate base maps with poor scale or low resolution demonstrate the need for contemporary topographic maps when conducting geological mapping. In neotectonic regimes and areas of dynamic geomorphology, archival or large-scale maps require time-consuming, on-site manual updating while mapping bedrock and superficial geology. In contrast, stable ground conditions may have suitable legacy maps in some locations but not in others, such as where surveying is absent, incomplete or subject to legal restrictions. The geologist tasked with mapping may have to do this on short notice at their first site visit with no time to search for or create digital or physical copies of background maps on a suitable scale. The field mapper may encounter any of the above scenarios, especially the Geoforensic specialist tasked with Search and Rescue, hazard assessment or preparation and desktop study for subsequent search teams or law enforcement. Drone-derived orthoimagery and digital surface modelling can be conducted on-site in near real time to provide high resolution georeferenced maps for direct input of geological information, thus bypassing either non-existent or unsuitable base maps.

Abstract Cryptococcal meningoencephalitis (CM) is an opportunistic fungal infection and a major cause of death among people living with human immunodeficiency virus in sub‐Saharan Africa. 5‐flucytosine (5‐FC) is a unique, brain‐permeable antifungal agent used to reduce mortality from CM and to prevent disease in individuals carrying cryptococcal antigen. 5‐FC has a short plasma half‐life, requiring 6‐hourly oral dosing with an immediate‐release (IR) formulation, a significant challenge in hospital and outpatient settings, risking a lack of compliance. We recently reported the relative bioavailability in fasting conditions of a sustained release (SR) oral pellet formulation of 5‐FC. In this phase I study, we assessed the safety and pharmacokinetic profiles of the new 5‐FC SR formulation in a single dose (2 × 3000 mg), relative to 5‐FC IR tablets (Ancotil®; 1500 mg b.i.d.) in healthy participants in fed conditions. This randomized, two‐period crossover study was conducted in South Africa to confirm the dose of the identified 5‐FC SR formulation for a twice‐daily 5‐FC regimen in patients. Thirty‐six healthy participants were included. All treatments were well tolerated and no serious adverse event was reported. Cmax and AUC(0–t) for the SR formulation (49.2 ± 10.49 μg/mL and 640.4 ± 126.4 h.μg/mL, respectively) were significantly higher than for the IR formulation (36.8 ± 7.61 μg/mL and 456.6 ± 72.8 h.μg/mL, respectively). A physiological based pharmacokinetic model (PBPK) predicted that under fasting conditions, 6000 mg SR pellets would show a good overlap with the IR product (3000 mg b.i.d), thus 6000 mg SR 5‐FC b.i.d. in fasting conditions is recommended.

Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain axis, may also have a role in mediating the positive effects of psychedelics on behaviour. In this review, we present existing evidence that the composition of the gut microbiota may be responsive to psychedelic drugs, and in turn, that the effect of psychedelics could be modulated by microbial metabolism. We discuss various alternative mechanistic models and emphasize the importance of incorporating hypotheses that address the contributions of the microbiome in future research. Awareness of the microbial contribution to psychedelic action has the potential to significantly shape clinical practice, for example, by allowing personalised psychedelic therapies based on the heterogeneity of the gut microbiota.

The unusual body deposition site described comprised three elements of concealment: i) a covert stream-based ravine some 60 m from the suspect’s home; ii) partial grave dug into the ravine bank and iii) final concealment using concrete slabs. Disaggregation and sieving of concrete samples from the site, suspect residence(s) and control samples was carried out. These allowed informative exclusion of all but one control sample and provided a range of possible comparisons that may reflect the sequence of concrete slab selection, transport and use in covering the victim. The textures/colours of disaggregated, dried sediment size fractions also proved useful in conveying principles of exclusion to the court and jury at a subsequent murder trial. This work flows from basic (visual) observation of dry, cut blocks, through regular laboratory procedures of thin section work to disaggregation and size separation of aggregate-cement fractions. Graphical presentation of each analysis provided effective communication of geological science during the trial at court, concluding with a verdict of guilty by aggravated murder.

Few methods exist detailing the extraction of microplastics from organic matrices. A validated method for the successful extraction of microplastics from solid biowastes including biosolids, compost, and soil for spectroscopic analysis by micro-Fourier transform infrared spectroscopy (µ-FTIR) was developed. Solid dry biowastes were first digested with a wet peroxide oxidation (WPO) with iron (II) solution and 30% hydrogen peroxide followed by sequential density separations with ultra-pure water and 1.8 g cm−3 NaI in an optimised sediment-microplastic isolation (SMI) unit. The average recoveries for spiked microplastics were 92, 95 and 98% for bagged compost, biosolids, and soil, respectively. This method ensures a high microplastic recovery by first chemically disintegrating biowaste aggregates without employing destructive methods like milling and allows for successful density separations where the settled fraction is isolated off from the supernatant, allowing thorough rinsing of the equipment and thus a greater transferal of particles into the vacuum filtering device. Minimal processing steps reduce the instance of introducing contamination and particle loss. • Digestion as a first step to disintegrate aggregates to release entrapped microplastics • Density separation with SMI unit with the method adapted for biowastes • Minimal steps to reduce contamination and particle loss

Submarine canyons and channels are globally important pathways for sediment, organic carbon, nutrients and pollutants to the deep sea, and they form the largest sediment accumulations on Earth. However, studying these remote submarine systems comprehensively remains a challenge. In this study, we used the only complete-coverage and repeated bathymetric surveys yet for a very large submarine system, which is the Congo Fan off West Africa. Our aim is to understand channel-modifying features such as subaqueous landslides, meander-bend evolution, knickpoints and avulsions by analyzing their morphometric characteristics. We used a new approach to identify these channel-modifying features via morphometric fingerprints, which allows a systematic and efficient search in low-resolution bathymetry data. These observations have led us to identify three morphodynamic reaches within the Congo Canyon-Channel. The upper reach of the system is characterized by landslides that can locally block the channel, storing material for extended periods and re-excavating material through a new incised channel. The middle reach of the system is dominated by the sweep and swing of meander bends, although their importance depends on the channel’s age, and the time since the last up-channel avulsion. In the distal and youngest part of the system, an upstream migrating knickpoint is present, which causes multi-stage sediment transport and overspill through an underdeveloped channel with shallow depths. These findings complement previous less-detailed morphometric analyses of the Congo Canyon-Channel, offering a clearer understanding of how submarine canyon-channels can store sediment (due to channel-damming landslides, meander point bars, levee building due to overspill), re-excavate that sediment (via thalweg incision, meander propagation, knickpoint migration) and finally transport it to the deep sea. This improved understanding of the morphodynamics of the Congo Canyon-Channel may help to understand the evolution of other submarine canyon-channels, and assessment of hazards faced by seabed infrastructure such as telecommunication cables.

Abstract The opportunistic fungal infection cryptococcal meningoencephalitis is a major cause of death among people living with HIV in sub‐Saharan Africa. We report pharmacokinetic (PK) and safety data from a randomized, four‐period crossover phase I trial of three sustained‐release (SR) oral pellet formulations of 5‐flucytosine conducted in South Africa. These formulations were developed to require less frequent administration, to provide a convenient alternative to the current immediate release (IR) formulation, A. Formulations B, C, and D were designed to release 5‐flucytosine as a percentage of the nominal dose in vitro. We assessed their safety and PK profiles in a single dose (1 × 3000 mg at 0 h), relative to commercial IR tablets (Ancotil 500 mg tablets; 3 × 500 mg at 0 h and 3 × 500 mg at 6 h) in healthy, fasted participants. Forty‐two healthy participants were included. All treatments were well‐tolerated. The primary PK parameters, maximum observed plasma concentration (Cmax) and area under the concentration‐time profiles, were significantly lower for the SR formulations than for the IR tablets, and the geometric mean ratios fell outside the conventional bioequivalence limits. The median maximum time to Cmax was delayed for the SR pellets. Physiologically‐based PK modeling indicated a twice‐daily 6400 mg dose of SR formulation D in fasted condition would be optimal for further clinical development. This regimen is predicted to result in a rapid steady‐state plasma exposure with effective and safe trough plasma concentration and Cmax values, within the therapeutic boundaries relative to plasma exposure after four times per day administration of IR tablets (PACTR202201760181404).

Abstract Preclinical genetically engineered mouse models (GEMMs) of lung adenocarcinoma are invaluable for investigating molecular drivers of tumor formation, progression, and therapeutic resistance. However, histological analysis of these GEMMs requires significant time and training to ensure accuracy and consistency. To achieve a more objective and standardized analysis, we used machine learning to create GLASS-AI, a histological image analysis tool that the broader cancer research community can utilize to grade, segment, and analyze tumors in preclinical models of lung adenocarcinoma. GLASS-AI demonstrates strong agreement with expert human raters while uncovering a significant degree of unreported intratumor heterogeneity. Integrating immunohistochemical staining with high-resolution grade analysis by GLASS-AI identified dysregulation of Mapk/Erk signaling in high-grade lung adenocarcinomas and locally advanced tumor regions. Our work demonstrates the benefit of employing GLASS-AI in preclinical lung adenocarcinoma models and the power of integrating machine learning and molecular biology techniques for studying the molecular pathways that underlie cancer progression.

Plastic pollution is pervasive in our environment, with impacts seen across ecosystems and taxa. While plastic has become an integral part of our daily lives, not all of it is readily apparent, making it challenging to effectively reduce plastic pollution. A hidden source of plastic pollution is plastic-based printing, which is used on a wide range of items including single-use products like plastic food containers and multi-use plastic items like credit cards. This also includes items that we would not consider to be sources of plastic pollution such as glass bottles with surface printing. The widespread use of this printing, therefore, results in even non-plastic items contributing to plastic pollution, potentially contaminating recycling streams and exacerbating nano- and microplastic (NMP) dispersion. Given the challenges of remediating NMP plastic pollution once it has entered the environment, prevention becomes paramount. With significant efforts underway to reduce plastic production, it is important to take a holistic approach to redesigning objects and materials to avoid false solutions, which will continue to contribute to ecosystem degradation and planetary boundary transgressions. To make meaningful progress and avoid ineffective solutions, it is imperative to consider all sources of plastic pollution, including those concealed within apparently non-plastic objects.

Abstract Ayahuasca is a psychedelic plant brew originating from the Amazon rainforest. It is formed from two basic components, the Banisteriopsis caapi vine and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. Here we review the history of ayahuasca and describe recent work on its pharmacology, phenomenological responses, and clinical applications. There has been a significant increase in interest in ayahuasca since the turn of the millennium. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. The effects of the brew on personality and mental health outcomes are discussed in this review. Furthermore, phenomenological analyses of the ayahuasca experience are explored. Ayahuasca is a promising psychedelic agent that warrants greater empirical attention regarding its basic neurochemical mechanisms of action and potential therapeutic application.

The cold case search for clandestine graves can be challenging due to the length of time elapsed since the crime and the search environment changing itself. This paper reports on a cold case search for “Christine”, a young girl who was reported missing in the mid-1970s in the East Midlands, UK. Once a search sub-area was determined by case reports and new intelligence in rural woodland, a police ground search proved unsuccessful. A multi-phased geoforensic search investigation, using remote sensing and UAV drones, metal detector, EM and dGPS surveys, was subsequently undertaken, with collected data processed and analysed. Results showed 36 discrete dGPS-surveyed metal detector and 3 EM priority targets to be identified which were all intrusively investigated but nothing case-relevant was found. Study implications suggest careful multi-phase remote and geoforensic investigations can give confidence in cold case no-body searches, saving police operational time and costs in such cold case investigations.

Stromal stiffening accompanies malignancy, compromises treatment and promotes tumour aggression. Clarifying the molecular nature and the factors that regulate stromal stiffening in tumours should identify biomarkers to stratify patients for therapy and interventions to improve outcome. We profiled lysyl hydroxylase-mediated and lysyl oxidase-mediated collagen crosslinks and quantified the greatest abundance of total and complex collagen crosslinks in aggressive human breast cancer subtypes with the stiffest stroma. These tissues harbour the highest number of tumour-associated macrophages, whose therapeutic ablation in experimental models reduced metastasis, and decreased collagen crosslinks and stromal stiffening. Epithelial-targeted expression of the crosslinking enzyme, lysyl oxidase, had no impact on collagen crosslinking in PyMT mammary tumours, whereas stromal cell targeting did. Stromal cells in microdissected human tumours expressed the highest level of collagen crosslinking enzymes. Immunohistochemical analysis of biopsies from a cohort of patients with breast cancer revealed that stromal expression of lysyl hydroxylase 2, an enzyme that induces hydroxylysine aldehyde-derived collagen crosslinks and stromal stiffening, correlated significantly with disease specific mortality. The findings link tissue inflammation, stromal cell-mediated collagen crosslinking and stiffening to tumour aggression and identify lysyl hydroxylase 2 as a stromal biomarker.

Abstract Despite the extensive use of sulphur isotope ratios (δ34S) for understanding ancient biogeochemical cycles, many studies focus on specific time-points of interest, such as the end-Permian mass extinction (EPME). We have generated an 80 million-year Permian–Triassic δ34Sevap curve from the Staithes S-20 borehole, Yorkshire, England. The Staithes δ34Sevap record replicates the major features of the global curve, while confirming a new excursion at the Olenekian/Anisian boundary at ~ 247 million years ago. We incorporate the resultant δ34Sevap curve into a sulphur isotope box model. Our modelling approach reveals three significant pyrite burial events (i.e. PBEs) in the Triassic. In particular, it predicts a significant biogeochemical response across the EPME, resulting in a substantial increase in pyrite burial, possibly driven by Siberian Traps volcanism. Our model suggests that after ~ 10 million years pyrite burial achieves relative long-term stability until the latest Triassic.

This paper analyses the longest sediment flows measured in action on Earth. These seabed flows were caused by floods and spring tides, and flushed prodigious sediment and carbon volumes into the deep sea, as they accelerated for a thousand kilometres.

In recent years, airborne microplastics have been identified in a range of remote environments. However, data throughout the Southern Hemisphere, in particular Antarctica, are largely absent to date. We collected snow samples from 19 sites across the Ross Island region of Antarctica. Suspected microplastic particles were isolated and their composition confirmed using micro-Fourier transform infrared spectroscopy (µFTIR). We identified microplastics in all Antarctic snow samples at an average concentration of 29 particles L−1, with fibres the most common morphotype and polyethylene terephthalate (PET) the most common polymer. To investigate sources, backward air mass trajectories were run from the time of sampling. These indicate potential long-range transportation of up to 6000 km, assuming a residence time of 6.5 d. Local sources were also identified as potential inputs into the environment as the polymers identified were consistent with those used in clothing and equipment from nearby research stations. This study adds to the growing body of literature regarding microplastics as a ubiquitous airborne pollutant and establishes their presence in Antarctica.

Cryptococcal meningoencephalitis (CM) is an opportunistic fungal infection and a major cause of death among people living with human immunodeficiency virus in sub‐Saharan Africa. 5‐flucytosine (5‐FC) is a unique, brain‐permeable antifungal agent used to reduce mortality from CM and to prevent disease in individuals carrying cryptococcal antigen. 5‐FC has a short plasma half‐life, requiring 6‐hourly oral dosing with an immediate‐release (IR) formulation, a significant challenge in hospital and outpatient settings, risking a lack of compliance. We recently reported the relative bioavailability in fasting conditions of a sustained release (SR) oral pellet formulation of 5‐FC. In this phase I study, we assessed the safety and pharmacokinetic profiles of the new 5‐FC SR formulation in a single dose (2 × 3000 mg), relative to 5‐FC IR tablets (Ancotil®; 1500 mg b.i.d.) in healthy participants in fed conditions. This randomized, two‐period crossover study was conducted in South Africa to confirm the dose of the identified 5‐FC SR formulation for a twice‐daily 5‐FC regimen in patients. Thirty‐six healthy participants were included. All treatments were well tolerated and no serious adverse event was reported. Cmax and AUC(0–t) for the SR formulation (49.2 ± 10.49 μg/mL and 640.4 ± 126.4 h.μg/mL, respectively) were significantly higher than for the IR formulation (36.8 ± 7.61 μg/mL and 456.6 ± 72.8 h.μg/mL, respectively). A physiological based pharmacokinetic model (PBPK) predicted that under fasting conditions, 6000 mg SR pellets would show a good overlap with the IR product (3000 mg b.i.d), thus 6000 mg SR 5‐FC b.i.d. in fasting conditions is recommended. [ABSTRACT FROM AUTHOR]

Derived ornithopods, such as hadrosaurids, show a high occurrence of fossilized lesions and diseases. However, paleopathologies in iguanodontians seem to be less common, considering the rich fossil record of these taxa in Europe, in particular in Belgium, Britain and Spain. Here, we describe an iguanodontian femur discovered in England that exhibits a large overgrowth of its lateral aspect, not previously recognized in any other similar remains. The specimen was scanned with micro‐computed tomography (microCT) and later sectioned in three sites of the overgrowth for histological analysis. The femur belongs to an early adult Iguanodontia indet., based on the presence of a woven parallel fibered complex in the outer cortex and three to four lines of arrested growth. Internal analysis of the dome‐like overgrowth suggests it can be diagnosed as a fracture callus. The injury might have negatively impacted upon the animal's locomotion as the trauma had occurred in the region above the knee, a crucial spot for hindlimb musculature. Finally, a cancellous medullary bone‐like tissue was recognized in the medullary cavity next to the pathological overgrowth. An attempt was made to determine the precise nature of this tissue, as medullary bone is linked with the ovulation period in (avian) dinosaurs, whereas other types of endosteal, medullary bone‐like tissue have previously been recognized in pathological bones. [ABSTRACT FROM AUTHOR]

Plastics are an emerging class of environmental contaminants whose impacts are not yet fully understood. Trace elements, another class of environmental contaminant and commonly associated with plastics, have been widely researched and are known to be toxic to organisms. However, the combined impacts of these two contaminants on the environment remain unclear. Here, we reviewed the current knowledge of the types and concentrations of trace elements associated with plastics, the role of plastics in creating new exposure routes, the processes involved in the release of trace elements from plastics, and the transport of plastics through environmental compartments. Trace elements inherent in plastics, due to addition during manufacture for formation or functional properties, are typically present at higher concentrations than those that are acquired from the environment, and consequently are likely to have greater impacts. Trace elements are continuously released into environmental matrices from plastics but may be released at higher concentrations when exposed to rapid changes in environmental conditions (pH, ionic strength, redox potential, salinity, UV levels). Plastics potentially provide additional exposure routes for organisms to trace elements. For example, exposure to trace elements may occur when organisms ingest plastics, use them for shelter and nest building or as a surface to attach onto. Further research to improve our understanding of this complex contaminant should focus on environmentally relevant studies on trace element release and their effects.

Ayahuasca is a psychoactive Amazonian plant brew. It is usually made from the Banisteriopsis caapi vine (Spruce ex Griseb. Morton, Malpighiaceae), which contains three primary harmala alkaloids, along with the leaves of Psychotria viridis (Ruiz et Pavon, Rubiaceae) in which the potent psychedelic dimethyltryptamine (DMT) is found. DMT-harmaloid concoctions have gained popularity in recent years, due to growing anecdotal and scientific reports of therapeutic benefits associated with their consumption. Ayahuasca is now ingested in a variety of different settings across the globe, from traditional ethnobotanical to so called “neo-shamanic” ceremonies. Furthermore, related preparations involving alternative sources of DMT and harmala alkaloids are becoming increasingly common as knowledge of ayahuasca continues to spread internationally. This article reviews the existing literature and draws on original qualitative data from a large cross-sectional study of ayahuasca drinkers, to propose a model of psychotherapeutic processes associated with the consumption of ayahuasca. We assert that it is these processes, facilitated by a range of neurobiological effects, that lead to beneficial mental health and wellbeing outcomes. Our proposed model identifies five key psychotherapeutic processes or effects inherent to the ayahuasca experience; somatic effects; introspection and emotional processing; increased Self-connection; increased spiritual connection, and finally the gaining of insights and new perspectives. We note some important differences in these processes compared with other classic psychedelics as well as the implications of the model for the therapeutic use of ayahuasca. Improved understanding of the psychotherapeutic processes involved with the ayahuasca experience will better equip practitioners to work with this potentially transformative concoction and enable the optimization of therapeutic treatment models for potential clinical use.

Intratumoral CD103+ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103+ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8+ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors. Gene expression analysis identified upregulation of Cxcl9 within intratumoral DCs during combination therapy, and therapeutic efficacy was ablated by CXCR3 blockade, Batf3 deficiency, or Irf8 deficiency.