Temporal patterns in habitat use by small cetaceans at an oceanographically dynamic marine renewable energy test site in the Celtic Sea

Shelf-seas are highly dynamic and oceanographically complex environments, which likely influences the spatio-temporal distributions of marine megafauna such as marine mammals. As such, understanding natural patterns in habitat use by these animals is essential when attempting to ascertain and assess the impacts of anthropogenically induced disturbances, such as those associated with marine renewable energy installations (MREIs). This study uses a five year (2009–2013) passive acoustics (C-POD) dataset to examine the use of an oceanographically dynamic marine renewable energy test site by small cetaceans, dolphins (unspecified delphinids) and harbour porpoises Phocoena phocoena, in the southern Celtic Sea. To examine how temporal patterns in habitat use across the site related to oceanographic changes occurring over broad seasonal scales as well as those driven by fine scale (bi-weekly) localised processes (that may be masked by seasonal trends), separate analyses were conducted using (1) all daily animal detection rates spanning the entire five year dataset and (2) daily animal detection rates taken only during the summer months (defined as mid-June to mid-October) of 2010 (when continuous monitoring was carried out at multiple discrete locations across the site). In both instances, generalised additive mixed effects models (GAMMs) were used to link detection rates to a suite of environmental variables representative of the oceanography of the region. We show that increased harbour porpoise detection rates in the late winter/early spring (January–March) are associated with low sea surface temperatures (SST), whilst peaks in dolphin detection rates in the summer (July–September) coincide with increased SSTs and the presence of a tidal-mixing front. Moreover, across the summer months of 2010, dolphin detection rates were found to respond to small scale changes in SST and position in the spring-neap cycle, possibly reflective of a preference for the stratified waters immediately offshore of the front. Together, these findings suggest that habitat use by small cetaceans within shelf-seas is temporally variable, species specific and likely driven by complex bottom-up processes. As such, the effective conservation management of shelf-seas requires that we understand the dynamic complexities of these systems and the species that inhabit them. In particular, we emphasise the need for a good understanding of the natural drivers of habitat use by marine megafauna before the potential impacts of anthropogenically induced disturbances, such as those associated with the construction, maintenance and operation of MREIs, can be assessed

Treatment of bone tumours by radiofrequency thermal ablation

Radiofrequency thermal ablation (RFTA) is considered the treatment of choice for osteoid osteomas, in which it has long been safely used. Other benign conditions (chondroblastoma, osteoblastoma, giant cell tumour, etc.) can also be treated by this technique, which is less invasive than traditional surgical procedures. RFTA ablation is also an option for the palliation of localized, painful osteolytic metastatic and myeloma lesions. The reduction in pain improves the quality of life of patients with cancer, who often have multiple morbidities and a limited life expectancy. In some cases, these patients are treated with RFTA because conventional therapies (surgery, radiotherapy, chemotherapy, etc.) have been exhausted. In other cases, it is combined with conventional therapies or other percutaneous treatments, e.g., cementoplasty, offering faster pain relief and bone strengthening. A multidisciplinary approach to the management of these patients is recommended to select the optimal treatment, including orthopaedic surgeons, neurosurgeons, medical and radiation oncologists and interventional radiologists

Using citizen science data to assess the vulnerability of bottlenose dolphins to human impacts along England's South Coast

Coastal bottlenose dolphin populations are highly vulnerable due to their small population sizes and proximity to human activities. Long‐term studies in the UK have monitored populations protected within Special Areas of Conservation (SACs) since the 1990s, but a small community of bottlenose dolphins inhabiting the coastal waters of southern England has received much less attention. The English Channel is one of the most heavily impacted marine ecosystems worldwide and increasing anthropogenic pressures pose a severe threat to the long‐term viability of this population. Conservation measures to protect these animals have been hindered by a lack of knowledge of population size, distribution and ranging behaviour. This study aimed to fill these knowledge gaps. A citizen science sighting network yielded 7458 sighting reports of bottlenose dolphins between 2000 and 2020. Resightings of identified individuals were used to estimate abundance, distribution, and ranging behaviour. Social structure analysis revealed a discrete interconnected group of animals in shallow coastal waters, which did not appear to mix with conspecifics identified further offshore. A Bayesian multi‐site mark–recapture analysis estimated that this population comprises around 48 animals (CV = 0.18, 95% HPDI = 38–66). These dolphins ranged between North Cornwall and Sussex, with an average individual range of 530 km (68–760 km). Areas of high‐modelled habitat suitability were found to overlap with high levels of anthropogenic pressure, with pollution and boat traffic identified as the most pervasive threats. Although adult survival rates indicated that the population was relatively stable from 2008 to 2019 (0.945 (0.017 ± SE)), the small population size implies a significant risk to their long‐term viability and resilience to environmental change. By highlighting the most deleterious anthropogenic activities and regions of conservation significance, our results will be useful for developing management policies for threat mitigation and population conservation, to protect this vulnerable group of dolphins

The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

\ua9 2023, The Author(s).BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system–penetrant, type II RAF inhibitor tovorafenib (420 mg m−2 once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n = 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485

An economic evaluation of Alexander Technique lessons or acupuncture sessions for patients with chronic neck pain : A randomized trial (ATLAS)

OBJECTIVES: To assess the cost-effectiveness of acupuncture and usual care, and Alexander Technique lessons and usual care, compared with usual GP care alone for chronic neck pain patients. METHODS: An economic evaluation was undertaken alongside the ATLAS trial, taking both NHS and wider societal viewpoints. Participants were offered up to twelve acupuncture sessions or twenty Alexander lessons (equivalent overall contact time). Costs were in pounds sterling. Effectiveness was measured using the generic EQ-5D to calculate quality adjusted life years (QALYs), as well as using a specific neck pain measure-the Northwick Park Neck Pain Questionnaire (NPQ). RESULTS: In the base case analysis, incremental QALY gains were 0.032 and 0.025 in the acupuncture and Alexander groups, respectively, in comparison to usual GP care, indicating moderate health benefits for both interventions. Incremental costs were £451 for acupuncture and £667 for Alexander, mainly driven by intervention costs. Acupuncture was likely to be cost-effective (ICER = £18,767/QALY bootstrapped 95% CI £4,426 to £74,562) and was robust to most sensitivity analyses. Alexander lessons were not cost-effective at the lower NICE threshold of £20,000/QALY (£25,101/QALY bootstrapped 95% CI -£150,208 to £248,697) but may be at £30,000/QALY, however, there was considerable statistical uncertainty in all tested scenarios. CONCLUSIONS: In comparison with usual care, acupuncture is likely to be cost-effective for chronic neck pain, whereas, largely due to higher intervention costs, Alexander lessons are unlikely to be cost-effective. However, there were high levels of missing data and further research is needed to assess the long-term cost-effectiveness of these interventions

Sexually dimorphic gene expression in the heart of mice and men

The prevalence and clinical manifestation of several cardiovascular diseases vary considerably with sex and age. Thus, a better understanding of the molecular basis of these differences may represent a starting point for an improved gender-specific medicine. Despite the fact that sex-specific differences have been observed in the cardiovascular system of humans and animal models, systematic analyses of sexual dimorphisms at the transcriptional level in the healthy heart are missing. Therefore we performed gene expression profiling on mouse and human cardiac samples of both sexes and young as well as aged individuals and verified our results for a subset of genes using real-time polymerase chain reaction in independent left ventricular samples. To tackle the question whether sex differences are evolutionarily conserved, we also compared sexually dimorphic genes between both species. We found that genes located on sex chromosomes were the most abundant ones among the sexually dimorphic genes. Male-specific expression of Y-linked genes was observed in mouse hearts as well as in the human myocardium (e.g. Ddx3y, Eif2s3y and Jarid1d). Higher expression levels of X-linked genes were detected in female mice for Xist, Timp1 and Car5b and XIST, EIF2S3X and GPM6B in women. Furthermore, genes on autosomal chromosomes encoding cytochromes of the monoxygenase family (e.g. Cyp2b10), carbonic anhydrases (e.g. Car2 and Car3) and natriuretic peptides (e.g. Nppb) were identified with sex- and/or age-specific expression levels. This study underlines the relevance of sex and age as modifiers of cardiac gene expression

Computational and mathematical approaches to societal transitions

After an introduction of the theoretical framework and concepts of transition studies, this article gives an overview of how structural change in social systems has been studied from various disciplinary perspectives. This overview first leads to the conclusion that computational and mathematical approaches and their practical form, modeling, up till now, have been almost absent in the research and theorizing of structural change or transitions in social systems. Second, this review of the social science literature suggests numerous theoretical constructs relevant for transition modeling. Relevant concepts include the conceptualization of the micro-to-macro link, the importance of explaining both stability and change, quantitative and qualitative definitions of structural change, the use of dichotomies, synchronic and diachronic reasoning in explaining structural change, definitions of basic patterns of social change, the conceptualization of resistance to change and intentional and normative aspects of social change. This article employs these theoretical concepts to describe and discuss the models presented in this special issue in order to develop an understanding of what exactly entails a computational or mathematical approach to societal transitions

Concordant Signaling Pathways Produced by Pesticide Exposure in Mice Correspond to Pathways Identified in Human Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disease in which the etiology of 90 percent of the patients is unknown. Pesticide exposure is a major risk factor for PD, and paraquat (PQ), pyridaben (PY) and maneb (MN) are amongst the most widely used pesticides. We studied mRNA expression using transcriptome sequencing (RNA-Seq) in the ventral midbrain (VMB) and striatum (STR) of PQ, PY and paraquat+maneb (MNPQ) treated mice, followed by pathway analysis. We found concordance of signaling pathways between the three pesticide models in both the VMB and STR as well as concordance in these two brain areas. The concordant signaling pathways with relevance to PD pathogenesis were e.g. axonal guidance signaling, Wnt/β-catenin signaling, as well as pathways not previously linked to PD, e.g. basal cell carcinoma, human embryonic stem cell pluripotency and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Human PD pathways previously identified by expression analysis, concordant with VMB pathways identified in our study were axonal guidance signaling, Wnt/β-catenin signaling, IL-6 signaling, ephrin receptor signaling, TGF-β signaling, PPAR signaling and G-protein coupled receptor signaling. Human PD pathways concordant with the STR pathways in our study were Wnt/β-catenin signaling, axonal guidance signaling and G-protein coupled receptor signaling. Peroxisome proliferator activated receptor delta (Ppard) and G-Protein Coupled Receptors (GPCRs) were common genes in VMB and STR identified by network analysis. In conclusion, the pesticides PQ, PY and MNPQ elicit common signaling pathways in the VMB and STR in mice, which are concordant with known signaling pathways identified in human PD, suggesting that these pathways contribute to the pathogenesis of idiopathic PD. The analysis of these networks and pathways may therefore lead to improved understanding of disease pathogenesis, and potential novel therapeutic targets