Recent heavy metal contamination of the Thurne Broads

The banning of tributyltin (TBT) from boat antifouling paints in the late 1980s led to its replacement by alternative biocide additives (Voulvoulis et al., 2000; Marcheselli et al., 2010), including Cu (Dahl & Blanck, 1996) and Zn as active ingredients. It has been reported that Cu and Zn compounds associated with these biocides have caused substantial contamination of harbour and marina sediments (Eklund et al., 2010; Parks et al., 2010), with negative toxic consequences for aquatic organisms (Ytreberg et al., 2010). Indeed, it is evident that Cu and Zn compounds present in paint fragments are readily leached into the water column allowing entry into aquatic food webs (Jessop & Turner, 2011). Nevertheless, relatively little is known regarding antifoulant-derived metals contamination in freshwater lakes. The Norfolk and Suffolk Broads (Eastern England, UK) have been contaminated by antifoulant-derived heavy metals, particularly Cu and Zn which have increased since the banning of TBT (post-1987) in parts of the boated system (Boyle et al., in prep.). Further, recent studies suggest that current levels of sediment contamination by Cu may have negative ecological effects for aquatic ecosystems including inhibition of aquatic macrophyte germination and performance (Boyle et al., submitted; S. Lambert, unpublished data). In Hickling Broad (Thurne Broads system), post-TBT increases in Cu and Zn are also evident, with an interesting peak in Cu for the late 1990s in core HICK1 (Figure 1). This coincides with the large-scale loss of aquatic macrophytes (especially Characeae) from the lake in 1999 (Barker et al., 2008). HICK1 was collected in 2003. In the proposed study we sought to gain a fuller understanding of recent metal contamination in Hickling Broad up to the present day, whilst looking to verify and better contextualise the late 1990s Cu peak. Further, we aimed to determine whether the peak in Cu for Hickling Broad was also recorded at Horsey Mere which is used as a control site in this study i.e. is it just a Hickling phenomenon? Or is it a Thurne Broads system-wide effect

The ‘Pritchard Trap’: a novel quantitative survey method for crayfish

1. As crayfish invasions continue to threaten native freshwater biota, a detailed understanding of crayfish distribution and population structure becomes imperative. Nonetheless, most current survey methods provide inadequate demographic data. The quantitative ‘Triple Drawdown’ (TDD) dewatering method has highlighted the importance of such data, yet practical constraints prevent its large-scale application. 2. Here, we introduce the ‘Pritchard Trap’, a novel passive sampling method that reliably generates quantitative crayfish population data while requiring substantially lower sampling effort than TDDs. This quadrat-style sampler was extensively tested in headwater streams of North Yorkshire, England, along an invasion gradient for signal crayfish (Pacifastacus leniusculus) from well-established sites to mixed populations of signal crayfish and native white-clawed crayfish (Austropotamobius pallipes). 3. The Pritchard Trap was trialled over several time intervals to determine the minimum required trap deployment time. TDDs at the same sites allowed for a robust evaluation of Pritchard Trap sampling accuracy in representing crayfish densities and population structure. 4. The Pritchard Trap successfully sampled both invasive and native crayfish (8–42 mm carapace length). A minimum passive deployment time of 4 days was required. At low crayfish densities (0.5 individuals m−2), increased trapping effort was necessary to achieve accurate population density and size class distribution estimates. The Pritchard Trap required substantially less sampling effort (working hours) and resources than the TDD, whilst also posing less risk to non-target species. 5. The Pritchard Trap, for the first time, affords logistically simple, truly quantitative investigations of crayfish population demographics for headwater systems. It could be integrated into crayfish research and management, for example to explore density-dependent ecological impacts of invasive crayfish and their management responses or to monitor populations and recruitment in native crayfish conservation initiatives

Palliative care specialists' perceptions concerning referral of haematology patients to their services : findings from a qualitative study

Background: Haematological malignancies (leukaemias, lymphomas and myeloma) are complex cancers that are relatively common, affect all ages and have divergent outcomes. Although the symptom burden of these diseases is comparable to other cancers, patients do not access specialist palliative care (SPC) services as often as those with other cancers. To determine the reasons for this, we asked SPC practitioners about their perspectives regarding the barriers and facilitators influencing haematology patient referrals. Methods: We conducted a qualitative study, set within the United Kingdom’s (UK’s) Haematological Malignancy Research Network (HMRN: www.hmrn.org), a population-based cohort in the North of England. In-depth, semistructured interviews were conducted with 20 SPC doctors and nurses working in hospital, community and hospice settings between 2012 and 2014. Interviews were digitally audio-recorded, transcribed and analysed for thematic content using the ‘Framework’ method. Results: Study participants identified a range of barriers and facilitators influencing the referral of patients with haematological malignancies to SPC services. Barriers included: the characteristics and pathways of haematological malignancies; the close patient/haematology team relationship; lack of role clarity; late end of life discussions and SPC referrals; policy issues; and organisational issues. The main facilitators identified were: establishment of interdisciplinary working patterns (co-working) and enhanced understanding of roles; timely discussions with patients and early SPC referral; access to information platforms able to support information sharing; and use of indicators to ‘flag’ patients’ needs for SPC. Collaboration between haematology and SPC was perceived as beneficial and desirable, and was said to be increasing over time. Conclusions: This is the first UK study to explore SPC practitioners’ perceptions concerning haematology patient referrals. Numerous factors were found to influence the likelihood of referral, some of which related to the organisation and delivery of SPC services, so were amenable to change, and others relating to the complex and unique characteristics and pathways of haematological cancers. Further research is needed to assess the extent to which palliative care is provided by haematology doctors and nurses and other generalists and ways in which clinical uncertainty could be used as a trigger, rather than a barrier, to referral. Keywords: Cancer, Leukaemia, Lymphoma, Myeloma, Haematology, Specialist palliative care, End of life, Hospice, Qualitativ

Recovery of the crucian carp Carassius carassius (L.): Approach and early results of an English conservation project

Aquatic Conservation: Marine and Freshwater Ecosystems published by John Wiley & Sons Ltd The crucian carp Carassius carassius, a cyprinid fish characteristic of small ponds, is in decline throughout most of its European range, including in England where it is currently thought to be non-native. The present study, undertaken by the Norfolk Crucian Project, reports on reductions in pond populations of crucian carp in Norfolk, eastern England as well as the success of recent introduction/re-introduction efforts in terms of crucian survival, recruitment and growth over the last 10 years. A 72% decline in crucian carp distribution was observed between the 1950s–1980s and the 2010s. Of 18 crucian carp introductions/re-introductions to restored and suitable existing ponds, 17 were successful in terms of survival, increasing the number of current crucian sites in Norfolk by 37%. Recruitment of young crucian carp was demonstrated for 12 of the 18 stocked ponds, with apparent elevated juvenile growth relative to other English and European populations. Delays in, or a lack of, crucian recruitment in some ponds appeared to result from the presence of other fish species (especially threespine stickleback Gasterosteus aculeatus) with predation and interspecific competition possible contributory factors. This study shows that, through combinations of pond rehabilitation and stocking, it has been possible to achieve a substantial recovery of crucian carp populations in the study region. Although the crucian carp is currently presumed to be non-native within England, given other scientific studies that show a lack of adverse impacts of this species on native biota, and because it is greatly threatened in its native range, the call is sounded for more crucian carp conservation projects in other parts of England as well as in Europe more generally

Pathways of patients with chronic haematological malignancies: a report from the UK’s population-based HMRN

\ua9 2024 Roman et al. Background: Arising in blood and lymph-forming tissues, haematological malignancies (leukaemias, lymphomas and myelomas) are the fifth most common group of cancers. Around 60% are currently incurable and follow a chronic, remitting–relapsing pathway often initially managed by ‘watch & wait’. This involves hospital-based monitoring, followed by treatment if the cancer progresses (which not all do) and then further observation, in a process that may continually repeat. New treatments are constantly emerging, survival is improving and prevalence is rising, but population-based data documenting entire care pathway are sparse. Hence, empirically-based incidence and prevalence estimates about various treatment states (watch and wait, first-line treatment, observation, second-line treatment, etc.) and patterns of healthcare activity are lacking. Likewise, despite complex trajectories, anxiety-provoking watch and wait, and therapies that impede quality of life and incur marked healthcare costs, evidence about patient preferences for information sharing and treatment decisions is scant. Objectives: Primary – to generate high-quality, evidence-based information about the care pathways of the general population of patients with chronic haematological malignancies. Secondary – to produce information resources suitable for testing in routine National Health Service practice. Design: Population-based cohort of ≈ 8000 patients with chronic haematological malignancies, incorporating five nested work packages, each with its own individual design: (1) exploration of patient experiences: information and treatment decisions; (2) population-based analyses; (3) health economics; (4) development of information resources to support decision-making; and (5) patient well-being and decision-making survey. Setting: This programme is predicated on the infrastructure of the United Kingdom’s Haematological Malignancy Research Network (www.hmrn.org); which provides ‘real-world’, robust, generalisable data to inform research and clinical practice, nationally and internationally. Set in Yorkshire and Humberside, the Haematological Malignancy Research Network’s catchment population of ≈ 4 million has a comparable sex, age, urban/rural, and area-based deprivation (Index of Multiple Deprivation, income domain) distribution to the United Kingdom as a whole; and in terms of ethnic diversity the region is centrally ranked, with around 80% of residents identifying as White British, 9% as Asian and 2% as black. Within the Haematological Malignancy Research Network, clinical practice adheres to national guidelines, and all patients with blood cancers are centrally diagnosed (≈ 2500 each year), tracked through their treatment pathways and linked to national databases (deaths, cancer registrations and Hospital Episode Statistics). Linked to the same national databases, the Haematological Malignancy Research Network also contains an age-and sex-matched general-population cohort. Participants: Patients aged ≥ 18 years, resident in the study region, and diagnosed with chronic lymphocytic leukaemia, follicular lymphoma or myeloma. Methods: Core Haematological Malignancy Research Network data were used to compare the hospital activity of patients with chronic lymphocytic leukaemia, follicular lymphoma and myeloma with that of the general population. Following additional linkages to genetic and clinical data, follicular lymphoma prognostic factors were examined. Two self-administered questionnaires addressing (1) quality of life and well-being and (2) decision-making were iteratively developed, piloted and deployed. Linkage to quality of life, clinical information and Hospital Episode Statistics enabled economic (myeloma) model development. In-depth interviews were conducted with 35 patients (10 alongside relatives). Results: Trajectories of ≈ 8000 patients were mapped, and patient-pathway visualisations summarising individual and aggregate information were developed. As expected, patients with chronic blood cancers experienced higher levels of hospital activity than their general population counterparts, the largest effects being for myeloma. Following survey deployment, 3153 patients were recruited across 14 hospitals, 1282 with chronic lymphocytic leukaemia, follicular lymphoma or myeloma. Over half of the questionnaires were completed by patients on watch and wait; the remainder were completed during treatment or post-chemotherapy monitoring. Information gathered, coupled with in-depth interviews, demonstrated patients’ marked anxiety and fluctuating preferences for information sharing and decision-making, contingent on complex, inter-related factors. In turn, prognostic and microsimulation economic models were used to predict individual-level trajectories across multiple treatment lines, examining associated overall survival, costs and quality-adjusted life-years. Limitations: Survey mapping to individual care pathways could not be completed because the COVID-19 pandemic delayed clinical data collection. Patients who attended clinics and participated in the survey were more likely than non-attenders to have had first-line chemotherapy, be slightly younger and live in more affluent areas. Conclusions: This programme collated high-quality, population-based evidence. Previously lacking, this, coupled with new findings on preferences for information sharing and treatment decisions, provides the foundation for future research. Future work: The translation of information accrued into resources suitable for testing in routine NHS practice is key. In this regard, COVID-19 has changed the communication landscape. The visualisations developed by this programme require further refinement/testing using participatory co-design with stakeholder groups. Underpinned by a suitable protocol applied within a single multidisciplinary team setting, prior to further evaluation within/outside the region, such outputs require testing in a cluster-randomised trial

DDX3X suppresses the susceptibility of hindbrain lineages to medulloblastoma

DEAD-Box Helicase 3 X-Linked (DDX3X) is frequently mutated in the Wingless (WNT) and Sonic hedghog (SHH) subtypes of medulloblastoma—the commonest malignant childhood brain tumor, but whether DDX3X functions as a medulloblastoma oncogene or tumor suppressor gene is not known. Here, we show that Ddx3x regulates hindbrain patterning and development by controlling Hox gene expression and cell stress signaling. In mice predisposed to Wnt- or Shh medulloblastoma, Ddx3x sensed oncogenic stress and suppressed tumor formation. WNT and SHH medulloblastomas normally arise only in the lower and upper rhombic lips, respectively. Deletion of Ddx3x removed this lineage restriction, enabling both medulloblastoma subtypes to arise in either germinal zone. Thus, DDX3X is a medulloblastoma tumor suppressor that regulates hindbrain development and restricts the competence of cell lineages to form medulloblastoma subtypes

Connectivity and zebra mussel invasion offer short‐term buffering of eutrophication impacts on floodplain lake landscape biodiversity

Aim To investigate if connectivity and zebra mussel (Dreissena polymorpha) occurrence can mitigate effects of eutrophication in a lowland lake landscape. Location Upper Lough Erne, Northern Ireland, UK. Methods Data on environment, macrophytes and invertebrates were assembled for three basins of a large central lake and its satellite floodplain lakes via field surveys and palaeolimnological analyses. Space–time interaction analyses of palaeoecological data were compared pre‐1950 and post‐1950. Multivariate analyses examined how connectivity, environment and zebra mussels influenced contemporary lake communities, and explain their divergence from historical communities in the past. Results Pre‐1950, we found high community variation across sites and low within‐lake variation in macrophytes, but progressive eutrophication accentuated within‐lake community variation after 1950. Partitioning analysis showed larger effects of connectivity than nutrient enrichment on contemporary macrophyte composition, while local effects structured invertebrate communities. Three clusters of lakes were revealed according to variation in macrophyte composition, isolation from the central lake and nutrient enrichment: Group 1– the central lake and six nearby lakes were meso‐eutrophic (TP = 66.7 ± 47.6 μg/L; TN = 0.79 ± 0.41 mg/L) and had the highest zebra mussel abundances and organismal biodiversity; Group 2– Eight eutrophic (TP = 112±36.6 μg/L; TN = 1.25 ± 0.5 mg/L) and connected lakes; Group 3– Seven isolated and hypertrophic (TP = 163.2 ± 101.5 μg/L; TN = 1.55 ± 0.3 mg/L) lakes. Pre‐1950 palaeolimnological data for macrophytes and invertebrates for 5 lakes and a basin in the central lake most resembled extant lake communities of Group 1. However, palaeo‐records revealed that macrophytes and invertebrates subsequently converged towards those of Groups 2 and 3. Main conclusions Our study reveals that the central “mother” lake acts as a hub for preserving biodiversity via shared hydrological connectivity with satellite lakes and high zebra mussel abundances. These may buffer the impoverishing effects of eutrophication and sustain unexpectedly high biodiversity in the short term. Such protective buffering, however, cannot be relied upon indefinitely to conserve biodiversity

Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling

In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG- GCaMP2 expressing construct, and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver, and blood cells. No pathological alterations were found in these animals, and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects, and provide evidence for the role of Na+/Ca2+ exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies