Mitigating the impacts of river flow regulation and barriers to fish spawning migrations

Globally, migratory fish are threatened by anthropogenic modification to rivers. These create barriers that prevent fish accessing spawning grounds required for completion of life cycles. In order to make informed decsions, for mitigating the associated negative impacts, an understanding migratory behaviour when reaching barriers during the spawning migration is required. That said, there is a lack of information about the response of migratory fish to operational regimes in regulated rivers and the areas occupied, delays caused and routes taken around infrastructures. This study investigated the behaviour of three migratory fish species under operational regimes of three different infrastructures during each species’ respective spawning season. The efficiency of a bypass channel that utilised the relationship between migratory behaviour and flow was also investigated for a further species.The literature was reviewed to identify the different types of migratory life histories of fish, the impact of different riverine modification on the respective spawning migrations and how this can be mitigated. Fish have evolved in direct response to the natural flow regime and connectivity of riverine habitats, but barriers to migration exist from source to sea. This regulates or disrupts the flow regime and connectivity that fish depend upon, which has had considerable detriment to many migratory fish species globally. The main conclusion of the review was that knowledge gaps exist for the target species, and understanding the behaviour of the study species during the spawning migration is essential to improve access to spawning grounds in regulated rivers and ultimately conserve populations.The effects of timing, magnitude and duration of eleven artificial flow (freshet) releases from two impounding reservoirs on river-resident brown trout (Salmo trutta L.), a species known to undertake spawning migrations, was investigated using radio telemetry in a regulated upland river in northern England. Most did not perform movements characteristic of spawning migrations; all were located within 10 m of the location occupied before freshets, and fish in a control reach behaved comparably. The largest unidirectional movements mostly occurred during elevated river level due to rainfall and reservoir overtopping events; other varied length movements occurred during natural peaks or low flow, indicating artificial freshets were not directly responsible, and may not be suitable to stimulate migration in river-resident fish in regulated rivers.An acoustic telemetry study was conducted to determine the impact of a high- head hydropower station, associated diversion weir and spillway on downstream migrating shortfin eel (Anguilla australis) in the regulated Wairua catchment, Northland, New Zealand. Despite the diversion weir providing an alternative route, 88% (n = 21) of tagged eels that were detected here entered the power station forebay; of these, 52% were impinged onto intake screens, always when turbines were operating at greater than 3.04 MW/day. The rest (48%) passed the spillway and continued their migration, sometimes after long delays and having spent time immediately upstream of the intake where fitness could have been reduced due to high flows. Based on findings, the most effective mitigation here and at similar power schemes is considered to be operational or physical changes at the diversion weir to minimise entry of downstream migrating eels into the power canal during the migration period. Also discussed as potential solutions are turbine shutdowns, ensuring the spillway is available and provision of a bypass channel in the forebay.At a pumping station in the Anglian region, UK, where the upstream river level is maintained primarily by a co-located gravity sluice door, route choice and behaviour of downstream migrating European eel (Anguilla anguilla) (n = 7) immediately upstream of both routes was investigated using acoustic telemetry. During the study, three eels passed through pumps despite only operating for 8% of the time the gravity sluice was open, and only two passed through the gravity sluice after arriving when it was closed; the remaining two retreated upstream. No eels were detected within 15 m of the gravity sluice when it was open and eel behaviour was indicative of reluctance to pass through pumps. Findings are discussed in terms of water resource management to implement operational changes, to make the gravity sluice an attractive downstream passage route for migrating eels and thus reduce passage through hazardous pumps.The efficacy of two bypasses in attracting and passing downstream migrating American eels (Anguilla rostrata), designed to utilise the relationship between eel migratory behaviour and flow through two methods of flow creation, i.e. an airlift and a siphon, was tested in a simulated forebay environment, as a potential remediation measure at infrastructures requiring eel passage. Under entrance velocity of 1.2 m/s in eight test runs, both bypasses performed comparably and eels tested in each readily located, entered and passed. Test findings are discussed in relation to real-world application at sites with different characteristics, and the suitability of each design in successfully providing a safe route for downstream migrating eels

Evaluating the impact of hydropower on downstream migrating anguillid eels: Catchment-wide and fine-scale approaches to identify cost-effective solutions

Hydropower is an increasingly popular source of renewable and ‘green’ (in terms of emissions) energy, but reduced longitudinal connectivity and diverting flow through turbines can have negative impacts on catadromous anguillid eel species that have declined globally. There is an urgent need for environmental managers to perform remediation actions, such as protecting flows for migratory fish and providing passage solutions at infrastructure, under increasing legislative pressure. To deliver this, a more comprehensive understanding of eel migration in catchments with hydropower is required. Here, we illustrate the importance of catchment-wide and fine-scale acoustic telemetry, coupled with the influence of eel maturation (i.e. sex steroid levels), to determine the impact of Wairua run-of-river Power Station (WPS) on downstream migrating shortfin eels (Anguilla australis; n = 25) in Wairua River, New Zealand. Migration speed through the unregulated reach upstream of WPS was positively correlated with flow, but not eel length or sex steroids. Three eels passed a diversion weir (DW) to follow the natural watercourse and eight entered the WPS canal. Eels predominantly entered (95.2%) and were last detected (85.7%) in WPS forebay during hours of darkness. Eleven (52%) of the 21 eels that entered WPS forebay were impinged or entrained, all when three or four turbines were in operation (power generation >3.04 MW). Ten (48%) passed WPS spillway during significantly higher spill than impinged or entrained eels, with four passing during no turbine operation, after experiencing high flows near the intake (multiple receivers in WPS forebay used to quantify fine-scale behaviour). On average, eels were impinged or entrained at WPS significantly quicker (6.40 ± 11.13 days) than eels that entered the spillway (25.17 ± 15.12 days), but eel length and sex steroids did not significantly influence fate. Of the eels that migrated through the entire 55 km study reach, passage time at DW and WPS equated to 0.01–0.02% and 47.62–92.17% of their migration, respectively. Mitigation for WPS (and similar power schemes) should focus on operational or physical changes at DW to minimise eels entering power station forebay(s). Turbine shutdowns, ensuring WPS spillway is available and the provision of a bypass channel in WPS forebay are also discussed as ways to conserve the species with the potential to save costs for water resource managers

Mapping the developing human cardiac endothelium at single cell resolution identifies MECOM as a regulator of arteriovenous gene expression

AIMS: Coronary vasculature formation is a critical event during cardiac development, essential for heart function throughout perinatal and adult life. However, current understanding of coronary vascular development has largely been derived from transgenic mouse models. The aim of this study was to characterize the transcriptome of the human foetal cardiac endothelium using single-cell RNA sequencing (scRNA-seq) to provide critical new insights into the cellular heterogeneity and transcriptional dynamics that underpin endothelial specification within the vasculature of the developing heart. METHODS AND RESULTS: We acquired scRNA-seq data of over 10 000 foetal cardiac endothelial cells (ECs), revealing divergent EC subtypes including endocardial, capillary, venous, arterial, and lymphatic populations. Gene regulatory network analyses predicted roles for SMAD1 and MECOM in determining the identity of capillary and arterial populations, respectively. Trajectory inference analysis suggested an endocardial contribution to the coronary vasculature and subsequent arterialization of capillary endothelium accompanied by increasing MECOM expression. Comparative analysis of equivalent data from murine cardiac development demonstrated that transcriptional signatures defining endothelial subpopulations are largely conserved between human and mouse. Comprehensive characterization of the transcriptional response to MECOM knockdown in human embryonic stem cell-derived EC (hESC-EC) demonstrated an increase in the expression of non-arterial markers, including those enriched in venous EC. CONCLUSIONS: scRNA-seq of the human foetal cardiac endothelium identified distinct EC populations. A predicted endocardial contribution to the developing coronary vasculature was identified, as well as subsequent arterial specification of capillary EC. Loss of MECOM in hESC-EC increased expression of non-arterial markers, suggesting a role in maintaining arterial EC identity

The low recombining pericentromeric region of barley restricts gene diversity and evolution but not gene expression

The low-recombining pericentromeric region of the barley genome contains roughly a quarter of the genes of the species, embedded in low recombining DNA that is rich in repeats and repressive chromatin signatures. We have investigated the effects of pericentromeric region residency upon the expression, diversity and evolution of these genes. We observe no significant difference in average transcript level or developmental RNA specificity between the barley pericentromeric region and the rest of the genome. In contrast, all of the evolutionary parameters studied here show evidence of compromised gene evolution in this region. First, genes within the pericentromeric region of wild barley show reduced diversity and significantly weakened purifying selection compared to the rest of the genome. Second, gene duplicates (ohnolog pairs) derived from the cereal whole genome duplication event ca. 60MYa have been completely eliminated from the barley pericentromeric region. Third, local gene duplication in the pericentromeric region is reduced by 29% relative to the rest of the genome. Thus, the pericentromeric region of barley is a permissive environment for gene expression but has restricted gene evolution in a sizeable fraction of barley's genes. This article is protected by copyright. All rights reserved

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Deletion of Genes Implicated in Protecting the Integrity of Male Germ Cells Has Differential Effects on the Incidence of DNA Breaks and Germ Cell Loss

Infertility affects approximately 20% of couples in Europe and in 50% of cases the problem lies with the male partner. The impact of damaged DNA originating in the male germ line on infertility is poorly understood but may increase miscarriage. Mouse models allow us to investigate how deficiencies in DNA repair/damage response pathways impact on formation and function of male germ cells. We have investigated mice with deletions of ERCC1 (excision repair cross-complementing gene 1), MSH2 (MutS homolog 2, involved in mismatch repair pathway), and p53 (tumour suppressor gene implicated in elimination of germ cells with DNA damage).We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic) germ cells. Sertoli cell-only tubules were detected in testes from mice lacking expression of ERCC1 or MSH2 but not p53. The number of sperm recovered from epididymes was significantly reduced in mice lacking testicular ERCC1 and 40% of sperm contained DNA breaks whereas the numbers of sperm were not different to controls in adult Msh2 -/- or p53 -/- mice nor did they have significantly compromised DNA.These data have demonstrated that deletion of Ercc1, Msh2 and p53 can have differential but overlapping affects on germ cell function and sperm production. These findings increase our understanding of the ways in which gene mutations can have an impact on male fertility

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention