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This paper examines the operation of An Fóram Uisce (The Water Forum) and its role as a statutory body in formally engaging stakeholders in policy deliberation at the national level. An Fóram Uisce was established in 2018 and consists of twenty-six members, including stakeholders from agriculture, fisheries, business, trade unions and environmental organisations. The research finds a number of benefits of An Fóram as a means of stakeholder engagement. An Fóram is gradually evolving a role for itself in highlighting or putting an issue on the political and public agenda, and helping determine ways in which problems are addressed. It also provides members with a means of developing a shared understanding of the issues and agreeing potential solutions. Limitations exist, however. Notably, there is limited evidence to date of the impact of An Fóram on policy development in practice.

Persistent sciatic arteries are rare congenital abnormalities, with an incidence between .01-.6%. Whilst most patients with the pathology are asymptomatic during their younger years, up to 48% of patients will suffer aneurysmal degeneration of the persistent sciatic artery and present with claudication or lower limb ischaemia (from distal embolisation of mural thrombus). Due to the rare nature of persistent sciatic artery aneurysms, optimal management of the pathology is yet to be determined. Both endovascular and open techniques have been described in the management of this pathology, however hybrid management approaches are reported infrequently. The authors present a case of a persistent sciatic artery aneurysm successfully treated in a 69-year-old male utilising a hybrid approach with a femoropopliteal bypass (below knee), Amplatzer plug occlusion of the aneurysm and subsequent resection of the aneurysm.

Vertebrates use weight-lending otoconia in the inner ear otolith organs to enable detection of their translation during self or imposed movements and a change in their orientation with respect to gravity. In spaceflight, otoconia are near weightless. It has been hypothesized that otoconia undergo structural remodeling after exposure to weightlessness to restore normal sensation. A structural remodeling is reasoned to occur for hypergravity but in the opposite sense. We explored these hypotheses in several strains of mice within a Biospecimen Sharing Program in separate space- and ground-based projects. Mice were housed 90 days on the International Space Station, 13 days on two Shuttle Orbiter missions, or exposed to 90 days of hindlimb unloading or net 2.38 g via centrifugation. Corresponding flight habitat and standard cage vivarium controls were used. Utricular otoliths were visually analyzed using scanning electron microscopy and in selected samples before and after focused ion beam (FIB) milling. Results suggest a possible mass addition to the otoconia outer shell might occur after exposure to longer-duration spaceflight, but not short ones or hindlimb unloading. A destructive process is clearly seen after centrifugation: an ablation or thinning of the outer shell and cavitation of the inner core. This study provides a purely descriptive account of otoconia remodeling after exposures to altered gravity. The mechanism(s) underlying these processes must be identified and quantitatively validated to develop countermeasures to altered gravity levels during exploration missions.

This article starts off by presenting a brief history of public service reform initiatives in Ireland, at both central and local government level, from the foundation of the state to the present day. Reasons for the reforms and the main issues addressed are highlighted. Common themes are identified. These common themes provide the basis for identifying and examining five enduring reform challenges: building the capability of public servants; involving and empowering the public; coordination and collaboration; centralisation versus decentralisation; and policy and evidence. Drawing from insights from previous reform efforts, and particularly those following the financial crisis, suggestions are made as to what steps might be taken in the next phase of reform to deal with them.

Purpose Joint dynamics following Total Knee Arthroplasty (TKA) may influence patient-reported outcome. Simulations allow many knee alignment approaches to a single patient to be considered prior to surgery. The simulated kinematics can be matched to patient-reported outcome to predict kinematic patterns most likely to give the best outcome. This study aims to validate one such previously developed algorithm based on a simulated deep knee bend (the Dynamic Knee Score, DKS). Methods 1074 TKA patients with pre- and post-operative Computerised Tomography (CT) scans and 12-month post-operative Knee Injury and Osteoarthritis Outcomes (KOOS) Scores were identified from the 360 Med Care Joint Registry. Landmarking and registration of implant position was performed on all CT scans, and each of the achieved TKAs was computationally simulated and received a predictive outcome score from the DKS. In addition, a set of potential alternative surgical plans which might have been followed were simulated. Comparison of patient-reported issues and DKS score was evaluated in a counter-factual study design. Results Patient-reported impairment with the knee catching and squatting was shown to be 30% lower (p = 0.005) and 22% lower (p = 0.026) in patients where the best possible DKS result was the one surgically achieved. Similar findings were found relating attainment of the best tibial slope and posterior femoral resection DKS plans to patient-reported difficulty straightening the knee (40% less likely, p p = 0.006). Conclusion The DKS has been shown to correlate with presence of patient-reported impairments post-TKA and the resultant algorithm can be applied in a pre-operative planning setting. Outcome optimization in the future may come from patient-specific selection of an alignment strategy and simulations may be a technological enabler of this trend. Level of evidence. III (Retrospective Cohort Study).

Mesenchymal chondrosarcoma (MCS) is an ultra-rare sarcoma that follows a more aggressive course than conventional chondrosarcoma. This study evaluates prognostic factors, treatments (surgery, chemotherapy, and radiation), and outcomes in an Australian setting.We collected demographics, clinicopathological variables, treatment characteristics, and survival status from patients with MCS registered on the national ACCORD sarcoma database. Outcomes include overall survival (OS) and progression-free survival (PFS).We identified 22 patients with MCS between 2001-2022. Median age was 28 (range 10-59) years, 19 (86%) had localised disease at diagnosis of whom 16 had surgery (84%), 11 received radiation (58%), and 10 chemotherapy (53%). Ten (52%) developed recurrence and/or metastases on follow-up and three patients with initial metastatic disease received surgery, radiation, and chemotherapy. At a median follow-up of 50.9 (range 0.4-210) months nine patients had died. The median OS was 104.1 months (95% CI 25.8-182.3). There was improved OS for patients with localised disease who had surgical resection of the primary (p = 0.003) and those with ECOG 0-1 compared to 2-3 (p = 0.023) on univariate analysis.This study demonstrates contemporary Australian treatment patterns of MCS. The role of chemotherapy for localised disease remains uncertain. Understanding treatment patterns and outcomes help support treatment decisions and design of trials for novel therapeutic strategies.

Simple Summary Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a rare disease that can be located on the knee joints'anterior and posterior sides. Surgery approaching both sides of the knee is often performed to remove the tumor. However, there is no consensus on whether surgery on both sides should be performed during one procedure or in two separate interventions. In this retrospective, cohort study, 191 patients were included from nine sarcoma centers worldwide. The goal was to compare the short-term postoperative outcomes of two-sided surgeries for D-TGCTs of the knee, performed in either one or two stages. Surgery on the knee's anterior and posterior sides performed in one stage did not result in impaired rehabilitation compared to two-stage surgery. Additionally, patients undergoing surgery in one stage had a shorter hospital stay and no more complications. Diffuse-type tenosynovial giant cell tumors' (D-TGCTs) intra- and extra-articular expansion about the knee often necessitates an anterior and posterior surgical approach to facilitate an extensive synovectomy. There is no consensus on whether two-sided synovectomies should be performed in one or two stages. This retrospective study included 191 D-TGCT patients from nine sarcoma centers worldwide to compare the postoperative short-term outcomes between both treatments. Secondary outcomes were rates of radiological progression and subsequent treatments. Between 2000 and 2020, 117 patients underwent one-stage and 74 patients underwent two-stage synovectomies. The maximum range of motion achieved within one year postoperatively was similar (flexion 123-120 degrees, p = 0.109; extension 0 degrees, p = 0.093). Patients undergoing two-stage synovectomies stayed longer in the hospital (6 vs. 4 days, p < 0.0001). Complications occurred more often after two-stage synovectomies, although this was not statistically different (36% vs. 24%, p = 0.095). Patients treated with two-stage synovectomies exhibited more radiological progression and required subsequent treatments more often than patients treated with one-stage synovectomies (52% vs. 37%, p = 0.036) (54% vs. 34%, p = 0.007). In conclusion, D-TGCT of the knee requiring two-side synovectomies should be treated by one-stage synovectomies if feasible, since patients achieve a similar range of motion, do not have more complications, but stay for a shorter time in the hospital.

Background: Reconstructive procedure following resection of large pelvic tumours around the hip joint remains a complex challenge. Methods: This study presents a retrospective case series of patients presenting with benign or malignant pelvic tumour for which an internal hemipelvectomy including the hip joint and subsequent reconstruction with a custom designed 3-dimensional printed titanium pelvic implant (3DPPI) has been performed between August 2013 and January 2018. Results: 15 consecutive patients with a median age of 33.9 years (IQR 26.4–72.2) and a median BMI of 20.7 kg/m2 (IQR 19.0–33.3) were reviewed after median follow-up of 33.8 months (IQR 24.0–78.1). The majority of patients presented with a malignant tumour as their principal diagnosis ( n = 13, 86.7%). The median surgical time was 5.5 hours (IQR 4.5–8.5) and median peri-operative blood loss was 5000 ml (IQR 2000–10000). The median MSTS score at follow-up was 63.3% (IQR 51.7–86.7%). The median NRS in rest was 0.0 (IQR 0.0–5.0), the median NRS during activity was 2.0 (IQR 0.5–7.0) and the median HOOS-PS was 76.6% (IQR 67.9–91.0). 4 patients had implant-specific complications ( n = 4, 26.6%); 1 hip dislocation (Henderson type 1a), 3 structural complications (type 3a), 1 deep infection (type 4a) and 1 local tumour recurrence (type 5b). At follow-up, 4 out of 15 implants were classified as a failure, resulting in an implant survival rate of 73.3%. Conclusions: Acceptable peri-operative outcomes, functional results, complication rates and short-term implant survival can be achieved in a cohort of complex patients undergoing 3DPPI reconstruction after hemipelvectomy including the acetabulum.

A 29-year-old female presented with 12 months of polyuria, polydipsia, nausea, headaches and worsening left hip pain, beginning 7 months into her first pregnancy. Galactorrhea persisted after cessa...

The Bay of Bengal hosts persistent, measurable, but sub-micromolar, concentrations of oxygenin its oxygen-minimum zone (OMZ). Such low-oxygen conditions are not necessarily rare in theglobal ocean and seem also to characterize the OMZ of the Pescadero Basin in the Gulf of California,as well as the outer edges of otherwise anoxic OMZs, such as can be found, for example, in theEastern Tropical North Pacific. We show here that biological controls on oxygen consumption arerequired to allow the semistable persistence of low-oxygen conditions in OMZ settings; otherwise,only small changes in physical mixing or rates of primary production would drive the OMZ betweenanoxic and oxic states with potentially large swings in oxygen concentration. We propose that twocontrols are active: an oxygen-dependent control on oxygen respiration and an oxygen inhibition ofdenitrification. These controls, working alone and together, can generate low-oxygen concentrationsover a wide variability in ocean mixing parameters. More broadly, we discuss the oxygen regulationof organic matter cycling and N2 production in OMZ settings. Modern biogeochemical models ofnitrogen and oxygen cycling in OMZ settings do contain some of the parameterizations that weexplore here. However, these models have not been applied to understanding the persistence of low,but measurable, concentrations of oxygen in settings like the Bay of Bengal, nor have they been appliedto understanding what biological/physical processes control the transition from a weakly oxygenatedstate to a “functionally” anoxic state with implications for nitrogen cycling. Therefore, we believethat the approach here illuminates the relationship between oxygen and the biogeochemical cycling ofcarbon and nitrogen in settings like the Bay of Bengal. Furthermore, we believe that our results couldfurther inform large-scale ocean models seeking to explore how global warming might influence thespread of low-oxygen waters, influencing the cycles of oxygen, carbon, and nitrogen in OMZ settings.Keywords: oxygen-minimum zone, OMZ, denitrification, aerobic respiration, climate change,model, feedback, Bay of Bengal

Aims NTRK-rearranged sarcomas are emerging as a distinct class of sarcomas of particular importance in the era of targeted therapy. The aim of this study was to use array comparative genomic hybridisation (aCGH) to explore the cytogenetic profile of six adult soft tissue sarcomas harbouring NTRK gene fusions. Methods and results aCGH was performed on six adult soft tissue sarcomas with proven NTRK rearrangements [NTRK1, n = 1 (TPM3-NTRK1); NTRK2, n = 1 (MTMR2-NTRK2); NTRK3, n = 4 (two ETV6-NTRK3; two with unknown partners). The morphological patterns of these cases included inflammatory myofibroblastic tumour-like, fibrosarcoma/malignant peripheral nerve sheath tumour-like, and Ewing sarcoma-like. On the basis of the number of chromosomal copy number variations (CNVs), ranging from two to 15 per sample, NTRK-associated sarcomas could be subdivided into two groups: one with a relatively simple karyotype (n = 2; median of three genomic alterations), and those with a more complex karyotype (n = 4; median of 11 genomic imbalances). Recurrent chromosomal CNVs included gains at chromosomes 6p, 1q, 7 (whole chromosome), and 12p, and losses at chromosomes 10q, 13q, 19q, and 9p. Conclusions NTRK-rearranged sarcomas constitute a heterogeneous group of tumours that can show a relatively simple or a complex karyotype. Although there were some, but inconsistent, associations between karyotype complexity and morphology, our study showed that a more complex karyotype in this group of tumours appeared to correlate with more aggressive clinical behaviour. Gains at chromosome 6p and 1q were the most common recurrent genomic alterations, being present in 67% of the samples (4/6), followed by gains at chromosome 7, which were present in 50% of the samples (3/6).

Chapter Eight examines the development of policy analysis in the civil service. Policy analysis is central to the role of the civil service at the intersection of politics and administration. In the Whitehall tradition, inherited by Ireland, civil servants were expected to be generalists with unpartisan perspectives. Recruits to the civil service came from the liberal arts rather than professional or technical backgrounds. But, the 1960s and 1970s saw the gradual emergence of the policy analysis concept. Policy analysis requires knowledge of the relevant discipline under scrutiny, some skills in quantitative analysis, combined with the more traditional policy capabilities. Throughout the chapter it is clear that a stronger evidence base is emerging to better inform policy making. A balance between generalists with broad conceptual skills and specialists with quantitative analytical skills continues to influence developments with regard to policy analysis in the civil service.

Background Computer simulations of knee movement allow Total Knee Arthroplasty (TKA) dynamic outcomes to be studied. This study aims to build a model predicting patient reported outcome from a simulation of post-operative TKA joint dynamics. Methods Landmark localisation was performed on 239 segmented pre-operative computerized tomography (CT) scans to capture patient specific soft tissue attachments. The pre-operative bones and 3D implant files were registered to post-operative CT scans following TKA. Each post-operative knee was simulated undergoing a deep knee bend with assumed ligament balancing of the extension space. The kinematic results from this simulation were used in a Multivariate Adaptive Regression Spline algorithm, predicting attainment of a Patient Acceptable Symptom State (PASS) score in captured 12 month post-operative Knee Injury and Osteoarthritis Outcome Scores (KOOS). An independent series of 250 patients was evaluated by the predictive model to assess how the predictive model behaved in a pre-operative planning context. Results The generated predictive algorithm, called the Dynamic Knee Score (DKS) contained features, in order of significance, related to tibio-femoral force, patello-femoral motion and tibio-femoral motion. Area Under the Curve for predicting attainment of the PASS KOOS Score was 0.64. The predictive model produced a bimodal spread of predictions, reflecting a tendency to either strongly prefer one alignment plan over another or be ambivalent. Conclusion A predictive algorithm relating patient reported outcome to the outputs of a computational simulation of a deep knee bend has been derived (the DKS). Simulation outcomes related to tibio-femoral balance had the highest correlation with patient reported outcome.

Space travel presents a number of environmental challenges to the central nervous system, including changes in gravitational acceleration that alter the terrestrial synergies between perception and action, galactic cosmic radiation that can damage sensitive neurons and structures, and multiple factors (isolation, confinement, altered atmosphere, and mission parameters, including distance from Earth) that can affect cognition and behavior. Travelers to Mars will be exposed to these environmental challenges for up to 3 years, and space-faring nations continue to direct vigorous research investments to help elucidate and mitigate the consequences of these long-duration exposures. This article reviews the findings of more than 50 years of space-related neuroscience research on humans and animals exposed to spaceflight or analogs of spaceflight environments, and projects the implications and the forward work necessary to ensure successful Mars missions. It also reviews fundamental neurophysiology responses that will help us understand and maintain human health and performance on Earth.

Many aspects of the supposed hyperthermal Toarcian Oceanic Anoxic Event (T-OAE, Early Jurassic, c. 182 Ma) are well understood but a lack of robust palaeotemperature data severely limits reconstruction of the processes that drove the T-OAE and associated environmental and biotic changes. New oxygen isotope data from calcite shells of the benthic fauna suggest that bottom water temperatures in the western Tethys were elevated by c. 3.5 °C through the entire T-OAE. Modelling supports the idea that widespread marine anoxia was induced by a greenhouse-driven weathering pulse, and is compatible with the OAE duration being extended by limitation of the global silicate weathering flux. In the western Tethys Ocean, the later part of the T-OAE is characterized by abundant occurrences of the brachiopod Soaresirhynchia, which exhibits characteristics of slow-growing, deep sea brachiopods. The unlikely success of Soaresirhynchia in a hyperthermal event is attributed here to low metabolic rate, which put it at an advantage over other species from shallow epicontinental environments with higher metabolic demand.

peer-reviewed The Reform and Delivery Office (RDO) in the Department of Public Expenditure and Reform has developed a series of case studies on citizen engagement, in partnership with researchers and public bodies, as a commitment under the Our Public Service 2020 development and innovation framework.

Aim To determine the outcome after radiation therapy for desmoid fibromatosis. Materials and methods A retrospective review of 50 patients treated between 1988 and 2016 in a specialised bone and soft tissue tumour clinic. Results The median age at the time of radiation therapy was 36.8 years (range 15.1–69.0) and the median follow-up time was 51 months. Forty-three patients underwent radiation therapy as the definitive treatment with a median dose of 56 Gy (range 30–58.8 Gy). The median dose for the seven patients treated with postoperative radiation therapy was 50.4 Gy (range 48–56 Gy). Eleven patients (22%) developed progressive disease after radiation therapy at a median time of 41 months (range 12–113 months). The recurrences were within the radiation therapy field in four patients and outside the field in seven patients. One patient developed a radiation-induced malignancy 20 years after treatment. Conclusions Radiation therapy is an alternative treatment in the management of desmoid fibromatosis. It should be considered in patients for whom surgical resection is not feasible, or as adjuvant therapy after surgery with involved margins where any further recurrences would cause significant morbidity.

The Proterozoic Earth system is popularly viewed as having comprised prolonged periods of invariant conditions separating intervals of extreme change. Against this backdrop the earliest evidence of eukaryotic organisms is found, raising the (highly uncertain) possibility of an environmental impetus for this fundamental evolutionary transition. Here I review the eukaryotic fossil record and the theoretical issues surrounding eukaryogenesis, with the aim of relating these ideas to the broad context of the Proterozoic Earth system. In terms of fossils, either eukaryotes were present in Proterozoic oceans, (conceivably as early as 2.1Ga, but at the latest by 1.4 Ga), or the macroscopic fossils that are found from this period are prokaryotic colonies that converged on form very close to modern eukaryotes before going extinct (the first possibility is far more parsimonious). In terms of DNA, phylogenetic evidence indicates that eukaryotes derive from a symbiosis between an archaeon host cell and a eubacterial proto-mitochondrion. Bar a tiny number of isolated examples contemporary prokaryotic cells do not simply end up inside the cells of other prokaryotes as a consequence of ecological interactions (however synergistic). Therefore the capacity for phagocytosis in the host cell is by far the most plausible way in which to explain the acquisition of the mitochondrial symbiont. But phagocytosis, and indeed the larger cell size of eukaryotes, is probably incompatible with use of the external cell membrane to sustain a proton gradient for ATP generation (as occurs in prokaryotes). By contrast, the “multi-bacterial power” of ATP generation in numerous mitochondria results in eukaryotes having considerably more free energy available per gene than prokaryotes. Importantly, this can be achieved whilst minimizing the (potentially extreme) free radical damage from “misfiring” electron transport chains, by a “co-location for redox regulation” involving transfer of most mitochondrial genes to the host nucleus, but transcription of key respiratory components near the site of their activity. Thus, debate persists about a “catch-22” situation: Arguably, the host cell requires a cytoskeleton in order to acquire (proto) mitochondria, but cannot energetically sustain a cytoskeleton without ATP generation in multiple mitochondria. Explaining why an initially transient, facultative interaction progressed to full endosymbiosis amounts to aligning the fitness interests of the host and symbiont. I conclude by tentatively speculating that the Paleoproterozoic global-scale glaciations may have provided an impetus for eukaryogenesis by providing some form of extreme bottleneck, in which: (a) Ancestral host and symbiont organisms were physically forced into close proximity for an unprecedented length of evolutionary time, and (b) Restricted dispersal, small populations, and low resource availability rendered survival, rather than fecundity, the dominant component of fitness, permitting sequential fixation of multiple cooperative traits in host and symbiont genomes. Though admittedly speculative, a clear testable prediction is invoked by my suggestion: fossils with unequivocal proto-mitochondria (and perhaps nuclei), after, but not before, the Paleoproterozoic glaciations, should eventually be found.

Blau syndrome (BS) is a rare autosomal dominant familial granulomatous inflammatory disease presenting in early childhood with dermatitis, arthritis and uveitis. Early-onset sarcoidosis represents the sporadic form, and both are characterised by mutations in the CARD15/NOD2 gene on chromosome 16. We describe a 38-year-old man with known BS who presented for orthopaedic review following right-sided patellar dislocation. MRI of the injured knee demonstrated diffuse synovitis and prominent fatty tissue resembling lipoma arborescens with evidence of recent patellar dislocation. Synovectomy was performed and confirmed granulomatous synovitis. Knee imaging findings are described for the first time. Combining distinct morphological bone changes with synovitis which resembles lipoma arborescens and histology which includes sarcoidal-type granulomatous synovitis should lead the radiologist and pathologist to consider the diagnosis of BS.

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