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In 2021 JET exploited its unique capabilities to operate with T and D–T fuel with an ITER-like Be/W wall (JET-ILW). This second major JET D–T campaign (DTE2), after DTE1 in 1997, represented the culmination of a series of JET enhancements—new fusion diagnostics, new T injection capabilities, refurbishment of the T plant, increased auxiliary heating, in-vessel calibration of 14 MeV neutron yield monitors—as well as significant advances in plasma theory and modelling in the fusion community. DTE2 was complemented by a sequence of isotope physics campaigns encompassing operation in pure tritium at high T-NBI power. Carefully conducted for safe operation with tritium, the new T and D–T experiments used 1 kg of T (vs 100 g in DTE1), yielding the most fusion reactor relevant D–T plasmas to date and expanding our understanding of isotopes and D–T mixture physics. Furthermore, since the JET T and DTE2 campaigns occurred almost 25 years after the last major D–T tokamak experiment, it was also a strategic goal of the European fusion programme to refresh operational experience of a nuclear tokamak to prepare staff for ITER operation. The key physics results of the JET T and DTE2 experiments, carried out within the EUROfusion JET1 work package, are reported in this paper. Progress in the technological exploitation of JET D–T operations, development and validation of nuclear codes, neutronic tools and techniques for ITER operations carried out by EUROfusion (started within the Horizon 2020 Framework Programme and continuing under the Horizon Europe FP) are reported in (Litaudon et al Nucl. Fusion accepted), while JET experience on T and D–T operations is presented in (King et al Nucl. Fusion submitted).

ITER is of key importance in the European fusion roadmap as it aims to prove the scientific and technological feasibility of fusion as a future energy source. The EUROfusion consortium of labs within Europe is contributing to the preparation of ITER scientific exploitation and operation and aspires to exploit ITER outcomes in view of DEMO. The paper provides an overview of the major progress obtained recently, carried out in the frame of the new (initiated in 2021) EUROfusion work-package called ‘ Pr eparation of I TER O peration’ (PrIO). The overview paper is directly supported by the eleven EUROfusion PrIO contributions given at the 29th Fusion Energy Conference (16–21 October 2023) London, UK [ https://www.iaea.org/events/fec2023 ]. The paper covers the following topics: (i) development and validation of tools in support to ITER operation (plasma breakdown/burn-through with evolving plasma volume, new infra-red synthetic diagnostic for off-line analysis and wall monitoring using Artificial Intelligence techniques, synthetic diagnostics development, development and exploitation of multi-machine databases); (ii) R&D for the radio-frequency ITER neutral beam sources leading to long duration of negative deuterium/hydrogen ions current extraction at ELISE and participation in the neutral beam test facility with progress on the ITER source SPIDER, and, the commissioning of the 1 MV high voltage accelerator (MITICA) with lessons learned for ITER; (iii) validation of neutronic tools for ITER nuclear operation following the second JET deuterium–tritium experimental campaigns carried out in 2021 and in 2023 (neutron streaming and shutdown dose rate calculation, water activation and activated corrosion products with advanced fluid dynamic simulation; irradiation of several materials under 14.1 MeV neutron flux etc).

JET, the world’s largest operating tokamak with unique Be/W wall and tritium handling capability, completed a Deuterium-Tritium (D-T) campaign in 2021 (Maggi et al 29th Fusion Energy Conf. ) following a decade of preparatory experiments, dedicated enhancements, technical rehearsals and training (Horton et al 2016 Fusion Eng. Des. 109–111 925). Operation with tritium raises significant technical, safety and scientific challenges not encountered in standard protium or deuterium operation. This contribution describes the tritium operational requirements, pulses and technical preparations, new operating procedures, lessons learned and details on the achieved operational availability and performance. The preparation and execution of the recent JET tritium experiments benefitted from the previous experience in 1991 (Preliminary Tritium Experiment), 1997 (DTE1 campaign) and 2003 (Trace Tritium Campaigns) and consisted of the following five phases: technical rehearsals and scenario preparation, tritium commissioning, 100% tritium campaign, D-T campaign (DTE2), tritium clean-up. Following the clean-up JET resumed normal operation and is currently undertaking a further D-T campaign (DTE3).

A global heat flux model based on a fractional derivative of plasma pressure is proposed for the heat transport in fusion plasmas. The degree of the fractional derivative of the heat flux, α, is defined through the power balance analysis of the steady state. The model was used to obtain the experimental values of α for a large database of the Joint European Torus (JET) carbon-wall as well as ITER like-wall plasmas. The fractional degrees of the electron heat flux are found to be α

Collision tumours of two different histopathological processes are rare. We describe a case of a patient with known low grade prostate adenocarcinoma developing a rectal GIST, which was diagnosed with combined imaging modalities of MR and ultrasound and confirmed by transrectal ultrasound guided biopsy.

The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH) secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

Dental erosion continues to be a significant global health concern affecting nearly 30% of adults worldwide. With increasing soft drink consumption predominantly driving its prevalence, strategies for prevention and control are often implemented when erosion is severe, or rates are high in the populace. While factors affecting dental erosion such as pH on enamel have received much attention, the effect of dietary acid concentration when factored out to a commercially available pH has yet to be determined. Furthermore, understanding these effects on dentine, which is known to be more susceptible to erosion than enamel can unravel structure-property relationships between acid characteristics and hard tissue types. This study aimed to develop structure-property relationships between dietary acid concentration, and pH, on the nano-textural and nano-mechanical properties of human enamel and dentine during short-term simulated drinking. To achieve this, a novel sample preparation methodology and analysis approach was developed by applying atomic force microscopy (AFM) in quantitative imaging mode. This enabled simultaneous measurement of enamel and dentine morphology and mechanical properties. Flow-cells were used to simulate drinking, exposing polished and smear layer-free human enamel and dentine to 30 s repeated cycles of unbuffered citric acid 6% (pH = 1.88) and 1% (w/v) (pH = 2.55) and commercially available buffered pH = 3.8 states, for up to 180 s. The same 50 µm × 50 µm area of specimen morphology was analysed using in-house developed nanotextural analysis using the bearing area curve (BAC) with a focus on roughness (Ra), normalised peak (PA) and valley areas (VA). Mechanical properties were simultaneously measured for stiffness (N/m) after each 30 s. While all studies agree pH is a major factor in the erosion of enamel, here its dominance over the treatment time varied, with concentration surpassing the importance of pH after initial acid contact. Conversely, dentine erosion showed concentration-dependent changes in morpho-mechanical properties only. These results not only highlight the dynamic process of erosion but also how the interplay between acid characteristics and dental tissue type impacts the progression of very early-stage erosion.

Hyperspectral imaging (HSI) enables recording both morphological and biochemical information, but image acquisition time and geometric distortions limit its clinical applicability. Here the authors overcome these challenges with an endoscope combining HSI and white light to correct for image distortion during freehand operation.

Elizabeth J Waterhouse, Kimberly N Mims, Soundarya N GowdaDepartment of Neurology, Virginia Commonwealth University School of Medicine, Richmond, VA, USAAbstract: Vigabatrin (VGB) is an antiepileptic drug that was designed to inhibit GABA-transaminase, and increase levels of γ-amino-butyric acid (GABA), a major inhibitory neurotransmitter in the brain. VGB has demonstrated efficacy as an adjunctive antiepileptic drug for refractory complex partial seizures (CPS) and for infantile spasms (IS). This review focuses on its use for complex partial seizures. Although VGB is well tolerated, there have been significant safety concerns about intramyelinic edema and visual field defects. VGB is associated with a risk of developing bilateral concentric visual field defects. Therefore, the use of VGB for complex partial seizures should be limited to those patients with seizures refractory to other treatments. Patients must have baseline and follow-up monitoring of visual fields, early assessment of its efficacy, and ongoing evaluation of the benefits and risks of VGB therapy.Keywords: vigabatrin, epilepsy, complex partial seizures, review

In west-central British Columbia, terrestrial lichens located in older, lodgepole pine (Pinus contorta) forests are important winter forage for woodland caribou (Rangifer tarandus caribou). Clearcut harvesting effectively removes winter forage habitat for decades, so management approaches based on partial cutting were designed to maintain continuous lichen-bearing habitat for caribou. This study tested a group selection system, based on removal of 33% of the forest every 80 years in small openings (15 m diameter), and two irregular shelterwood treatments (whole-tree and stem-only harvesting methods) where 50% of the stand area is cut every 70 years in 20 to 30 m diameter openings. The abundance of common terrestrial lichens among the partial cutting and no-harvest treatments was compared across five replicate blocks, pre-harvest (1995) and post-harvest (1998, 2000 and 2004). The initial loss of preferred forage lichens (Cladonia, Cladina, Cetraria and Stereocaulon) was similar among harvesting treatments, but there was greater reduction in these lichens in the openings than in the residual forest. After eight years, forage lichens in the group selection treatment recovered to pre-harvest amounts, while lichen in the shelterwood treatments steadily increased from 49 to 57% in 1998 to about 70% of pre-harvest amounts in 2004. Although not part of the randomized block design, there was substantially less lichen in three adjacent clearcut blocks than in the partial cuts. Regression analysis pre- and post-harvest indicated that increased cover of trees, shrubs, herbs, woody debris and logging slash corresponded with decreased forage lichen abundance. In the short-term, forestry activities that minimize inputs of woody debris, control herb and shrub development, and moderate the changes in light and temperatures associated with canopy removal will lessen the impact on lichen. Implementation of stand level prescriptions is only one aspect of caribou habitat management. A comprehensive approach should consider all factors and their interactions to maintain a viable population of woodland caribou in west-central British Columbia.

Group selection silvicultural systems have been recommended for managing mountain caribou (Rangifer tarandus caribou) habitat in high elevation Engelmann spruce – subalpine fir forests in east-central British Columbia. We measured the response of arboreal lichen (a key winter forage) to harvesting of 30% of the forested area using three partial cutting treatments, which created small (0.03 ha), medium (0.13 ha), and large (1.0 ha) openings, and a no-harvest treatment. Treatments were replicated on four sites, and monitored over a ten year post-harvest period. The short-term loss of lichen associated with removal of approximately one third of the trees was partially offset by a significant (P=0.01) increase in lichen abundance on trees in the caribou feeding zone (up to 4.5 m) in the three partial cutting treatments relative to trees in the uncut forest. Differences among treatments in the change in lichen composition, as measured by the percentage of Alectoria sarmentosa and Bryoria spp., were marginally significant (P=0.10). The partial cutting treatments showing a greater likelihood of shifting towards more Bryoria spp. than no-harvest treatment (P=0.04). In the year of harvest (1993), larger trees were found to hold more lichen than smaller trees (P=0.04), and live trees supported more lichen than dead trees (P=0.01), but lichen loading was similar among tree species (P=0.51). Tree fall rates were similar among treatments, based on the ten year average (0.6–0.8% of sample trees per year). The results indicate that caribou foraging habitat is maintained in the residual forest when group selection systems that remove only 30% of the trees are applied. Information on the distribution of lichen is useful for developing stand level prescriptions. Providing lichen bearing habitat meets just one of the needs of caribou. A comprehensive approach that considers all factors and their interactions is essential to maintain and recover the threatened mountain caribou.

Background Levodopa remains the mainstay of treatment of Parkinson’s disease, however, over time motor fluctuations and levodopa-induced dyskinesia develop, requiring add-on therapies to control emerging symptoms. To date, however, there is no clear consensus in Australia, or elsewhere, at which dose of levodopa that add-on therapies should be considered.Objectives The purpose of this study was to examine the treatment patterns of patients with Parkinson’s disease in Australia, with particular focus on levodopa doses at the time of first add-on.Methods This was a retrospective, observational, non-interventional study of patients with Parkinson’s disease within the Australian Department of Human Services Pharmaceutical Benefits Scheme (PBS) 10% sample. Data on all reimbursed prescriptions (both general and concession), prescriber type and item code were extracted for patients who were dispensed at least three PBS reimbursed prescriptions for levodopa in the previous 12 months prescription from 1 January 2007 to 31 December 2021.Results 154 850 unique patients were included, of whom 42 330 (27%) commenced add-on therapy during the period. In the 12 months prior to add-on therapy, levodopa doses ranged from 100 mg/day to 1000 mg/day. The majority of patients were prescribed add-on therapy by a neurologist and approximately 40% of patients were prescribed levodopa doses of 600 mg/day or more prior to the first add-on therapy being initiated.Conclusions A large proportion of patients in Australia are managed with levodopa monotherapy doses that are considered high and many of these patients may benefit from the addition of add-on therapy to their regimen.

Background Pixatimod is a unique activator of the Toll-like Receptor 9 pathway. This phase I trial evaluated safety, efficacy and pharmacodynamics of pixatimod and PD-1 inhibitor nivolumab in immunologically cold cancers.Methods 3+3 dose escalation with microsatellite stable metastatic colorectal cancer (MSS mCRC) and metastatic pancreatic ductal adenocarcinoma (mPDAC) expansion cohorts. Participants received pixatimod once weekly as a 1-hour intravenous infusion plus nivolumab every 2 weeks. Objectives included assessment of safety, antitumor activity, pharmacodynamics, and pharmacokinetic profile.Results Fifty-eight participants started treatment. The maximum tolerated dose of pixatimod was 25 mg in combination with 240 mg nivolumab, which was used in the expansion phases of the study. Twenty-one grade 3–5 treatment-related adverse events were reported in 12 participants (21%); one participant receiving 50 mg pixatimod/nivolumab had a treatment-related grade 5 AE. The grade 3/4 rate in the MSS mCRC cohort (n=33) was 12%. There were no responders in the mPDAC cohort (n=18). In the MSS mCRC cohort, 25 participants were evaluable (initial postbaseline assessment scans >6 weeks); of these, three participants had confirmed partial responses (PR) and eight had stable disease (SD) for at least 9 weeks. Clinical benefit (PR+SD) was associated with lower Pan-Immune-Inflammation Value and plasma IL-6 but increased IP-10 and IP-10/IL-8 ratio. In an MSS mCRC participant with PR as best response, increased infiltration of T cells, dendritic cells, and to a lesser extent NK cells, were evident 5 weeks post-treatment.Conclusions Pixatimod is well tolerated at 25 mg in combination with nivolumab. The efficacy signal and pharmacodynamic changes in MSS mCRC warrants further investigation.Trial registration number NCT05061017.

Nonsteroidal anti-inflammatory drugs (NSAID) reduce the risk for cancer, due to their anti proliferative and apoptosis-inducing effects. A critical pathway for apoptosis involves the release of cytochrome c from mitochondria, which then interacts with Apaf-1 to activate caspase proteases that orchestrate cell death. In this study we found that treatment of a human cancer cell line with aspirin induced caspase activation and the apoptotic cell morphology, which was blocked by the caspase inhibitor zVAD-fmk. Further analysis of the mechanism underlying this apoptotic event showed that aspirin induces translocation of Bax to the mitochondria and triggers release of cytochrome c into the cytosol. The release of cytochrome c from mitochondria was inhibited by overexpression of the antiapoptotic protein Bcl-2 and cells that lack Apaf-1 were resistant to aspirin-induced apoptosis. These data provide evidence that the release of cytochrome c is an important part of the apoptotic mechanism of aspirin.

Protease-activated receptor-2 (PAR2) is a G protein coupled receptor (GPCR) activated by proteolytic cleavage of its amino terminal domain by trypsin-like serine proteases. This irreversible activation mechanism leads to rapid receptor desensitization by internalisation and degradation. We have explored the role of palmitoylation, the post-translational addition of palmitate, in PAR2 signalling, trafficking, cell surface expression and desensitization. Experiments using the palmitoylation inhibitor 2-bromopalmitate indicated that palmitate addition is important in trafficking of PAR2 endogenously expressed by prostate cancer cell lines. This was supported by palmitate labelling using two approaches, which showed that PAR2 stably expressed by CHO-K1 cells is palmitoylated and that palmitoylation occurs on cysteine 361. Palmitoylation is required for optimal PAR2 signalling as Ca²⁺ flux assays indicated that in response to trypsin agonism, palmitoylation deficient PAR2 is ∼9 fold less potent than wildtype receptor with a reduction of about 33% in the maximum signal induced via the mutant receptor. Confocal microscopy, flow cytometry and cell surface biotinylation analyses demonstrated that palmitoylation is required for efficient cell surface expression of PAR2. We also show that receptor palmitoylation occurs within the Golgi apparatus and is required for efficient agonist-induced rab11a-mediated trafficking of PAR2 to the cell surface. Palmitoylation is also required for receptor desensitization, as agonist-induced β-arrestin recruitment and receptor endocytosis and degradation were markedly reduced in CHO-PAR2-C361A cells compared with CHO-PAR2 cells. These data provide new insights on the life cycle of PAR2 and demonstrate that palmitoylation is critical for efficient signalling, trafficking, cell surface localization and degradation of this receptor.

Background Multipotent mesenchymal stromal cells suppress T-cell function in vitro, a property that has underpinned their use in treating clinical steroid-refractory graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. However the potential of mesenchymal stromal cells to resolve graft-versus-host disease is confounded by a paucity of pre-clinical data delineating their immunomodulatory effects in vivo.Design and Methods We examined the influence of timing and dose of donor-derived mesenchymal stromal cells on the kinetics of graft-versus-host disease in two murine models of graft-versus-host disease (major histocompatibility complex-mismatched: UBI-GFP/BL6 [H-2b]→BALB/c [H-2d] and the sibling transplant mimic, UBI-GFP/BL6 [H-2b]→BALB.B [H-2b]) using clinically relevant conditioning regimens. We also examined the effect of mesenchymal stromal cell infusion on bone marrow and spleen cellular composition and cytokine secretion in transplant recipients.Results Despite T-cell suppression in vitro, mesenchymal stromal cells delayed but did not prevent graft-versus-host disease in the major histocompatibility complex-mismatched model. In the sibling transplant model, however, 30% of mesenchymal stromal cell-treated mice did not develop graft-versus-host disease. The timing of administration and dose of the mesenchymal stromal cells influenced their effectiveness in attenuating graft-versus-host disease, such that a low dose of mesenchymal stromal cells administered early was more effective than a high dose of mesenchymal stromal cells given late. Compared to control-treated mice, mesenchymal stromal cell-treated mice had significant reductions in serum and splenic interferon-γ, an important mediator of graft-versus-host disease.Conclusions Mesenchymal stromal cells appear to delay death from graft-versus-host disease by transiently altering the inflammatory milieu and reducing levels of interferon-γ. Our data suggest that both the timing of infusion and the dose of mesenchymal stromal cells likely influence these cells’ effectiveness in attenuating graft-versus-host disease.

Purpose: Many patients with early breast cancer (eBC) undergoing neoadjuvant chemotherapy do not achieve pathological complete response (pCR), which is a prognostic factor. We examined the role of HER2-low expression in predicting pCR and prognosis in HER2-negative eBC., Methods: We evaluated patients with stage I-III HER2-negative BC, treated between 2013 and 2023 at The Royal Marsden NHS Foundation Trust, London. Tumors were classified based on estrogen receptor (ER) status and into HER2-low and HER2-zero subgroups. We analyzed pCR rates, relapse-free survival (RFS) and overall survival (OS)., Results: 754 patients were included in the analysis. pCR rate was 8.9% in the ER+ /HER2-low, 16.5% in the ER+ /HER2-zero, 38.9% in the ER- ER-/HER2-low and 35.9% in the ER-/HER2-zero eBC (p < 0.001). Multivariable analysis showed a significantly lower pCR rate in HER2-low compared to HER2-zero BC in the ER+ subgroup. At a median follow-up of 63.8 months (59.9-67.4), we observed longer OS in HER2-low compared to HER2-zero patients in the overall and in the ER+ population. There was no predictive or prognostic impact of HER2-low status in the ER- population., Conclusion: This study supports the interpretation of HER2 status as a possible prognostic and predictive biomarker for HER2-negative eBC, especially among patients with ER+ disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sulfonamides, which are drugs commonly prescribed in hospital and outpatient settings, have historically been associated with a high incidence of hypersensitivity reactions. It is believed that there is an increased risk of cross-reactions with other drugs that contain this functional group in their structure. However, it has not been conclusively established that the sulfonamide group is the sole cause of hypersensitivity reactions, as non-antibiotic sulfonamides do not share the same accessory groups with antibiotic sulfonamides. Therefore, cross-reactivity between different types of sulfonamides and sulfonamide-type antibiotics is not clearly demonstrated, and allergic reactions may involve other mechanisms. Misinformation about this topic can lead to inappropriate use of alternative antibiotics with lower efficacy or higher adverse effects, contributing to antibiotic resistance. It is crucial to individualize and monitor patients with a history of allergies to sulfonamide-type antibiotics when introducing a new drug containing sulfa and manage any adverse reactions promptly. Desensitization protocols may be a viable option for patients who specifically benefit from these antibiotics, particularly those who are immunosuppressed. This article provides a descriptive bibliographic review to update information on sulfa allergy, its prevalence, management, and recommendations to prevent such reactions and optimize pharmacotherapy, without underusing these drugs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Monitoring programs are fundamental to understanding the state and trend of aquatic ecosystems. Sampling designs are a crucial component of monitoring programs and ensure that measurements evaluate progress toward clearly stated management objectives, which provides a mechanism for adaptive management. Here, we use a well-established marine monitoring program for inshore water quality in the Great Barrier Reef (GBR), Australia to investigate whether a sampling re-design has increased the program's capacity to meet its primary objectives. Specifically, we use bootstrap resampling to assess the change in statistical power to detect temporal water quality trends in a 15-year inshore marine water quality data set that includes data from both before and after the sampling re-design. We perform a comprehensive power analysis for six water quality analytes at four separate study areas in the GBR Marine Park and find that the sampling re-design (i) increased power to detect trends in 23 of the 24 analyte-study area combinations, and (ii) resulted in an average increase in power of 34% to detect increasing or decreasing trends in water quality analytes. This increase in power is attributed more to the addition of sampling locations than increasing the sampling rate. Therefore, the sampling re-design has substantially increased the capacity of the program to detect temporal trends in inshore marine water quality. Further improvements in sampling design need to focus on the program's capability to reliably detect trends within realistic timeframes where inshore improvements to water quality can be expected to occur., Competing Interests: The authors have declared that no competing interests exist.

Oxygen saturation (SO 2 ) in tissue is a crucially important physiological parameter with ubiquitous clinical utility in diagnosis, treatment, and monitoring, as well as widespread use as an invaluable preclinical research tool. Multispectral imaging can be used to visualize SO 2 non-invasively, non-destructively and without contact in real-time using narrow spectral filter sets, but typically, these spectral filter sets are poorly suited to a specific clinical task, application, or tissue type. In this work, we demonstrate the merit of optimizing spectral filter sets for more accurate estimation of SO 2 . Using tissue modelling and simulated multispectral imaging, we demonstrate filter optimization reduces the root-mean-square-error (RMSE) in estimating SO 2 by up to 37% compared with evenly spaced filters. Moreover, we demonstrate up to a 79% decrease in RMSE for optimized filter sets compared with filter sets chosen to minimize mutual information. Wider adoption of this approach will result in more effective multispectral imaging systems that can address specific clinical needs and consequently, more widespread adoption of multispectral imaging technologies in disease diagnosis and treatment., Competing Interests: The authors declare no conflicts of interest., (Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

Many coastal and marine ecosystems around the world are under increasing threat from a range of anthropogenic influences. The management of these threats continues to present ongoing challenges, with many ecosystems increasingly requiring active restoration to support or re-establish the ecosystem's biological, cultural, social and economic values. The current condition of Australia's Great Barrier Reef (GBR) and its threats, including water quality, climate change and the loss of wetlands, causing the continuing decline in the GBR's ecological condition and function, has received global attention. Activities aimed at halting these declines and system restoration have been underway for over forty years. These activities are challenging to implement, and much has been learnt from their various outcomes. This paper considers the GBR and the associated management activities as a case study for regional scale catchment to reef management. It summarises the management approaches to date, describing the key role that science, policy and community have played in underpinning various investments. Four criteria for success are proposed: the lead role of the community, the need for a systems approach, the need for targeted, cost-effective and sustainable long-term investment, and importantly, building knowledge and maintaining consensus and political commitment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Hospital based follow-up has been the standard of care for endometrial cancer. Patient initiated follow-up is a useful adjunct for lower risk cancers. The purpose of this study was to evaluate outcomes of endometrial cancer patients after stratification into risk groupings, with particular attention to salvageable relapses., Methods: All patients treated surgically for International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA endometrial cancer of all histological subtypes, from January 2009 until March 2019, were analyzed. Patient and tumor characteristics, treatment details, relapse, death, and last follow-up dates were collected. Site of relapse, presence of symptoms, and whether relapses were salvageable were also identified. The European Society of Medical Oncology-European Society of Gynecological Oncology 2020 risk stratification was assigned, and relapse free and overall survival were estimated., Results: 900 patients met the eligibility criteria. Median age was 66 years (range 28-96) and follow-up duration was 35 months (interquartile range 19-57). In total, 16% (n=144) of patients relapsed, 1.3% (n=12) from the low risk group, 3.9% (n=35) from the intermediate risk group, 2.2% (n=20) from the high-intermediate risk group, and 8.7% (n=77) from the high risk group. Salvageable relapses were less frequent at 2% (n=18), of which 33% (n=6) were from the low risk group, 22% (n=4) from the intermediate risk group, 11% (n=2) from the high-intermediate risk group, and 33% (n=6) from the high risk group. There were only three asymptomatic relapses in the low risk patients, accounting for 0.33% of the entire cohort., Conclusions: Relapses were infrequent and most presented with symptoms; prognosis after relapse remains favorable. Overall salvageable relapses were infrequent and cannot justify intensive hospital based follow-up. Use of patient initiated follow-up is therefore appropriate, as per the British Gynaecological Cancer Society's guidelines, for all risk groupings., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Eutrophication of coastal and nearshore receiving environments downstream of intensive agricultural production areas is a global issue. The Reef 2050 Water Quality Improvement Plan (2017-2022) sets ambitious targets for reducing pollutant loads entering the Great Barrier Reef from contributing agricultural catchments. At a regional scale, the Wet Tropics end-of-catchment target load reduction for dissolved inorganic nitrogen (DIN) is 60% from the 2012-2013 anthropogenic load level. However, not even with the combined efforts of the Reef Regulations (December 2019) mandate and adoption of best practice nutrient management on farm, is it likely that these DIN targets will be reached. Thus, there is a need for innovative and cost-effective approaches to deliver further water quality improvement. Transitioning low-lying, marginal sugarcane land to alternative land uses that require lower or no nitrogen inputs, but still provide farmers with income streams, is a potentially attractive solution. In this study, a multi-criteria analysis was conducted to identify sites suitable for such alternative land uses. The cost-effectiveness of DIN reductions from these land use changes were calculated, accounting for reductions in annuity gross margins and land conversion cost. In certain locations (where conversion costs are low and DIN reductions are high) treatment wetlands and no-input cattle grazing offer cost-effective DIN reduction in the range of 20-26$/kg DIN. This compares favourably with existing agricultural extension-based approaches (c. $50/kg DIN reduction). Ecosystem service wetlands (i.e., wetland restoration for fish production) - again when appropriately situated - offer the prospect of even more cost-effective performance (11-14 $/kg DIN reduction). These results, in conjunction with best management practices, support the premise that alternative land uses are cost-effective options for improving water quality in certain areas of low-lying, low productivity sugarcane land. On-going investments by government in addition to private market funding mechanisms could be appropriate for supporting such land use transitions. These approaches need to be tested and refined via targeted pilot projects, as part of a whole-of-landscape approach to achieve broader reef water quality targets., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

There is a concern that the Fly River plume from Papua New Guinea (PNG) may be delivering mine-derived polluted mud along the southern PNG coast into the northern Torres Strait, which is the northernmost extent of the Great Barrier Reef. To quantify this threat, the mud transport dynamics along the southern PNG coast were studied using the SLIM model. The model was qualitatively verified using historical field data on sediment dynamics and compared with more recent satellite-derived turbidity data. During strong south east winds and spring tides, about 5.4% of the Fly River mud discharge enters the Torres Strait, in agreement with previous field-derived results. The annual net movement of mud is westward, thus polluted Fly River mud progressively intrudes into Torres Strait. This intrusion is slow and may take a century to reach in significant quantities at Saibai Island, the nearest Australian island to the Fly River. Field data are needed to fully validate the model and provide greater confidence in these results., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

An operational method to assess trends in marine water composition and ecosystem health during flood periods has been developed for the Great Barrier Reef (GBR), Queensland, Australia. This method integrates satellite water colour data with field water quality and ecosystem monitoring data and involves the classification of Moderate-Resolution Imaging Spectroradiometer (MODIS satellite) pixels into six distinct water bodies using a "wet season" colour scale developed specifically for the GBR. Using this information, several monitoring and reporting products have been derived and are operationally implemented into a long-term water quality monitoring program for the GBR. However, MODIS sensors are aging and a long-term monitoring solution is needed. This study reviewed the water colour monitoring products currently used in the GBR. It tested the feasibility to transition these methods from historical MODIS satellite imagery to the new Sentinel-3 satellite of the European Space Agency and from the wet season colour scale to the historical Forel-Ule colour scale, using a freely-distributed Forel Ule (FU) Satellite Toolbox. Monitoring products derived from both satellites and colour scales showed very similar patterns across two case study regions of the GBR, the Wet Tropics and Burdekin marine regions, over the 2017-18 wet season. The results obtained in this study highlighted the potential of using FU Sentinel-3 imagery for the mapping of GBR marine water bodies, including flood conditions. Furthermore, the operational monitoring products and frameworks developed for the GBR are likely to provide valuable foundations for analysis of FU Sentinel-3 data in the future. Such satellite water colour datasets and frameworks will be instrumental to better understand the impact of floods and reduced water clarity on marine ecosystems, as well as to support water quality management and facilitate catchment management policy in the GBR and worldwide., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: This feasibility study aimed to assess the acceptability of inspiratory muscle training (IMT) in people with chronic obstructive pulmonary disease (COPD) who declined pulmonary rehabilitation (PR) as a potential treatment option or precursor to PR. Objectives were to assess attitudes to IMT, PR and alternatives to PR; factors influencing adherence with IMT and acceptability of outcome measures, research tools and study protocol., Design: A pragmatic, mixed methods, prepost feasibility study was conducted. Recruitment took place over a 4-month period. Participants were followed up for a period of 6 months., Settings: IMT sessions and assessments were conducted in the domiciliary setting., Participants: Inclusion criteria: people over the age of 35, stable COPD, Medical Research Council Dyspnoea scale of 3 or above, declined PR., Exclusion Criteria: history of spontaneous pneumothorax, incomplete recovery from a traumatic pneumothorax, asthma, known recently perforated eardrum, unstable angina, ventricular dysrhythmias, cerebrovascular event or myocardial infarction within the last 2 months. Participants were selected from a purposive sample. Of the 22 potential participants screened, 11 were recruited and interviewed. Ten participants commenced IMT. Seven participants completed the follow-up assessment., Intervention: Eight weeks of IMT twice a day, 5 days a week with visits once weekly by a physiotherapist. Unsupervised IMT twice a day three times a week until follow-up at 6 months., Outcomes: Acceptability of IMT and the study process was explored via semi-structured interviews. Adherence with IMT was assessed by the Powerbreathe K3 device and participant diaries. Uptake of PR was identified., Results: IMT was found to be acceptable. Adherence was explored. Four people went on to participate in PR., Conclusions: Feasibility was established. A randomised controlled trial is warranted to establish efficacy and cost-effectiveness of IMT in those who decline PR and IMT as an intervention to promote uptake of PR., Trial Registration Number: NCT01956565; Post-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Biliary dyskinesia (BD) is a common indication for pediatric cholecystectomy. While diagnosis is primarily based on diminished gallbladder ejection fraction (GB-EF), work-up and management in pediatrics is controversial., Methods: We conducted a multi-institutional retrospective review of children undergoing cholecystectomy for BD to compare perioperative work-up and outcomes., Results: Six hundred seventy-eight patients across 16 institutions were included. There was no significant difference in gender, age, or BMI between institutions. Most patients were white (86.3%), non-Hispanic (79.9%), and had private insurance (55.2%). Gallbladder ejection fraction (EF) was reported in 84.5% of patients, and 44.8% had an EF <15%. 30.7% of patients were initially seen by pediatric surgeons, 31.3% by pediatric gastroenterologists, and 23.4% by the emergency department with significant variability between institutions (p < 0.001). Symptoms persisted in 35.3% of patients post-operatively with a median follow-up of 21 days (IQR 13, 34). On multivariate analysis, only non-white race and the presence of psychiatric comorbidities were associated with increased risk of post-operative symptoms., Conclusion: There is significant variability in evaluation and follow-up both before and after cholecystectomy for BD. Prospective research with standardized data collection and follow-up is needed to develop and validate optimal care pathways for pediatric patients with suspected BD., Study Type: Case Series, Retrospective Review., Level of Evidence: Level IV., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Studies documenting the effects of land-derived suspended particulate matter (SPM, i.e., particulate organic matter and mineral sediment) on marine ecosystems are typically disconnected from terrestrial studies that determine their origin, transport and fate. This study reviews sources, transport, transformations, fate and effects of SPM along the 'ridge-to-reef' continuum. We show that some of the SPM can be transported over long distances and transformed into large and easily resuspendible organic-rich sediment flocs. These flocs may lead to prolonged reductions in water clarity, impacting upon coral reef, seagrass and fish communities. Using the Great Barrier Reef (NE Australia) as a case study, we identify the latest research tools to determine thresholds of SPM exposure, allowing for an improved appreciation of marine risk. These tools are used to determine ecologically-relevant end-of-basin load targets and reliable marine water quality guidelines, thereby enabling enhanced prioritisation and management of SPM export from ridge-to-reef., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: The natural history of prostatic lesions identified on multiparametric magnetic resonance imaging (mpMRI) is largely unknown. We aimed to describe changes observed over time on serial MRI., Methods: All patients with ≥2 MRI studies between 2008 and 2015 at our institution were identified. MRI progression was defined as an increase in Prostate Imaging Reporting and Data System (PI-RADS; version 2) or size of existing lesions, or the appearance of a new lesion PIRADS ≥4. Patients on active surveillance (AS) were analyzed for correlation of MRI progression to biopsy reclassification., Results: A total of 83 patients (54 on AS and 29 for diagnostic purposes) underwent serial MRI, with a mean interval of 1.9 years between scans. At baseline, 115 lesions (66 index, 49 non-index) were identified. Index lesions were more likely than non-index lesions to increase in size ≥2 mm (36.2 vs. 7.3 %; p=0.002). Overall progression was more likely to be seen among the index cohort (34.8 vs. 7.6%; p<0.001). New lesions with PI-RADS ≥4 were seen on second imaging in 13 (16.5%) men, and became the index lesion in 29 cases (34.9%). Eighteen men on AS showed evidence of MRI progression (five with new lesions, 13 with progression of a previous lesion). Biopsy reclassification was present in three men (16.7%) with and seven men without MRI progression (19.4%)., Conclusions: Overall changes in size and PI-RADS scores of index lesions on MRI were small. New lesions were common, but usually did not alter management.

Optically active water quality components (OAC) transported by flood plumes to nearshore marine environments affect light levels. The definition of minimum OAC concentrations that must be maintained to sustain sufficient light levels for conservation of light-dependant coastal ecosystems exposed to flood waters is necessary to guide management actions in adjacent catchments. In this study, a framework for defining OAC target concentrations using empirical light attenuation models is proposed and applied to the Wet Tropics region of the Great Barrier Reef (GBR) (Queensland, Australia). This framework comprises several steps: (i) light attenuation (Kd(PAR)) profiles and OAC measurements, including coloured dissolved organic matter (CDOM), chlorophyll-a (Chl-a) and suspended particulate matter (SPM) concentrations collected in flood waters; (ii) empirical light attenuation models used to define the contribution of CDOM, Chl-a and SPM to the light attenuation, and; (iii) translation of empirical models into manageable OAC target concentrations specific for wet season conditions. Results showed that (i) Kd(PAR) variability in the Wet Tropics flood waters is driven primarily by SPM and CDOM, with a lower contribution from Chl-a (r2 = 0.5, p < 0.01), (ii) the relative contributions of each OAC varies across the different water bodies existing along flood waters and strongest Kd(PAR) predictions were achieved when the in-situ data were clustered into water bodies with similar satellite-derived colour characteristics ('brownish flood waters', r2 = 0.8, p < 0.01, 'greenish flood waters', r2 = 0.5, p < 0.01), and (iii) that Kd(PAR) simulations are sensitive to the angular distribution of the light field in the clearest flood water bodies. Empirical models developed were used to translate regional light guidelines (established for the GBR) into manageable OAC target concentrations. Preliminary results suggested that a 90th percentile SPM concentration of 11.4 mg L -1 should be maintained during the wet season to sustain favourable light levels for Wet Tropics coral reefs and seagrass ecosystems exposed to 'brownish' flood waters. Additional data will be collected to validate the light attenuation models and the wet season target concentration which in future will be incorporated into wider catchment modelling efforts to improve coastal water quality in the Wet Tropics and the GBR., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Subjective responses to meals are altered by shortened sleep time and anxiety state, but this effect has been poorly studied in shift workers - who act as a typical model concerning sleep restriction and present high levels of anxiety. The objective of this study was to compare subjective perceptions of meals and the levels of anxiety in the same subjects after working night shifts and after taking a nocturnal sleep, and to investigate associations between the responses to meals and the levels of anxiety under these two conditions. The study evaluated 34 male permanent night-shift workers who worked a 12-h shift followed by a 36-h rest period. Evaluations included: sleep pattern (on three days after working night shifts and after sleeping at night); hunger, enjoyment of eating foods and satiety after a meal (evaluated by visual analogue scales on three non-consecutive days after working night shifts and after nocturnal sleeps); and state of anxiety (on a day after working a night shift and a day after a nocturnal sleep). In the days following a night shift, workers had higher mean hunger scores before lunch and higher anxiety scores than when they had slept at night (p = 0.007 and 0.001, respectively). Linear regression indicated that, after a night shift, anxiety scores were negatively associated with hunger before breakfast (p = 0.04) and lunch (p = 0.03), the enjoyment of eating foods (p = 0.03) and the number of meals eaten during the course of the 24 h (p = 0.03). It is concluded that night shifts increase mean hunger and anxiety scores. Anxiety levels seem to interfere with the responses associated with food consumption., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The United States Food and Drug Administration (FDA) ensures that patients in the U.S. have access to safe and effective medical devices. The Division of Neurological and Physical Medicine Devices reviews medical technologies that interface with the nervous system. This article addresses how to navigate the FDA's regulatory landscape to successfully bring medical devices to patients., (Published by Elsevier Inc.)

Collision tumours of two different histopathological processes are rare. We describe a case of a patient with known low grade prostate adenocarcinoma developing a rectal GIST, which was diagnosed with combined imaging modalities of MR and ultrasound and confirmed by transrectal ultrasound guided biopsy.

Undergraduate students experience a form of circadian misalignment - known as "social jetlag" - that represents the discrepancy in timing between their circadian and social clocks. Whilst social jetlag is not dependent upon chronotype, the two phenomena tend to be related; evening types show a tendency to have a greater social jetlag, for example. Moreover, evening types have been found to be more likely to have inadequate eating habits than do morning types. The objective of this study was to examine the relationship between chronotype, social jetlag, perceived sleep debt and dietary intake in Brazilian undergraduate students. The chronotype was derived from mid-sleep time on free days (MSF) at the weekend. Social jetlag was calculated as the absolute difference between mid-sleep time on weekdays and weekends. Perceived sleep debt was calculated using the difference between students' preferred weekday sleep duration and their self-reported actual weekday sleep duration. Correlations were found between chronotype and breakfast time (r = 0.24, p = 0.003) and lunch time (r = 0.19, p = 0.01). Multiple regression analyses showed that chronotype was positively associated with consumption of meat (β = 0.21; p = 0.003); social jetlag was negatively associated with consumption of beans (β = -0.16; p = 0.02) and perceived sleep debt was positively associated with consumption of beverages (β = 0.15; p = 0.02) and dairy products (β = 0.17; p = 0.01) and negatively associated with consumption of cereals and pasta (β = -0.16; p = 0.02). It is concluded that, in undergraduate students, chronotype (MSF), social jetlag and perceived sleep debt can influence the type and amount of some food groups consumed at mealtimes.

An individual's chronotype is a trait which reflects his/her diurnal preferences for the times of rest and activities, and displays a continuum from morningness to eveningness. Studies have shown that eveningness tends to be associated with a less healthy lifestyle, including increased likelihood of developing obesity. In this study, we examined the relationship between chronotype and food intake, physical sleep and activity in 72 resident physicians (52 women and 20 men). Assessments included chronotype evaluation by the Horne and Ostberg Morningness-Eveningness questionnaire (MEQ); food intake pattern through a self-administered food diary that was kept over the course of 3 non-successive days; physical activity level, using the Baecke questionnaire (BQ); sleep quality and quantity using the Pittsburgh Sleep Quality Index (PSQI); and sleepiness, Epworth Sleepiness Scale (ESS). Linear regression analyses, after adjustments for age, sex, body mass index (BMI), hours of additional work per week ESS and total physical activity score, showed that the chronotype score was negatively associated with cholesterol (coefficient = -0.24; p = 0.04), sweets (coefficient = -0.27, p = 0.03) and vegetables (coefficient = -0.26; p = 0.04) intakes. Following the same statistical adjustments, the chronotype score was positivity associated with leisure-time index (coefficient = 0.26, p = 0.03) and BQ total score (coefficient = 0.27, p = 0.03). We concluded that most issues related to nutrition problems and unhealthy lifestyle were associated with scores indicative of eveningness. These findings emphasize the importance of assessing an individual's chronotype when examining feeding behavior.

Purpose: Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity, including impaired health-related quality of life (HRQoL). Despite the prominent role of occupational factors in the aetiology of COPD, the relationship between these exposures and HRQoL has not been well elucidated., Methods: A subpopulation from an epidemiological study, designed to assess the workplace contribution to COPD, was administered the EQ5D HRQoL tool. Demographics, an index of economic deprivation, health endpoints including the presence of COPD and lung function were also recorded. Workplace exposures were categorised using both self-reported exposures and also by the use of an established job exposure matrix (JEM)., Results: A total of 623 individuals participated (mean age 67.1 years). One hundred and forty-eight (24%) reported having received a physician diagnosis of COPD, 355 (57%) were male, and 386 (62%) were ever smokers. As anticipated, the presence of COPD was associated with a poorer HRQoL. Additionally, however, HRQoL was significantly lower in the presence of both self-reported vapours, gases, dusts and fumes exposure and JEM-based exposure irrespective of the presence of COPD. Regression analysis, adjusting for a variety of covariates including the presence of COPD, confirmed a persisting higher likelihood of occupational exposure categorised by JEM being associated with poorer HRQoL scores (β estimate: -0.069; p < 0.05)., Conclusions: Our findings suggest that work may have an important link to HRQoL and that this effect can persist even among those who have retired. In those with COPD, HRQoL is worse than among those without this condition, but the work-associated decrement appears to be similar across both groups.

Shift work and long hours of work are common in medical training and have been associated with a higher propensity for developing nutritional problems and obesity. Changes in leptin and ghrelin concentrations - two hormones that contribute importantly to the central regulation of food intake - are poorly described in this population. The aim of this study was to identify possible negative associations between sleep patterns, nutritional status and serum levels of adipokines. The study included 72 resident physicians (52 women and 20 men) who underwent the following assessments: nutritional assessment (3-day dietary recall evaluated by the Adapted Healthy Eating Index), anthropometric variables, fasting metabolism, physical activity level, sleep quality and sleepiness. Resident physicians with poor sleep quality reported greater weight gain after the beginning of residency (5.1 and 3.0 kg, respectively; p = 0.01) and higher frequency of abnormal waist circumference (44.2 and 17.6%, respectively; p = 0.04) than those with better sleep quality. Mean ghrelin concentration was greater in volunteers with poor sleep quality (64.6 ± 67.8 and 26.2 ± 25.0 pg/mL, respectively; p = 0.04). Women identified as having excessive daytime sleepiness had lower levels of leptin (9.57 ± 10.4 ng/mL versus 16.49 ± 11.4 ng/mL, respectively; p = 0.03) than those without excessive sleepiness. Furthermore, correlations were found between hours of additional work per week and: intake of cereals, bread and pasta (r = 0.22, p = 0.01); intake of servings of fruits (r = -0.20; p = 0.02) and beans (r = -0.21; p = 0.01); and global score for Adapted Healthy Eating Index (r = -0.23; p = 0.008; Table 3). The sleep quality total score correlated with servings of beans (r = -0.22; p = 0.01) and servings of oils (r = 0.23; p = 0.008). Significant correlations were found between mean of time of sleep and servings of cereals, bread and pasta (r = 0.20; p = 0.02), servings of meat (r = -0.29; p = 0.02) and cholesterol levels (r = 0.27; p = 0.03). These observations indicate that sleep patterns and long working hours of resident physicians are negatively associated with biological markers related to central food control, the lipid profile, cholesterol levels and eating healthy foods. These factors may predispose these shift workers to become overweight and develop metabolic disorders.

The aim of this study was to compare anthropometry and food intake patterns in bus drivers working during the day and night. One hundred and fifty males (81 night workers and 69 day workers) participated in the study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Measurements of height, weight, waist circumference (WC), systolic and diastolic blood pressure, blood glucose, and lipid profile were obtained. A significant difference between groups was observed for mean WC (98.5 ± 10.7 cm in day workers versus 103.2 ± 9.7 cm in night workers; p = 0.005). Night workers had higher prevalence of being overweight and obese (BMI ≥ 25 kg/m(2)) than day workers (78.2% day workers versus 90.2% night workers; p = 0.004) and increased WC (>94 cm) (72.4% day workers versus 86.4% night workers; p = 0.03). Significant differences were found for meat consumption (2.3 servings ±0.9 for night workers versus 2.0 servings ±0.7 day workers, p = 0.04) and fruit intake (0.9 servings ±0.4 for night workers versus 0.7 servings for day workers ±0.5; p = 0.006). Night workers had a lower intake of vegetables than recommended compared to day workers (100 versus 92.7%, respectively, p = 0.01) and higher intake of oil (40.7 versus 24.6%, p = 0.03). Multivariate logistic regression analysis indicated that night work was associated with being overweight (OR = 2.94, 95% IC: 1.14-7.66, p = 0.03) and abnormal values of WC (OR = 2.82, 95% IC: 1.20-6.69, p = 0.009) after adjusting for potential confounders. It is concluded that night workers had a higher prevalence and risk of being overweight/obese and increased WC compared with day workers. Night workers also presented a higher proportion of inappropriate intakes of food groups when compared to day workers, even though both groups were eating poor diets. These results demonstrate the need of lifestyle-intervention programs in these workers.

The disruption of the circadian timing system (CTS), which rhythmically controls cellular metabolism and proliferation, accelerated experimental cancer progression. A measure of CTS function in cancer patients could thus provide novel prediction information for outcomes, and help to identify novel specific therapies. The rest-activity circadian rhythm is a reliable and non-invasive CTS biomarker, which was monitored using a wrist watch accelerometer for 2 days in 436 patients with metastatic colorectal cancer. The relative percentage of activity in-bed versus out-of-bed (I < O) constituted the tested CTS measure, whose prognostic value for overall survival (OS) and progression-free survival (PFS) was determined in a pooled analysis of three patient cohorts with different treatment exposures. Median OS was 21.6 months [17.8-25.5] for patients with I < O above the median value of 97.5% as compared to 11.9 months [10.4-13.3] for those with a lower I < O (Log-rank p < 0.001). Multivariate analyses retained continuous I < O as a joint predictor of both OS and PFS, with respective hazard ratios (HR) of 0.954 (p < 0.001) and 0.970 (p < 0.001) for each 1% increase in I < O. HRs had similar values in all the patient subgroups tested. The circadian physiology biomarker I < O constitutes a robust and independent quantitative predictor of cancer patient outcomes, that can be easily and cost-effectively measured during daily living. Interventional studies involving 24-h schedules of clock-targeted drugs, light intensity, exercise and/or meals are needed for testing the relevance of circadian synchronization for the survival of patients with disrupted rhythms.

Objectives: This project evaluated the implementation of use of the StatLock stabilization device (Bard Access Systems, Inc, Salt Lake City, Utah) for peripherally inserted central catheters (PICCs) in pediatric cardiology patients. The aim was to implement the use of the StatLock device and evaluate its effects on the following 4 outcomes: incidence of dislodgement, infection, catheter dwell time, and the number of catheter replacements. The primary goal was to determine whether the StatLock device offered advantages over tape and sutures., Methods: A quality improvement design was used to evaluate whether the use of the StatLock stabilization device for PICC securement on 30 pediatric cardiology patients decreased the number of PICC complications compared with 30 historical comparison patients., Results: The comparison group had a significantly higher number of catheter dislodgements (n = 16; 59.3%) than the StatLock group (n = 8; 30.8%; P = .035). The comparison group did not have a significantly higher number of catheter replacements (n = 16; 59.3%) than the StatLock group (n = 10; 34.5%; P = .10). No significant differences were found in the rate of infection or in the catheter dwell time between the 2 groups (StatLock group, mean ± SD = 33.13 ± 22.71 days; comparison group, mean ± SD = 28.10 ± 24.83 days; P > .20)., Conclusions: Use of the StatLock device resulted in better outcomes when compared with the use of sutures, and it provided a more effective way to stabilize and secure PICCs.