Isotopic and microbial evidence for biodegradation of diluted bitumen in the unsaturated zone.

The oil sands region in Western Canada is one of the world's largest proven oil reserves. To facilitate pipeline transport, highly viscous oil sands bitumen is blended with lighter hydrocarbon fractions to produce diluted bitumen (dilbit). Anticipated increases in dilbit production and transport raise the risk of inland spills. To understand the behaviour of dilbit in the unsaturated or vadose zone following a surface spill, we ran parallel dilbit and conventional heavy crude exposures, along with an untreated control, using large soil-filled columns over 104 days. Phospholipid fatty acids (PLFAs), biomarkers for the active microbial population, were extracted from column soil cores. Stable carbon isotope contents (δ13C) of individual PLFAs and radiocarbon contents (Δ14C) of bulk PLFAs were characterized over the course of the experiment. The Δ14CPLFA values in soils impacted by dilbit (-221.1 to -54.7‰) and conventional heavy crude (-259.4 to -97.9‰) indicated similar levels of microbial uptake of fossil carbon. In contrast, Δ14CPLFA values in the control column (-46.1 to +53.7‰) reflected assimilation of more recently fixed organic carbon. Sequencing of 16S ribosomal RNA genes extracted from soil cores revealed a significant increase in the relative abundance of Polaromonas, a known hydrocarbon-degrader, following exposure to both types of oil. This study demonstrates that in the first several months following a surface spill, dilbit has a similar potential for biodegradation by a native shallow subsurface microbial community as conventional heavy crude oil.

Brief Report: A Specialized Fitness Program for Individuals with Autism Spectrum Disorder Benefits Physical, Behavioral, and Emotional Outcomes.

Individuals with autism spectrum disorder (ASD) engage in less physical activity than typically-developing peers. This can result in serious negative consequences for individual well-being and may contribute to the physical, behavioral, and emotional challenges associated with ASD. This study explored the potential benefits of trainer-led, individualized, physical fitness sessions specialized for ASD. Eleven individuals (ages 7-24 years) with ASD were assessed at baseline and following 15 fitness sessions. Participants demonstrated improvements in core and lower-body strength and reductions in restricted and repetitive patterns of behavior, along with non-significant but marked reductions in issues with daytime sleepiness. Results suggest the merit of specialized fitness programs and emphasize the need for larger and more rigorous research studies on this topic.

Brief Report: Exploratory Evaluation of Clinical Features Associated with Suicidal Ideation in Youth with Autism Spectrum Disorder.

There has been a heightened awareness of an increased risk of suicidality among individuals with autism spectrum disorder (ASD) due to high rates of suicidal ideation (SI) in this population (11-66%). The current study investigated the rate of parent-endorsed SI and associated clinical features in 48 youths with ASD (Age; M: 12.97 years, SD: 2.33). SI was endorsed in 18.75% of participants. Youth with SI exhibited significantly higher levels of affective problems, externalizing problems, feelings of humiliation and rejection, and symptoms related to perfectionism. Results indicate that co-occurring mental health problems are associated with suicidal ideation and provide relevant targets for psychotherapeutic intervention. This preliminary study in a modest sample suggests the value of further research in larger samples to replicate and generalize these findings.

The lampricide 3-trifluoromethyl-4-nitrophenol causes temporary metabolic disturbances in juvenile lake sturgeon (Acipenser fulvescens): implications for sea lamprey control and fish conservation.

The pesticide 3-trifluoromethyl-4-nitrophenol (TFM) is applied to rivers and streams draining into the Laurentian Great Lakes to control populations of invasive sea lamprey (Petromyzon marinus), which are ongoing threats to fisheries during the lamprey's hematophagous, parasitic juvenile life stage. While TFM targets larval sea lamprey during treatments, threatened populations of juvenile lake sturgeon (Acipenser fulvescens), particularly young-of-the-year (<100 mm in length), may be adversely affected by TFM when their habitats overlap with larval sea lamprey. Exposure to TFM causes marked reductions in tissue glycogen and high energy phosphagens in lamprey and rainbow trout (Oncorhynchus mykiss) by interfering with oxidative ATP production in the mitochondria. To test that environmentally relevant concentrations of TFM would similarly affect juvenile lake sturgeon, we exposed them to the larval sea lamprey minimum lethal concentration (9-h LC99.9), which mimicked concentrations of a typical lampricide application and quantified energy stores and metabolites in the carcass, liver and brain. Exposure to TFM reduced brain ATP, PCr and glycogen by 50-60%, while lactate increased by 45-50% at 6 and 9 h. A rapid and sustained depletion of liver glucose and glycogen of more than 50% was also observed, whereas the respective concentrations of ATP and glycogen were reduced by 60% and 80% after 9 h, along with higher lactate and a slight metabolic acidosis (~0.1 pH unit). We conclude that exposure to environmentally relevant concentrations of TFM causes metabolic disturbances in lake sturgeon that can lead to impaired physiological performance and, in some cases, mortality. Our observations support practices such as delaying TFM treatments to late summer/fall or using alternative TFM application strategies to mitigate non-target effects in waters where lake sturgeon are present. These actions would help to conserve this historically and culturally significant species in the Great Lakes.

A Toxic Unit and Additive Index Approach to Understanding the Interactions of 2 Piscicides, 3-Trifluoromethyl-4-Nitrophenol and Niclosamide, in Rainbow Trout.

The toxic unit and additive index approaches were used to understand how 2 pesticides, 3-trifluoromethyl-4-nitrophenol (TFM) and 2,5-dichloro-4-nitrosalicylanilide (niclosamide; Nic), interact in mixtures. Our first objective was to determine whether the interaction was strictly additive or greater than additive at doses comparable to those used to control invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes, and our second was to compare the utility of the toxic unit and additive index models for determining how TFM and Nic interacted. Typically, TFM is mixed with Nic (1-2%, w/v) to increase its potency and reduce TFM use. However, there is little information on how the 2 chemicals interact. Using a well-studied, resident nontarget fish, the rainbow trout (Oncorhynchus mykiss), we conducted toxicity tests with TFM, Nic, and TFM:Nic (100:1, w/v; TFM/1% Nic) mixtures over 12 h to determine if the interaction was strictly additive, less than additive (antagonistic), or greater than additive (synergistic). The toxic unit and additive index approaches indicated synergistic interactions at environmentally relevant concentrations, suggesting that both are valid approaches for predicting how TFM and Nic interact. The toxic unit approach was simpler to conceptualize and to calculate, and we recommend that it be used when describing how TFM and Nic, and other similar organic compounds, interact with each other in aquatic ecosystems. Environ Toxicol Chem 2021;40:1419-1430. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Correction to: Delafloxacin: A Review in Acute Bacterial Skin and Skin Structure Infections.

The original article can be found online.

Delafloxacin: A Review in Acute Bacterial Skin and Skin Structure Infections.

The global spread of antibacterial-resistant strains, especially methicillin-resistant Staphylococcus aureus (MRSA) for acute bacterial skin and skin structure infections (ABSSSIs), has driven the need for novel antibacterials. Delafloxacin [Quofenix™ (EU); Baxdela® (USA)], a new fluoroquinolone (FQ), has a unique chemical structure that enhances its antibacterial activity in acidic environments such as occurs in ABSSSIs (including S. aureus infections). Delafloxacin (intravenous and oral formulations) is approved in several countries for the treatment of adults with ABSSSIs (featured indication). In intent-to-treat analyses in pivotal phase 3 trials in adults with ABSSSIs, including those with comorbid disease, intravenous delafloxacin monotherapy (± oral switch after six doses) twice daily was noninferior to intravenous vancomycin + aztreonam for primary endpoints, as specified by the FDA (objective response rate at 48-78 h after initiation of therapy) and the EMA [investigator-assessed clinical cure rate at the follow-up visit at day 14 (± 1 day)]. Delafloxacin was generally well tolerated, with most treatment-related adverse events mild to moderate in severity and few patients discontinuing treatment because of these events. Relative to vancomycin + aztreonam (a non-FQ regimen), delafloxacin treatment was not associated with an increased risk of FQ-associated AEs of special interest. Given its unique chemical structure that confers novel properties relative to other FQ and its broad spectrum of activity against common clinically relevant Gram-positive pathogens, including against MRSA strains (± FQ-resistance mutations), and Gram-negative pathogens, intravenous delafloxacin (± oral switch) provides a novel emerging option for the treatment of adult patients with ABSSSIs.

Mitigation of lampricide toxicity to juvenile lake sturgeon: the importance of water alkalinity and life stage.

The pesticide, 3-trifluoromethyl-4-nitrophenol (TFM), is used to control invasive sea lamprey (Petromyzon marinus) populations in the Laurentian Great Lakes. Applied to infested tributaries, it is most toxic to larval sea lamprey, which have a low capacity to detoxify TFM. However, TFM can be toxic to lake sturgeon (Acipenser fulvescens), whose populations are at risk throughout the basin. They are most vulnerable to TFM in early life stages, with the greatest risk of non-target mortality occurring in waters with high alkalinity. We quantified TFM toxicity and used radio-labelled TFM (14C-TFM) to measure TFM uptake rates in lake sturgeon in waters of different pH and alkalinity. Regardless of pH or alkalinity, TFM uptake was 2-3-fold higher in young-of-the-year (YOY) than in age 1-year-plus (1+) sturgeon, likely due to higher mass-specific metabolic rates in the smaller YOY fish. As expected, TFM uptake was highest at lower (pH 6.5) versus higher (pH 9.0) pH, indicating that it is taken up across the gills by diffusion in its unionized form. Uptake decreased as alkalinity increased from low (~50 mg L-1 as CaCO3) to moderate alkalinity (~150 mg L-1 as CaCO3), before plateauing at high alkalinity (~250 mg L-1 as CaCO3). Toxicity curves revealed that the 12-h LC50 and 12-h LC99.9 of TFM to lake sturgeon were in fact higher (less toxic) than in sea lamprey, regardless of alkalinity. However, in actual treatments, 1.3-1.5 times the minimum lethal TFM concentration (MLC = LC99.9) to lamprey is applied to maximize mortality, disproportionately amplifying TFM toxicity to sturgeon at higher alkalinities. We conclude that limiting TFM treatments to late summer/early fall in waters of moderate-high alkalinity, when lake sturgeon are larger with lower rates of TFM uptake, would mitigate non-target TFM effects and help conserve populations of these ancient, culturally important fishes.

Systematic review of interventions for the prevention and treatment of postoperative urinary retention.

Background: Postoperative urinary retention (PO-UR) is an acute and painful inability to void after surgery that can lead to complications and delayed hospital discharge. Standard treatment with a urinary catheter is associated with a risk of infection and can be distressing, undignified and uncomfortable. This systematic review aimed to identify effective interventions for the prevention and treatment of PO-UR that might be alternatives to urinary catheterization. Methods: Electronic databases were searched from inception to September 2017. Randomized trials of interventions for the prevention or treatment of PO-UR were eligible for inclusion. Studies were assessed for risk of bias using the Cochrane (2.0) tool. Two reviewers were involved at all review stages. Where possible, data were pooled using random-effects meta-analysis. The overall quality of the body of evidence was rated using the GRADE approach. Results: Some 48 studies involving 5644 participants were included. Most interventions were pharmacological strategies to prevent PO-UR. Based on GRADE, there was high-certainty evidence to support replacing morphine in a regional anaesthetic regimen, using alpha-blockers (number needed to treat to prevent one case of PO-UR (NNT) 5, 95 per cent c.i. 5 to 7), the antispasmodic drug drotaverine (NNT 9, 7 to 30) and early postoperative mobilization (NNT 5, 4 to 8) for prevention, and employing hot packs or gauze soaked in warm water for treatment (NNT 2, 2 to 4). Very few studies reported on secondary outcomes of pain, incidence of urinary tract infection or duration of hospital stay. Conclusion: Promising interventions exist for PO-UR, but they need to be evaluated in randomized trials investigating comparative clinical and cost effectiveness, and acceptability to patients.

Correction to: The help for people with money, employment or housing problems (HOPE) intervention: pilot randomised trial with mixed methods feasibility research.

[This corrects the article DOI: 10.1186/s40814-018-0365-6.].

The help for people with money, employment or housing problems (HOPE) intervention: pilot randomised trial with mixed methods feasibility research.

BACKGROUND: Job loss, austerity measures, financial difficulties and house repossession contribute to the risk of self-harm and suicide during recessions. Navigating the benefits system and accessing sources of welfare and debt advice is a difficult experience for vulnerable people, further contributing to their distress. Whilst there is some evidence that advice-type interventions can lead to financial gain, there is mixed evidence for their effectiveness in improving mental health in those experiencing financial difficulties. There have been no interventions targeting those who have self-harmed due to economic hardship. METHODS: Our aim was to determine the feasibility and acceptability of a brief psychosocial intervention (the 'HOPE' service) for people presenting to hospital emergency departments (ED) following self-harm or in acute distress because of financial, employment or welfare (benefit) difficulties. Nineteen people consented to random allocation to the intervention or control arm on a 2:1 basis. Participants randomised to the intervention arm (n = 13) received up to six sessions of 1:1 support provided by community support staff trained in Motivational Interviewing (MI). Control participants (n = 6) received a one-off session signposting them to relevant support organisations. Fourteen participants were followed up after 3 months. Participants and mental health workers took part in qualitative interviews. The acceptability of outcome measures including the PHQ-9, GAD-7, repeat self-harm, EQ5D-5 L and questions about debt, employment and welfare benefits were explored. RESULTS: Interviews indicated the main benefits of the service as the resolution of specific financial problems and receiving support when participants were feeling most vulnerable. Randomisation was acceptable to most participants although not always fully understood and control participants could be disappointed. Recruitment was slow (1-2 per month). The outcome measures were acceptable and appeared sensitive to change. DISCUSSION: The HOPE intervention is feasible and acceptable. There was evidence of need and it is a relatively inexpensive intervention. Refining aspects of the intervention would be straightforward. A full-scale RCT would be feasible, if broadened eligibility criteria led to increased recruitment and improvements were made to staff training and support. TRIAL REGISTRATION: ISRCTN58531248.

Brief Report: Self-Reported Academic, Social, and Mental Health Experiences of Post-Secondary Students with Autism Spectrum Disorder.

Increasing numbers of individuals with autism spectrum disorder (ASD) are enrolling in post-secondary academic institutions. However, research indicates that post-secondary students with ASD are struggling more than their typically developing peers, with high rates of loneliness, anxiety, depression, and an increased incidence of dropping-out before completion of their degrees. The current study utilized an online survey to gain insight into the self-reported academic, social, and mental health experiences of post-secondary students with ASD. Participants reported high levels of academic comfort, but struggled with issues of isolation/loneliness and high levels of stress, anxiety, and depression. Of greatest concern, were the nearly three-quarters of participants who reported lifetime suicidal behaviors. Further analysis on collected data and implications of findings are discussed.

Transition Issues and Challenges for Youth with Autism Spectrum Disorders.

Earlier detection and effective, evidence-based practices are gradually improving outcomes for people with autism spectrum disorder (ASD). Although some continue to need intensive support as adults, an increasing number are now going to college, becoming independent, and marrying. With the transition to adulthood, people with ASD will face a number of significant challenges. Health care providers who are knowledgeable about these challenges can help foster better outcomes and support those requiring higher levels of care. We summarize the challenges faced by youth with ASD as they transition into adulthood and note areas where more research is needed. [Pediatr Ann. 2017;46(6):e219-e223.].

Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial.

OBJECTIVES: To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals. DESIGN: A model-based cost-effectiveness analysis with a 4-week time horizon, based on a 'virtual' non-inferiority randomised trial designed to emulate a parallel group design. SETTING: A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics. PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes. INTERVENTIONS: The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants' classifications were validated against experts' classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions. MAIN OUTCOME MEASURES: Correct classification of whether further treatment is needed, compared with a reference standard. RESULTS: The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI -£18 to £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference -1.0%; 95% CI -4.5% to 2.5%). CONCLUSIONS: In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although in light of the uncertainty around differences in outcome and cost it remains unclear whether the differences between the 2 care pathways are significant in economic terms. TRIAL REGISTRATION NUMBER: ISRCTN07479761; Pre-results.

High CIP2A levels correlate with an antiapoptotic phenotype that can be overcome by targeting BCL-XL in chronic myeloid leukemia.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a predictive biomarker of disease progression in many malignancies, including imatinib-treated chronic myeloid leukemia (CML). Although high CIP2A levels correlate with disease progression in CML, the underlying molecular mechanisms remain elusive. In a screen of diagnostic chronic phase samples from patients with high and low CIP2A protein levels, high CIP2A levels correlate with an antiapoptotic phenotype, characterized by downregulation of proapoptotic BCL-2 family members, including BIM, PUMA and HRK, and upregulation of the antiapoptotic protein BCL-XL. These results suggest that the poor prognosis of patients with high CIP2A levels is due to an antiapoptotic phenotype. Disrupting this antiapoptotic phenotype by inhibition of BCL-XL via RNA interference or A-1331852, a novel, potent and BCL-XL-selective inhibitor, resulted in extensive apoptosis either alone or in combination with imatinib, dasatinib or nilotinib, both in cell lines and in primary CD34(+) cells from patients with high levels of CIP2A. These results demonstrate that BCL-XL is the major antiapoptotic survival protein and may be a novel therapeutic target in CML.

The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease.

IntroductionStandard treatment for neovascular age-related macular degeneration (nAMD) is intravitreal injections of anti-VEGF drugs. Following multiple injections, nAMD lesions often become quiescent but there is a high risk of reactivation, and regular review by hospital ophthalmologists is the norm. The present trial examines the feasibility of community optometrists making lesion reactivation decisions.MethodsThe Effectiveness of Community vs Hospital Eye Service (ECHoES) trial is a virtual trial; lesion reactivation decisions were made about vignettes that comprised clinical data, colour fundus photographs, and optical coherence tomograms displayed on a web-based platform. Participants were either hospital ophthalmologists or community optometrists. All participants were provided with webinar training on the disease, its management, and assessment of the retinal imaging outputs. In a balanced design, 96 participants each assessed 42 vignettes; a total of 288 vignettes were assessed seven times by each professional group.The primary outcome is a participant's judgement of lesion reactivation compared with a reference standard. Secondary outcomes are the frequency of sight threatening errors; judgements about specific lesion components; participant-rated confidence in their decisions about the primary outcome; cost effectiveness of follow-up by optometrists rather than ophthalmologists.DiscussionThis trial addresses an important question for the NHS, namely whether, with appropriate training, community optometrists can make retreatment decisions for patients with nAMD to the same standard as hospital ophthalmologists. The trial employed a novel approach as participation was entirely through a web-based application; the trial required very few resources compared with those that would have been needed for a conventional randomised controlled clinical trial.

Second generation tyrosine kinase inhibitors prevent disease progression in high-risk (high CIP2A) chronic myeloid leukaemia patients.

High cancerous inhibitor of PP2A (CIP2A) protein levels at diagnosis of chronic myeloid leukaemia (CML) are predictive of disease progression in imatinib-treated patients. It is not known whether this is true in patients treated with second generation tyrosine kinase inhibitors (2G TKI) from diagnosis, and whether 2G TKIs modulate the CIP2A pathway. Here, we show that patients with high diagnostic CIP2A levels who receive a 2G TKI do not progress, unlike those treated with imatinib (P=<0.0001). 2G TKIs induce more potent suppression of CIP2A and c-Myc than imatinib. The transcription factor E2F1 is elevated in high CIP2A patients and following 1 month of in vivo treatment 2G TKIs suppress E2F1 and reduce CIP2A; these effects are not seen with imatinib. Silencing of CIP2A, c-Myc or E2F1 in K562 cells or CML CD34+ cells reactivates PP2A leading to BCR-ABL suppression. CIP2A increases proliferation and this is only reduced by 2G TKIs. Patients with high CIP2A levels should be offered 2G TKI treatment in preference to imatinib. 2G TKIs disrupt the CIP2A/c-Myc/E2F1 positive feedback loop, leading to lower disease progression risk. The data supports the view that CIP2A inhibits PP2Ac, stabilising E2F1, creating a CIP2A/c-Myc/E2F1 positive feedback loop, which imatinib cannot overcome.

Validation of scale-age determination in European grayling Thymallus thymallus using tag-recapture analysis.

To validate age determination from scales in European grayling Thymallus thymallus, the scale-read age of fish was compared with the true age obtained by tag-recapture analysis. A total of 3997 individuals were tagged with visible implant tags and passive integrated transponder (PIT) tags in the River Wylye, south-west England during 1999-2007. Annual repeat surveys were undertaken and collected scales read without prior knowledge of tag-recapture age. Accuracy of fish ageing by scales was highest in 1 and 2 year-old fish but decreased in older fish. In later life stages (>4 years old), underestimation of age occurred and the error in reading scales rose to 51.9% in 5 year-old fish. Age assigned from scales underestimated the tag-recapture assigned age by as much as 3 years. This study suggests that use of scales is an appropriate method to age a short-lived population of T. thymallus inhabiting productive lotic systems. The underestimation of age in older fish, however, needs to be considered in the management of fish stocks because it may lead to undesirable exploitation of population.