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The application of organic amendments is one way to manage low water irrigation in paddy soils. In this 60-day greenhouse pot experiment involving paddy soil undergoing drying-rewetting cycles, we examined the effects of two organic amendments: azo-compost with a low carbon to phosphorus ratio (C:P) of 40 and rice straw with a high C:P ratio of 202. Both were applied at rates of 1.5% of soil weight (w/w). The investigation focused on changes in certain soil biochemical characteristics related to C and P in the rice rhizosphere, as well as rice plant characteristics. The irrigation regimes applied in this study included constant soil moisture in a waterlogged state (130% water holding capacity (WHC)), mild drying-rewetting (from 130 to 100% WHC), and severe drying-rewetting (from 130 to 70% WHC). The results indicated that the application of amendments was effective in severe drying-rewetting irrigation regimes on soil characteristics. Drying-rewetting decreased soil respiration rate (by 60%), microbial biomass carbon (by 70%), C:P ratio (by 12%), soil organic P (by 16%), shoot P concentration (by 7%), and rice shoot biomass (by 30%). However, organic amendments increased soil respiration rate (by 8 times), soil microbial biomass C (51%), total C (TC) (53%), dissolved organic carbon (3 times), soil available P (AP) (100%), soil organic P (63%), microbial biomass P (4.5 times), and shoot P concentration (21%). The highest significant correlation was observed between dissolved organic carbon and total C (r= 0.89**). Organic amendments also increased P uptake by the rice plant in the order: azo-compost > rice straw > control treatments, respectively, and eliminated the undesirable effect of mild drying-rewetting irrigation regime on rice plant biomass. Overall, using suitable organic amendments proves promising for enhancing soil properties and rice growth under drying-rewetting conditions, highlighting the interdependence of P and C biochemical changes in the rhizosphere during the rice vegetative stage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Owing to major advances in the field of radiation oncology, patients with lung cancer can now receive technically individualized radiotherapy treatments. Nevertheless, in the era of precision oncology, radiotherapy-based treatment selection needs to be improved as many patients do not benefit or are not offered optimum therapies. Cost-effective robust biomarkers can address this knowledge gap and lead to individuals being offered more bespoke treatments leading to improved outcome. This narrative review discusses some of the current achievements and challenges in the realization of personalized radiotherapy delivery in patients with lung cancer., Competing Interests: Disclosure Dr. Brown reports receiving grants from CRUK Lung Cancer Centre of Excellence (institutional award). Dr. Chua reports receiving grants from the National Medical Research Council Singapore Clinician Scientist; an individual research grant from New Investigator Grant (NMRC/CS-IRG-NIG/CNIG20nov-0029); support from the Duke-NUS Medical School Khoo Pilot Award (collaborative); payment or honoraria for lectures from Varian Medical Systems and PeerVoice; support for attending meetings from Varian Medical Systems; and having participation on data safety monitoring board from AstraZeneca, Regeneron, Roche, Seagen, Merck Sharp & Dohme, Takeda. Dr. McDonald reports receiving consulting fees, payment, or honoraria for lectures from AstraZeneca. Dr. Price reports being supported by Cancer Research UK RadNET Manchester, NIHR Manchester Biomedial Research Centre, and National Institute of Health Research. Prof. Faivre-Finn reports receiving consulting fees and payment or honoraria for lectures (to the institution) and having participation on data safety monitoring (to the institution) from AstraZeneca. The remaining authors declare no conflicts of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Municipal biosolids are a nitrogen (N)-rich agricultural fertilizer which may emit nitrous oxide (N 2 O) after rainfall events. Due to sparse empirical data, there is a lack of biosolids-specific N 2 O emission factors to determine how land-applied biosolids contribute to the national greenhouse gas inventory. This study estimated N 2 O emissions from biosolids-amended land in Canada using Tier 1, Tier 2 (Canadian), and Tier 3 (Denitrification and Decomposition model [DNDC]) methodologies recommended by the Intergovernmental Panel on Climate Change (IPCC). Field data was from replicated plots at 8 site-years between 2017 and 2019 in the provinces of Quebec, Nova Scotia and Alberta, Canada, representing three distinct ecozones. Municipal biosolids were the major N source for the crop, applied as mesophilic anaerobically digested biosolids, composted biosolids, or alkaline-stabilized biosolids alone or combined with an equal amount of urea-N fertilizer to meet the crop N requirements. Fluxes of N 2 O were measured during the growing season with manual chambers and compared to N 2 O emissions estimated using the IPCC methods. In all site-years, the mean emission of N 2 O in the growing season was greater with digested biosolids than other biosolids sources or urea fertilizer alone. The emissions of N 2 O in the growing season were similar with composted or alkaline-stabilized biosolids, and no greater than the unfertilized control. The best estimates of N 2 O emissions, relative to measured values, were with the Tier 3 > adapted Tier 2 with biosolids-specific correction factors > standard Tier 2 = Tier 1 methods of the IPCC, according to the root mean square error statistic. The Tier 3 IPCC method was the best estimator of N 2 O emissions in the Canadian ecozones evaluated in this study. These results will be used to improve methods for estimating N 2 O emissions from agricultural soils amended with biosolids and to generate more accurate GHG inventories., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Emerging data supports radical intent therapy for oligometastatic (OM) relapsed human papilloma virus (HPV+) related oropharyngeal cancer (OPC). We assess the association of follow-up imaging frequency amongst HPV + OPC, with temporal and spatial patterns of distant relapse, to inform rationalisation of routine post-treatment imaging., Materials and Methods: A retrospective single centre cohort study was carried out of consecutive HPV + OPC patients treated with radical intent (chemo)radiotherapy ((CT)RT) between 2011 and 2019. OM state was defined as ≤ 5 metastasis, none larger than 3 cm (OM s ) or, if interval from last negative surveillance imaging > 6-months, then ≤ 10 metastasis, none larger than 5 cm, (OM p ). Patients not meeting OM s / OM p criteria were deemed to have incurable diffuse metastatic disease (DM diffuse )., Results: 793 HPV-OPC patients were identified with median follow-up 3.15years (range 0.2-8.9). 52 (6.6 %) patients had radiologically identified DM at first failure and were considered for analysis. The median time to recurrence was 15.1 months (range: 2.6-63 months). 87 % of distant metastasis (DM) occurred in the first two years after treatment. Twenty-seven (52 %) patients had OM (OM s or OM p ) at time of failure, with 31 % having OM s . The median time from completion of treatment to diagnosis of DM diffuse vs OM was 22.2 months (range: 2.6-63.1 months) vs 11.6 months (range: 3.5-32.5 months). The probability of being diagnosed with OM vs DM diffuse increased with reducing interval from last negative surveillance scan to imaging identifying DM (≤6 months 88.9 %, 7-12 months 71.4 %, 13-24 months 35 %, > 24 months 22.2 %)., Conclusion: We demonstrate that a reduced interval between last negative imaging and subsequent radiological diagnosis of DM is associated with increased likelihood of identification of OM disease. Consideration of increased frequency of surveillance imaging during the first two years of follow up is supported, particularly for patients at high risk of distant failure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Increased use of nanoscale particles have benefited many industries, including medicine, electronics, and environmental cleaning. These particles provide higher material performance, greater reactivity, and improved drug delivery. However, the main concern is the generation of nanowastes that can spread in different environmental matrices, posing threat to our environment and human health. Nanoparticles (NPs) have the potential to enter the food chain through a variety of pathways, including agriculture, food processing, packaging, and environmental contamination. These particles can negatively impact plant and animal physiology and growth. Due to the assessment of their environmental damage, nanoparticles are the particles of size between 1 and 100 nm that is the recent topic to be discussed. Nanoparticles' absorption, distribution, and toxicity to plants and animals can all be significantly influenced by their size, shape, and surface chemistry. Due to their absorptive capacity and potential to combine with other harmful substances, they can alter the metabolic pathways of living organisms. Nevertheless, despite the continuous research and availability of data, there are still knowledge gaps related to the ecotoxicology, prevalence and workable ways to address the impact of nanoparticles. This review focuses on the impact of nanoparticles on different organisms and the application of advanced techniques to remediate ecosystems using hyperaccumulator plant species. Future considerations are explored around nano-phytoremediation, as an eco-friendly, convenient and cost effective technology that can be applied at field scales., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Plastic pollution has emerged as a global challenge affecting ecosystem health and biodiversity conservation. Terrestrial environments exhibit significantly higher plastic concentrations compared to aquatic systems. Micro/nano plastics (MNPs) have the potential to disrupt soil biology, alter soil properties, and influence soil-borne pathogens and roundworms. However, limited research has explored the presence and impact of MNPs on aquaculture systems. MNPs have been found to inhibit plant and seedling growth and affect gene expression, leading to cytogenotoxicity through increased oxygen radical production. The article discusses the potential phytotoxicity process caused by large-scale microplastics, particularly those unable to penetrate cell pores. It also examines the available data, albeit limited, to assess the potential risks to human health through plant uptake., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Data on the effectiveness of transcranioplasty ultrasonography through sonolucent cranioplasty (SC) are new and heterogeneous. We performed the first systematic literature review on SC. Ovid Embase, Ovid Medline, and Web of Science Core Collection were systematically searched and published full text articles detailing new use of SC for the purpose of neuroimaging were critically appraised and extracted. Of 16 eligible studies, 6 reported preclinical research and 12 reported clinical experiences encompassing 189 total patients with SC. The cohort age ranged from teens to 80s and was 60% (113/189) female. Sonolucent materials in clinical use are clear PMMA (polymethylmethacrylate), opaque PMMA, polyetheretherketone, and polyolefin. Overall indications included hydrocephalus (20%, 37/189), tumor (15%, 29/189), posterior fossa decompression (14%, 26/189), traumatic brain injury (11%, 20/189), bypass (27%, 52/189), intracerebral hemorrhage (4%, 7/189), ischemic stroke (3%, 5/189), aneurysm and subarachnoid hemorrhage (3%, 5/189), subdural hematoma (2%, 4/189), and vasculitis and other bone revisions (2%, 4/189). Complications described in the entire cohort included revision or delayed scalp healing (3%, 6/189), wound infection (3%, 5/189), epidural hematoma (2%, 3/189), cerebrospinal fluid leaks (1%, 2/189), new seizure (1%, 2/189), and oncologic relapse with subsequent prosthesis removal (<1%, 1/189). Most studies utilized linear or phased array ultrasound transducers at 3-12 MHz. Sources of artifact on sonographic imaging included prosthesis curvature, pneumocephalus, plating system, and dural sealant. Reported findings were mainly qualitative. We, therefore, suggest that future studies should collect quantitative measurement data during transcranioplasty ultrasonography to validate imaging techniques., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: We aimed to catalog past and present clinical trials on immunotherapy treatments for glioblastoma (GBM) and discover relevant trends in this field., Methods: Former and ongoing clinical trials involving the use of immunotherapy to treat GBM were queried in July 2022 within the clinicaltrials.gov registry (https://clinicaltrials.gov/). Pertinent trials were categorized by variables including immunotherapy classification, tumor type (newly diagnosed versus recurrent), country of origin, start date, clinical phase, study completion status, estimated subject enrollment, design, publication status, and funding source., Results: A list of 173 trials was identified in total. The number of immunotherapy clinical trials to treat GBM has increased over time. The largest proportion of trials were gene therapies (97 studies; 56.1%) and viral therapies (37 studies; 21.4%). Studies were designated as a biologic (45.1%), drug (43.9%), genetic (2.3%), or procedure (1.2%). Trials spanned 19 countries; China, the second largest contributor (5.8%) after the United States (70.0%), has increased clinical trial development in the past years. The average time to completion was 52.3 months. Trials were primarily funded by academic centers; however, one-fourth of the trials were funded by industry and 2 were funded by foundations. One-t of the trials were active and over one-third were linked to publications., Conclusions: Our findings provide a comprehensive summary of the state of immunotherapy clinical trials for GBM, highlighting the evolving nature and growing scope of this field., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The main challenge of the twenty-first century is to find a balance between environmental sustainability and crop productivity in a world with a rapidly growing population. Soil health is the backbone of a resilient environment and stable food production systems. In recent years, the use of biochar to bind nutrients, sorption of pollutants, and increase crop productivity has gained popularity. This article reviews key recent studies on the environmental impacts of biochar and the benefits of its unique physicochemical features in paddy soils. This review provides critical information on the role of biochar properties on environmental pollutants, carbon and nitrogen cycling, plant growth regulation, and microbial activities. Biochar improves the soil properties of paddy soils through increasing microbial activities and nutrient availability, accelerating carbon and nitrogen cycle, and reducing the availability of heavy metals and micropollutants. For example, a study showed that the application of a maximum of 40 t ha -1 of biochar from rice husks prior to cultivation (at high temperature and slow pyrolysis) increases nutrient utilization and rice grain yield by 40%. Biochar can be used to minimize the use of chemical fertilizers to ensure sustainable food production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To estimate the cost and cost-effectiveness of Bright Bodies, a high-intensity, family-based intervention that has been demonstrated to improve body mass index (BMI) among children with obesity in a randomized controlled trial., Methods: We developed a microsimulation model to project 10-year BMI trajectories of 8 to 16-year-old children with obesity, using data from the National Longitudinal Surveys and Centers for Disease Control and Prevention growth charts, and we validated the model using data from the Bright Bodies trial and a follow-up study. We used the trial data to estimate the average reduction in BMI per person-year over 10 years and the incremental costs of Bright Bodies, compared with the traditional clinical weight management (control), from a health system's perspective in 2020 US dollars. Using results from studies of Medical Expenditure Panel Survey data, we projected the long-term obesity-related medical expenditure., Results: In the primary analysis, assuming depreciating effects postintervention, Bright Bodies is expected to reduce a participant's BMI by 1.67 kg/m 2 (95% uncertainty interval 1.43-1.94) per year over 10 years as compared with control. The incremental intervention cost of Bright Bodies was $360 ($292-$421) per person compared with the clinical control. Nevertheless, savings in obesity-related healthcare expenditure offset these costs and the expected cost-savings of Bright Bodies is $1126 ($689-$1693) per person over 10-years. The projected time to achieve cost-savings compared with clinical control was 3.58 (2.63-5.17) years., Conclusions: Although resource-intensive, our findings suggest that Bright Bodies is cost-saving compared to the clinical control by averting future obesity-related healthcare costs among children with obesity., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: No current guidance exists to inform the content area credit hours for doctor of pharmacy (PharmD) programs in the United States (US)., Methods: Public websites were accessed for all Accreditation Council for Pharmacy Education (ACPE) accredited PharmD programs in the US to record the credit hours devoted to drug therapy, clinical skills, experiential learning, scholarship, social and administrative sciences, physiology/pathophysiology, pharmacogenomics, medicinal chemistry, pharmacology, pharmaceutics, and pharmacokinetics/pharmacodynamics in the didactic curricula. Due to the high prevalence of programs that integrate drug therapy, pharmacology, and medicinal chemistry into a single course, we subdivided programs based upon whether drug therapy courses were "integrated" or "non-integrated." A regression analyses was conducted to explore the relationship between each content area and North American Pharmacist Licensure Examination (NAPLEX) pass rates and residency match rates., Results: Data were available for 140 accredited PharmD programs. Drug therapy had the highest credit hours in programs with both integrated and non-integrated drug therapy courses. Programs with integrated drug therapy courses had significantly more credit hours in experiential and scholarship and fewer credit hours in stand-alone courses for pathophysiology, medicinal chemistry, and pharmacology. Credit hours in content areas did not predict NAPLEX pass rate nor residency match success rate., Conclusions: This is the first comprehensive description of all ACPE accredited pharmacy schools with credit hours broken down by content areas. While content areas did not directly predict success criteria, these results may still be useful to describe curricular norms or inform the design of future pharmacy curricula., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pyrolytic biochar (PL-BC, pyrochar) and hydrothermal biochar (HT-BC, hydrochar) derived from branches and leaves of tea plants had different pH, electrical conductivity (EC), total carbon nitrogen content, BET surface area, total pore volume, average pore diameter, and functional groups. HT-BC had a larger specific surface area and more functional groups than PL-BC. Ralstonia Bcul-1 (R-B) was the dominant and functional bacteria in a fertilized vegetable soil supplemented with TBB-immobilized R-B (TBB + R-B). R-B vitality was more closely related to BET surface area, total pore volume, and functional groups of tea-based biochar (TBB: PL-BC and HT-BC). R-B was able to maintain high oxidase activity. R-B and TBB + R-B can increase the activities of urease and peroxidase in vegetable soil playing an essential role in the biotransformation of ammonium nitrogen (NH 4 + -N) and nitrate nitrogen (NO 3 - -N). TBB was able to simultaneously increase the content of NO 3 - -N and NH 4 + -N, and TBB + R-B also significantly increased NO 3 - -N content but decreased NH 4 + -N content in a fertilized vegetable soil. These results indicated that R-B promoted nitrification in the soil, i.e. conversion of NH 4 + -N into NO 3 - -N, by enhancing the activities of urease and peroxidase. R-B had high adsorption capacity for cadmium (Cd) and chromium (Cr) (Cd&Cr: Cd and Cr). Moreover, TBB + R-B was able to convert weak acid extractable and reducible Cd&Cr into a more stable residual fraction and oxidizable Cd&Cr. The overall effect of the treatments was to reduce plant uptake of Cd&Cr by cabbage. TBB + R-B significantly promoted R-B growth, changed inorganic nitrogen speciation, increased NO 3 - -N supply, reduced Cd&Cr bioavailability, and decreased plant tissue Cd&Cr content., Competing Interests: Declaration of Competing Interest All the authors claim that they have no conflict of interest with the work. We declare that there is no commercial or related conflict of interest in the work submitted., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Spine abnormalities are a common manifestation of Neurofibromatosis Type 1 (NF1); however, the outcomes of surgical treatment for NF1-associated spinal deformity are not well explored. The purpose of this study was to investigate the outcome and risk profiles of multilevel fusion surgery for NF1 patients., Methods: The National Inpatient Sample was queried for NF1 and non-NF1 patient populations with neuromuscular scoliosis who underwent multilevel fusion surgery involving eight or more vertebral levels between 2004 and 2017. Multivariate regression modeling was used to explore the relationship between perioperative variables and pertinent outcomes., Results: Of the 55,485 patients with scoliosis, 533 patients (0.96%) had NF1. Patients with NF1 were more likely to have comorbid solid tumors (P < 0.0001), clinical depression (P < 0.0001), peripheral vascular disease (P < 0.0001), and hypertension (P < 0.001). Following surgery, NF1 patients had a higher incidence of hydrocephalus (0.6% vs. 1.9% P = 0.002), seizures (4.9% vs. 5.7% P = 0.006), and accidental vessel laceration (0.3% vs.1.9% P = 0.011). Although there were no differences in overall complication rates or in-hospital mortality, multivariate regression revealed NF1 patients had an increased probability of pulmonary (OR 0.5, 95%CI 0.3-0.8, P = 0.004) complications. There were no significant differences in utilization, including nonhome discharge or extended hospitalization; however, patients with NF1 had higher total hospital charges (mean -$18739, SE 3384, P < 0.0001)., Conclusions: These findings indicate that NF1 is associated with certain complications following multilevel fusion surgery but does not appear to be associated with differences in quality or cost outcomes. These results provide some guidance to surgeons and other healthcare professionals in their perioperative decision making by raising awareness about risk factors for NF1 patients undergoing multilevel fusion surgery. We intend for this study to set the national baseline for complications after multilevel fusion in the NF1 population., (Copyright © 2022. Published by Elsevier Inc.)

Poly- and perfluoroalkyl substances (PFAS) are a class of emerging organic contaminants that are impervious to standard physicochemical treatments. The widespread use of PFAS poses serious environmental issues. PFAS pollution of soils and water has become a significant issue due to the harmful effects of these chemicals both on the environment and public health. Owing to their complex chemical structures and interaction with soil and water, PFAS are difficult to remove from the environment. Traditional soil remediation procedures have not been successful in reducing or removing them from the environment. Therefore, this review focuses on new phytoremediation techniques for PFAS contamination of soils and water. The bioaccumulation and dispersion of PFAS inside plant compartments has shown great potential for phytoremediation, which is a promising and unique technology that is realistic, cost-effective, and may be employed as a wide scale in situ remediation strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Heart dose has emerged as an independent predictor of overall survival in patients with NSCLC treated with radiotherapy. Several studies have identified the base of the heart as a region of enhanced dose sensitivity and a potential target for cardiac sparing. We present a dosimetric analysis of overall survival in the multicenter, randomized PET-Plan trial (NCT00697333) and for the first time include left ventricular ejection fraction (EF) at baseline as a metric of cardiac function., Methods: A total of 205 patients with inoperable stage II or III NSCLC treated with 60 to 72 Gy in 2 Gy fractions were included in this study. A voxel-wise image-based data mining methodology was used to identify anatomical regions where higher dose was significantly associated with worse overall survival. Univariable and multivariable Cox proportional hazards models tested the association of survival with dose to the identified region, established prognostic factors, and baseline cardiac function., Results: A total of 172 patients remained after processing and censoring for follow-up. At 2-years posttreatment, a highly significant region was identified within the base of the heart (p < 0.005), centered on the origin of the left coronary artery and the region of the atrioventricular node. In multivariable analysis, the number of positron emission tomography-positive nodes (p = 0.02, hazard ratio = 1.13, 95% confidence interval: 1.02-1.25) and mean dose to the cardiac subregion (p = 0.02, hazard ratio = 1.11 Gy -1 , 95% confidence interval: 1.02-1.21) were significantly associated with overall survival. There was a significant interaction between EF and region dose (p = 0.04) for survival, with contrast plots revealing a larger effect of region dose on survival in patients with lower EF values., Conclusions: This work validates previous image-based data mining studies by revealing a strong association between dose to the base of the heart and overall survival. For the first time, an interaction between baseline cardiac health and heart base dose was identified, potentially suggesting preexisting cardiac dysfunction exacerbates the impact of heart dose on survival., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Municipal wastewater sludge may be processed into biosolids and applied to farmland for crop production, rather than be disposed of in landfills. Biosolids supply plant nutrients and increase soil organic carbon but also contribute to the production of greenhouse gases (GHGs). Computational models must therefore be refined to estimate the contribution of these gases to national GHG inventories. The DeNitrification and DeComposition (DNDC) model was evaluated for processes regulating crop growth, GHGs and soil C&N dynamics to determine its suitability for informing policy decision-making and advancing Canada's GHG inventory. Three years (2017-2019) of data were collected from replicated corn (Zea mays L.) plots in Quebec, Canada. The plots received 120 kg of available N ha -1 y -1 in mesophilic anaerobically digested biosolids, composted biosolids, alkaline-stabilized biosolids, urea, or combinations of these, while control plots were left unfertilized. Treatments receiving digested biosolids emitted more nitrous oxide (N 2 O) during the growing season than other treatments, while carbon dioxide (CO 2 ) emissions were similar between treatments. After calibration, DNDC estimates were within the 95% confidence interval of the measured variables. Correlation coefficients (r) indicated discrepancies in trends between the estimated and measured values for daily CO 2 and N 2 O emissions. These emissions were underestimated in the early and mid-growing season of 2018. They were more variable from plots fertilized with composted or alkaline-stabilized biosolids than from those with digested biosolids. Annual N 2 O emissions (r = 0.8), crop yields (r = 0.5), and soil organic carbon (r = 0.4) were modelled with higher accuracy than cumulative CO 2 emissions (r = 0.3) and total soil N (r = 0.1). These findings suggest that DNDC is suitable for estimating field-scale N 2 O emissions following biosolids application, but estimates of CO 2 emissions could be improved, perhaps by disaggregating the biosolids from the soil organic matter pools in the decomposition subroutines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The uptake of inorganic carbon in cyanobacteria is facilitated by an energetically intensive CO 2 -concentrating mechanism (CCM). This includes specialized Type-1 NDH complexes that function to couple photosynthetic redox energy to CO 2 hydration forming the bicarbonate that accumulates to high cytoplasmic concentrations during the operation of the CCM, required for effective carbon fixation. Here we used a Synechococcus PCC7942 expression system to investigate the role of conserved histidine and cysteine residues in the CupB (also designated, ChpX) protein, which has been hypothesized to participate in a vectoral CO 2 hydration reaction near the interface between CupB protein and the proton-pumping subunits of the NDH-1 complex. A homology model has been constructed and most of the targeted conserved residues are in the vicinity of a Zn ion modeled to form the catalytic site of deprotonation and CO 2 hydration. Growth and CO 2 uptake assays show that the most severe defects in activity among the targeted residues are due to a substitution of the predicted Zn ligand, CupB-His86. Mutations at other sites produced intermediate effects. Proteomic analysis revealed that some amino acid substitution mutations of CupB caused the induction of bicarbonate uptake proteins to a greater extent than complete deletion of CupB, despite growth under CO 2 -enriched conditions. The results are discussed in terms of hypotheses on the catalytic function of this unusual enzyme., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A novel Ralstonia Bcul-1 strain was isolated from soil samples that was closest to Ralstonia pickettii. Broad-spectrum resistance was identified to a group of heavy metal ions and tolerance to concentrations of Cd 2+ up to 400 mg L -1 . Low concentrations of heavy metal ions did not have distinctive impact on heavy metal resistance genes and appeared to induce greater expression. Under exposure to Cd 2+ , cell wall components were significantly enhanced, and some proteins were also simultaneously expressed allowing the bacteria to adapt to the high Cd 2+ living environment. The maximum removal rate of Cd 2+ by the Ralstonia Bcul-1 strain was 78.97% in the culture medium supplemented with 100 mg L -1 Cd 2+ . Ralstonia Bcul-1 was able to survive and grow in a low nutrient and cadmium contaminated (0.42 mg kg -1 ) vegetable soil, and the cadmium removal rate was up to 65.76% in 9th growth. Ralstonia Bcul-1 mixed with biochar could maintain sustainable growth of this strain in the soil up to 75 d and the adsorption efficiency of cadmium increased by 16.23-40.80% as compared to biochar application alone. Results from this work suggests that Ralstonia Bcul-1 is an ideal candidate for bioremediation of nutrient deficient heavy metal contaminated soil., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) and disease-related poor prognostic factors are not well characterized. We aimed to describe patient demographics, disease characteristics, treatment patterns and patient-reported outcomes in a subset of HR+/HER2- ABC patients with these factors [at the time when cyclin-dependent kinase (CDK) 4 and 6 inhibitors were being introduced] and understand how these factors informed treatment decisions at the time of the survey., Methods: Real-world data were derived from a large, multinational, point-in-time survey of oncologists and their consulting patients with HR+/HER2- ABC in the EU5 and USA over March-June 2017, at the start of the changing treatment landscape. Analysis focused on four poor prognostic factors: visceral metastases, liver metastases (subset of visceral metastases), progesterone receptor-negative status and high tumor grade., Results: In total, 2259 patients with HR+/HER2- ABC had records eligible for this analysis. At least one poor prognostic factor was present in 63% of patients (most common visceral metastases; least common progesterone receptor-negative status), with varying degrees of overlap between factors. For physician-reported outcomes, pain increased, whereas performance status and activities of daily living declined with presence of poor prognostic factors, especially liver metastases. No clear trends were observed for patient-reported outcomes. Treatment with combined endocrine therapy plus CDK4 and 6 inhibitors was infrequent, as these agents were entering the market., Conclusions: More than 60% of the HR+/HER2- ABC Adelphi Real World Disease Specific Programme™ sample had ≥1 disease-related poor prognostic factor, and patients appeared to be heterogeneous regarding occurrence and distribution of these factors. These patients typically have increased pain and reduced performance status, highlighting the importance of implementing effective therapy with CDK4 and 6 inhibitors. Future studies could inform how the treatment landscape has evolved over time with respect to patients with poor prognostic factors., Competing Interests: Disclosure AD, GCC and GP have disclosed that they are employees of Eli Lilly and Company. FR and HO have disclosed they were employees of Eli Lilly and Company during the development of the analysis. AB, AR and KL have disclosed that they are employees of Adelphi Real World Ltd, who own the multi-sponsored Disease Specific Programme, and were paid by Eli Lilly and Company Ltd in the development of this analysis and manuscript. XP has disclosed an advisory role with Eli Lilly and Company, for which an honorarium was received from Eli Lilly and Company Ltd for consultancy support in the development of this analysis., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The neurosurgery residency match is a competitive process. While medical research offers esteemed learning opportunities, productivity is closely evaluated by residency programs. Accordingly, students work diligently to make contributions on projects within their neurosurgery departments. The present study evaluated medical student research productivity for each of the 118 U.S. neurosurgery residency programs., Methods: A retrospective review of publications for 118 neurosurgery programs from January 1, 2015, to April 1, 2020, was performed. The primary outcome was any publication with a medical student as the first author. Secondary outcomes included number of faculty in each department, department region, and medical school ranking. The number of student first author publications was compared among programs, regions, and medical schools., Results: Mean numbers of medical student first author publications and faculty members per institution were 16.27 and 14.46, respectively. The top 3 neurosurgery departments with the greatest number of student first author publications were Johns Hopkins University, Brigham and Women's Hospital, and University of California, San Francisco. Salient findings included a positive correlation between the number of medical student first author publications from a neurosurgery department and the number of departmental faculty (P < 0.001, R = 0.69). Additionally, the mean number of first author medical student publications at the top 30 programs was higher than the mean for the remaining programs (P < 0.0001)., Conclusions: This study is the first to evaluate neurosurgery medical student productivity in North America. By systematizing first authorships, incoming students who desire to pursue neurosurgery can be informed of institutions with student involvement, and departments that use medical student expertise can be recognized., (Published by Elsevier Inc.)

Land application of biosolids is one potential source of pharmaceuticals and personal care products (PPCPs) into agricultural soils. Degradation is an important natural attenuation pathway that affects the fate and transport of PPCPs in the soil system and biosolids application could alter the process. The present study assessed the effect of individual and mixture compound environments on the biodegradation rate and half-life of three non-steroidal anti-inflammatory drugs (NSAIDs), naproxen (NPX), ibuprofen (IBF), and ketoprofen (KTF), in a loamy sand textured agricultural soil receiving an alkaline treated biosolid (ATB) amendment. A prolonged half-life of the target NSAIDs was determined for sterile soils and shorter half-lives in unsterile soils, indicating the loss of target compounds in all treatments was mainly attributed to biodegradation and followed first-order kinetics. IBF and NPX showed low to moderate persistence in soil and ATB amended soil, with half-lives ranging from 4.9 to 14.8 days, while KTF appeared to be highly persistent with an average half-life of 33 days. The order in which the target NSAIDs disappeared in both soil and ATB amended soil was: IBF > NPX > KTF, for both individual and mixture compound treatments. Soils that received the ATB amendment demonstrated inhibited degradation of NPX in all treatments, as well as IBF and KTF in individual compound treatment over the 14-day incubation study. We also observed an inhibition effect from the ATB amendment in sterile soil treatments. In mixture compound treatments, IBF degradation was inhibited in both soil and ATB amended soil. The degradation rate of KTF in mixture compound environment in soil was lower, while the opposite effects were observed in ATB amended soils. For NPX, the degradation was enhanced in mixture compound environment in ATB amended soil, while the same degradation rate of NPX was calculated in soil., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Agricultural soils are inherently disturbed systems where organic matter additions are considered to enhance microbial community structure and resilience. High-throughput sequencing of community was applied to soils receiving annual applications of an alkaline stabilized biosolid (ATB), at four increasing rates over 10 years, as an environmental stressor in contrast to a one-time application of ATB ten years prior. Bacterial community structure was more greatly influenced by annual ATB applications relative to fungi and eukaryotes. Specifically, higher relative abundances of Proteobacteria, Acidobacteria, Bacteroidetes, and Chloroflexi were measured in annual ATB rates relative to the single ATB rates and the control. High rates of annual ATB applications resulted in lower bacterial alpha-diversity, as well as fungal and eukaryotic Shannon diversity, but single ATB or lower rates of ATB applied annually showed increased alpha -diversity relative to the control. Soil microbiome responses to annual ATB and single ATB rates were also examined using co-occurrence network analysis. High rates and frequency of ATB application resulted in a decrease in network interactions, lower average number of neighbors, and reduced network density compared to control soils. A concomitant increase in network diameter and characteristic path length further suggests annual additions of ATB led to a more adapted, but less cooperative, state in the microbiome. The data suggest a more universal functional response of microbiomes to the stressors compared to community structure and local diversity. In particular, beta-analysis and network analysis were both able to resolve significant effects on soil microbiomes 10 years post-application of low rates of ATB. Community complexity and stability were increased by single low rate of ATB additions and decreased by single high rate and annual moderate rates of ATB additions. These results provide insights into the effects that ATB additions have on soil community after only one-time use and after annual additions over a decade., Competing Interests: Declaration of competing interest The authors have declared that no conflicts of interest exist., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Receptor activator of NF-kB ligand stimulates NF-kB-dependent cell signaling and acts as the primary signal for bone resorption. Retrospective analysis of a large trial comparing denosumab versus zoledronic acid in bone metastatic solid tumors suggested significant overall survival (OS) advantage for patients with lung cancer with denosumab (p = 0.01). The randomized open-label phase III SPLENDOUR trial was designed to evaluate whether the addition of denosumab to standard first-line platinum-based doublet chemotherapy improved OS in advanced NSCLC., Methods: Patients with stage IV NSCLC were randomized in a 1:1 ratio to either chemotherapy with or without denosumab (120 mg every 3-4 wks), stratified by the presence of bone metastases (at diagnosis), Eastern Cooperative Oncology Group performance status, histology, and region. To detect an OS increase from 9 to 11.25 months (hazard ratio [HR] = 0.80), 847 OS events were required. The trial closed prematurely owing to decreasing accrual rate., Results: A total of 514 patients were randomized, with 509 receiving one or more doses of the assigned treatment (chemotherapy: 252, chemotherapy-denosumab: 257). The median age was 66.1 years, 71% were men, and 59% were former smokers. Bone metastases were identified in 275 patients (53%). Median OS (95% confidence interval [CI]) was 8.7 (7.6-11.0) months in the control arm versus 8.2 (7.5-10.4) months in the chemotherapy-denosumab arm (HR = 0.96; 95% CI: 0.78-1.19; one-sided p = 0.36). For patients with bone metastasis, HR was 1.02 (95% CI: 0.77-1.35), whereas for those without, HR was 0.90 (95% CI: 0.66-1.23). Adverse events grade 3 or greater were observed in 40.9%, 5.2%, 8.7% versus 45.5%, 10.9%, 10.5% of patients. Conditional power for OS benefit was less than or equal to 10%., Conclusions: Denosumab was well-tolerated without unexpected safety concerns. There was no OS improvement for denosumab when added to chemotherapy in the intention-to-treat population and the subgroups with and without bone metastases. Our data do not provide evidence of a clinical benefit for denosumab in patients with NSCLC without bone metastases., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Phthalate esters (PAEs) are prevalent in the environment due to the broad range of industrial, agriculture and domestic applications. The ubiquitous use of PAEs has resulted in their potential to reach groundwater sources through application of agri-chemicals and municipal biosolids. A study was conducted to monitor the fate and transport of seven commonly detected PAEs in the environment including: dimethyl phthalate (DMP), diethyl phthalate (DEP), benzyl butyl phthalate (BBP), bis(di-ethyl hexyl) phthalate (DEHP), di-n-octyl phthalate (DnOP), dipentyl phthalate (DPP), and di-n-butyl phthalate (DnBP). Biosolids sourced from the Halifax Regional Municipality were applied at three rates on field-based lysimeter cells which were cropped to corn (Zea mays) for one growing season. In the present study, breakthrough curves (BTCs) were established for phthalates leaching from a corn-cultivated agricultural soil profile. The HYDRUS-1D model and a two-site sorption model were applied to predict transport parameters of PAEs using an inverse solution approach. Results of our research revealed that higher PAE adsorption was observed based on increasing carbon chain number. In addition, higher values of F (i.e. the fraction of type-1 sorption sites assumed to be in equilibrium with the solution phase) and lower values of D (i.e. dispersion coefficient) were observed for PAEs with large carbon chains which was validated both through the empirical dataset and the model simulations., (Copyright © 2016. Published by Elsevier B.V.)

Auditory P3 amplitude reduction is one of the most robust and replicated findings in schizophrenia. Recent evidence suggests that these reductions are due to reductions in both power and phase-locking at delta and theta frequencies. We have previously shown that the auditory, but not visual, P3 is reduced in healthy participants given the catecholamine releasing agent dexamphetamine. Our aim was to determine whether the auditory P3 amplitude reduction induced by dexamphetamine has similar power and phase locking characteristics to that seen in schizophrenia. Forty-four healthy participants were given 0.45 mg/kg dexamphetamine and placebo, in a double-blinded, placebo-controlled, cross-over design. The task was a three-stimulus auditory odd-ball task, target stimuli were the major stimuli of interest. Individual target trials underwent wavelet analysis to give power and phase-locking of delta (3 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz) and gamma (30-50 Hz) frequencies for a 50 ms time window centred around the peak of the target P3. Delta power around the P3 peak was significantly reduced when participants were given dexamphetamine. Delta phase-locking was also reduced but only when analysis was targeted at the location of the peak P3 amplitude. In contrast, theta power and phase-locking were not affected by dexamphetamine. These findings suggest that increased catecholamine activity may be responsible for the power and phase-locking reductions of the auditory P3 delta component in patients with schizophrenia. Interestingly, dexamphetamine significantly increased gamma power around the P3 peak. We attempt to link this finding with the gamma alterations that have been found in patients with schizophrenia., (Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.)

In Nova Scotia (NS), approximately 2700 tonnes of Specified Risk Materials (SRM) are produced annually. SRM disposal is a serious concern for abattoirs and the beef industry. Composting offers a low risk and simple means to transform raw SRM into a more stable and easily managed material. In this project, wheat straw and sawdust were used to compost with SRM on a pilot scale. The study evaluated changes over time in total carbon, total nitrogen, pH, temperature, moisture content and electrical conductivity. Compost temperatures in all treatments met the Canadian Council of Ministers of the Environment (CCME) guidelines for pathogen kill. The compost maturity tests showed that the evolution of CO(2)-C in all the final compost products was less than 1 mg g(-1) organic matter day(-1). Wheat straw performed well as a composting feedstock for raw SRM as sawdust. While the wheat straw has advantages including greater availability, lower cost and easily decomposable carbon compounds more management is required to maintain adequate compost temperatures. The influences of seasonal variations due to temperate climatic conditions on SRM composting were also studied with wheat straw. The results suggest no significant differences in composting effectiveness between the two seasons., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Loss of cortical volume in frontotemporal regions has been reported in patients with schizophrenia and their relatives. Cortical area and thickness are determined by different genetic processes, and measuring these parameters separately may clarify disturbances in corticogenesis relevant to schizophrenia. Our study also explored clinical and cognitive correlates of these parameters., Methods: Thirty-seven patients with first-episode psychosis (34 schizophrenia, 3 schizoaffective disorder) and 38 healthy control subjects matched for age and sex took part in the study. Imaging was performed on an magnetic resonance imaging 1.5-T scanner. Area and thickness of the frontotemporal cortex were measured using a surface-based morphometry method (Freesurfer). All subjects underwent neuropsychologic testing that included measures of premorbid and current IQ, working and verbal memory, and executive function., Results: Reductions in cortical area, more marked in the temporal cortex, were present in patients. Overall frontotemporal cortical thickness did not differ between groups, although regional thinning of the right superior temporal region was observed in patients. There was a significant association of both premorbid IQ and IQ at disease onset with area, but not thickness, of the frontotemporal cortex, and working memory span was associated with area of the frontal cortex. These associations remained significant when only patients with schizophrenia were considered., Conclusions: Our results suggest an early disruption of corticogenesis in schizophrenia, although the effect of subsequent environmental factors cannot be excluded. In addition, cortical abnormalities are subject to regional variations and differ from those present in neurodegenerative diseases., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Open abdominal aortic aneurysm (AAA) repair is associated with cardiac and respiratory complications and an overall mortality rate of 2 to 8%. We hypothesised that excessive fluid administration during the perioperative period contributes to complications and poor outcome after AAA repair., Methods: This was a retrospective cohort study. Medical records were analysed for fluid balance and complications in 100 consecutive patients treated by open AAA repair at a single centre between 2002-2005. Mortality and all major adverse events (MAE) such as myocardial infarction (MI), cardiac arrhythmia (Arr), pulmonary oedema (PO), pulmonary infection (PI), and acute renal failure (ARF) were included in the analysis. Level of care and hospital stay, were also recorded., Results: There were no in-hospital deaths. MAE occurred in 40/100 (40%): MI (6%); Arr (14%); PO (14%); PI (25%); ARF (8%). Complications were not predicted by preoperative cardiovascular risk factors, operative and clamp time, or blood loss. Patients with complications had significantly greater cumulative positive fluid balance on postoperative day 0 (p<0.01), day 1 (p<0.05), day 2 (p<0.03) and day 3 (p<0.04). This relationship also existed for individual complications such as MI, and pulmonary oedema. These patients had significantly longer ICU/HDU (p<0.002) and hospital stay (p<0.0001)., Conclusions: Serious complications are common after elective open AAA repair, and we have shown that positive fluid balance is predictive of major adverse events increased HDU/ICU and overall hospital stay.

Background: Most current paper- and computer-based formats for patient documentation use a two-dimensional dental chart, a design that originated almost 150 years ago in the United States. No studies have investigated the inclusion of a three-dimensional (3-D) charting interface in a general dental record., Methods: A multidisciplinary research team with expertise in human-computer interaction, dental informatics and computer science conducted a 14-week project to develop and evaluate a proof of concept for a 3-D dental record. Through several iterations of paper- and computer-based prototypes, the project produced a high-fidelity (hi-fi) prototype that was evaluated by two dentists and two dental students., Results: The project implemented a prototypical patient record built around a 3-D model of a patient's maxillofacial structures. Novel features include automatic retrieval of images and radiographs; a flexible view of teeth, soft tissue and bone; access to historical patient data through a timeline; and the ability to focus on a single tooth., Conclusions: Users tests demonstrated acceptance for the basic design of the prototype, but also identified several challenges in developing intuitive, easy-to-use navigation methods and hi-fi representations in a 3-D record., Clinical Implications: Test participants in this project accepted the preliminary design of a 3-D dental record. Significant further research must be conducted before the concept can be applied and evaluated in clinical practice.

Objective: To determine the relationship between hospital admissions for falls and hip fracture in elderly people and area characteristics such as socio-economic deprivation., Study Design: Ecological study of routinely collected hospital admissions data for falls and hip fracture in people aged 75 years or over for 1992-1997, linked at electoral ward level with characteristics from census data., Methods: In total, 42,293 and 17,390 admissions were identified for falls and hip fracture, respectively, from 858 electoral wards in Trent. Rate ratios (RRs) for hospital admissions for falls and hip fracture were calculated by the electoral wards' Townsend score divided by quintiles. RRs were estimated by negative binomial regression and adjusted for the ward characteristics of age, gender, ethnicity, rurality, proportion of elderly people living alone and distance from hospital., Results: There was a small but statistically significant association at electoral ward level between hospital admissions for falls and the Townsend score, with the most deprived wards having a 10% higher admission rate for falls compared with the most affluent wards (adjusted RR 1.10, 95% CI 1.01-1.19). No association was found between hospital admission for hip fracture and deprivation (adjusted RR 1.05, 95% CI 0.95-1.16)., Conclusion: There is some evidence of an association at electoral ward level between hospital admissions for falls and socio-economic deprivation, with higher rates in deprived areas. No such association was found for hip fracture. Further work is required to assess the impact of interventions on reducing inequalities in hospital admission rates for falls in elderly people.

Ongoing bleeding from patients who have an acquired coagulopathy post-surgery is a common problem. Strategies that are available to combat this problem revolve around the replacement of coagulation factors, platelets, and red blood cells as necessary. These strategies are not always successful and a more direct approach to activating the coagulation system can be more effective and in some instances life saving. We describe the use of recombinant factor VIIa in a patient with ongoing post partum bleeding.

A patient with acute renal failure associated with lactic acidosis as a result of concurrent treatment with metformin is described. Rofecoxib may have been a precipitating factor. The risk of renal failure with the use of traditional NSAIDs is well known. However, what is less well appreciated is the role that the COX 2 inhibitors may play in the development of renal failure which, when it occurs in a patient on metformin, can lead to a potentially disastrous outcome.

We have recently cloned the human nucleosome assembly protein 2 (NAP-2). Here, we demonstrate that casein kinase 2 (CKII) from HeLa cell nuclear extracts interacts with immobilized NAP-II, and phosphorylates both NAP-2 and nucleosome assembly protein 1 (NAP-1) in vitro. Furthermore, NAP-1 and NAP-2 phosphorylation in crude HeLa cell extracts is abolished by heparin, a specific inhibitor of CKII. Addition of core histones can stimulate phosphorylation of NAP-1 and NAP-2 by CKII. NAP-2 is also a phosphoprotein in vivo. The protein is phosphorylated at the G0/G1 boundary but it is not phosphorylated in S-phase. Here, we show that NAP-2 is a histone chaperone throughout the cell cycle and that its cell-cycle distribution might be governed by its phosphorylation status. Phosphorylated NAP-2 remains in the cytoplasm in a complex with histones during the G0/G1 transition, whereas its dephosphorylation triggers its transport into the nucleus, at the G1/S-boundary, with the histone cargo, suggesting that binding to histones does not depend on phosphorylation status. Finally, indirect immunofluorescence shows that NAP-2 is present during metaphase of HeLa and COS cells, and its localization is distinct from metaphase chromosomes., (Copyright 2000 Academic Press.)

An anxiety reduction protocol was developed and evaluated for routine use with neurology and neuropsychiatry patients undergoing brain or spinal scans. Thirty five patients underwent standard procedures, with limited information given in advance. Twenty nine experimental patients received a booklet giving information about the scanning procedure and advice on cognitive strategies for anxiety reduction, a tape-recorded demonstration of scanner noise, a visit to the control room before entering the scanner, a device to signal for adjustment of music volume, precise timings of each scan, and a clock visible during scanning. Anxiety was measured before, during, and after scanning, using subjective ratings and a retrospective version of the Spielberger State Anxiety Scale. There was no difference in anxiety between groups immediately prior to the scan and immediately after entering the scanner. Patients in the experimental group were significantly less anxious during the scan than control patients, as measured by mean anxiety ratings made during the imaging procedure and by retrospective State Anxiety scores completed immediately after leaving the scanner. The results show that scan-related anxiety can be reduced by introducing these simple changes to MR imaging procedures, with minimal cost, no special training of staff, and no disruption of the running of the MR Unit.

A modification of the extrusion method for the isolation of nascent DNA from mammalian cells and a PCR-based assay has been used in order to compare the in vivo activities of DNA replication origins in different cell lines. Conventional PCR was firstly applied to detect the chromosomal activities of several known (origins associated with c-myc, hsp70, beta-globin, immunoglobulin mu-chain enhancer) and putative DNA replication origins (autonomously replicating sequences obtained from enriched libraries of human origins of DNA replication from normal and transformed cells) in four human cell lines (HeLa, NSF, WI-38 and SK-MG-1). Then, in nascent DNA samples from normal skin fibroblast (NSF) and HeLa cells, abundance of DNA sequences in the regions of five of these origins was determined by competitive PCR. Our results suggest that autonomously replicating sequences NOA3, S14, S3 and F15 are associated with functional chromosomal origins of replication. Quantitative comparison of origin activities demonstrates that origins associated with c-myc and NOA3 are approximately twice as active in HeLa cells as in NSF cells. The described approach can facilitate the identification of origins which may be differentially active in normal cells and transformed cells or in different cell types., (Copyright 1997 Academic Press Limited.)

Background: Short-term studies suggest that cardiac transplant immunosuppression without maintenance corticosteroids is feasible in selected patients. However, concern exists as to the long-term effects, specifically the possibility of increased morbidity and mortality because of late allograft rejection and allograft coronary artery disease., Methods: We retrospectively reviewed the records from 441 consecutive heart transplantation procedures done in 416 patients with use of an immunosuppressive protocol that attempted corticosteroid withdrawal within 2 months of transplantation. forty-two patients died or underwent retransplantation during the first 3 months and were excluded from further analysis. Analysis focused on demographic and long-term outcome variables (including death, rejection, retransplantation, and infection)., Results: Thirty percent (111) of eligible patients (374) met the definition of successful early steroid withdrawal. Only male gender independently predicted successful withdrawal. Mortality, both short and long term, was significantly lower in patients in whom successful early withdrawal from corticosteroids was achieved than in patients in whom the early attempts failed (1.7% per year versus 4.7% per year; p < 0.0001). The prevalence of late acute allograft rejection (more than 1 year after transplantation) was lower in patients successfully withdrawn from steroid therapy early after transplantation (0.07 pt-yr of follow-up versus 0.15 pt-yr; p = 0.002). Multivariate analysis of the entire group identified incidence of infection (p = 0.001), older age (p = 0.001), failed early steroid withdrawal (p = 0.006), and female gender (p = 0.016) as independent predictors of mortality., Conclusions: Successful early corticosteroid withdrawal identifies a subgroup of "immunologically privileged" patients with a low risk for long-term mortality and is not associated with an increased prevalence of late rejection or clinically significant coronary artery disease.

Cruciform DNA structure, as a structural feature, has been associated with regulation of transcription, recombination and replication. Previously used to successfully modify DNA replication and affinity-purify origins and autonomously replicating sequences. Using enzyme protection assays, their binding activity has been localized to the base (elbow) of the cruciform stem. We report here the hydroxyl radical footprinting of 2D3 (kappa IgG1) anti-cruciform monoclonal antibody on a stable cruciform structure created by heteroduplexing fragments from two plasmids, identical except for two centrally located palindromes of different sequence. The footprinting was performed at near-physiological salt concentrations, conditions favouring the stacked X-structure of the cruciform. Our data show that binding by the antibody occurs at the four-way junction (elbows) of the stable cruciform. The binding of the antibody seems also to cause associated structural distortions in the heteroduplex, which generally result in greater sensitivity to hydroxyl radicals at the tips of the cruciforms. The data are consistent to hydroxyl radicals at the tips of the cruciforms. The data are consistent with the binding of a single antibody to an antigen-combining site. The results of this study compare favourably with the hydroxyl radical footprinting studies reported recently for a human cruciform binding protein (CBP), which binds at the base of the stem-loop structure and causes similar distortions of the stable cruciform structure. These studies indicate that the four-way junction of the cruciform possesses certain unique structural qualities that are antigenic; the association of this structural determinant with DNA replication and the existence of a novel cellular protein, CBP, of similar binding specificity as the antibody specificity support a role for cruciforms as important regulatory recognition signals in replication.

A model that unifies all types of selection (chemical, sociological, genetical, and every other kind of selection) may open the way to develop a general "Mathematical Theory of Selection" analogous to communication theory. [Note added by S. A. Frank: This previously unpublished manuscript was found among Dr. Price's papers when he died in 1975. In this paper Dr. Price did not provide a complete, general theory of selection. Rather, he argued why such a theory is needed and what some of its properties might be. The accompanying article provides commentary on this paper and describes Dr. Price's significant contributions to evolutionary genetics (S. A. Frank, 1995, J. theor. Biol. 175, 373-388).]

Insulin-like growth factor-I (IGF-I) is a peptide growth factor whose activity is modulated by interaction with the family of six IGF binding proteins (IGFBPs). IGF-I is detected in rat kidney and has metabolic and growth effects. We have used in situ hybridization to localize mRNAs for the IGFBPs in rat kidney. Messenger RNAs for all six IGFBPs were detected, each with a distinctive distribution. IGFBP-1 mRNA was expressed in the distal nephron, from the thick ascending limb of the loop of Henle to the cortical collecting ducts. IGFBP-2 mRNA expression was confined to epithelial cells of the glomeruli and the thin limbs of the loop of Henle. IGFBP-3 mRNA was localized to the cortical interstitium while IGFBP-4 was the only IGFBP mRNA found in the proximal tubule. IGFBP-5 mRNA, the most abundant and widely distributed of the IGFBP mRNAs in the kidney, occurred in the glomerular mesangium and the medullary interstitium as well as in the epithelial cells of the distal nephron. IGFBP-6 mRNA, the least abundant, was expressed mainly in fibroblasts associated with renal blood vessels and the ureter. This heterogeneous distribution of the IGFBPs may enable IGF action to be regulated by multiple factors in a site-specific manner.

Thirty-five children were tested with an auditory oddball P300 paradigm both before and 2 hr after a single-dose trial of methylphenidate (MPH). A prediction of the long-term benefit of medication was then made based on the magnitude of the acute changes in P3b amplitude. Those with postdrug amplitude increases of at least 30% were predicted to respond favorably to stimulants. All children were followed-up at 6 months. The original MPH Challenge Test predictions (based on acute post drug P3b amplitude changes) were then compared with the clinicians' evaluations of outcome. The MPH challenge classification accurately predicted outcome in 81% of cases.