Search

The first search for the lepton number violating decay K+→π0π−μ+e+ and lepton flavour violating decays K+→π0π+μ−e+, K+→π0π+μ+e− has been performed using a dataset collected by the NA62 experiment at CERN in 2016–2018. Upper limits of 2.9×10−10, 3.1×10−10 and 5.0×10−10, respectively, are obtained at 90% CL for the branching ratios of the three decays on the assumption of uniform phase-space distributions.

A sample of 3984 candidates of the K+→π+γγ decay, with an estimated background of 291±14 events, was collected by the NA62 experiment at CERN during 2017–2018. In order to describe the observed di-photon mass spectrum, the next-to-leading order contribution in chiral perturbation theory was found to be necessary. The decay branching ratio in the full kinematic range is measured to be (9.61±0.17)×10−7. The first search for production and prompt decay of an axion-like particle with gluon coupling in the process K+→π+a, a→γγ is also reported.

The first search for ultra-rare K+ decays into the π+e+e−e+e− final state is reported, using a dataset collected by the NA62 experiment at CERN in 2017–2018. An upper limit of 1.4×10−8 at 90% CL is obtained for the branching ratio of the K+→π+e+e−e+e− decay, predicted in the Standard Model to be (7.2±0.7)×10−11. Upper limits at 90% CL are obtained at the level of 10−9 for the branching ratios of two prompt decay chains involving pair-production of hidden-sector mediators: K+→π+aa, a→e+e− and K+→π+S, S→A′A′, A′→e+e−.

A search for the K+→μ−νe+e+ decay, forbidden within the Standard Model by either lepton number or lepton flavour conservation depending on the flavour of the emitted neutrino, has been performed using the dataset collected by the NA62 experiment at CERN in 2016–2018. An upper limit of 8.1×10−11 is obtained for the decay branching fraction at 90% CL, improving by a factor of 250 over the previous search.

Searches for lepton number violating K+→π−e+e+ and K+→π−π0e+e+ decays have been performed using the complete dataset collected by the NA62 experiment at CERN in 2016–2018. Upper limits of 5.3×10−11 and 8.5×10−10 are obtained on the decay branching fractions at 90% confidence level. The former result improves by a factor of four over the previous best limit, while the latter result represents the first limit on the K+→π−π0e+e+ decay rate.

The NA62 experiment at the CERN SPS reports the first search for K+→π+νν¯ using the decay-in-flight technique, based on a sample of 1.21×1011 K+ decays collected in 2016. The single event sensitivity is 3.15×10−10, corresponding to 0.267 Standard Model events. One signal candidate is observed while the expected background is 0.152 events. This leads to an upper limit of 14×10−10 on the K+→π+νν¯ branching ratio at 95% CL.

The NA62 experiment at CERN reports searches for K+→μ+N and K+→μ+νX decays, where N and X are massive invisible particles, using the 2016–2018 data set. The N particle is assumed to be a heavy neutral lepton, and the results are expressed as upper limits of O(10−8) of the neutrino mixing parameter |Uμ4|2 for N masses in the range 200–384 MeV/c2 and lifetime exceeding 50 ns. The X particle is considered a scalar or vector hidden sector mediator decaying to an invisible final state, and upper limits of the decay branching fraction for X masses in the range 10–370 MeV/c2 are reported for the first time, ranging from O(10−5) to O(10−7). An improved upper limit of 1.0×10−6 is established at 90% CL on the K+→μ+ννν¯ branching fraction.

A search for heavy neutral lepton (N) production in K+→e+N decays using the data sample collected by the NA62 experiment at CERN in 2017–2018 is reported. Upper limits of the extended neutrino mixing matrix element |Ue4|2 are established at the level of 10−9 over most of the accessible heavy neutral lepton mass range 144–462 MeV/c2, with the assumption that the lifetime exceeds 50 ns. These limits improve significantly upon those of previous production and decay searches. The |Ue4|2 range favoured by Big Bang Nucleosynthesis is excluded up to a mass of about 340 MeV/c2.

The NA62 experiment at CERN reports a search for the lepton number violating decays K+→π−e+e+ and K+→π−μ+μ+ using a data sample collected in 2017. No signals are observed, and upper limits on the branching fractions of these decays of 2.2×10−10 and 4.2×10−11 are obtained, respectively, at 90% confidence level. These upper limits improve on previously reported measurements by factors of 3 and 2, respectively.

Background: In recent years, the medical field has made significant progress toward promoting gender equality. Despite this progress, orthopaaedic surgery remains the least diverse specialty among other surgical specialties. In response, our Department of Orthopaedics developed a specialized orthopaedic curriculum, Women in ORTHopaedics (WORTH), tailored specifically for young women in high school. This program offers early exposure and mentorship opportunities within the orthopaedic field. Methods: Participants were asked to complete a preliminary survey prior to the workshop. Subsequently, a corresponding survey was administered following the workshop, mirroring the questions from the pre-event survey. Participants shared their impressions of orthopaedics, interest in pursuing a career in this field, and awareness of available career pathways within this specialty. Results: In both workshops, the consensus among participants in the pre-event surveys included a sense of novelty and a desire to learn more about orthopaedics. However, post-workshop responses revealed a shift in perceptions, with participants expressing that orthopaedics encompasses a much broader array of subjects than initially expected. A comparison between pre- and post-survey responses indicates a heightened interest in pursuing a career in orthopaedics following the workshop. Additionally, 100% of attendees expressed their intention to participate in future WORTH events. Conclusions: Findings indicate that WORTH played a constructive role in guiding young women toward trajectories beyond secondary education. Additionally, it provided insights into the multitude of career options available in Orthopaedics apart from surgery, including physiotherapy, occupational therapy, nursing, research, and biomedical engineering. Key Concepts: (1) Early exposure and mentorship allow for increased representation and retention of women in orthopaedics. (2) Representation of women in orthopaedics improves patient care and contributes to a more holistic approach to healthcare. (3) Outreach initiatives influence participants' interest and perceptions of pursuing a career in orthopaedics. Level of Evidence: Level IV

Seven individuals with unilateral anterior inferior temporal (AIT) lobectomies performed two types of shape recognition tasks with line drawings of 3D objects briefy presented in either the left or the right visual field. In one task, subjects named familiar objects in a name priming paradigm. In the other task, subjects judged whether two objects, presented sequentially with an intervening mask, were the same or different in shape, disregarding differences in orientation of up to 60˚ in depth. They could not use names or basic level concepts to do the matching as the stimuli were either nonsense objects or, if familiar objects, were of same name -different-shaped exemplars on different trials. The disadvantage of presenting an image to the lobectomized hemisphere was negligible in both tasks. Two non-exclusive possibilities are suggested by this result: (a) Object recognition is completed posterior to AIT, likely at the temporal occipital boundary, with no deleterious retrograde effects on object recognition from the AIT section, or (b) Callosal transfer of object information prior to AIT is completely effcient. These results, along with results of single unit recording and lesion experiments in the monkey, PET and MRI imaging in humans, and a plausibility argument based on the pattern of callosal connections suggest both are correct. Rather than mediating real-time object recognition, AIT may code representations for visual episodes and scenes.

This study details the novel self-assembly of sodium titanate converted Ti-based microspheres into hierarchical porous 3D constructs, with macro-, micro-, and nanoporosity, for the first time. Ti6Al4V microspheres were suspended into 5 M NaOH (60 °C/24 h) solutions, with extensive variations in microsphere:solution ratios to modify microsphere interaction and initiate self-assembly through proximity merging of titanate surface dendritic growth. The formed structures, which either produced 1) unbonded, sodium titanate-converted microspheres; 2) flat (non-macroporous) scaffolds; or 3) open, hierarchically porous scaffolds, were then assessed in terms of their formation mechanism, chemical composition, porosity, as well as the effect of post-heat treatments on compressive mechanical properties. It was found that specific microsphere:solution ratios tended to form certain structures (3 flat non-macroporous, >8 powder) due to a combination of microsphere freedom of movement, H2 gas bubble formation, and exposed surface reactivity. This promising discovery highlights the potential for lower temperature, simplistic production of 3D constructs with modifiable chemical properties due to the ion-exchange potential of titanate structures, with clear applications in a wide-range of fields, from medical materials to catalysts.

The cerebellum is involved in higher-order cognitive functions, e.g., learning and memory, and is susceptible to age-related atrophy. Yet, the cerebellum's role in age-related cognitive decline remains largely unknown. We investigated cross-sectional and longitudinal associations between cerebellar volume and verbal learning and memory. Linear mixed effects models and partial correlations were used to examine the relationship between changes in cerebellum volumes (total cerebellum, cerebellum white matter [WM], cerebellum hemisphere gray matter [GM], and cerebellum vermis subregions) and changes in verbal learning and memory performance among 549 Baltimore Longitudinal Study of Aging participants (2,292 visits). All models were adjusted by baseline demographic characteristics (age, sex, race, education), and APOE e4 carrier status. In examining associations between change with change, we tested an additional model that included either hippocampal (HC), cuneus, or postcentral gyrus (PoCG) volumes to assess whether cerebellar volumes were uniquely associated with verbal learning and memory. Cross-sectionally, the association of baseline cerebellum GM and WM with baseline verbal learning and memory was age-dependent, with the oldest individuals showing the strongest association between volume and performance. Baseline volume was not significantly associated with change in learning and memory. However, analysis of associations between change in volumes and changes in verbal learning and memory showed that greater declines in verbal memory were associated with greater volume loss in cerebellum white matter, and preserved GM volume in cerebellum vermis lobules VI-VII. The association between decline in verbal memory and decline in cerebellar WM volume remained after adjustment for HC, cuneus, and PoCG volume. Our findings highlight that associations between cerebellum volume and verbal learning and memory are age-dependent and regionally specific.

To use piston engines and their pressure and temperature histories as a chemical rector to produce valuable chemicals, accurate chemical kinetics models are necessary so the engine parameters and mixtures can be designed. Using piston engines in such a way could lead to the production of target chemicals with net-negative CO2 emissions. This benefit is especially true for ethanol, a very common biofuel. To validate models, the dry reforming of ethanol and CO2 was investigated experimentally in a shock tube (50/50 ethanol/CO2 in 99.75% dilution) by following the formation of CO with a laser absorption setup. The effect of the presence of CO2 in the mixture was also investigated by comparing the results of the 50/50 ethanol/CO2 mixture with those from the pyrolysis of ethanol (without CO2) at various concentrations (99.75 and 98% dilution). The 98% dilution results compare extremely well with results from the literature, whereas the other conditions had never been investigated prior. The experimental data were compared to modern detailed kinetics mechanisms, and the experimental CO profiles were poorly predicted overall. Recent literature developments on ethanol pyrolysis were incorporated into the models, and the predictions were improved in some cases and conditions, although further improvements are still necessary. A numerical analysis (rate of production and sensitivity) was performed for the most accurate modified model to highlight the most important reactions involved in the formation of CO under our conditions.

The disadvantaged populations eGFR (estimated glomerular filtration rate) epidemiology (DEGREE) study was designed to gain insight into the burden of chronic kidney disease (CKD) of undetermined cause (CKDu) using standard protocols to estimate the general-population prevalence of low eGFR internationally. Therefore, we estimated the age-standardized prevalence of eGFR under 60 ml/min per 1.73m 2 in adults aged 18-60, excluding participants with commonly known causes of CKD; an ACR (albumin/creatinine ratio) over 300 mg/g or equivalent, or self-reported or measured (HT) hypertension or (DM) diabetes mellitus, stratified by sex and location. We included population-representative surveys conducted around the world that were either designed to estimate CKDu burden or were re-analyses of large surveys. There were 60,964 participants from 43 areas across 14 countries, with data collected 2007- 2023. The highest prevalence was seen in rural men in Uddanam, India (14%) and Northwest Nicaragua (14%). Prevalence above 5% was generally only observed in rural men, with exceptions for rural women in Ecuador (6%) and parts of Uddanam (6%‒8%), and for urban men in Leon, Nicaragua (7%). Outside of Central America and South Asia, prevalence was below 2%. Our observations represent the first attempts to estimate the prevalence of eGFR under 60 without commonly known causes of CKD around the world, as an estimate of CKDu burden, and provide a starting point for global monitoring. It is not yet clear what drives the differences, but available evidence supports a high general-population burden of CKDu in multiple areas within Central America and South Asia, although the possibility that unidentified clusters of disease may exist elsewhere cannot be excluded., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Long-term effects of early, recurrent human exposure to general anaesthesia remain unknown. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial provided an opportunity to examine this issue in children randomly assigned in infancy to either repeated bronchoalveolar-lavage (BAL)-directed therapy with general anaesthesia or standard care with no planned lavages up to 5 years of age when all children received BAL-directed therapy under general anaesthesia., Methods: This multicentre, randomised, open-label phase 4 trial (CF-GAIN) used the original ACFBAL trial randomisation at 3·6 months (SD 1·6) to BAL-directed therapy or standard-care groups to assess the impact of general anaesthesia exposures over early childhood. Children who completed the ACFBAL trial, with a mean age of 5·1 (SD 0·18) years, received standardised neurobehavioural and health-related-quality-of-life assessment and brain MRI scans between Oct 8, 2013, and June 30, 2017, at a mean age of 12·8 (SD 1·7) years at three hospitals in Australia and one hospital in New Zealand. The primary outcome was a composite score of performance on a standardised, computer-based assessment of child attention, processing speed, and response inhibition skills (Conners Continuous Performance test, second edition). Secondary outcomes included intellectual function, other neurobehavioural measures, and brain imaging as an exploratory outcome. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12613000057785) and is completed., Findings: At 2 years, the BAL-directed therapy group (n=52) and standard-care group (n=45) had a median of 2·0 (IQR 1·0-3·0) and 0·0 (0·0-0·0) exposures, respectively. At completion of the ACFBAL trial, the BAL-directed therapy group had a median of 6·0 (4·0-9·5) exposures and the standard-care group 2·0 (1·0-4·0) exposures. At CF-GAIN completion, the BAL-directed therapy group had a median of 10·0 (IQR 6·5-14·5) exposures and the standard-care group 4·0 (3·0-7·0) exposures. Cumulative general anaesthesia exposure time was not prospectively collected but, for those with complete cumulative exposure time data to the end of the ACFBAL trial, the median cumulative exposure time for the BAL-directed therapy group (n=29) was 180 (IQR 140-285) min and for the standard-care group (n=32) was 48 (30-122) min. The mean Conners Continuous Performance test, second edition composite score was 51 (SD 8·1) in BAL-directed therapy group and 53 (8·8) in the standard-care group; difference -1·7 (95% CI -5·2 to 1·7; p=0·32) with similar performance on other neurobehavioural measures, including measures of executive function, intellectual quotient scores, and brain imaging., Interpretation: Our findings suggest that repeated general anaesthesia exposure in young children with cystic fibrosis is not related to functional impairment in attention, intellectual quotient, executive function, or brain structure compared with a group with fewer and shorter cumulative anaesthesia durations., Funding: National Health and Medical Research Council Australia, Queensland Government Health Service and Clinical Innovation Fellowship, and the Children's Hospital Foundation Queensland., Competing Interests: Declaration of interests CEW has participated as a principal investigator, a consultant, and as a member of advisory boards sponsored by Vertex Pharmaceuticals, with all funding received by her institution. AQ received funding for other studies from the US Cystic Fibrosis Foundation with all funding being received by her institution. AQ also received personal honoraria from the Cystic Fibrosis Foundation for advisory committee contributions, from Vertex Pharmaceuticals for consultancy, and licensing fees from IQVIA for Cystic Fibrosis Questionnaire-Revised (a tool used in this study). CEW, AD, AQ, CB, OS, CR, PC, JBC, and FDA were all named investigators on the National Health and Medical Research Council grant that supported the trial. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Landfill leachate contains dissolved organic matter (DOM) exhibiting high ultraviolet absorbance at 254 nm (UVA 254 ). The UVA 254 limits leachate co-treatment with municipal sewage by hindering the downstream UV disinfection efficiency at wastewater treatment plants. Here, we alleviated the UVA 254 by timing the radiation in a UV/electrooxidation (UV/EO) process to accelerate reactive species formation. At 200 A·m -2 , the UV radiation was delayed by 10 min to accumulate 21 mg·L -1 as Cl 2 , which enhanced the initial radical formation rate by 5.25 times compared with a simultaneous UV/EO. The timed operation increased the steady-state concentrations of ClO • by 700 times to 4.11 × 10 -14 M and reduced the leachate UVA 254 by 78.2% after 60 min. We identified that aromatic formulas with low oxygen content were susceptible to UV/EO from Fourier-transform ion cyclotron resonance mass spectrometry analysis. The toxicity of the treated leachate and generated byproducts was assessed through specific oxygen uptake rates (SOUR) and developmental assays with Platynereis dumerilii. After quenching the residual chlorine, leachate co-treatment at 3.5% v/v presented minimal toxicological risk. Our findings provide operational insights for applying UV/EO in high UVA 254 matrices such as landfill leachate., 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.)

Purpose: We reviewed all prisoners diagnosed with epilepsy within a large UK category B prison: collecting demographic information and the prevalence and nature of their seizure disorder; and reviewed standards of their epilepsy healthcare provision. Previous work has highlighted poorer seizure control and limited access to specialist services in this patient group., Methods: Fifty-five male prisoners with a previously established diagnosis of epilepsy were identified by the prison healthcare manager during the six-month audit period. Anonymised audit data was collected during clinical interviews undertaken by members of a regional specialist epilepsy service and recorded on a standardised proforma. Data collection occurred during six prison visits within the audit period., Results: Point prevalence of epilepsy was 2%. Data suggest that demographics are complex and challenging in this patient group. We found increased rates of alcohol (40%) and drug (82%) misuse and mental health problems (85.5%). Just over one third of cases were prescribed medications with potential for misuse (diversion). Further optimization of anti-seizure medication (ASM) regimens was required in 67.3% of the study sample, with only 12.7% of cases being free of seizures for the last 12 months. Access to specialist epilepsy services was limited; only 38.2% had a specialist review in the last 12 months. Most cases (76.4%) did not recall receiving guidance on precautions that should be taken regarding duties or cell arrangements in relation to having a diagnosis of epilepsy., Conclusions: Tighter collaboration between prison healthcare and local NHS specialist services is recommended to optimise epilepsy healthcare in UK prison settings., (Copyright © 2022. Published by Elsevier Ltd.)

Current and historic pesticide use has potential to compromise e.g. drinking water sources due to both primary and secondary emission sources. Understanding the spatial and temporal dynamics of emissions might help inform management decisions. To explore this potential; water, sediment and soil samples were concurrently collected from the River Ugie, Scotland over four seasons. Occurrence and fate of nine pesticides including four historic-use pesticides (HUPs): simazine, atrazine, isoproturon and permethrin, and five current-use pesticides (CUPs): metaldehyde, chlorpyrifos, chlortoluron, epoxiconazole and cypermethrin were analysed. Concentrations of target pesticides in water, sediments and soils were 4.5-45.6 ng·L -1 , 0.9-4.6 ng·g -1 dw (dry weight) and 1.7-8.0 ng·g -1 dw, respectively. Concentrations of pesticides in water were found to significantly differ between seasons (p < 0.05). Significant differences in pesticide concentrations also occurred spatially within sediments (p < 0.01), indicating spatial and temporal associations with pesticide use. Sediment-water exchange showed that the sediment acts as an important secondary emission source particularly for the HUPs, while current local application and sediment emission are both major driving forces for CUPs in the riverine environment. These findings were supported by concentration ratios between different media, which showed potential as a preliminary assessment tool for identifying the source of pollutants in aquatic environments., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Field coupled samples in soil and grass were collected to determine the concentrations and identify the uptake pathways of PCBs into the grass at a pasture from Scotland, UK. Concentrations of indicator PCBs (∑ 7 PCBs) in soils ranged from 0.20 to 0.88 ng g -1 dw (dry weight), with a mean of 0.33 ng g -1 dw, and in grass ranged from 0.20 to 2.14 ng g -1 dw, with a mean of 0.48 ng g -1 dw. The comprehensive factors of low concentrations and detection rate (PCB28: 18.8%; PCB52: 37.5%) of PCBs in soil, as well as continuously declined air concentrations of PCBs in the UK since the 1990s suggested that the secondary emission from the soil is becoming the supplied source of PCBs to air and grass. The significant correlations between bioconcentration factor (BCF) values and the log K OW (R = -0.850, p < 0.05) and log K OA (R = -0.860, p < 0.05) of indicator PCB congeners were found in the present study, indicating that these two parameters are likely to affect the bioaccumulation and uptake of grass. A generic one-compartment model was employed to identify uptake pathways of grass and evaluate the uptake amounts for PCBs. This suggested that the most important pathway for uptake of PCBs by grass was at the aerial part, and the difference of PCBs concentrations between leaves and roots was about four orders of magnitude. Removing and risk transfer of PCBs or other organic pollutants by grass need to be investigated and assessed further., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Clinical and prognostic value of preschool Multiple Breath Washout (MBW) remains unclear., Methods: Initial MBW results (Exhalyzer® D, EcoMedics AG) in preschool Cystic Fibrosis (CF) subjects (age 2-6 years) at a time of clinical stability were compared to (1) concurrent clinical status measures and (2) later spirometry outcomes. Abnormal Lung Clearance Index (LCI) was defined using published reference data (ULN for LCI 8.0)., Results: LCI was abnormal in 56% (28/50), with mean (SD) LCI 8.61(1.85) at age 4.71(1.3) years. Abnormal LCI was associated with higher dornase alfa use, previous positive bacterial cultures and pF508.del homozygous genotype. Later spirometry (n = 44; mean (SD) 2.3(0.5) years after MBW) demonstrated that abnormal initial preschool LCI was a strong predictor of lower later spirometry outcomes., Conclusion: Abnormal preschool LCI was associated with concurrent measures of clinical status and later spirometry deficits, suggesting early prognostic utility of MBW testing in this age range., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Management of carious teeth with signs and symptoms indicative of irreversible pulpitis is traditionally invasive, but emerging evidence suggests successful treatment outcomes with less invasive vital pulp treatment such as coronal pulpotomy. The objective of this systematic review is to determine whether coronal pulpotomy is clinically effective in treating carious teeth with signs and symptoms indicative of irreversible pulpitis., Sources: MEDLINE; PubMed; Embase, Web of Science, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform and ClinicalTrials.gov were searched until December 2018., Study Selection: Prospective, retrospective and randomised clinical trials investigating coronal pulpotomy or comparing pulpotomy to root canal treatment in permanent mature carious teeth with signs and symptoms indicative of irreversible pulpitis were included. Studies were independently assessed for risk of bias using Cochrane Systematic Reviews of intervention criteria and modified Downs and Black quality assessment checklist., Data: Eight articles were selected for analysis. The average success rate for coronal pulpotomy was 97.4% clinical and 95.4% radiographic at 12 month follow-up. This was reduced to 93.97% clinical and 88.39% radiographic success at 36 months follow-up. Results from the only comparative clinical trial showed pulpotomy to have comparable success to root canal treatment at 12, 24 and 60 month follow-up., Conclusions: The evidence suggests high success for pulpotomy for teeth with signs and symptoms of irreversible pulpitis, however, results are based on heterogeneous studies with high risk of bias. Well-designed, adequately powered randomised controlled trials are required for evidence to change clinical practice., Clinical Significance: Management of carious teeth with irreversible pulpitis is traditionally invasive, but emerging evidence suggests potentially successful treatment outcomes with less invasive therapies such as coronal pulpotomy., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Background: Procoagulant activity attributed to tissue factor (TF, CD142) bound to lipid microvesicles has previously been shown to be elevated in urine of patients with various solid cancers. The phosphorylation of the C-terminal signal transduction peptide (STP) at Ser253 and Ser258 has been determined to be important for the formation of TF-microvesicles. The purpose of this work was to investigate the marker potential of the TF-STP domain in urine of patients with cancer using immunologic methods to quantitate unphosphorylated TF and TF phosphorylated at Ser253 and Ser258., Materials and Methods: We developed monoclonal and polyclonal antibodies directed against the 3 C-terminal STP species of TF and constructed 3 enzyme-linked immunosorbent assays (ELISAs) that specifically recognize unphosphorylated TF and TF phosphorylated at either Ser253 or Ser258. As proof of principle, a preliminary pilot study with stored Biobank-sourced urinary specimens from 45 healthy individuals and 38 patients with bladder cancer were studied using these ELISAs., Results: We report that all 3 species of TF were found in the urine. Two species, TF-pSer258 and unphosphorylated TF, were significantly elevated in the cohort with bladder cancer. The sensitivity of TF-pSer258 by the receiver operator characteristic technique was 86.8%, with a specificity of 97.8% at a cutoff value of 0.55 ng/mL. Using a simplified sample preparation method for the ELISAs on the same clinical specimens, the sensitivity of TF-pSer258 was 86.8%, with a specificity of 93.3% at a cutoff value of 0.53 ng/mL. The unphosphorylated TF species was significantly elevated in later stage bladder cancer with best results seen for the unfractionated preparation technique (95% confidence interval, 10.55-15.74; N = 20) but not early stage non-muscle-invasive bladder cancer (95% confidence interval, 4.71-10.73; N = 18; P < .02)., Conclusions: The development of these new ELISAs allows the quantitation of the urinary biomarkers TF-pSer258 and unphosphorylated TF, which may lead to a new diagnostic approach to the early detection of bladder cancer and warrant further investigation in a prospective trial., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Different interfaces (mouthpiece/nose clip vs. facemask) are used during multiple breath washout (MBW) tests in young children., Methods: We investigated the effect of interface choice and breathing modalities on MBW outcomes in healthy adults and preschool children., Results: In adults (n = 26) facemask breathing significantly increased LCI, compared to mouthpiece use (mean difference (95% CI) 0.4 (0.2; 0.6)), with results generalizable across sites and different equipment. Exclusively nasal breathing within the facemask increased LCI, as compared to oral breathing. In preschoolers (2-6 years, n = 46), no significant inter-test difference was observed across interfaces for LCI or FRC. Feasibility and breathing stability were significantly greater with facemask (incorporating dead space volume minimization), vs. mouthpiece. This was more pronounced in subjects <4 years of age., Conclusion: Both nasal vs. oral breathing and mouthpiece vs. facemask affect LCI measurements in adults. This effect was minimal in preschool children, where switching between interfaces is most likely to occur., (Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: In Cystic Fibrosis (CF), early detection and treatment of respiratory disease is considered the standard for respiratory care. Overnight polysomnography (PSG) may help identify respiratory deterioration in young patients with CF., Methods: A prospective cohort study of 46 patients with CF, aged 8-12years, from a specialist clinic in a tertiary paediatric hospital. Daytime pulmonary function, shuttle test exercise testing and overnight PSG were studied., Results: Of 81 children aged 8-12years, 46 (57%) agreed to participate. FEV 1 (% predicted, mean 74.6%) was normal in 23 (50%), mildly abnormal in 12 (26.1%), moderately abnormal in 10 (21.7%) and severely abnormal in 1 (2.2%). Amongst sleep study parameters, FEV 1 (% predicted) showed significant correlation with the respiratory rate (RR) in slow wave sleep (SWS), CO 2 change in REM, baseline SaO 2 , and the arousal index (h -1 ). Backward, stepwise linear regression modelling for FEV 1 (% predicted) included the entire group with a wide spectrum of clinical severity. From sleep, variables remaining in the multivariate model for FEV 1 (F=16.81, p<0.001) were the RR in SWS (min -1 ) and the CO 2 change in REM (p=0.003, and 0.014, respectively). When daytime tests were included, the variables remaining were RR in SWS and SD score for BMI (BMIsds) (F=18.70, p<0.001)., Conclusions: Respiratory abnormalities on overnight sleep studies included elevated respiratory rates during SWS and mild CO 2 retention in REM sleep, and these incorporated into a model correlating with FEV 1 (% predicted). Thus, mild mechanical impairment of ventilation is evident on overnight sleep studies in children with cystic fibrosis although the significance of this finding will require further investigation., (Copyright © 2016 European Cystic Fibrosis Society. All rights reserved.)

Background: Guided Parent-delivered Cognitive Behaviour Therapy (GPD-CBT) is a brief, effective treatment for childhood anxiety disorders, however not all children respond favourably., Aims: To examine predictors of response to GPD-CBT., Methods: Parents of 125 children (7-12 years) with an anxiety disorder received GPD-CBT over 2.6 or 5.3h. Recovery was measured post treatment and six months later., Results: Younger children and those with primary Generalised Anxiety Disorder (GAD) improved more post treatment, but older children and those without primary GAD had better outcomes at six month follow up. Fewer children allocated to 2.6h had recovered post treatment compared to those allocated to the 5.2h intervention, but did not differ significantly six months later., Conclusions: The identification of predictors of short and longer-term treatment outcomes can guide treatment decisions following this low-intensity approach., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Inadequate medication adherence is a pervasive, under-recognized cause of poor health outcomes. Many intervention trials designed to improve medication adherence have targeted adults with adherence problems. No previous reviews have synthesized the effectiveness of medication adherence interventions focused on subjects with medication adherence difficulties., Objective: This systematic review and meta-analysis synthesized findings from medication adherence intervention studies conducted among adults with medication adherence difficulties., Methods: Primary research studies were eligible for inclusion if they tested an intervention designed to increase medication adherence among adults with documented adherence difficulties and reported medication adherence behavior outcomes. Comprehensive search strategies of 13 computerized databases, author and ancestry searches, and hand searches of 57 journals were used to locate eligible primary research. Participant demographics, intervention characteristics, and methodological features were reliably coded from reports along with medication adherence outcomes. Effect sizes for outcomes were calculated as standardized mean differences, and random effects models were used to estimate overall mean effects. Exploratory dichotomous and continuous variable moderator analyses were employed to examine potential associations between medication adherence effect size and sample, intervention, and methodological characteristics., Results: Data were extracted from 53 reports of studies involving 8243 individual primary study participants. The overall standardized mean difference effect size for treatment vs. control subjects was 0.301. For treatment pre- vs. post-intervention comparisons, the overall effect size was 0.533. Significantly larger effect sizes were associated with interventions incorporating prompts to take medications than interventions lacking medication prompts (0.497 vs. 0.234). Larger effect sizes were also found for interventions that linked medication taking with existing habits compared to interventions that did not (0.574 vs. 0.222). Effect sizes were largest among studies that measured adherence by pill counts or electronic event monitoring systems. Analysis of study design features identified several potential risks of bias. Statistically significant publication bias was detected, but adherence effect sizes were not significantly associated with other risks of bias., Conclusions: These findings document that interventions targeting individuals with medication adherence problems can have modest but significant effects on medication-taking behavior. The findings support the use of behavioral strategies such as prompts and linking medications to habits to increase medication adherence in adults with adherence challenges. Face-to-face interventions appear to be critical for patients who have experienced past problems with medication adherence., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined demographic and clinical predictors of response to CBT. We hypothesized that the child's gender, type of anxiety disorder, initial severity and comorbidity, and parents' psychopathology would significantly predict outcome., Method: A sample of 1,519 children 5 to 18 years of age with a primary anxiety diagnosis received CBT across 11 sites. Outcome was defined as response (change in diagnostic severity) and remission (absence of the primary diagnosis) at each time point (posttreatment, 3-, 6-, and/or 12-month follow-up) and analyzed using linear and logistic mixed models. Separate analyses were conducted using data from posttreatment and follow-up assessments to explore the relative importance of predictors at these time points., Results: Individuals with social anxiety disorder (SoAD) had significantly poorer outcomes (poorer response and lower rates of remission) than those with generalized anxiety disorder (GAD). Although individuals with specific phobia (SP) also had poorer outcomes than those with GAD at posttreatment, these differences were not maintained at follow-up. Both comorbid mood and externalizing disorders significantly predicted poorer outcomes at posttreatment and follow-up, whereas self-reported parental psychopathology had little effect on posttreatment outcomes but significantly predicted response (although not remission) at follow-up., Conclusion: SoAD, nonanxiety comorbidity, and parental psychopathology were associated with poorer outcomes after CBT. The results highlight the need for enhanced treatments for children at risk for poorer outcomes., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

The disposal of metal-bearing treated wood wastes is becoming an environmental challenge. An efficient recycling process based on sulfuric acid leaching has been developed to remove metals from copper-based treated wood chips (07.3 kgm(-3)) and more than 94.5% of Cu was removed from ACQ-, CA- and MCQ-treated wood. The treatment of effluents by precipitation-coagulation was highly efficient; allowing removals more than 93% for the As, Cr, and Cu contained in the effluent. The economic analysis included operating costs, indirect costs and revenues related to remediated wood sales. The economic analysis concluded that CCA-treated wood wastes remediation can lead to a benefit of 53.7 US$t(-1) or a cost of 35.5 US$t(-1) and that ACQ-, CA- and MCQ-treated wood wastes recycling led to benefits ranging from 9.3 to 21.2 US$t(-1)., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to standardize an "in house" immunoassay to detect anti-Toxocara IgG antibodies in human serum to estimate the seroprevalence of Toxocara infection, and to identify its potential risk factors in children living in poor areas of Salvador, a large northeastern Brazilian city., Methods: Parents of 1309 children answered a questionnaire containing possible risk factor for acquisition of this infection. Blood was collected and the presence of anti-Toxocara IgG antibodies was detected by indirect ELISA using T. canis larval excretory-secretory antigens in sera previously absorbed with Ascaris lumbricoides antigens., Results: Seroprevalence of Toxocara infection was 48.4%. Children's age, low maternal schooling, contact with dogs and cats, and household located in paved streets were shown to be risk factors for Toxocara infection., Conclusions: The seroprevalence of Toxocara infection is high among children living in a poor urban setting of Brazil. The association of low maternal education with higher Toxocara infection supports studies showing that low socioeconomic status is a risk factor for the acquisition of this infection as a reflection of hygiene habits of the family. And both infected-dogs and cats may be involved in this parasite transmission in this children population., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Clostridium scindens American Type Culture Collection 35704 is capable of converting primary bile acids to toxic secondary bile acids, as well as converting glucocorticoids to androgens by side-chain cleavage. The molecular structure of the side-chain cleavage product of cortisol produced by C. scindens was determined to be 11β-hydroxyandrost-4-ene-3,17-dione (11β-OHA) by high-resolution mass spectrometry, (1)H and (13)C NMR spectroscopy, and X-ray crystallography. Using RNA-Seq technology, we identified a cortisol-inducible (≈ 1,000-fold) operon (desABCD) encoding at least one enzyme involved in anaerobic side-chain cleavage. The desC gene was cloned, overexpressed, purified, and found to encode a 20α-hydroxysteroid dehydrogenase (HSDH). This operon also encodes a putative "transketolase" (desAB) hypothesized to have steroid-17,20-desmolase/oxidase activity, and a possible corticosteroid transporter (desD). RNA-Seq data suggests that the two-carbon side chain of glucocorticords may feed into the pentose-phosphate pathway and are used as a carbon source. The 20α-HSDH is hypothesized to function as a metabolic "rheostat" controlling rates of side-chain cleavage. Phylogenetic analysis suggests this operon is rare in nature and the desC gene evolved from a gene encoding threonine dehydrogenase. The physiological effect of 11β-OHAD on the host or other gut microbes is currently unknown.

Hexanucleotide repeat expansions in C9ORF72 are a common cause of familial and apparently sporadic amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The mechanism by which expansions cause neurodegeneration is unknown, but current evidence supports both loss-of-function and gain-of-function mechanisms. We used pooled next-generation sequencing of the C9ORF72 gene in 389 ALS patients to look for traditional loss-of-function mutations. Although rare variants were identified, none were likely to be pathogenic, suggesting that mutations other than the repeat expansion are not a common cause of ALS, and providing supportive evidence for a gain-of-function mechanism. We also show by repeat-primed PCR genotyping that the C9ORF72 expansion frequency varies by geographical region within the United States, with an unexpectedly high frequency in the Mid-West. Finally we also show evidence of somatic instability of the expansion size by Southern blot, with the largest expansions occurring in brain tissue., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: To evaluate safety and efficacy of inhaled mannitol treatment in subgroups of a large global CF population., Methods: Data were pooled from two multicentre, double-blind, randomised, controlled, parallel group phase III studies in which 600 patients inhaled either mannitol (400 mg) or control (mannitol 50 mg) twice a day for 26 weeks., Results: Both the mean absolute change in FEV(1) (mL) and relative change in FEV(1) by % predicted from baseline for mannitol (400 mg) versus control were statistically significant (73.42 mL, 3.56%, both p<0.001). Increases in FEV(1) were observed irrespective of rhDNase use. Significant improvements in FEV1 occurred in adults but not children (6-11) or adolescents (aged 12-17). Pulmonary exacerbation incidence was reduced by 29% (p=0.039) in the mannitol (400 mg) group., Conclusions: Sustained six-month improvements in lung function and decreased pulmonary exacerbation incidence indicate that inhaled mannitol is an important additional drug in the treatment of CF., (Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

D-Fructose was analysed by NMR spectroscopy and previously unidentified (1)H NMR resonances were assigned to the keto and α-pyranose tautomers. The full assignment of shifts for the various fructose tautomers enabled the use of (1)H NMR spectroscopy in studies of the mutarotation (5-25°C) and tautomeric composition at equilibrium (5-50°C). The mutarotation of β-pyranose to furanose tautomers in D(2)O at a concentration of 0.18 M was found to have an activation energy of 62.6 kJmol(-1). At tautomeric equilibrium (20°C in D(2)O) the distribution of the β-pyranose, β-furanose, α-furanose, α-pyranose and the keto tautomers was found to be 68.23%, 22.35%, 6.24%, 2.67% and 0.50%, respectively. This tautomeric composition was not significantly affected by varying concentrations between 0.089 and 0.36 M or acidification to pH 3. Upon equilibrating at 6 temperatures between 5 and 50°C there was a linear relationship between the change in concentration and temperature for all forms., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers., Method: This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702 mothers were screened, and probable cases interviewed. In all, 58 depressed mothers (95% of identified cases) and 42 nondepressed controls were recruited. A total of 93% were assessed through to 16-year follow-up. The main study outcome was offspring lifetime clinical depression (major depression episode and dysthymia) by 16 years, assessed via interview at 8, 13, and 16 years. It was analysed in relation to postnatal depression, repeated measures of child vulnerability (insecure infant attachment and lower childhood resilience), and family adversity., Results: Children of index mothers were more likely than controls to experience depression by 16 years (41.5% versus 12.5%; odds ratio = 4.99; 95% confidence interval = 1.68-14.70). Lower childhood resilience predicted adolescent depression, and insecure infant attachment influenced adolescent depression via lower resilience (model R(2) = 31%). Family adversity added further to offspring risk (expanded model R(2) = 43%)., Conclusions: Offspring of postnatally depressed mothers are at increased risk for depression by 16 years of age. This may be partially explained by within child vulnerability established in infancy and the early years, and by exposure to family adversity. Routine screening for postnatal depression, and parenting support for postnatally depressed mothers, might reduce offspring developmental risks for clinical depression in childhood and adolescence., (Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Chromated copper arsenate (CCA)-treated wood was widely used until 2004 for residential and industrial applications. Since 2004, CCA was replaced by alternative copper preservatives such as alkaline copper quaternary (ACQ), copper azole (CA) and micronized copper quaternary (MCQ), for residential applications due to health concerns. Treated wood waste disposal is becoming an issue. Previous studies identified a chemical process for decontaminating CCA-treated wood waste based on sulfuric acid leaching. The potential application of this process to wood treated with the copper-based preservatives (alkaline copper quaternary (ACQ), copper azole (CA) and micronized copper quaternary (MCQ)) is investigated here. Three consecutive leaching steps with 0.1 M sulfuric acid at 75°C for 2 h were successful for all the types of treated wood and achieved more than 98% copper solubilisation. The different acidic leachates produced were successively treated by coagulation using ferric chloride and precipitation (pH=7) using sodium hydroxide. Between 94 and 99% of copper in leachates could be recovered by electrodeposition after 90 min using 2 A electrical current. Thus, the process previously developed for CCA-treated wood waste decontamination could be efficiently applied for CA-, ACQ- or MCQ-treated wood., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: The airways in patients with cystic fibrosis (CF) are characterized by the accumulation of tenacious, dehydrated mucus that is a precursor for chronic infection, inflammation, and tissue destruction. The clearance of mucus is an integral component of daily therapy. Inhaled mannitol is an osmotic agent that increases the water content of the airway surface liquid, and improves the clearance of mucus with the potential to improve lung function and respiratory health. To this end, this study examined the efficacy and safety of therapy with inhaled mannitol over a 2-week period., Methods: This was a randomized, double-blind, placebo-controlled, crossover study. Thirty-nine subjects with mild-to-moderate CF lung disease inhaled 420 mg of mannitol or placebo twice daily for 2 weeks. Following a 2-week washout period, subjects were entered in the reciprocal treatment arm. Lung function, respiratory symptoms, quality of life, and safety were assessed., Results: Mannitol treatment increased FEV(1) from baseline by a mean of 7.0% (95% confidence interval [CI], 3.3 to 10.7) compared to placebo 0.3% (95% CI, - 3.4 to 4.0; p < 0.001). The absolute improvement with mannitol therapy was 121 mL (95% CI, 56.3 to 185.7), which was significantly more than that with placebo (0 mL; 95% CI, - 64.7 to 64.7). The forced expiratory flow in the middle half of the FVC increased by 15.5% (95% CI, - 6.5 to 24.6) compared to that with placebo (increase, 0.7%; 95% CI, - 8.3 to 9.7; p < 0.02). The safety profile of mannitol was adequate, and no serious adverse events related to treatment were observed., Conclusions: Inhaled mannitol treatment over a period of 2 weeks significantly improved lung function in patients with CF. Mannitol therapy was safe and well tolerated., Trial Registration: (ClinicalTrials.gov) Identifier: NCT00455130.

This study was designed to examine perceptions of type, source, and amount of social support reported by pregnant and/or parenting (PP) and nonpregnant, nonparenting (NPNP) adolescents. Greater support generally was reported by NPNP than by PP adolescents. The groups did not differ with respect to their perceptions of types of support reported on either the Inventory of Socially Supportive Behaviors (ISSB) or the Arizona Social Support Interview Schedule (ASSIS). PP adolescents reported more support from teachers on the ASSIS than did NPNP adolescents. NPNP adolescents reported more support from best friends and sisters than did the PP group.