ASCEND-Eye: Effects of Aspirin on Diabetic Retinopathy.

PURPOSE: Preclinical studies support a protective role for aspirin in early diabetic retinopathy (DR), but the findings from randomized trials are limited. We present randomized evidence for the efficacy and safety of aspirin on DR outcomes. DESIGN: A substudy of the A Study of Cardiovascular Events in Diabetes (ASCEND) double-masked, randomized, placebo-controlled trial of 100 mg aspirin daily for the primary prevention of serious cardiovascular events in people with diabetes. PARTICIPANTS: Fifteen thousand four hundred eighty United Kingdom adults at least 40 years of age with diabetes. METHODS: Linkage to electronic National Health Service Diabetic Eye Screening Programme records in England and Wales and confirmation of participant-reported eye events via medical record review were carried out. Log-rank methods were used for intention-to-treat analyses of time until the first primary efficacy and safety outcomes. MAIN OUTCOME MEASURES: The primary efficacy end point was the first record of referable disease after randomization, a composite of referable retinopathy or referable maculopathy based on the grading criteria defined by the United Kingdom National Screening Committee. The primary safety outcome was the first sight-threatening eye bleed, defined as clinically significant bleeding in the eye that resulted in unresolved visual loss or required an urgent intervention such as laser photocoagulation, vitreoretinal surgery, intraocular injection, or a combination thereof. RESULTS: Linkage data were obtained for 7360 participants (48% of those randomized in ASCEND). During the mean follow-up of 6.5 years, 539 participants (14.6%) experienced a referable disease event in the aspirin group, compared with 522 participants (14.2%) in the placebo group (rate ratio, 1.03; 95% confidence interval [CI], 0.91-1.16; P = 0.64). No statistically significant between-group difference was found in the proportions of sight-threatening eye bleed events (57 participants [0.7%] and 64 participants [0.8%], respectively; rate ratio, 0.89; 95% CI, 0.62-1.27). DISCUSSION: These data exclude any clinically meaningful benefits of aspirin for DR, but give reassurance regarding the ophthalmologic safety of aspirin. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

ASCEND-Eye: Effects of Omega-3 Fatty Acids on Diabetic Retinopathy.

PURPOSE: Preclinical studies support a protective role for omega-3 fatty acids (FAs) on diabetic retinopathy (DR), but these observations have not been confirmed in randomized trials. We present randomized evidence for the effects of omega-3 FAs on DR outcomes. DESIGN: A substudy of the A Study of Cardiovascular Events iN Diabetes (ASCEND) double-blind, randomized, placebo-controlled trial of 1 g omega-3 fatty acids (containing 460 mg eicosapentaenoic acid and 380 mg docosahexaenoic acid) daily for the primary prevention of serious cardiovascular events, in 15 480 UK adults at least 40 years of age, with diabetes. PARTICIPANTS: Fifteen thousand four hundred eighty adults at least 40 years of age from the United Kingdom with diabetes from the ASCEND cohort. METHODS: Linkage to electronic National Health Service Diabetic Eye Screening Programme records in England and Wales and confirmation of participant-reported eye events via medical record review. Log-rank and stratified log-rank methods were used for intention-to-treat analyses of time until the main outcomes of interest. MAIN OUTCOME MEASURES: The primary efficacy endpoint was time to the first postrandomization recording of referable disease, a composite of referable retinopathy (R2 or R3a/s) or referable maculopathy (M1) based on the grading criteria defined by the United Kingdom National Screening Committee. Secondary and tertiary outcomes included the referable disease outcome stratified by the severity of DR at baseline, any progression in retinopathy grade, and incident diabetic maculopathy. RESULTS: Linkage data were obtained for 7360 participants (48% of those who were randomized in ASCEND). During their mean follow-up of 6.5 years, 548 participants (14.8%) had a referable disease event in the omega-3 FAs group, compared with 513 participants (13.9%) in the placebo group (rate ratio, 1.07; 95% confidence interval, 0.95-1.20; P = 0.29). There were no statistically significant between-group differences in the proportion of events for either of the secondary or tertiary outcomes. CONCLUSIONS: Representing the largest prospective test of its kind to date, these data exclude any clinically meaningful benefits of 1 g daily omega-3 FAs on DR. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Novel Diagnostic and Therapeutic Approaches to Temporomandibular Dysfunction: A Narrative Review.

Temporomandibular dysfunction (TMD) is a burgeoning area of study within the dental field. TMD is caused by abnormalities in the temporomandibular joint or muscles of mastication and can lead to pain, loss of function, and other complications. As this area of patient care receives increased focus, the ability to accurately diagnose TMD becomes paramount. The aim of this review is to summarize novel diagnostic and therapeutic techniques that have been proposed within the last approximately 3 years in order to inform readers of the cutting-edge advances in the field of TMD diagnosis and management, while also analyzing the clinical relevance of each study. A PubMed search was completed on 1 March 2023, using MeSH terms related to TMD diagnosis and treatment. The search yielded seven articles that pertained to the aim of this review article. The main findings from each study are summarized in this review article. These novel methods of diagnosing and treating TMD may improve our ability to assess and treat patients suffering from TMD.

ASCEND-Eye: Rationale, design and baseline characteristics for a sub-study of the ASCEND randomised trial, exploring the effects of aspirin and omega-3 fatty acids on diabetic retinopathy and age-related macular degeneration.

Background: Aspirin and omega-3 fatty acids (FAs) have potential disease-modifying roles in diabetic retinopathy (DR) and age-related macular degeneration (AMD), but randomized evidence of these effects is limited. We present the rationale and baseline characteristics of ASCEND-Eye, a sub-study of the double-blind, 2x2 factorial design, randomized placebo-controlled ASCEND (A Study of Cardiovascular Events iN Diabetes) trial of 100 mg aspirin daily and, separately, 1g omega-3 FAs daily for the primary prevention of serious cardiovascular events, in 15,480 British adults, aged 40 years or older with diabetes. Methods: Eye events will be derived from three sources: 1) participant follow-up questionnaires from ASCEND, 2) electronic NHS Diabetic Eye Screening Programme (DESP) data and 3) responses to the National Eye Institute's Visual Function Questionnaire-25 (NEI-VFQ-25) sent to a subset of participants after the main trial ended. Analytic cohorts and outcomes relevant to these data sources are described. The primary outcome is referable diabetic eye disease, a secondary outcome is incident AMD events. Results: Participant-reported events were ascertained for the full cohort of randomized individuals who were followed up over 7.4 years in ASCEND (n = 15,480). Linked DESP data were available for 48% of those (n = 7360), and 57% completed the NEI-VFQ-25 (n = 8839). The baseline characteristics of these three cohorts are presented. Discussion: Establishing the risks and benefits of drugs commonly taken by people with diabetes, the elderly, or both, and finding new treatments for DR and AMD is important. ASCEND-Eye provides the opportunity to evaluate the effect of aspirin and, separately, omega-3 FAs for both conditions. Study registration: Eudract No. 2004-000991-15; Multicentre Research Ethics Committee Ref No. 03/8/087; ClinicalTrials.gov No. NCT00135226; ISRCTN No. ISRCTN60635500.

Is Likert better than PI-RADS at predicting prostate cancer on MRI and can a mathematical algorithm achieve similar results?

BACKGROUND: Prostate Imaging Reporting & Data System (PI-RADS) is an internationally recognized system to quantify risk of prostate cancer on magnetic resonance imaging (MRI). However, studies have suggested methods to improve predictive accuracy. PURPOSE: To assess two different methods that aim to improve the accuracy of PI-RADS scores: a subjective Likert score given by experienced reporters, and an objective Calculated Adjustment of PI-RADS Equivocal Score (CAPES). MATERIAL AND METHODS: Five experienced reporters in a quaternary referral unit used a standardized reporting template to prospectively collect PI-RADS and Likert scores for 1467 multiparametric MRI (mpMRI) scans between January 2021 and June 2022. Histology results were recorded for patients who underwent trans-perineal biopsy. The CAPES tool was retrospectively applied to the cases scoring PI-RADS 3. A theoretical standardized biopsy protocol (assuming all patients scoring ≥3 were referred for biopsy) was used to compare the three scoring systems for sensitivity, specificity, and positive predictive value (PPV). RESULTS: Across all reporters, significantly fewer equivocal "3" scores were given using Likert (15.7%) or CAPES (2.2%) compared to PI-RADS (24.1%). Assuming a protocol where all patients scoring ≥3 were biopsied, Likert had a higher specificity (69.0% vs. 54.4%), sensitivity (98.3% vs. 97.7%), and PPV (49.9% vs. 40.3%) than PI-RADS for identifying ISUP ≥2 cancer. The CAPES tool had an even higher specificity (81.4%) and PPV (61.2%) with only a slightly lower sensitivity (93.4%) resulting in 37.1% (n = 316) fewer biopsies than PI-RADS, and 22.4% (n = 155) fewer biopsies than Likert across 1467 patients. CONCLUSIONS: Compared to PI-RADS scoring, Likert scoring or CAPES can result in fewer equivocal scores, greater PPV, and fewer unnecessary biopsies.

Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data.

OBJECTIVE: To assess how reliable UK routine data are for ascertaining major bleeding events compared with adjudicated follow-up. METHODS: The ASCEND (A Study of Cardiovascular Events iN Diabetes) primary prevention trial randomised 15 480 UK people with diabetes to aspirin versus matching placebo. The primary safety outcome was major bleeding (including intracranial haemorrhage, sight-threatening eye bleeding, serious gastrointestinal bleeding and other major bleeding (epistaxis, haemoptysis, haematuria, vaginal and other bleeding)) ascertained by direct-participant mail-based follow-up, with >90% of outcomes undergoing adjudication. Nearly all participants were linked to routinely collected hospitalisation and death data (ie, routine data). An algorithm categorised bleeding events from routine data as major/minor. Kappa statistics were used to assess agreement between data sources, and randomised comparisons were re-run using routine data. RESULTS: When adjudicated follow-up and routine data were compared, there was agreement for 318 major bleeding events, with routine data identifying 281 additional-potential events, and not identifying 241 participant-reported events (kappa 0.53, 95% CI 0.49 to 0.57). Repeating ASCEND's randomised comparisons using routine data only found estimated relative and absolute effects of allocation to aspirin versus placebo on major bleeding similar to adjudicated follow-up (adjudicated follow-up: aspirin 314 (4.1%) vs placebo 245 (3.2%); rate ratio (RR) 1.29, 95% CI 1.09 to 1.52; absolute excess +6.3/5000 person-years (mean SE±2.1); vs routine data: 327 (4.2%) vs 272 (3.5%); RR 1.21, 95% CI 1.03 to 1.41; absolute excess +5.0/5000 (±2.2)). CONCLUSIONS: Analyses of the ASCEND randomised trial found that major bleeding events ascertained via UK routine data sources provided relative and absolute treatment effects similar to adjudicated follow-up. TRIAL REGISTRATION NUMBER: ISRCTN60635500; NCT00135226.

Does including histological outcomes in a multiparametric MRI report improve prostate biopsy decision making?

OBJECTIVES: To see if inserting audited histological outcome data for each Likert score into prostate mpMRI reports was helpful for clinicians counselling patients and influenced prostate biopsy uptake. METHODS: A single radiologist reported 791 mpMRI scans for query prostate cancer between 2017 and 2019. A structured template which included histological outcome data from this cohort was devised and included in 207 mpMRI reports between January and June 2021. The outcomes of the new cohort were compared with the historical cohort, and with 160 contemporaneous reports without histological outcome data from the four other radiologists in the department. The opinion of this template was sought from referring clinicians who counselled patients. RESULTS: The proportion of patients biopsied fell from 58.0 to 32.9% overall between the n = 791 cohort and the n = 207 cohort. This was most noticeable in those scoring Likert 3, where the proportion biopsied fell from 78.4 to 42.9%. This reduction was also seen when comparing the biopsy rates of patients scored Likert 3 by other reporters in a contemporaneous n = 160 cohort without the audit information (65.2%) with the n = 207 cohort (42.9%). 100% of counselling clinicians were in favour and 66.7% said it gave them greater confidence to advise the patient when they did not need a biopsy. CONCLUSION: Fewer low-risk patients choose unnecessary biopsies when audited histological outcomes for the radiologist's Likert scores are included in mpMRI reports. ADVANCES IN KNOWLEDGE: Clinicians welcome reporter-specific audit information in mpMRI reports which could result in fewer biopsies.

Making an art into a science: a mathematical "Likert tool" can change PI-RADS (v2) scores into Likert scores when reporting multiparametric MRI for prostate cancer.

BACKGROUND: When reporting multiparametric magnetic resonance imaging (mpMRI) for prostate cancer, UK national guidelines recommend allocating both Likert and PI-RAD scores. Likert scores have been shown to better predict clinically significant cancer (csPCa) but are subjective and lack standardization. PURPOSE: To compare differences in outcomes between the scoring systems and create a mathematical tool that can help to objectively allocate Likert scores. MATERIAL AND METHODS: A total of 791 patients referred with query prostate cancer between 2017 and 2019 were prospectively allocated PI-RADS and Likert scores by a single experienced reporter. Histology results were used to compare the predictive accuracy of both scoring systems. A "Likert tool" was created based on a logistic regression of features found to be predictors of csPCa in a cohort of 2018-2019 patients (n = 411). Its performance was evaluated. RESULTS: Assuming a policy whereby patients with a PI-RADS/Likert score of ≥3 are biopsied, Likert scoring (sensitivity 0.92, specificity 0.77) would have resulted in 107 fewer biopsies and 20.3% higher cancer yields than the PI-RADS score (sensitivity 0.99, specificity 0.43). Thirteen patients would have avoided over-diagnosis of clinically insignificant prostate cancer (iPCa). Similar outcomes (111 fewer biopsies, 22.3% increase in cancer yield, iPCa diagnosis avoided in 16 patients) could be seen when the "Likert tool" was applied to the same patient cohort (sensitivity 0.93, specificity 0.79) and to a separate cohort (n = 380). CONCLUSION: PI-RADS and Likert scores are different. A "Likert tool" could reduce inter-reporter variability, decrease the number of patients unnecessarily biopsied, increase csPCa yield, and decrease over-diagnosis of iPCa.

Effects of aspirin on dementia and cognitive function in diabetic patients: the ASCEND trial.

AIMS: Aspirin is widely used in cardiovascular disease prevention but is also associated with an increased risk of bleeding. The net effect of aspirin on dementia and cognitive impairment is uncertain. METHODS AND RESULTS: In the ASCEND trial, 15 480 people from the UK with diabetes and no history of cardiovascular disease were randomized to aspirin 100 mg daily or matching placebo for a mean of 7.4 years. The 15 427 ASCEND participants with no recorded dementia prior to baseline were included in this cognitive study with a primary pre-specified outcome of 'broad dementia', comprising dementia, cognitive impairment, or confusion. This was ascertained through participant, carer, or general practitioner report or hospital admission diagnosis, by 31 March 2019 (∼2 years beyond the scheduled treatment period). The broad dementia outcome occurred in a similar percentage of participants in the aspirin group and placebo group: 548 participants (7.1%) vs. 598 (7.8%), rate ratio 0.91 [95% confidence interval (CI), 0.81-1.02]. Thus, the CI excluded proportional hazards of >2% and proportional benefits of >19%. CONCLUSION: Aspirin does not have a large proportional effect on the risk of dementia. Trials or meta-analyses with larger total numbers of incident dementia cases to increase statistical power are needed to assess whether any modest proportional 10-15% benefits of 5-7 years of aspirin use on dementia exist. CLINICAL TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN60635500; ClinicalTrials.gov number: NCT00135226.

Comparison of the Accuracy and Completeness of Records of Serious Vascular Events in Routinely Collected Data vs Clinical Trial-Adjudicated Direct Follow-up Data in the UK: Secondary Analysis of the ASCEND Randomized Clinical Trial.

Importance: Routinely collected data could substantially decrease the cost of conducting trials. Objective: To assess the accuracy and completeness of UK routine data for ascertaining serious vascular events (SVEs) compared with adjudicated follow-up data. Design, Setting, and Participants: This was a secondary analysis of a randomized clinical trial. From June 24, 2005, to July 28, 2011, the ASCEND (A Study of Cardiovascular Events in Diabetes) primary prevention trial used mail-based methods to randomize people with diabetes without evidence of atherosclerotic vascular disease using a 2 × 2 factorial design to aspirin and/or ω-fatty acids vs matching placebo in the UK. Direct participant mail-based follow-up was the main source of outcome data, with more than 90% of the primary outcome events undergoing adjudication. Follow-up was completed on July 31, 2017. In parallel, more than 99% of participants were linked to routinely collected hospital admission and death registry data (ie, routine data), enabling post hoc randomized comparisons of different sources of outcome data (conducted from September 1, 2018, to October 1, 2021). Interventions: Random allocation to 100 mg of aspirin once daily vs matching placebo and separately to 1 g of ω-3 fatty acids once daily vs placebo. Main Outcomes and Measures: The primary outcome consisted of SVEs (a composite of nonfatal myocardial infarction, ischemic stroke, transient ischemic attack [TIA], or vascular death, excluding hemorrhagic stroke). Results: A total of 15 480 participants were randomized (mean [SD] age, 63 [9] years; 9684 [62.6%] men) and followed up for a mean (SD) of 7.4 (1.8) years. For SVEs, agreement between adjudicated direct follow-up and routine data sources was strong (1401 vs 1127 events; κ = 0.78 [95% CI, 0.76-0.80]; sensitivity, 72.0% [95% CI, 69.7%-74.4%]; specificity, 99.2% [95% CI, 99.0%-99.3%]), and sensitivity improved for SVEs excluding transient ischemic attack (1129 vs 1026 events; sensitivity, 80.6% [95% CI, 78.3%-82.9%]). Rate ratios for the aspirin-randomized comparison for adjudicated direct follow-up vs follow-up solely through routine data alone were 0.88 (95% CI, 0.79-0.97) vs 0.91 (95% CI, 0.81-1.02) for the primary outcome and 0.92 (95% CI, 0.82-1.03) vs 0.91 (95% CI, 0.80-1.02) for SVEs excluding TIA. Results were similar for the ω-3 fatty acid comparison, and adjudication did not seem to markedly change rate ratios. Conclusions and Relevance: Post hoc analyses of the ASCEND trial suggest that routinely collected hospital admission and death registry data in the UK could be used as the sole method of follow-up for myocardial infarction, ischemic stroke resulting in hospitalization, vascular death, and arterial revascularization in primary prevention cardiovascular trials, without the need for verification by clinical adjudication.

Breast tumour volume and blood flow measured by MRI after one cycle of epirubicin and cyclophosphamide-based neoadjuvant chemotherapy as predictors of pathological response.

OBJECTIVES: Better markers of early response to neoadjuvant chemotherapy (NACT) in patients with breast cancer are required to enable the timely identification of non-responders and reduce unnecessary treatment side-effects. Early functional imaging may better predict response to treatment than conventional measures of tumour size. The purpose of this study was to test the hypothesis that the change in tumour blood flow after one cycle of NACT would predict pathological response. METHODS: In this prospective cohort study, dynamic contrast-enhanced MRI was performed in 35 females with breast cancer before and after one cycle of epirubicin and cyclophosphamide-based NACT (EC90). Estimates of tumour blood flow and tumour volume were compared with pathological response obtained at surgery following completion of NACT. RESULTS: Tumour blood flow at baseline (mean ± SD; 0.32 ± 0.17 ml/min/ml) reduced slightly after one cycle of NACT (0.28 ± 0.18 ml/min/ml). Following treatment 15 patients were identified as pathological responders and 20 as non-responders. There were no relationships found between tumour blood flow and pathological response. Conversely, tumour volume was found to be a good predictor of pathological response (smaller tumours did better) at both baseline (area under the receiver operating characteristic curve 0.80) and after one cycle of NACT (area under the receiver operating characteristic curve 0.81). CONCLUSION & ADVANCES IN KNOWLEDGE: The change in breast tumour blood flow following one cycle of EC90 did not predict pathological response. Tumour volume may be a better early marker of response with such agents.

Online measurement of 1,2,4-trichlorobenzene as dioxin indicator on multi-walled carbon nanotubes.

Polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) emission is one of main concerns for the secondary pollution of municipal solid waste incinerators (MSWI). For timely response to emission, 1,2,4-trichlorobenzene (1,2,4-TrClBz) as dioxin indicator can be monitored via online measurement techniques. In this study, multi-walled carbon nanotubes (MWCNTs) were investigated for their suitability as a 1,2,4-TrClBz sorbent for MSWI stack gas analysis. The tests include, batch adsorption, continuous adsorption-desorption of 1,2,4-TrClBz via thermal desorption coupled with gas chromatography (TD-GC-ECD), temperature and concentration stability of MWCNTs, and adsorption performance of the system. Thermogravimetric/derivative thermogravimetric (TGA/DTG) analysis reveals that MWCNTs has higher capacity in terms of weight loss (14.34%) to adsorb 1,2,4-TrClBz compared to Tenax TA (9.46%) and also shows fast desorption of adsorbate at temperature of 87 °C compared to Tenax TA (130 °C). Interestingly, carbon nanotubes and Tenax TA gave almost similar adsorption-desorption response, and from TD-GC-ECD analysis it was found that with increasing mass flow of 1,2,4-TrClBz (7.42 × 10-6 - 44.52 × 10-6 mg ml-1) through sorbent traps, average peak areas increased from 2.86 ± 0.02 to 13.54 ± 0.26 for MWCNTs and 2.89 ± 0.02 to 13.38 ± 0.12 for Tenax TA, respectively. The stability of MWCNTs for temperature was 400 °C and for concentration of 1,2,4-TrClBz was 50 ppbv. However, regeneration of sorbent at 100 ppbv (1,2,4-TrClBz) was not possible. TD-GC-ECD system showed high adsorption performance with 3.86% and 3.59% relative standard deviation at 250 °C and 300 °C, respectively. Further Fourier Transform Infrared Spectroscopy (FTIR) analysis confirmed that adsorbate can be fully desorbed at 300 °C.

The True Colours Remote Symptom Monitoring System: A Decade of Evolution.

The True Colours remote mood monitoring system was developed over a decade ago by researchers, psychiatrists, and software engineers at the University of Oxford to allow patients to report on a range of symptoms via text messages, Web interfaces, or mobile phone apps. The system has evolved to encompass a wide range of measures, including psychiatric symptoms, quality of life, and medication. Patients are prompted to provide data according to an agreed personal schedule: weekly, daily, or at specific times during the day. The system has been applied across a number of different populations, for the reporting of mood, anxiety, substance use, eating and personality disorders, psychosis, self-harm, and inflammatory bowel disease, and it has shown good compliance. Over the past decade, there have been over 36,000 registered True Colours patients and participants in the United Kingdom, with more than 20 deployments of the system supporting clinical service and research delivery. The system has been adopted for routine clinical care in mental health services, supporting more than 3000 adult patients in secondary care, and 27,263 adolescent patients are currently registered within Oxfordshire and Buckinghamshire. The system has also proven to be an invaluable scientific resource as a platform for research into mood instability and as an electronic outcome measure in randomized controlled trials. This paper aimed to report on the existing applications of the system, setting out lessons learned, and to discuss the implications for tailored symptom monitoring, as well as the barriers to implementation at a larger scale.

Biochemical and Anatomical Investigation of Sesbania herbacea (Mill.) McVaugh Nodules Grown under Flooded and Non-Flooded Conditions.

Sesbania herbacea, a native North American fast-growing legume, thrives in wet and waterlogged conditions. This legume enters into symbiotic association with rhizobia, resulting in the formation of nitrogen-fixing nodules on the roots. A flooding-induced anaerobic environment imposes a challenge for the survival of rhizobia and negatively impacts nodulation. Very little information is available on how S. herbacea is able to thrive and efficiently fix N2 in flooded conditions. In this study, we found that Sesbania plants grown under flooded conditions were significantly taller, produced more biomass, and formed more nodules when compared to plants grown on dry land. Transmission electron microscopy of Sesbania nodules revealed bacteroids from flooded nodules contained prominent polyhydroxybutyrate crystals, which were absent in non-flooded nodules. Gas and ion chromatography mass spectrometry analysis of nodule metabolites revealed a marked decrease in asparagine and an increase in the levels of gamma aminobutyric acid in flooded nodules. 2-D gel electrophoresis of nodule bacteroid proteins revealed flooding-induced changes in their protein profiles. Several of the bacteroid proteins that were prominent in flooded nodules were identified by mass spectrometry to be members of the ABC transporter family. The activities of several key enzymes involved in nitrogen metabolism was altered in Sesbania flooded nodules. Aspartate aminotransferase (AspAT), an enzyme with a vital role in the assimilation of reduced nitrogen, was dramatically elevated in flooded nodules. The results of our study highlight the potential of S. herbacea as a green manure and sheds light on the morphological, structural, and biochemical adaptations that enable S. herbacea to thrive and efficiently fix N2 in flooded conditions.

Atline measurement of 1,2,4-trichlorobenzene for polychlorinated dibenzo-p-dioxin and dibenzofuran International Toxic Equivalent Quantity prediction in the stack gas.

A home-made analytical instrument based on thermal desorption gas chromatography coupled to resonance enhanced multiphoton ionization time-of-flight mass spectrometry (TD-GC-REMPI-TOFMS) was applied for atline measurement of 1,2,4-trichlorobenzene for the prediction of polychlorinated dibenzodioxin and dibenzofuran (PCDD/F) concentrations in the stack gas of a municipal solid waste incinerator (400 ton/day). Conventional high resolution gas chromatography/high resolution mass spectroscopy (HRGC/HRMS) measurements for the determination of PCDD/F concentrations were performed to compare with TD-GC-REMPI-TOFMS measurements. 1,2,4-Trichlorobenzene correlated with I-TEQ at r = 0.867, 0.953 and 0.944 in unstable, stable and integrated conditions. The correlation was independent of the facility operating conditions observed in this study. Using a linear model to predict I-TEQ by 1,2,4-trichlorobenzene over the test, the average of the relative difference between predicted and measured I-TEQ was 18.9%. 1,2,4-Trichlorobenzene measured by TD-GC-REMPI-TOFMS can be used as a robust indicator of I-TEQ in stack gas.

Comprehensive diagnosis of PCDD/F emission from three hazardous waste incinerators.

Comprehensive diagnosis of polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) emissions was systematically conducted on three hazardous waste incinerators (HWIs). Results indicated that PCDD/F mainly existed in the solid phase before the bag filter. This was especially true for higher chlorinated dioxin and furan congeners (hexa-, hepta- and octa-). The aged bag filters tended to increase the gas-phase PCDD/F. Emissions also increased due to PCDD/F desorption from circulated scrubbing solution and plastic packing media used in the wet scrubber. The PCDD/F concentrations were elevated during the start-up process, reaching up to 5.4 times higher than those measured during the normal operating period. The ratios of PCDFs/PCDDs revealed that the surface-catalysed de novo synthesis was the dominant pathway of PCDD/F formation. Installation of more efficient fabric filters, intermittent replacement of circulated scrubbing solution will result in reduced PCDD/F emission. Additionally, 2,3,4,7,8-PeCDF correlated well with the international toxic equivalent quantity (I-TEQ) value, which suggests that 2,3,4,7,8-PeCDF could act as an I-TEQ indicator.

Stable Coronary Artery Disease: Treatment.

Stable coronary artery disease refers to a reversible supply/demand mismatch related to ischemia, a history of myocardial infarction, or the presence of plaque documented by catheterization or computed tomography angiography. Patients are considered stable if they are asymptomatic or their symptoms are controlled by medications or revascularization. Treatment involves risk factor management, antiplatelet therapy, and antianginal medications. Tobacco cessation, exercise, and weight loss are the most important lifestyle modifications. Treatment of comorbidities such as diabetes mellitus, hyperlipidemia, and hypertension should be optimized to reduce cardiovascular risk. All patients should be started on a statin unless contraindicated. No data support the routine use of monotherapy with nonstatin drugs such as bile acid sequestrants, niacin, ezetimibe, or fibrates. Studies of niacin and fibrates as adjunctive therapy found no improvement in patient outcomes. Aspirin is the mainstay of antiplatelet therapy; clopidogrel is an alternative. Antianginal medications should be added in a stepwise approach beginning with a beta blocker. Calcium channel blockers, nitrates, and ranolazine are used as adjunctive or second-line therapy when beta blockers are ineffective or contraindicated. Select patients may benefit from coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

ASCEND: A Study of Cardiovascular Events iN Diabetes: Characteristics of a randomized trial of aspirin and of omega-3 fatty acid supplementation in 15,480 people with diabetes.

OBJECTIVES: The use of aspirin for the secondary prevention of cardiovascular disease (CVD) is firmly established, and the proportional reductions in heart attacks and strokes appear to be similar in people with and without diabetes. Uncertainty remains about the role of antiplatelet treatments for primary prevention of CVD, and guidelines vary in their recommendations. It has also been hypothesized that long-term aspirin can prevent gastro-intestinal and other cancers. Observational studies suggest associations between higher intakes of omega-3 fatty acids (FA) and lower rates of CVD, but there is no large-scale randomized evidence to support using prophylactic omega-3 FA supplementation in primary prevention. ASCEND is a randomized trial assessing whether 100 mg daily aspirin safely prevents CVD and cancer in patients with diabetes without known arterial disease. It is also assessing whether supplementation with 1 g omega-3 FA daily prevents CVD. This paper describes the methods and baseline characteristics of the randomized participants. METHODS AND RESULTS: Between 2005 and 2011, using mail-based methods, 15,480 people with diabetes were randomized to aspirin versus placebo and, in a factorial design, to omega-3 FA supplementation versus placebo. Blood and urine samples were collected to allow baseline stratification by biochemical prognostic variables (e.g. HbA1c, blood lipids). Follow-up is for a median of at least 7 years. CONCLUSIONS: Demonstrating that prophylactic aspirin safely reduces the risk of CVD or cancer in the primary prevention setting, or that omega-3 FA supplementation prevents CVD, would be relevant to hundreds of millions of people worldwide who are currently not receiving such therapies. The results of ASCEND will be reported in 2018.

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease.

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .).