Association between direct transport to a cardiac arrest centre and survival following out-of-hospital cardiac arrest: A propensity-matched Aotearoa New Zealand study.

Background and Objectives: Direct transport to a cardiac arrest centre following out-of-hospital cardiac arrest may be associated with higher survival. However, there is limited evidence available to support this within the New Zealand context. This study used a propensity score-matched cohort to investigate whether direct transport to a cardiac arrest centre improved survival in New Zealand. Methods: A retrospective cohort study was conducted using the Aotearoa New Zealand Paramedic Care Collection (ANZPaCC) database for adults treated for out-of-hospital cardiac arrest of presumed cardiac aetiology between 1 July 2018 to 30 June 2023. Propensity score-matched analysis was used to investigate survival at 30-days post-event according to the receiving hospital being a cardiac arrest centre versus a non-cardiac arrest centre. Results: There were 2,297 OHCA patients included. Propensity matching resulted in 554 matched pairs (n = 1108). Thirty-day survival in propensity score-matched patients transported directly to a cardiac arrest centre (56%) versus a non-cardiac arrest centre (45%) was not significantly different (adjusted Odds Ratio 0.78 95%CI 0.54, 1.13, p = 0.19). Shockable presenting rhythm, bystander CPR, and presence of STEMI were associated with a higher odds of 30 day survival (p < 0.05). Maori or Pacific Peoples ethnicity and older age were associated with lower survival (p < 0.05). Conclusions: This study found no statistically significant difference in outcomes for OHCA patients transferred to a cardiac arrest compared to a non-cardiac arrest centre. However, the odds ratio of 0.78, equivalent to a 22% decrease in 30-day mortality, is consistent with benefit associated with management by a cardiac arrest centre. Further research in larger cohorts with detailed information on known outcome predictors, or large randomised clinical trials are needed.

A study protocol for a cluster-randomised controlled trial of smartphone-activated first responders with ultraportable defibrillators in out-of-hospital cardiac arrest: The First Responder Shock Trial (FIRST).

Objective: To describe the First Responder Shock Trial (FIRST), which aims to determine whether equipping frequently responding, smartphone-activated (GoodSAM) first responders with an ultraportable AED can increase 30-day survival rates in OHCA. Methods: The FIRST trial is an investigator-initiated, bi-national (Victoria, Australia and New Zealand), registry-nested cluster-randomised controlled trial where the unit of randomisation is the smartphone-activated (GoodSAM) first responder. High-frequency GoodSAM responders are randomised 1:1 to receive an ultraportable, single-use AED or standard alert procedures using the GoodSAM app.The primary outcome is survival to 30 days. The secondary outcome measures (shockable rhythm, return of spontaneous circulation, event survival, and time to first shock delivery) are routinely collected by OHCA registries in both regions. The trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) (Registration: ACTRN12622000448741) on 22 March 2022. Results: The trial started in November 2022 and the last patient is expected to be enrolled in November 2024. We aim to detect a 7% increase in the proportion of 30-day survivors, from 9% in patients attended by control responders to 16% in patients attended by responders randomised to the ultraportable AED intervention arm. With 80% power, an alpha of 0.05, a cluster size of 1.5 and a coefficient of variation for cluster sizes of 1, the sample size required to detect this difference is 714 (357 per arm). Conclusion: The FIRST study will increase our understanding of the potential role of portable AED use by smartphone-activated community responders and their impact on survival outcomes.

Long-term trends in yield variance of temperate managed grassland.

The management of climate-resilient grassland systems is important for stable livestock fodder production. In the face of climate change, maintaining productivity while minimizing yield variance of grassland systems is increasingly challenging. To achieve climate-resilient and stable productivity of grasslands, a better understanding of the climatic drivers of long-term trends in yield variance and its dependence on agronomic inputs is required. Based on the Park Grass Experiment at Rothamsted (UK), we report for the first time the long-term trends in yield variance of grassland (1965-2018) in plots given different fertilizer and lime applications, with contrasting productivity and plant species diversity. We implemented a statistical model that allowed yield variance to be determined independently of yield level. Environmental abiotic covariates were included in a novel criss-cross regression approach to determine climatic drivers of yield variance and its dependence on agronomic management. Our findings highlight that sufficient liming and moderate fertilization can reduce yield variance while maintaining productivity and limiting loss of plant species diversity. Plots receiving the highest rate of nitrogen fertilizer or farmyard manure had the highest yield but were also more responsive to environmental variability and had less plant species diversity. We identified the days of water stress from March to October and temperature from July to August as the two main climatic drivers, explaining approximately one-third of the observed yield variance. These drivers helped explain consistent unimodal trends in yield variance-with a peak in approximately 1995, after which variance declined. Here, for the first time, we provide a novel statistical framework and a unique long-term dataset for understanding the trends in yield variance of managed grassland. The application of the criss-cross regression approach in other long-term agro-ecological trials could help identify climatic drivers of production risk and to derive agronomic strategies for improving the climate resilience of cropping systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s13593-023-00885-w.

Total Synthesis and Stereochemical Assignment of (-)-Psychotridine.

We report the first enantioselective total synthesis and stereochemical assignment of (-)-psychotridine. The application of our diazene-directed assembly of enantiomerically enriched cyclotryptamines afforded a highly convergent synthesis of the pentameric alkaloid, allowing its detailed structural assignment. Highlights of the synthesis include the introduction of four quaternary stereocenters with complete stereochemical control in a single step via the photoextrusion of three molecules of dinitrogen from an advanced intermediate and metal-catalyzed C-H amination reactions in challenging settings.

The evolving role of weather types on rainfall chemistry under large reductions in pollutant emissions.

Long-term change and shorter-term variability in the atmospheric deposition of pollutants and marine salts can have major effects on the biogeochemistry and ecology of soils and surface water ecosystems. In the 1980s, at the time of peak acid deposition in the UK, deposition loads were highly dependent on prevailing weather types, and it was postulated that future pollution recovery trajectories would be partly dependent on any climate change-driven shifts in weather systems. Following three decades of substantial acidic emission reductions, we used monitoring data collected between 1992 and 2015 from four UK Environmental Change Network (ECN) sites in contrasting parts of Great Britain to examine the trends in precipitation chemistry in relation to prevailing weather conditions. Weather systems were classified on the basis of Lamb weather type (LWT) groupings, while emissions inventories and clustering of air mass trajectories were used to interpret the observed patterns. Concentrations of ions showed clear differences between cyclonic-westerly-dominated periods and others, reflecting higher marine and lower anthropogenic contributions in Atlantic air masses. Westerlies were associated with higher rainfall, higher sea salt concentrations, and lower pollutant concentrations at all sites, while air mass paths exerted additional controls. Westerlies therefore have continued to favour higher sea salt fluxes, whereas emission reductions are increasingly leading to positive correlations between westerlies and pollutant fluxes. Our results also suggest a shift from the influence of anthropogenic emissions to natural emissions (e.g., sea salt) and climate forcing as they are transported under relatively cleaner conditions to the UK. Westerlies have been relatively frequent over the ECN monitoring period, but longer-term cyclicity in these weather types suggests that current contributions to precipitation may not be sustained over coming years.

From Modified Newtonian Dynamics to Superfluid Vacuum Theory.

Herein is a review of the essentials of Modified Newtonian Dynamics (MOND) versus dark matter models based on Superfluids for modeling galactic rotation curves. We review the successes and issues of both approaches. We then mention a recent alternative based on the Superfluid Vacuum Theory (SVT) with a nonlinear logarithmic Schrödinger equation (LogSE) which reconciles both approaches, retains the essential success of MOND and the Superfluid nature but does not necessitate the hypothesis of processes including dark matter. We conclude with the implications of this SVT alternative on quantum theory itself.

An Intervention to Improve Medication Adherence in People With Heart Disease (Text4HeartII): Randomized Controlled Trial.

BACKGROUND: Mobile health technologies have the potential to improve the reach and delivery of interventions for promoting long-term secondary prevention of coronary heart disease. OBJECTIVE: This study aims to determine the effectiveness of an SMS text messaging intervention (Text4HeartII) for improving adherence to medication and lifestyle changes over and above usual care in people with coronary heart disease at 24 and 52 weeks. METHODS: A two-arm, parallel, randomized controlled trial was conducted in New Zealand. Participants with a recent acute coronary syndrome were randomized to receive usual cardiac services alone (control, n=153) or a 24-week SMS text message program for supporting self-management plus usual cardiac services (n=153). The primary outcome was adherence to medication at 24 weeks, defined as a medication possession ratio of 80% or more for aspirin, statin, and antihypertensive therapy. Secondary outcomes included medication possession ratio at 52 weeks, self-reported medication adherence, adherence to healthy lifestyle behaviors, and health-related quality of life at 24 and 52 weeks. RESULTS: Participants were predominantly male (113/306, 80.3%) and European New Zealanders (210/306, 68.6%), with a mean age of 61 years (SD 11 years). Groups were comparable at baseline. National hospitalization and pharmacy dispensing records were available for all participants; 92% (282/306, 92.1%) of participants completed a 24-week questionnaire and 95.1% (291/306) of participants completed a 52-week questionnaire. Adherence with 3 medication classes were lower in the intervention group than in the control group (87/153, 56.8% vs 105/153, 68.6%, odds ratio 0.60, 95% CI 0.38-0.96; P=.03) and 52 weeks (104/153, 67.9% vs 83/153, 54.2%; odds ratio 0.56, 95% CI 0.35-0.89; P=.01). Self-reported medication adherence scores showed the same trend at 52 weeks (mean difference 0.3; 95% CI 0.01-0.59; P=.04). Moreover, self-reported adherence to health-related behaviors was similar between groups. CONCLUSIONS: Text4HeartII did not improve dispensed medication or adherence to a favorable lifestyle over and above usual care. This finding contrasts with previous studies and highlights that the benefits of text interventions may depend on the context in which they are used. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616000422426; http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370398. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-018-2468-z.

High flow oxygen and risk of mortality in patients with a suspected acute coronary syndrome: pragmatic, cluster randomised, crossover trial.

OBJECTIVE: To determine the association between high flow supplementary oxygen and 30 day mortality in patients presenting with a suspected acute coronary syndrome (ACS). DESIGN: Pragmatic, cluster randomised, crossover trial. SETTING: Four geographical regions in New Zealand. PARTICIPANTS: 40 872 patients with suspected or confirmed ACS included in the All New Zealand Acute Coronary Syndrome Quality Improvement registry or ambulance ACS pathway during the study periods. 20 304 patients were managed using the high oxygen protocol and 20 568 were managed using the low oxygen protocol. Final diagnosis of ST elevation myocardial infarction (STEMI) and non-STEMI were determined from the registry and ICD-10 discharge codes. INTERVENTIONS: The four geographical regions were randomly allocated to each of two oxygen protocols in six month blocks over two years. The high oxygen protocol recommended oxygen at 6-8 L/min by face mask for ischaemic symptoms or electrocardiographic changes, irrespective of the transcapillary oxygen saturation (SpO2). The low oxygen protocol recommended oxygen only if SpO2 was less than 90%, with a target SpO2 of less than 95%. MAIN OUTCOME MEASURE: 30 day all cause mortality determined from linkage to administrative data. RESULTS: Personal and clinical characteristics of patients managed under both oxygen protocols were well matched. For patients with suspected ACS, 30 day mortality for the high and low oxygen groups was 613 (3.0%) and 642 (3.1%), respectively (odds ratio 0.97, 95% confidence interval 0.86 to 1.08). For 4159 (10%) patients with STEMI, 30 day mortality for the high and low oxygen groups was 8.8% (n=178) and 10.6% (n=225), respectively (0.81, 0.66 to 1.00) and for 10 218 (25%) patients with non-STEMI was 3.6% (n=187) and 3.5% (n=176), respectively (1.05, 0.85 to 1.29). CONCLUSION: In a large patient cohort presenting with suspected ACS, high flow oxygen was not associated with an increase or decrease in 30 day mortality. TRIAL REGISTRATION: ANZ Clinical Trials ACTRN12616000461493.

The impact of a national COVID-19 lockdown on acute coronary syndrome hospitalisations in New Zealand (ANZACS-QI 55).

BACKGROUND: Countries with a high incidence of coronavirus 2019 (COVID-19) reported reduced hospitalisations for acute coronary syndromes (ACS) during the pandemic. This study describes the impact of a nationwide lockdown on ACS hospitalisations in New Zealand (NZ), a country with a low incidence of COVID-19. METHODS: All patients admitted to a NZ Hospital with ACS who underwent coronary angiography in the All NZ ACS Quality Improvement registry during the lockdown (23 March - 26 April 2020) were compared with equivalent weeks in 2015-2019. Ambulance attendances and regional community troponin-I testing were compared for lockdown and non-lockdown (1 July 2019 to 16 February 2020) periods. FINDINGS: Hospitalisation for ACS was lower during the 5-week lockdown (105 vs. 146 per-week, rate ratio 0•72 [95% CI 0•61-0•83], p = 0.003). This was explained by fewer admissions for non-ST-segment elevation ACS (NSTE-ACS; p = 0•002) but not ST-segment elevation myocardial infarction (STEMI; p = 0•31). Patient characteristics and in-hospital mortality were similar. For STEMI, door-to-balloon times were similar (70 vs. 72 min, p = 0•52). For NSTE-ACS, there was an increase in percutaneous revascularisation (59% vs. 49%, p<0•001) and reduction in surgical revascularisation (9% vs. 15%, p = 0•005). There were fewer ambulance attendances for cardiac arrests (98 vs. 110 per-week, p = 0•04) but no difference for suspected ACS (408 vs. 420 per-week, p = 0•44). Community troponin testing was lower throughout the lockdown (182 vs. 394 per-week, p<0•001). INTERPRETATION: Despite the low incidence of COVID-19, there was a nationwide decrease in ACS hospitalisations during the lockdown. These findings have important implications for future pandemic planning. FUNDING: The ANZACS-QI registry receives funding from the New Zealand Ministry of Health.

What is the Optimal Rate of Invasive Coronary Angiography After Acute Coronary Syndrome? (ANZACS-QI 22).

BACKGROUND: Invasive coronary angiography plays a pivotal role in the management of acute coronary syndromes (ACS). Wide variability in its use has been previously documented. Our aim was to investigate whether coronary angiography is being used appropriately prior to discharge after ACS, taking into account relative contraindications of the procedure. METHODS: Patients presenting with ACS in 2015 to two large, demographically distinct New Zealand (NZ) District Health Boards (DHBs)-Counties Manukau (CMDHB) and Waitemata (WDHB)-were identified from the NZ Ministry of Health National Dataset using ICD-10-AM codes. Patients' clinical data were obtained from the electronic and paper clinical records. Pre-defined relative contraindications to coronary angiography were identified. RESULTS: Of the 3,809 patient admissions coded with ACS, 600 patient admissions (300 from each DHB) were reviewed. Sixty-one (61) (10%) did not meet diagnostic criteria for ACS on review of clinical data and were excluded. Of the patients reviewed, 55% received coronary angiography, with a higher rate in WDHB than CMDHB (61% and 49%, respectively) and 37.5% had relative contraindications documented. The overall rate of angiography was appropriately high in those without a relative contraindication (90.3%) and low in those with one (7.4%). There were fewer patients with relative contraindications in WDHB than CMDHB (36.7% and 48.5%) but the rate of angiography in those with (6.9% and 7.8%) and without (92.5% and 87.5%) contraindications in the two DHBs was similar. CONCLUSIONS: The decision to offer coronary angiography after ACS appears to be appropriately influenced by the presence or absence of relative contraindications. Approximately 60% of patients had no documented relative contraindication suggesting that this may be an appropriate angiography rate in New Zealand practice. However, differences between the two DHBs of around 10% appear to be clinically appropriate due to variation in contraindication rates.

Acute reperfusion for ST-elevation myocardial infarction in New Zealand (2015-2017): patient and system delay (ANZACS-QI 29).

AIM: Prompt access to cardiac defibrillation and reperfusion therapy improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The study aim was to describe the 'patient' and 'system' delay in patients who receive acute reperfusion therapy for ST-elevation myocardial infarction (STEMI) in New Zealand. METHODS: In 2015-17, 3,857 patients who received acute reperfusion therapy were captured in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. 'Patient delay' is the time from symptom onset to first medical contact (FMC), and 'system delay' the time from FMC until reperfusion therapy (primary percutaneous coronary intervention (PCI) or fibrinolysis). RESULTS: Seventy percent of patients received primary PCI and 30% fibrinolysis. Of those receiving fibrinolysis, 122 (10.5%) received pre-hospital fibrinolysis. Seventy-seven percent were transported to hospital by ambulance. After adjustment, people who were older, male and presented to a hospital without a routine primary PCI service were less likely to travel by ambulance. Patient delay: The median delay was 45 minutes for ambulance-transported patients and 97 minutes for those self-transported to hospital, with a quarter delayed by >2 hours and >3 hours, respectively. Delay >1 hour was more common in older patients, Maori and Indian patients and those self-transported to hospital. System delay: For ambulance-transported patients who received primary PCI, the median time was 119 minutes. For ambulance-transported patients who received fibrinolysis, the median system delay was 86 minutes, with Maori patients more often delayed than European/Other patients. For patients who received pre-hospital fibrinolysis the median delay was 46 minutes shorter. For the quarter of patients treated with rescue PCI after fibrinolysis, the median needle-to-rescue time was prolonged-four hours. CONCLUSIONS: Nationwide implementation of the NZ STEMI pathway is needed to reduce system delays in delivery of primary PCI, fibrinolysis and rescue PCI. Ongoing initiatives are required to reduce barriers to calling the ambulance early after symptom onset.

Relationship between socioeconomic factors, distribution of public access defibrillators and incidence of out-of-hospital cardiac arrest.

BACKGROUND: Survival from out-of-hospital cardiac arrest (OHCA) is improved when public access defibrillators are used. Areas of socioeconomic deprivation may have higher rates of OHCA and thus a greater demand for public access defibrillators. We aimed to determine if there was a relationship between socioeconomic factors, the geographic distribution of public access defibrillators (PADs) and incidence of OHCA. METHOD: Socioeconomic deprivation data was obtained from the Census-based 2013 Index of Deprivation. Spatial information for PADs was obtained from a New Zealand PAD database (AED Locations) in 2016 and 2018. Location data for OHCA was obtained from the St John New Zealand OHCA registry for the period 1 October 2013 to 30 June 2016. Relationships between these variables were analysed using a Poisson regression analysis. RESULTS: Cardiac arrest incidence increased with increasing deprivation. The incidence in the most deprived areas of 156.5 events per 100,000 person years (135.4-180.9, 95% CI) is double the incidence in the least deprived areas at 78.0 events per 100,000 person years (66.4-91.7, 95% CI). Significant increases in the rates of OHCA were observed with every 1% increase in proportions of Maori (1.0%, 0.61-1.4%, 95% CI, p = 0.001), Pacific Peoples (0.6%, 0.21-0.9%, p = 0.005), >65 year olds (3.7%, 3.0-4.3%, p < 0.001), and males (3.7%, 1.8-5.6%, p < 0.001). In 2018, the decile 10 areas had the lowest coverage of PADs (65% of these areas contained a PAD) compared with less deprived areas (68-84%, median 81%). CONCLUSIONS: The most socioeconomically deprived communities had the highest incidence of OHCA and the least availability of PADs. This provides impetus for targeted PAD placement in areas of higher deprivation.

The electronic Rothamsted Archive (e-RA), an online resource for data from the Rothamsted long-term experiments.

The electronic Rothamsted Archive, e-RA (www.era.rothamsted.ac.uk) provides a permanent managed database to both securely store and disseminate data from Rothamsted Research's long-term field experiments (since 1843) and meteorological stations (since 1853). Both historical and contemporary data are made available via this online database which provides the scientific community with access to a unique continuous record of agricultural experiments and weather measured since the mid-19th century. Qualitative information, such as treatment and management practices, plans and soil information, accompanies the data and are made available on the e-RA website. e-RA was released externally to the wider scientific community in 2013 and this paper describes its development, content, curation and the access process for data users. Case studies illustrate the diverse applications of the data, including its original intended purposes and recent unforeseen applications. Usage monitoring demonstrates the data are of increasing interest. Future developments, including adopting FAIR data principles, are proposed as the resource is increasingly recognised as a unique archive of data relevant to sustainable agriculture, agroecology and the environment.

Diagnostic Utility of High Sensitivity Troponins for Echocardiographic Markers of Structural Heart Disease.

The conventional use of high-sensitivity troponins (hs-troponins) is for diagnosing myocardial infarction however they also have a role in chronic disease management. This pilot study assessed the relationship of hs-troponins with echocardiographic markers of left ventricular hypertrophy (LVH) and structural heart disease (SHD). Patients undergoing computer gomography (CT) coronary angiogram for low-intermediate risk chest pain and healthy volunteers were recruited. Hs-troponins Singulex I, Abbott I and Roche T and N-terminal pro-brain natriuretic peptide (NT-proBNP) were evaluated in relation to SHD parameters including left ventricular hypertrophy (LVHEcho) and left atrial enlargement (LAEEcho) on echocardiography. 78 subjects who underwent echocardiography were included in this study. C-statistics (95% confidence interval) of the four biomarkers for predicting LVHEcho were 0.84 (0.72-0.92), 0.84 (0.73-0.92), 0.75 (0.63-0.85) and 0.62 (0.49-0.74); for LAEEcho 0.74 (0.6-0.85), 0.78 (0.66-0.88), 0.55 (0.42-0.67) and 0.68 (0.62-0.85); and composite SHD 0.79 (0.66-0.88), 0.87 (0.75-0.94), 0.62 (0.49-0.73) and 0.74 (0.62-0.84) respectively. Optimal cut points for SHD were >1.2 ng/L, >1.6 ng/L, >8 ng/L and >18 pmol/L respectively. These results advocate the potential role of hs-troponins as screening tools for structural heart disease with theranostic implications.

Text4Heart II - improving medication adherence in people with heart disease: a study protocol for a randomized controlled trial.

BACKGROUND: Cardiac rehabilitation (CR) is an essential component of contemporary management for patients with coronary heart disease, including following an acute coronary syndrome (ACS). CR typically involves education and support to assist people following an ACS to make lifestyle changes and prevent subsequent events. Despite its benefits, uptake and participation in tradition CR programs is low. The use of mobile technologies (mHealth) offers the potential to improve reach, access, and delivery of CR support. We aim to determine the effectiveness and cost-effectiveness of a text-messaging intervention (Text4Heart II) to improve adherence to medication and lifestyle change in addition to usual care in people following an ACS. A second aim is to use the RE-AIM framework to inform the potential implementation of Text4Heart II within health services in New Zealand. METHODS: Text4Heart II is a two-arm, parallel, superiority randomized controlled trial conducted in two large metropolitan hospitals in Auckland, New Zealand. Three hundred and thirty participants will be randomized to either a 24-week theory- and evidence-based personalized text message program to support self-management in addition to usual CR, or usual CR alone (control). Outcomes are assessed at 6 and 12 months. The primary outcome is the proportion of participants adhering to medication at 6 months as measured by dispensed records. Secondary outcomes include medication adherence at 12 months, the proportion of participants adhering to self-reported healthy behaviors (physical activity, fruit and vegetable consumption, moderating alcohol intake and smoking status) measured using a composite health behavior score, self-reported medication adherence, cardiovascular risk factors (lipids, blood pressure), readmissions and related hospital events at 6 and 12 months. A cost-effectiveness analysis will also be conducted. Using the RE-AIM framework, we will determine uptake and sustainability of the intervention. DISCUSSION: The Text4Heart II trial will determine the effectiveness of a text-messaging intervention to improve adherence to medication and lifestyle behaviors at both 6 and 12 months. Using the RE-AIM framework this trial will provide much needed data and insight into the potential implementation of Text4Heart II. This trial addresses many limitations/criticisms of previous mHealth trials; it builds on our Text4Heart pilot trial, it is adequately powered, has sufficient duration to elicit behavior change, and the follow-up assessments (6 and 12 months) are long enough to determine the sustained effect of the intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ID: ACTRN12616000422426 . Registered retrospectively on 1 April 2016.

A convergent approach to batzelladine alkaloids. Total syntheses of (+)-batzelladine E, (-)-dehydrobatzelladine C, and (+)-batzelladine K.

We recently reported a convergent strategy to access the polycyclic guanidinium alkaloid (+)-batzelladine B via an aldol addition-retro-aldol-aza-Michael addition cascade. Here we describe the application of this approach toward the total syntheses of (+)-batzelladine E, (-)-dehydrobatzelladine C, and (+)-batzelladine K. The identification of suitable methods to functionalize a common tropane core by electrophilic alkynylation and nucleophilic 1,2-addition were essential to generalizing this approach. We provide evidence for the intermediacy of an acylallene species in the cascade reaction.

ECG-derived spatial QRS-T angle is associated with ICD implantation, mortality and heart failure admissions in patients with LV systolic dysfunction.

BACKGROUND: Increased spatial QRS-T angle has been shown to predict appropriate implantable cardioverter defibrilIator (ICD) therapy in patients with left ventricular systolic dysfunction (LVSD). We performed a retrospective cohort study in patients with left ventricular ejection fraction (LVEF) 31-40% to assess the relationship between the spatial QRS-T angle and other advanced ECG (A-ECG) as well as echocardiographic metadata, with all-cause mortality or ICD implantation for secondary prevention. METHODS: 534 patients ≤75 years of age with LVEF 31-40% were identified through an echocardiography reporting database. Digital 12-lead ECGs were retrospectively matched to 295 of these patients, for whom echocardiographic and A-ECG metadata were then generated. Data mining was applied to discover novel ECG and echocardiographic markers of risk. Machine learning was used to develop a model to predict possible outcomes. RESULTS: 49 patients (17%) had events, defined as either mortality (n = 16) or ICD implantation for secondary prevention (n = 33). 72 parameters (58 A-ECG, 14 echocardiographic) were univariately different (p<0.05) in those with vs. without events. After adjustment for multiplicity, 24 A-ECG parameters and 3 echocardiographic parameters remained different (p<2x10-3). These included the posterior-to-leftward QRS loop ratio from the derived vectorcardiographic horizontal plane (previously associated with pulmonary artery pressure, p = 2x10-6); spatial mean QRS-T angle (134 vs. 112°, p = 1.6x10-4); various repolarisation vectors; and a previously described 5-parameter A-ECG score for LVSD (p = 4x10-6) that also correlated with echocardiographic global longitudinal strain (R2 = - 0.51, P < 0.0001). A spatial QRS-T angle >110° had an adjusted HR of 3.4 (95% CI 1.6 to 7.4) for secondary ICD implantation or all-cause death and adjusted HR of 4.1 (95% CI 1.2 to 13.9) for future heart failure admission. There was a loss of complexity between A-ECG and echocardiographic variables with an increasing degree of disease. CONCLUSION: Spatial QRS-T angle >110° was strongly associated with arrhythmic events and all-cause death. Deep analysis of global ECG and echocardiographic metadata revealed underlying relationships, which otherwise would not have been appreciated. Delivered at scale such techniques may prove useful in clinical decision making in the future.

Soil resilience and recovery: rapid community responses to management changes.

BACKGROUND AND AIMS: Soil degradation is a major global problem; to investigate the potential for recovery of soil biota and associated key functions, soils were monitored during the early years of conversion between permanent grassland, arable cropping and bare fallow (maintained by regular tilling). Distinct differences in soil properties had become apparent 50 years after a previous conversion. METHODS: Subplots on previously permanent grassland, arable and bare fallow soil were converted to the two alternatives, generating 9 treatments. Soil properties (soil organic carbon, mesofauna, microbial community structure and activity) were measured. RESULTS: After 2 years, mesofauna and microbial abundance increased where plants were grown on previously bare fallow soils and declined where grassland was converted to bare fallow treatment. Overall prokaryote community composition remained more similar to the previous treatments of the converted plots than to the new treatments but there were significant changes in the relative abundance of some groups and functional genes. Four years after conversion, SOC in arable and bare fallow soils converted to grassland had increased significantly. CONCLUSIONS: Conversion to permanent grassland effectively replenished C in previously degraded soil; the soil microbiome showed significant conversion-related changes; plant-driven recovery was quicker than C loss in the absence of plants.

National variation in coronary angiography rates and timing after an acute coronary syndrome in New Zealand (ANZACS-QI 6).

AIM: The New Zealand Cardiac Clinical Network and the Ministry of Health recommend a "3-day door-to-catheter target" for acute coronary syndromes (ACS) admissions, requiring that at least 70% of ACS patients referred for invasive coronary angiography (ICA) undergo this within 3 days of hospital admission. We assessed the variability in use of ICA, timing of ICA, and duration of hospital admission across New Zealand District Health Boards (DHBs). METHODS: All patients admitted to all New Zealand public hospitals with suspected ACS undergoing ICA over 1 year ending November 2014 had demographic, risk factor, and diagnostic data collected prospectively using the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. Complete datasets were available in 7,988 (98.4%) patients. DHBs were categorised as those able to perform percutaneous coronary intervention on-site (intervention-capable) or not. RESULTS: There was a near two-fold variation between DHBs in the age standardised rate (ASR) of ICA ranging from 16.8 per 10,000 to 34.1 per 10,000 population (New Zealand rate; 27.9 per 10,000). Patients in intervention-capable DHBs had a 30% higher ASR of ICA. The proportion of ACS patients meeting the 3-day target ranged from 56.7% to 92.9% (New Zealand; 76.4%). Those in intervention-capable DHBs were more likely to meet the target (78.7% vs 68.0%, p<0.0001) and spent 0.84 days (p<.0001) less in hospital. CONCLUSIONS: There is a considerable variation in the rate and timing of ICA in New Zealand. Patients with ACS admitted to DHBs without interventional-capability are disadvantaged. New initiatives to correct this discrepancy are needed.