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To meet international greenhouse gas reporting obligations, New Zealand must report on carbon stocks in forests established after 1989 (post-1989 forest). Although predominately comprised of planted forest, post-1989 forest also contains a component of natural vegetation amounting to less than 10% by area. New Zealand undertook a national inventory of this natural stratum of post-1989 forest to provide estimates of carbon stocks and stock change in woody species over the first commitment period (2008-2012) of the Kyoto Protocol. Plots were installed on a 4-km grid, and the basal diameters and heights of trees and shrubs were measured for the first time from November 2012, to March 2013. Carbon stocks in 2012 were calculated using allometric functions developed from biomass samples from each site. Basal disc samples provided data on diameter increment and shrub and tree age annually from 1990 to 2012. These were used to predict carbon stocks per ha for individual plots in 2008 and to provide annual predictions by pool back to 1990. Carbon stocks summed across live and dead biomass pools (excluding soil) averaged 3.04, 16.70 and 28.73 t C/ha in 1990, 2008 and 2012, respectively. The disposition by pool was 2.25, 12.54 and 21.84 t C/ha in aboveground biomass, 0.56, 3.13 and 5.46 t C/ha in belowground biomass (using a root/shoot ratio of 0.25), 0.03, 0.17 and 0.23 t C/ha in deadwood, and 0.18, 0.86 and 1.21 t C/ha in litter in 1990, 2008 and 2012, respectively. [ABSTRACT FROM AUTHOR]

We report on a prospective phase II trial of 32 patients who underwent unrelated-donor hematopoietic cell transplantation, with a tacrolimus, sirolimus and rabbit anti-thymoctye globulin GVHD prophylactic regimen. The primary study endpoint was incidence of grades II-IV acute (aGVHD), with 80% power to detect a 30% decrease compared with institutional historical controls. Median age at transplant was 60 (19-71). In total, 23 patients (72%) received reduced-intensity conditioning, whereas the remainder received full-intensity regimens. Median follow-up for surviving patients was 35 months (range: 21-49). The cumulative incidence of aGVHD was 37.3%, and the 2-year cumulative incidence of chronic GVHD was 63%. We observed thrombotic microangiopathy in seven patients (21.8%), one of whom also developed sinusoidal obstructive syndrome (SOS). Four of the 32 patients (12.5%) failed to engraft, and 3 of these 4 died. As a result, enrollment to this trial was closed before the targeted accrual of 60 patients. Two-year OS was 65.5% and EFS was 61.3%. Two-year cumulative incidence of relapse was 12.5% and non-relapse mortality (NRM) was 15.6%. NRM and aGVHD rates were lower than historical rates. However, the unexpectedly high incidence of graft failure requires caution in the design of future studies with this regimen. [ABSTRACT FROM AUTHOR]

Patients with poor-risk leukemia have a high relapse rate despite allogeneic transplant. We report on the phase-2 trial of an intensified allogeneic transplant regimen whose aim was tolerable toxicity and durable remission. Study patients (n=30) had unfavorable first remission cytogenetics, progression from myelodysplasia or active disease due to induction failure or relapse. Conditioning was i.v. BU, targeted to a first-dose plasma area under the curve (AUC) of 700-900 μM min, VP-16 at 30 mg/kg of adjusted ideal body weight and fractionated TBI (FTBI) at 1200 cGy in 10 fractions. GVHD prophylaxis was CsA and mycophenolate mofetil. Regimen-related toxicities (Bearman) included grade II mucositis in 29 patients (97%) and grade III in one patient, grade II-III sinusoidal obstructive syndrome in 2 patients (7%), and grade 2-3 (CTC) skin toxicity in 8 patients (27%). The 30- and 100-day TRMs were 0 and 7% respectively. The median follow-up was 83.7 months (60.7-96.4) for surviving patients. The 5-year overall and disease-free survival was 40% for all patients. Cumulative 5-year relapse incidence (RI) was 23% and TRM was 37%. We have shown promising OS and RI in these poor-risk patients, who typically have few curative options. [ABSTRACT FROM AUTHOR]

Objective: To describe the patterns and clinical features of toxicity related to recreational use of mephedrone and other cathinones in the U.K. using data collected by the National Poisons Information Service (NPIS).Methods: The number of accesses to TOXBASE, the NPIS online poisons information database, details of consecutive cases uploaded onto TOXBASE and the number and details of telephone enquiries made to the NPIS by health professionals in the U.K. were collected for the period March 2009 to February 2010.Results: Over the year of study there were 2901 TOXBASE accesses and 188 telephone enquiries relating to cathinones, the majority relating to mephedrone (TOXBASE 1664, telephone 157), with a month-on-month increase in numbers. In 131 telephone enquiries concerning mephedrone, alone or in combination with alcohol, common clinical features reported included agitation or aggression (n=32, 24%, 95% CI 18% to 33%), tachycardia (n=29, 22%, 95% CI 16% to 30%), confusion or psychosis (n=18, 14%, 95% CI 9% to 21%), chest pain (n=17, 13%, 95% CI 8% to 20%), nausea (n=15, 11%, 95% CI 7% to 18%), palpitations (n=14, 11%, 95% CI 6% to 18%), peripheral vasoconstriction (n=10, 8%, 95% CI 4% to 14%) and headache (n=7, 5%, 95% CI 2% to 11%). Convulsions were reported in four cases (3%, 95% CI 1% to 8%). One exposed person died following cardiac arrest (1%, 95% CI 0% to 4%), although subsequent investigation suggested that mephedrone was not responsible.Conclusions: Toxicity associated with recreational mephedrone use is increasingly common in the UK. Sympathomimetic adverse effects are common and severe effects are also reported. Structured data collected by the NPIS may be of use in identifying trends in poisoning and in establishing toxidromes for new drugs of abuse. [ABSTRACT FROM AUTHOR]

Thomas SHL, Drici MD, Hall GC, Crocq MA, Everitt B, Lader MH, Le Jeunne C, Naber D, Priori S, Sturkenboom M, Thibaut F, Peuskens J, Mittoux A, Tanghøj P, Toumi M, Moore ND, Mann RD. Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP) Objective: To explore whether sertindole increases all-cause mortality or cardiac events requiring hospitalization, compared with risperidone. Method: Multinational randomized, open-label, parallel-group study, with blinded classification of outcomes, in 9858 patients with schizophrenia. Results: After 14147 person-years, there was no effect of treatment on overall mortality (sertindole 64, risperidone 61 deaths, Hazard Ratio (HR) = 1.12 (90% CI: 0.83, 1.50)) or cardiac events requiring hospitalization [sertindole 10, risperidone 6, HR = 1.73 (95% CI: 0.63, 4.78)]: Of these, four were considered arrhythmia-related (three sertindole, one risperidone). Cardiac mortality was higher with sertindole (Independent Safety Committee (ISC): 31 vs. 12, HR=2.84 (95% CI: 1.45, 5.55), P = 0.0022; Investigators 17 vs. 8, HR=2.13 (95% CI: 0.91, 4.98), P = 0.081). There was no significant difference in completed suicide, but fewer sertindole recipients attempted suicide (ISC: 68 vs. 78, HR=0.93 (95% CI: 0.66, 1.29), P = 0.65; Investigators: 43 vs. 65, HR=0.67 (95% CI: 0.45, 0.99), P = 0.044). Conclusion: Sertindole did not increase all-cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole. [ABSTRACT FROM AUTHOR]

Background: The question of whether it is safe to provide analgesia for patients with undifferentiated acute abdominal pain is marked by longstanding controversy over the possible masking of physical findings. The goal of this review is to assess the pertinent studies. Method: A Medline search was performed in April 2002, using the terms 'analgesia', 'abdominal pain', 'acute abdomen' and 'morphine'. Other articles were identified using the bibliographies of papers found through Medline. All articles reporting clinical trials of analgesia and its effects on diagnosis or physical examination were reviewed. Results: A total of eight trials (one reported only as an abstract) were identified. Because of significant disparity in trial design, no formal analysis such as meta-analysis was performed. However, detailed review of the trials revealed a striking consistency in results. In no study was there an association between analgesia and diagnostic impairment or dangerous masking of the findings of physical examination. Conclusion: The literature addressing early pain relief for abdominal pain is characterized by weaknesses, but there is a common theme suggesting that analgesia is safe. Pending further research, which should address some of the shortcomings of extant studies, a practice of judicious provision of analgesia appears safe, reasonable and in the best interests of patients in pain. [ABSTRACT FROM AUTHOR]

Background: Sudden death has been linked to antipsychotic therapy, but the relative risk associated with specific drugs is unknown.Aims: To assess the risk of sudden unexplained death associated with antipsychotic drug therapy and its relation to drug dose and individual agents.Method: A case-control study of psychiatric in-patients dying suddenly in five hospitals in the north-east of England and surviving controls matched for age, gender and mental disorder. Logistic regression analysis was used to identify significant risk factors, and odds ratios were calculated.Results: Sixty-nine case-control clusters were identified. Probable sudden unexplained death was significantly associated with hypertension, ischaemic heart disease and current treatment with thioridazine (adjusted odds ratio=5.3, 95% CI 1.7-16.2, P=0.004). There was no significant association with other individual antipsychotic drugs.Conclusions: Thioridazine alone was associated with sudden unexplained death, the likely mechanism being drug-induced arrhythmia. [ABSTRACT FROM AUTHOR]

Aims The study was designed to investigate the effects of the H2-receptor antagonists, cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of nebivolol in healthy volunteers. Methods Twelve healthy volunteers took part in a randomized placebo-controlled cross-over study. Each subject received on three separate occasions placebo, cimetidine (400 mg twice daily) or ranitidine (150 mg twice daily) for 24 h before and 48 h after a single oral dose of nebivolol (5 mg). Nebivolol and its individual (+) and (−) enantiomers were determined tby h.p.l.c. Results Ranitidine had no significant effect on nebivolol pharmacokinetics. Cimetidine, however, resulted in a 21-23% increase in Cmax of unchanged nebivolol and of each enantiomer plus its hydroxylated metabolites. Cimetidine significantly ( P<0.05) increased the AUC [mean±s.d. (95% C.I. of differences in mean)] for unchanged (±)-nebivolol [7.76±3.07 ng ml−1h with placebo; 11.50±5.40 (1.75, 8.76) ng ml−1h with cimetidine], (+)-nebivolol plus its hydroxylated metabolites [73.0±18.0 ng ml−1h with placebo; 91.5±25.7 (1.0, 23.1) ng ml−1h with cimetidine] and (−)-nebivolol plus its hydroxylated metabolites [101±32 ng ml−1h with placebo; 123±38 (3.3, 27.0) ng ml−1h with cimetidine]. Statistical analysis of the resting blood pressure and heart rate and exercise data did not suggest any consistent effects of ranitidine or cimetidine upon the pharmacodynamic effects of nebivolol. Conclusions There was no interaction between ranitidine and nebivolol. Although cimetidine inhibited nebivolol metabolism, it did not have a significant influence on the pharmacodynamics of the drug. [ABSTRACT FROM AUTHOR]

This article studies the impact of settlement procedures on day-of-the-week effects, with focus on the Kuala Lumpur Stock Exchange in Malaysia. Extensive evidence exists of anomalies in the behaviour of stock-market returns, particularly for the U.S. market. With the growing international diversification of bond and equity portfolios, particularly in the direction of emerging markets, it is becoming increasingly important for investment managers to understand empirical regularities which may exist in such markets. Some recent and comprehensive studies of the behaviour of emerging market stock return data have focused on the degree of integration of emerging markets with more developed markets and the statistical properties of stock market returns. A number of explanations have been put forward for the weekend effect, including stocks going ex-dividend and the effect of settlement lags. Researchers also looked at the pattern of correlations and cross correlations for lagged and contemporaneous returns, and found that the Far Eastern markets tend to be more strongly correlated with the behaviour of non-Far Eastern markets of previous days than with the behaviour of those non-Far Eastern markets on the same day.

This is the first study to use daily data from a major capital market outside of the US to examine the role of corporate bond and commercial paper rating changes on common stock returns. Using data published by Standard and Poors' credit rating agency between 1984 and 1992, we examine the impact of new credit ratings, credit rating changes and CreditWatch announcements on UK common stock returns. We find significant negative excess returns around the date of a downgrade and positive returns close to the date of a positive CreditWatch announcement. Hence, the financial markets would appear to place some importance on rating agency pronouncements in the UK. New ratings, whether short or long-term, have no significant impact on returns. We also attempt to quantify the impact of a new credit rating upon firm cost of capital through measures of conditional volatility and systematic risk. However, we find only weak evidence to suggest that a stock's cost of capital is reduced after a long-term credit rating is awarded for the first time. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Terodiline, an antimuscarinic and calcium antagonist drug, was used to treat detrusor instability but was withdrawn in 1991 after provoking serious ventricular arrhythmias associated with increases in the corrected QT interval (QTc). This research was performed to relate drug induced electrocardiographic changes in asymptomatic recipients to plasma concentrations of the R(+) and S(-) terodiline enantiomers. SETTING--Urological and geriatric clinics and wards. SUBJECTS--Asymptomatic patients taking terodiline in stable dose. METHODS--Electrocardiograms (50 mm/s) were collected from patients while they were taking terodiline and compared with ECGs obtained before or after terodiline. QT interval, heart rate corrected QT interval (QTc), and QT dispersion (QTd) were measured. Drug induced electrocardiographic changes were related to plasma concentrations of R(+) and S(-) terodiline. RESULTS--During terodiline treatment mean QTc and QTd were prolonged (491(43) and 84 (35) ms 1/2) compared with measurements made off therapy (443 (33) and 42 (17) ms 1/2, paired t tests, P < 0.002 and P < 0.01 respectively) in the 12 patients in sinus rhythm. The mean (95% confidence interval) drug induced increases were 48 (23 to 74) ms 1/2 for QTc and 42 (13 to 70) ms 1/2 for QTd. These increases correlated with total plasma terodiline (QTc: r = 0.77, P < 0.006, QTd: r = 0.68, P < 0.025) and with plasma concentrations of both terodiline enantiomers. CONCLUSIONS--Terodiline increases QTc and QTd in a concentration dependent manner. It is not clear whether this is a stereoselective effect and, if so, which enantiomer is responsible. The results suggest that drug induced torsade de pointes is a type A (concentration dependent) adverse drug reaction. [ABSTRACT FROM PUBLISHER]

The article discusses a retrospective study which examines the outcomes of patients who required early discontinuation of tacrolimus and sirolimus, and were given with mycophenolate mofetil (MMF)-based salvage as acute graft-versus-host disease (GVHD) prophylaxis. It indicates the feasibility of prophylaxis for patients with high risk for toxicities. It shows that overall survival (OS) and nonrelapse mortality (NRM) rates were in an acceptable range given the high-risk nature of patients.

A letter to the editor is presented in response to the article Sclerodermatous chronic GVHD in patients receiving tyrosine kinase inhibitors after allogeneic hematopoietic cell transplantation published in the online September 29, 2014 issue of the journal Bone Marrow Transplantation.