Search

The stellar inclination angle – the angle between the rotation axis of a star and our line of sight – provides valuable information in many different areas, from the characterization of the geometry of exoplanetary and eclipsing binary systems to the formation and evolution of those systems. We propose a method based on asteroseismology and a Bayesian hierarchical scheme for extracting the inclination angle of a single star. This hierarchical method therefore provides a means to both accurately and robustly extract inclination angles from red giant stars. We successfully apply this technique to an artificial data set with an underlying isotropic inclination angle distribution to verify the method. We also apply this technique to 123 red giant stars observed with Kepler. We also show the need for a selection function to account for possible population-level biases, which are not present in individual star-by-star cases, in order to extend the hierarchical method towards inferring underlying population inclination angle distributions. [ABSTRACT FROM AUTHOR]

Editorial. Focuses on the treatment of thyrotoxicosis in pregnant or potentially pregnant women in Great Britain. Fetal risk of thyrotoxicosis; Suggested antithyroid drugs; Side effects of antithyroid drugs.

The article presents a study that investigates the effect of morphine sulphate (MS) analgesia in improving the diagnostic accuracy of patients with undifferentiated abdominal pain (UAP). It describes the method of the study that observes 74 patients who had severe abdominal pain with less than 72 hours duration presented at a tertiary care in Boston, Massachusetts. It notes the result of the study which shows that the method does not improve the diagnostic accuracy of the patients.

Guidelines on the appropriate availability and use of laboratory analysis have been produced by the National Poisons Information Service and the Association of Clinical Biochemists and are published in this issue. These are intended to support the consistent and high quality investigation of the poisoned patient. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoid receptor agonists (SCRA) are commonly encountered new psychoactive substances. Here we report the recent detection of ADB-BUTINACA in samples from patients attending United Kingdom emergency departments with toxicity after suspected drug misuse and describe the associated clinical features. Consenting adults (≥16 y) presenting to participating hospitals with toxicity after suspected drug misuse have been included in the Identification Of Novel psychoActive substances (IONA) study since March 2015. Demographic and clinical features are recorded and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry. By December 2021, analytical data were available for 1279 IONA participants and ADB-BUTINACA was detected in at least one sample from 10 (9 males, age range 16–51 median 45 years), all presenting since February 2021. Smoking 'spice' was reported by four patients, two had ingested edible "cannabis" gums and four reported heroin use (2 intravenous, 1 smoked, 1 route not known). Co-use of pregabalin (oral) and crack cocaine (smoked) were also reported. In 3 cases ADB-BUTINACA was the only substance detected, while in seven other substances of misuse were also detected including other SCRA, opioids, benzodiazepines cocaine and pregabalin. Clinical features reported in these 2 groups respectively included reduced level of consciousness (3/3, 6/7), agitation (0/3, 4/7), tachycardia (0/3, 3/7), seizures (1/3, 1/7), hallucinations (1/3, 1/7), hypotension (1/3, 1/7). Metabolic acidosis (1/3, 0/7) and respiratory acidosis (1/3, 0/7), All 10 patients recovered with supportive care, including intubation and ventilation for one case. The median length of hospital stay was 19 h (range 2.6–131 h). ADB-BUTINACA has recently emerged as a drug of misuse in England. Clinical features of toxicity are consistent with those of other SCRA and include reduced level of consciousness, respiratory and/or metabolic acidosis, seizures, confusion and hallucinations. [ABSTRACT FROM AUTHOR]

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.

Background: Reducing net greenhouse gas emissions through conserving existing forest carbon stocks and encouraging additional uptake of carbon in existing and new forests have become important climate change mitigation tools. The contribution of harvested wood products (HWPs) to increasing carbon uptake has been recognised and approaches to quantifying this pool developed. In New Zealand, harvesting has more than doubled since 1990 while log exports have increased by a factor of 11 due to past afforestation and comparatively little expansion in domestic processing. This paper documents New Zealand's application of the IPCC approaches for reporting contributions of the HWP pool to net emissions, in order to meet international greenhouse gas inventory reporting requirements. We examine the implications of the different approaches and assumptions used in calculating the HWP contribution and highlight model limitations. Results: Choice of system boundary has a large impact for a country with a small domestic market and significant HWP exports. Under the Production approach used for New Zealand's greenhouse gas inventory reporting, stock changes in planted forests and in HWPs both rank highly as key categories. The contribution from HWPs is even greater under the Atmospheric Flow approach, because emissions from exported HWPs are not included. Conversely the Stock Change approach minimises the contribution of HWPs because the domestic market is small. The use of country-specific data to backfill the time series from 1900 to 1960 has little impact but using country-specific parameters in place of IPCC defaults results in a smaller HWP sink for New Zealand. This is because of the dominance of plantation forestry based on a softwood mainly used in relatively short-lived products. Conclusions: The NZ HWP Model currently meets international inventory reporting requirements. Further disaggregation of the semi-finished HWP end uses both within New Zealand and in export markets is required to improve accuracy. Product end-uses and lifespans need to be continually assessed to capture changes. More extensive analyses that include the benefits of avoided emissions through product substitution and life cycle emissions from the forestry sector are required to fully assess the contribution of forests and forest products to climate change mitigation and a low emissions future. [ABSTRACT FROM AUTHOR]

Asteroseismology provides fundamental stellar parameters independent of distance, but subject to systematics under calibration. Gaia DR2 has provided parallaxes for a billion stars, which are offset by a parallax zero-point (ϖzp). Red Clump (RC) stars have a narrow spread in luminosity, thus functioning as standard candles to calibrate these systematics. This work measures how the magnitude and spread of the RC in the Kepler field are affected by changes to temperature and scaling relations for seismology, and changes to the parallax zero-point for Gaia. We use a sample of 5576 RC stars classified through asteroseismology. We apply hierarchical Bayesian latent variable models, finding the population-level properties of the RC with seismology, and use those as priors on Gaia parallaxes to find ϖzp. We then find the position of the RC, using published values for ϖzp. We find a seismic temperature-insensitive spread of the RC of |${\sim }0.03\, \rm mag$| in the 2MASS K band and a larger and slightly temperature-dependent spread of |${\sim }0.13\, \rm mag$| in the Gaia G band. This intrinsic dispersion in the K band provides a distance precision of |${\sim } 1{{\ \rm per\ cent}}$| for RC stars. Using Gaia data alone, we find a mean zero-point of |$-41\pm 10\, \mu \rm as$|⁠. This offset yields RC absolute magnitudes of −1.634 ± 0.018 in K and 0.546 ± 0.016 in G. Obtaining these same values through seismology would require a global temperature shift of |${\sim }-70\, \mathrm{K}$|⁠ , which is compatible with known systematics in spectroscopy. [ABSTRACT FROM AUTHOR]

Meloidogyne aegracyperi n. sp. is described from roots of purple nutsedge in southern New Mexico, USA. Mature females are small (310-460 µm), pearly white, with their egg masses completely contained inside root galls. The neck is often at a 90 to 130° angle to the protruding posterior end with the perineal pattern. The distance of the dorsal esophageal gland orifice (DGO) to the base of the stylet is relatively long (4.0-6.1 µm), and the excretory pore is level with the base of the stylet. The anterior portion of the rounded lumen lining of the metacorpus contains 3 to 10 small vesicles. The perineal pattern has a rounded dorsal arch with a tail terminal area that is smooth or marked with rope-like striae. Only two males were found. The body twists 90° throughout its length. The DGO to the base of the stylet is long (3.0-3.3) µm. The cephalic framework of the second-stage juvenile is weak, and the stylet is short (10.1-11.8 µm). The DGO to the base of the stylet is long (3-5 µm). The tail is very long (64-89 µm) and the hyaline portion of the tail is very narrow, making the tail finely pointed. Eggs are typical for the genus and vary in length (85.2-99.8 µm) and width (37.1-48.1 µm), having a L/W ratio of (2.1-2.6). Maximum likelihood phylogenetic analyses of the different molecular loci (partial 18S rRNA, D2-D3 of 28S rRNA, internal transcribed spacer (ITS) rRNA, cytochrome oxidase subunit II (COII)-16S rRNA of mitochondrial DNA gene fragments and partial Hsp90 gene) placed this nematode on an independent branch in between M. graminicola and M. naasi and a cluster of species containing M. chitwoodi. M. fallax, and M. minor. Greenhouse tests showed that yellow and purple nutsedge were the best hosts, but perennial ryegrass, wheat, bentgrass, and barley were also hosts. [ABSTRACT FROM AUTHOR]

The article presents a study which assessed the risk of child neurodevelopmental disorders (NDDs) following exposure to antiepileptic drugs (AED) during pregnancy. It discusses the comparative analysis of a cohort of 1018 mother-child pairs of women with epilepsy (WWE) recorded in the UK Clinical Practice Research Datalink (CPRD) and a cohort without epilepsy.

We performed a retrospective analysis of the European Group for Blood and Marrow Transplantation database comparing the outcomes of multiple myeloma patients who received tandem autologous followed by allogeneic PSCT (auto-allo) with the outcomes of patients who underwent a reduced intensity conditioning allograft (early RIC) without prior autologous transplant. From 1996 to 2013, we identified a total of 690 patients: 517 patients were planned to receive auto-allo and 173 received an early RIC allograft without prior autologous transplant. With a median follow-up of 93 months, 5-year PFS survival was significantly better in the auto-allo group, 34% compared with 22% in the early RIC group (P<0.001). OS was also significantly improved in the auto-allo group with a 5-year rate of 59% vs 42% in the early RIC group (P=0.001). The non-relapse mortality rate was lower in the auto-allo group than in the early RIC group, with 1- and 3-year rates of 8% and 13% vs 20% and 28%, respectively (P<0.001). The relapse/progression rate was similar in the two groups, with 5-year rates of 50% for auto-allo and 46% for early RIC (P=0.42). These data suggest that planned tandem autologous allograft can improve overall survival compared with upfront RIC allograft alone in patients with multiple myeloma. [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]

Background: Sudden unexplained death in psychiatric patients may be due to drug-induced arrhythmia, of which lengthening of the rate-corrected QT interval (QTc) on the electrocardiogram is a predictive marker. We estimated the point prevalence of QTc lengthening in psychiatric patients and the effects of various psychotropic drugs.Methods: Electrocardiograms were obtained from 101 healthy reference individuals and 495 psychiatric patients in various inpatient and community settings and were analysed with a previously validated digitiser technique. Patients with and without QTc lengthening, QTc dispersion, and T-wave abnormality were compared by logistic regression to calculate odds ratios for predictive variables.Findings: Abnormal QTc was defined from the healthy reference group as more than 456 ms and was present in 8% (40 of 495) of patients. Age over 65 years (odds ratio 3.0 [95% CI 1.1-8.3]), use of tricyclic antidepressants (4.4 [1.6-12.1]), thioridazine (5.4 [2.0-13.7]), and droperidol (6.7 [1.8-24.8]) were robust predictors of QTc lengthening, as was antipsychotic dose (high dose 5.3 [1.2-24.4]; very high dose 8.2 [1.5-43.6]). Abnormal QT dispersion or T-wave abnormalities were not significantly associated with antipsychotic treatment, but were associated with lithium therapy.Interpretation: Antipsychotic drugs cause QTc lengthening in a dose-related manner. Risks are substantially higher for thioridazine and droperidol. These drugs may therefore confer an increased risk of drug-induced arrhythmia. [ABSTRACT FROM AUTHOR]

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.

We report substantial reductions in the frequency of severe paracetamol hepatotoxicity locally and nationally after legislative limitations on its sale. These reductions were not explained by changes in referral patterns or use of N-acetylcysteine. [ABSTRACT FROM AUTHOR]

Prospective follow-up of 136 babies exposed to ecstasy in utero indicated that the drug may be associated with a significantly increased risk of congenital defects (15.4% [95% CI 8.2-25.4]). Cardiovascular anomalies (26 per 1000 livebirths [3.0-90.0]) and musculoskeletal anomalies (38 per 1000 [8.0-109.0]) were predominant. [ABSTRACT FROM AUTHOR]

Background: Conifers, mainly of the genus Pinus, have invaded natural and productive landscapes worldwide. Controlling dense conifer invasions is challenging and requires both effective initial control methods and long-term site management to prevent re-invasion. Broadcast aerial herbicide application is often the preferred treatment method for dense infestations of pines with high rates of complex herbicide mixtures used. The objective of this study was to: (i) test the efficacy of four simple herbicide mixes (containing two active ingredients and one adjuvant) as compared to an operational standard (four active ingredients and three adjuvants) for control of Pinus contorta invasions in a field trial and (ii) to quantify the effect of treatment mixes on non-target vegetation to determine impacts to plant community composition., Results: We found that a simplified herbicide mix containing two active ingredients and one adjuvant was equally as effective as the current operational standard, with efficacy for all treatments increasing as a function of stem density. All herbicide treatments significantly impacted the post-spray community composition with differences among treatments in post-spray vegetation composition also detected. Following all treatments plant communities transitioned from a mixed native/exotic grassland-herb community to a simplified community dominated by exotic grasses., Conclusions: Our results indicate a simpler herbicide mix could be used for broadcast aerial control of dense pine invasion reducing total herbicide input and cost of the operation. Post-spray vegetation community recovery could reflect the impact of the herbicides used in the operation compounded by soil biogeochemical processes already initiated through the pine invasion. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Penicillin "allergy" labels are prevalent but frequently misdiagnosed. Mislabelled allergies are associated with adverse outcomes and increased antimicrobial resistance. With an urgent need to delabel the overwhelming number of mislabeled allergies, nonallergist evaluations have been advocated for low-risk individuals. Despite growing interest in non-allergist-led initiatives, evidence on their effectiveness, safety, and impact by direct comparisons is lacking., Objective: To assess the comparative outcomes of penicillin allergy evaluations conducted by allergists versus nonallergists., Methods: A prospective, multicenter, pragmatic study was conducted at 4 tertiary hospitals (1 allergist- vs 3 non-allergist-led) for low-risk penicillin allergy patients in Hong Kong-the Hong Kong Drug Allergy Delabelling Initiative 2 (HK-DADI2)., Results: Among 228 low-risk patients who underwent testing (32.9% by allergists, 67.1% by nonallergists), only 14 (6.1%) had positive penicillin allergy testing results. Delabeling rates (94.1% vs 93.3%; P = .777), positive skin test results (2.6% vs 2.7%; P > .99), and drug provocation test results (3.3% vs 2.7%; P = 1.000) were similar between allergists and nonallergists. There were no systemic reactions in either cohort. All patients had significant improvements in health-related quality of life (Drug Hypersensitivity Quality of Life Questionnaire scores -5.00 vs -8.33; P = .072). Nonallergist evaluations had shorter waiting times (0.57 vs 15.7 months; P < .001), whereas allergists required fewer consultations with higher rate of completing evaluations within a single visit (odds ratio, 0.04; P < .001)., Conclusions: With training and support, nonallergists can independently evaluate low-risk penicillin allergies. Compared with allergists, evaluation of low-risk penicillin allergy by nonallergists can be comparably effective, safe, and impactful on quality of life. More multidisciplinary partnerships to empower nonallergists to conduct allergy evaluations should be encouraged., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Global climate change and shift towards a bio-economy has heightened the need to design sustainable forestry systems that balance economic, environmental and social benefits. In New Zealand, production forests are dominated by planted Pinus radiata, which makes up 90 % of the planted forest area. There is very little data driven evidence in New Zealand to support diversifying across a range of tree species and what timber and non-timber benefits may be gained by diversifying tree species in New Zealand's production forests. The New Zealand New Forest Trial Series (NFTS) was designed and established in 2013 on marginal pastoral land to address the knowledge gap for how afforesting land with different trees species, both exotic and indigenous to New Zealand, across a climate range can deliver to both timber and non-timber benefits. These trials were planted with Cupressocyparis ovensii, Eucalyptus fastigata, Fraxinus excelsior, Nothofagus fusca ( plus Leptospermum scoparium ), Pinus radiata, Podocarpus totara and Sequoia sempervirens plus a control with no planting to monitor natural succession. The Before-After-Control-Impact (BACI) experiment design has collected pre-planting data describing the present vegetation and a range of soil properties, presented in this paper. This will allow the comparative monitoring of the changes that will occur through planting the various tree species on marginal land in different environments through time. With time the long-term trials will deliver data evidence on tree species survival when planted into marginal pastoral land, tree productivity and the flow of economic, environmental and social benefits from the new plantings. This knowledge will strengthen New Zealand's forestry sector confidence to make informed decisions to diversify tree species with changing climatic and social challenges., (© 2024 The Authors.)

Introduction: Penicillin allergy testing has been traditionally performed by allergists, but there remains a huge deficit of specialists. A multidisciplinary effort with nonallergists would be invaluable to overcome the magnitude of penicillin allergy labels via the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI). These consensus statements (CSs) offer recommendations and guidance to enable nonallergists to screen for low-risk (LR) patients and perform penicillin allergy testing., Methods: CSs were formulated by the HK-DADI Group using the Delphi method. An agreement was defined as greater than or equal to 80% consensus., Results: A total of 26 CSs reached consensus after multiple rounds of Delphi. CSs were categorized into risk assessment, skin testing, drug provocation testing (DPT), and post-testing management. For risk assessment, the essentials of allergy history and exclusion criteria were detailed. Patients with only LR features can proceed with testing by nonallergists. Skin tests should be performed prior to DPT. Details regarding the timing, preparation, and interpretation of skin tests were elaborated. DPT remains the gold standard to diagnose genuine allergy or tolerance and should be performed when there is a low pretest probability following negative skin testing. Details of DPT preparations, dosing protocols, and interpretation were elaborated. For post-testing management, inaccurate allergy labels should be delabeled following negative DPT with proper patient counseling., Conclusion: CSs support penicillin allergy testing by nonallergists in Hong Kong. LR cases can be managed by nonallergists at Spoke Clinics, with training and support of an allergist-led Hub., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Li, Wong, Chan, Chik, Chu, Ho, Leung, Li, Ng, Shum, Sin, Tso, Wu and Au.)

Background: Increased interarm systolic blood pressure difference (IASBPD) is one of the major predictors of cardiovascular disease. An IASBPD of >10 mmHg is of clinical significance. However, studies have reported a high number of patients visiting the emergency department (ED) with high IASBPD and varying correlation of IASBPD to age, ethnic background, and comorbidities such as hypertension and diabetes. Objective: The CALIBRATE study aimed to measure the IABPDs in the multiethnic patient population presenting to the ED in Qatar and to assess the distribution of IASBPD in this population. Methods: In a sitting position, two consecutive blood pressure (BP) measurements were recorded from the right and left arms for each participant using a calibrated automated machine and appropriate cuff sizes. The data were recorded using predefined data fields, including patient demographics, past medical, and social and family history. The continuous variables were reported as mean or median based on the distribution of data. The data were analyzed using Stata MP 14.0. Results: A total of 1800 patients, with a mean age of 34 (10) years, were prospectively recruited from the ED. The median absolute systolic BP difference (ΔSBP) between the right and left arms was 6 (3-10) mmHg, and it was the same for the first (ΔSBP1) and the second readings (ΔSBP2). The absolute average of ΔSBP1 and ΔSBP2 was 7 (4-10) mmHg. The difference in systolic BP difference (SBP) of < 20 mmHg for interarm blood pressure was seen in the 95th percentile of the population. No meaningful association could be detected between the IABPD and the study variables such as age, demographics, regions of interest, and risk factors. Conclusion: In population presenting to the ED, the IASBPD of at least 20 mmHg reached at the 95th percentile, validating the known significant difference. The utility of SBP difference can be improved further by taking the average of two individual readings., (© 2020 Bhutta, Qureshi, Shujauddin, Thomas, Masood, Dsouza, Iqbal, Irfan, Pathan, Thomas, licensee HBKU Press.)

Background: There have been recent increases in use of new psychoactive substances (NPS) associated with acute health harms including hospital presentations due to toxicity and increasing numbers of deaths. In response, the UK Government enacted generic legislation on 26th May 2016 (the Psychoactive Substances Act) making it an offence to produce, possess with intent to supply, supply, import or export, or possess within a custodial setting a psychoactive substance. We studied the impact of this Act on monthly frequency of enquiries made by health professionals to the UK National Poisons Information Service (NPIS) about NPS. We also studied five commonly used 'conventional' drugs of misuse that had been controlled prior to January 2009., Method: Anonymised clinical enquiries to the NPIS and accesses to the poisons information database TOXBASE were reviewed retrospectively from January 2009 to December 2018 to ascertain the trends in reported toxicity for NPS, cocaine, heroin, cannabis, amphetamines and MDMA. Data were analysed using interrupted time series analysis with the date of the PSA used as an independent predictor., Results: Over the period of study there were 3,866 NPIS telephone enquiries and 79,271 TOXBASE user accesses made by UK health professionals concerning NPS. There were increases in monthly TOXBASE accesses (t = 7.408, P < 0.0001) and telephone enquiries (t = 4.74, P < 0.001) over the pre-specified period January 2009 to May 2016. Comparing the period after the PSA with that before, there were significant reductions in TOXBASE accesses (t = -3.327, P < 0.001) and telephone enquiries (t = -6.97, P < 0.001), although reductions started before May 2016. There were no significant changes for the five conventional drugs. There were significant reductions in telephone enquiries (t = -3.418, P < 0.001) and non-significant reductions in TOXBASE accesses (t = -1.713, P = 0.089) for NPS between June 2016 and December 2018. Increases in telephone enquiries for cocaine and reductions TOXBASE accesses for MDMA were also observed over that period., Conclusions: There have been significant recent reductions in NPIS enquiry activity relating to NPS; although these began before enactment of the PSA in May 2016., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Venlafaxine is a serotonin noradrenaline reuptake inhibitor used to treat major depressive episodes and anxiety disorders. The primary aim of this study was to investigate spontaneous abortion risks following gestational exposure., Methods: This prospective observational comparative cohort study utilised data collected by the UK Teratology Information Service (UKTIS) between 1995 and 2018. The study sample included 281 venlafaxine exposed pregnancies matched to antidepressant unexposed (n = 1405) and SSRI exposed (n = 843) comparator groups., Results: After correction for variation in competing outcome rates and the stage of pregnancy at reporting, no statistically significant differences in the hazard of spontaneous abortion was observed following gestational venlafaxine use compared with either antidepressant unexposed (HR 1.28, 95% CI; 0.850-1.94) or SSRI exposed (HR 1.03, 95% CI; 0.681-1.57) pregnancies., Conclusions: No conclusive evidence is provided from this study that venlafaxine increases the risk of adverse pregnancy or fetal outcomes., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Ultrasound can be used to modify the functional interactions between casein and whey proteins in dairy systems. This study reports on ongoing developments in understanding the effect of ultrasound and heating on milk proteins in systems with modified casein-whey protein ratios (97:3, 80:20 and 50:50), prepared from milk protein concentrates that were fractionated by microfiltration, based on protein size. Heating of concentrated casein streams (9% w/w) at 80.0 °C for up to 9 min resulted in reduced gelation functionality and increased viscosity, even in the absence of added whey proteins. 20 kHz ultrasonication at 20.8 W calorimetric power for 1 min was able to break protein aggregates formed during heating, resulting in improved gelation and reduced viscosity. Interestingly, when heated whey protein was recombined with unheated casein the gelation properties were similar to unheated controls. In contrast, when heat treated casein streams were recombined with unheated whey protein, the gel forming functionality was reduced. This study therefore shows that using specific combinations of heat and/or ultrasound, fractionated dairy streams can be tailored for specific functional outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rennet gelation is used to produce many types of cheese. The effect of native whey protein on rennet gelation kinetics was investigated. Milks with a wide range of whey protein:casein (WP:CN) ratios (with standardised casein concentrations) were made from powders produced by microfiltration. Measurements of casein macro peptide release showed that native whey protein inhibited the enzymatic action of chymosin, which delayed the onset and reduced the subsequent rate of gelation. Experiments in which increased chymosin concentrations compensated for the inhibition, demonstrated that other factors also contributed to the reduced gelation rate. Neither an increase in viscosity nor a reduction in soluble calcium was responsible, leading to the conclusion that in addition to inhibiting chymosin, native whey proteins present a physical barrier to para-casein aggregation. This study demonstrates and explains how casein-enriched retentates from microfiltration gel faster than regular cheese milk that contains higher amounts of native whey protein., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Three essential experimental parameters in the ultrasonic emulsification process, namely sonication time, acoustic amplitude and processing volume, were individually investigated, theoretically and experimentally, and correlated to the emulsion droplet sizes produced. The results showed that with a decrease in droplet size, two kinetic regions can be separately correlated prior to reaching a steady state droplet size: a fast size reduction region and a steady state transition region. In the fast size reduction region, the power input and sonication time could be correlated to the volume-mean diameter by a power-law relationship, with separate power-law indices of -1.4 and -1.1, respectively. A proportional relationship was found between droplet size and processing volume. The effectiveness and energy efficiency of droplet size reduction was compared between ultrasound and high-pressure homogenisation (HPH) based on both the effective power delivered to the emulsion and the total electric power consumed. Sonication could produce emulsions across a broad range of sizes, while high-pressure homogenisation was able to produce emulsions at the smaller end of the range. For ultrasonication, the energy efficiency was higher at increased power inputs due to more effective droplet breakage at high ultrasound intensities. For HPH the consumed energy efficiency was improved by operating at higher pressures for fewer passes. At the laboratory scale, the ultrasound system required less electrical power than HPH to produce an emulsion of comparable droplet size. The energy efficiency of HPH is greatly improved at large scale, which may also be true for larger scale ultrasonic reactors.

Encapsulation of materials in particles dispersed in water has many applications in nutritional foods, imaging, energy production and therapeutic/diagnostic medicine. Ultrasonic technology has been proven effective at creating encapsulating particles and droplets with specific physical and functional properties. Examples include highly stable emulsions, functional polymeric particles with environmental sensitivity, and microspheres for encapsulating drugs for targeted delivery. This article provides an overview of the primary mechanisms arising from ultrasonics responsible for the formation of these materials, highlighting examples that show promise particularly in the development of foods and bioproducts., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Varenicline is a smoking cessation aid for which limited data exist concerning safety during human pregnancy. This multicentre prospective observational comparative cohort study was undertaken using surveillance data collected by the European Network of Teratology Information Services. The study sample consisted of 89 varenicline exposed pregnancies and two matched comparator groups; 267 non-teratogen exposed (NTE) controls and 78 exposed to nicotine replacement therapy or bupropion (NRT/B) for smoking cessation. For all exposed pregnancies, varenicline use only occurred in the first trimester, with a considerable proportion discontinuing use in the very early stages of pregnancy. The major congenital malformation rate (n=2/89, 2.25%) was in keeping with the expected background rate (2-4%), and was not significantly increased for first trimester varenicline-exposed infants in comparison with non-exposed controls (vs. NTE: OR 2.02, 95%CI 0.166 to 17.9, vs., Nrt/b: OR 0.874, 95%CI 0.0620 to 12.3). However, the small sample size produced very imprecise risk estimates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To conduct enhanced surveillance for signals of teratogenesis following use of the neuraminidase inhibitors zanamivir and oseltamivir in the treatment or post-exposure prophylaxis of 2009 A/H1N1 influenza during pregnancy., Design: Prospective cohort study, using national surveillance data collected by the UK Teratology Information Service (UKTIS) during the 2009 A/H1N1 pandemic., Setting: United Kingdom., Population: Pregnant women who were reported to UKTIS by healthcare professionals seeking advice about exposure to zanamivir and oseltamivir or to other non-teratogenic drugs., Methods: Pregnancy outcomes were collected for prospectively reported pregnancies exposed to zanamivir (n = 180) or oseltamivir (n = 27), and compared with a reference group of 575 prospectively reported pregnancies exposed to non-teratogenic drugs over the same period., Main Outcome Measures: Rates of major congenital malformation, preterm delivery and low birth weight., Results: No significant differences in overall rates of major malformation in live-born infants [adjusted odds ratios (aOR): zanamivir 0.37 (95% confidence interval 0.02-2.70); oseltamivir aOR 0.81 (0.05, 14.15)], preterm delivery [aOR: zanamivir 0.95 (0.45, 1.89); oseltamivir aOR 1.68 (0.38, 5.38)] or low birth weight [aOR: zanamivir 0.94 (0.25, 2.90); oseltamivir aOR 4.12 (0.59, 17.99)] were observed following exposure at any gestation. No major malformations were reported in 37 zanamivir or eight oseltamivir first trimester exposures., Conclusion: These surveillance data do not provide a signal that use of zanamivir or oseltamivir in pregnancy is associated with an increased risk of the adverse pregnancy outcomes studied but the data are too limited to state conclusively that there is no increase in risk., (© 2014 Royal College of Obstetricians and Gynaecologists.)

To enable consistency of investigation and the establishment of best practice standards, consensus guidelines were formulated previously by the UK National Poisons Information Service and the Association for Clinical Biochemistry. These joint guidelines have now been updated to reflect current best practice. The types of laboratory investigation required for poisoned patients are categorized as either (a) essential common laboratory investigations or (b) specific toxicological assays, and also as either (i) common or (ii) specialist or infrequent. Tests in categories (a) and (bi) should be available 24 hours per day, with a maximum turnaround time of 2 h. For the specialist assays, i.e. category (bii), availability and turnaround times have been specified individually. The basis for selection of these times has been clinical utility. The adoption of these guidelines, along with the use of the National Poisons Information Service (0844 8920111) and its online poisons information resource TOXBASE(®) (www.toxbase.org) enable the poisoned patient to receive appropriate, 'best practice' investigations according to their clinical needs and will avoid unnecessary investigations.

Stakeholders in plantation forestry are increasingly aware of the importance of the ecosystem services and non-market values associated with forests. In New Zealand, there is significant interest in establishing species other than Pinus radiata D. Don (the dominant plantation species) in the belief that alternative species are better suited to deliver these services. Significant risk is associated with this position as there is little objective data to support these views. To identify which species were likely to be planted to deliver ecosystem services, a survey was distributed to examine stakeholder perceptions. Stakeholders were asked which of 15 tree attributes contributed to the provision of five ecosystem services (amenity value, bioenergy production, carbon capture, the diversity of native habitat, and erosion control/water quality) and to identify which of 22 candidate tree species possessed those attributes. These data were combined to identify the species perceived most suitable for the delivery of each ecosystem service. Sequoia sempervirens (D.Don) Endl. closely matched the stakeholder derived ideotypes associated with all five ecosystem services. Comparisons to data from growth, physiological and ecological studies demonstrated that many of the opinions held by stakeholders were inaccurate, leading to erroneous assumptions regarding the suitability of most candidate species. Stakeholder perceptions substantially influence tree species selection, and plantations established on the basis of inaccurate opinions are unlikely to deliver the desired outcomes. Attitudinal surveys associated with engagement campaigns are essential to improve stakeholder knowledge, advancing the development of fit-for-purpose forest management that provides the required ecosystem services.

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.

The incidence of suicide attempts (fatal and non-fatal) was analysed in a prospective cohort of patients with schizophrenia randomly assigned to sertindole (4905 patients) or risperidone (4904 patients) in a parallel-group open-label study with blinded classification of outcomes (the sertindole cohort prospective study--SCoP). The total exposure was 6978 and 7975 patient-years in the sertindole and risperidone groups, respectively. Suicide mortality in the study was low (0.21 and 0.28 per 100 patients per year with sertindole and risperidone, respectively). The majority (84%) of suicide attempts occurred within the first year of treatment. Cox's proportional hazards model analysis of the time to the first suicide attempt, reported by treating psychiatrists and blindly reviewed by an independent expert group according to the Columbia Classification Algorithm of Suicide Assessment (both defining suicide attempts by association of suicidal act and intent to die), showed a lower risk of suicide attempt for sertindole-treated patients than for risperidone-treated patients. The effect was statistically significant with both evaluation methods during the first year of randomized treatment (hazard ratios [95% CI]: 0.5 [0.31-0.82], p=0.006; and 0.57 [0.35-0.92], p=0.02, respectively). With classification by an independent safety committee using a broader definition including all incidences of intentional self-harm, also those without clear suicidal intent, the results were not significant. A history of previous suicide attempts was significantly associated with attempted suicides in both treatment groups., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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., (© 2010 John Wiley & Sons A/S.)

Background: In April 2009 a novel influenza A virus (AH1N1v) of swine origin (swine flu) emerged, spreading rapidly and achieving pandemic status in June 2009. Pregnant women were identified as being at high risk of severe influenza-related complications and as a priority group for vaccination against AH1N1v. Limited information was available about the maternal and fetal risks of AH1N1v infection or of antiviral drug or AH1N1v vaccine use in pregnancy., Objectives: To assess rates of and risk factors for adverse outcomes following AH1N1v infection in pregnancy and to assess the adverse effects of the antiviral drugs and vaccines used in prevention and management., Methods: Prospective national cohort studies were conducted to identify pregnant women who were (1) suspected to be infected with AH1N1v or being treated with antiviral medication in primary care; (2) vaccinated against AH1N1v; and (3) admitted to hospital with confirmed AH1N1v. Characteristics of women with influenza-like illness (ILI) in primary care were compared with those of women without symptoms accepting or declining immunisation. Characteristics of women admitted to hospital with confirmed AH1N1v infection in pregnancy were compared with a historical cohort of over 1200 women giving birth in the UK who were uninfected with AH1N1v. Outcomes examined in hospitalised women included maternal death, admission to an intensive care unit, perinatal mortality and preterm birth. Risk factors for hospital and intensive care unit admission were examined in a full regression model., Results: The weekly incidence of ILI among pregnant women averaged 51/100,000 over the study period. Antiviral drugs were offered to 4.8% [95% confidence interval (CI) 4.0% to 5.9%] and vaccination to 64.8% (95% CI 64.7% to 68.9%) of registered pregnant women. Ninety pregnant women with ILI presenting in primary care were reported to the research team, 55 of whom were prescribed antiviral drugs and in 42 (76%) cases this was within 2 days of symptom onset. After comparison with 1329 uninfected pregnant women offered vaccination, pre-existing asthma was the only maternal factor identified as increasing risk of ILI presentation [adjusted odds ratio (OR) 2.0, 95% CI 1.0 to 3.9]. Maternal obesity and smoking during pregnancy were also associated with hospital admission with AH1N1v infection. Overall, 241 pregnant women were admitted to hospital with laboratory-confirmed AH1N1v infection. Eighty-three per cent of these women were treated with antiviral agents, but only 6% received antiviral treatment before hospital admission. Treatment within 2 days of symptom onset was associated with an 84% reduction in the odds of admission to an intensive therapy unit (OR 0.16, 95% CI 0.08 to 0.34). Women admitted to hospital with AH1N1v infection were more likely to deliver preterm; a three times increased risk was suggested compared with an uninfected population cohort (OR 3.1, 95% CI 2.1 to 4.5)., Conclusions: Earlier treatment with antiviral agents is associated with improved outcomes for pregnant women and further actions are needed in future pandemics to ensure that antiviral agents and vaccines are provided promptly to pregnant women, particularly in the primary care setting. Further research is needed on longer-term outcomes for infants exposed to AH1N1v influenza, antiviral drugs or vaccines during pregnancy.

Objectives: Stimulants used in the management of attention-deficit hyperactivity disorder have been associated with an increased risk of sudden cardiac death. One mechanism could involve drug-induced repolarization delay, reflected as prolongation of the QT interval on the electrocardiogram, which has been described in some recipients of methylphenidate in therapeutic doses. Because QT prolongation is usually dose-related, this study was performed to investigate effects of methylphenidate overdose on the QT interval., Methods: Adults with methylphenidate overdose identified retrospectively were matched for sex and heart rate with a control subject with overdose of a noncardiotoxic substance, mainly acetaminophen. Notes were reviewed for clinical details and coingestants. Admission 12-lead electrocardiograms were individually calibrated and analyzed using a manual digitizer in a blinded manner by a single investigator. Mean QRS and QT intervals were calculated and differences between groups were analyzed., Results: Twenty-three cases of methylphenidate overdose (median reported dose 120 mg, range 40-1,500 mg) were identified (10 males, 13 females, mean age 27.8 years). There were multiple coingestants. Level of consciousness and mean hemodynamic variables were within normal limits for all cases. Symptoms recorded in cases included anxiety (32%), dilated pupils (20%), abdominal pain (16%), vomiting (12%), palpitations (12%), and chest pain (8%). No arrhythmias were recorded. Mean heart rate was 92.4/min in methylphenidate cases and 93.8/min in the heart rate-matched controls. There were no significant differences between the groups in mean QRS (cases 86.1, controls 86.2, mean difference 0.1, 95% confidence interval = -5.1 to 5.0 ms) or mean QT intervals (cases 354, controls 355, mean difference -0.8, 95% confidence interval = -10.7 to 9.2 ms)., Conclusions: Methylphenidate overdose is unlikely to have substantial effects on the QRS or QT intervals.