The "lessons" of the Australian "heroin shortage"

Heroin use causes considerable harm to individual users including dependence, fatal and nonfatal overdose, mental health problems, and blood borne virus transmission. It also adversely affects the community through drug dealing, property crime and reduced public amenity. During the mid to late 1990s in Australia the prevalence of heroin use increased as reflected in steeply rising overdose deaths. In January 2001, there were reports of an unpredicted and unprecedented reduction in heroin supply with an abrupt onset in all Australian jurisdictions. The shortage was most marked in New South Wales, the State with the largest heroin market, which saw increases in price, dramatic decreases in purity at the street level, and reductions in the ease with which injecting drug users reported being able to obtain the drug. The abrupt onset of the shortage and a subsequent dramatic reduction in overdose deaths prompted national debate about the causes of the shortage and later international debate about the policy significance of what has come to be called the "Australian heroin shortage". In this paper we summarise insights from four years' research into the causes, consequences and policy implications of the "heroin shortage"

Self-harm and suicide during and after opioid agonist treatment among primary care patients in England: a cohort study

BACKGROUND: The first 4 weeks after initiation and cessation of opioid agonist treatment for opioid dependence are associated with an increased risk of all-cause mortality and overdose. We aimed to investigate whether the rate of self-harm and suicide among people who were prescribed opioid agonist treatment differs during initiation, cessation, and the remainder of time on and off treatment. METHODS: We did a retrospective cohort study and used health-care records from UK Clinical Practice Research Datalink, linked to mortality and hospital admission data, for adults (age 18–75 years at cohort entry) who were prescribed opioid agonist treatment at least once in primary care in England between Jan 2, 1998, and Nov 30, 2018. We estimated rates and adjusted risk ratios (aRRs) of hospital admissions for self-harm and death by suicide, comparing time during and after treatment, as well as comparing stable periods of time on treatment with treatment initiation, cessation, and the remaining time off treatment. FINDINGS: Between Jan 2, 1998, and Nov 30, 2018, 8070 patients (5594 [69·3%] men and 2476 [30·7%] women) received 17 004 episodes of opioid agonist treatment over 40 599 person-years. Patients were mostly of White ethnicity (7006 [86·8%] patients). 807 episodes of self-harm (1·99 per 100 person-years) and 46 suicides (0·11 per 100 person-years) occurred during the study period. The overall age-standardised and sex-standardised mortality ratio for suicide was 7·5 times (95% CI 5·5–10·0) higher in the study cohort than in the general population. Opioid agonist treatment was associated with a reduced risk of self-harm (aRR in periods off treatment 1·50 [95% CI 1·21–1·88]), but was not significantly associated with suicide risk (aRR in periods off treatment 1·21 [0·64–2·28]). Risk of self-harm (aRR 2·60 [95% CI 1·83–3·70]) and suicide (4·68 [1·63–13·42]) were both elevated in the first 4 weeks after stopping opioid agonist treatment compared with stable periods on treatment. INTERPRETATION: Stable periods of opioid agonist treatment are associated with reduced risk of self-harm, emphasising the importance of improving retention of patients in treatment. The first month following cessation of opioid agonist treatment is a period of increased risk of suicide and self-harm, during which additional psychosocial support is required. FUNDING: Medical Research Council

Was an increase in cocaine use among injecting drug users in New South Wales, Australia, accompanied by an increase in violent crime?

BACKGROUND: A sharp reduction in heroin supply in Australia in 2001 was followed by a large but transient increase in cocaine use among injecting drug users (IDU) in Sydney. This paper assesses whether the increase in cocaine use among IDU was accompanied by increased rates of violent crime as occurred in the United States in the 1980s. Specifically, the paper aims to examine the impact of increased cocaine use among Sydney IDU upon police incidents of robbery with a weapon, assault and homicide. METHODS: Data on cocaine use among IDU was obtained from the Illicit Drug Reporting System (IDRS). Monthly NSW Police incident data on arrests for cocaine possession/use, robbery offences, homicides, and assaults, were obtained from the Bureau of Crime Statistics and Research. Time series analysis was conducted on the police data series where possible. Semi-structured interviews were conducted with representatives from law enforcement and health agencies about the impacts of cocaine use on crime and policing. RESULTS: There was a significant increase in cocaine use and cocaine possession offences in the months immediately following the reduction in heroin supply. There was also a significant increase in incidents of robbery where weapons were involved. There were no increases in offences involving firearms, homicides or reported assaults. CONCLUSION: The increased use of cocaine among injecting drug users following the heroin shortage led to increases in violent crime. Other States and territories that also experienced a heroin shortage but did not show any increases in cocaine use did not report any increase in violent crimes. The violent crimes committed did not involve guns, most likely because of its stringent gun laws, in contrast to the experience of American cities that have experienced high rates of cocaine use and violent crime

Ultrafast Electric Field-induced Phase Transition in Bulk Bi0.5Na0.5TiO3 under High Intensity Terahertz Irradiation

“This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Photonics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acsphotonics.0c01559”Ultrafast polarization switching is being considered for the next generation of ferroelectric based devices. Recently, the dynamics of the field-induced transitions associated with this switching have been difficult to explore, due to technological limitations. The advent of terahertz (THz) technology has now allowed for the study of these dynamic processes on the picosecond (ps) scale. In this paper, intense terahertz (THz) pulses were used as a high-frequency electric field to investigate ultrafast switching in the relaxor ferroelectric, Bi0.5Na0.5TiO3. Transient atomic-scale responses, which were evident as changes in reflectivity, were captured by THz probing. The high energy THz pulses induce an increase in reflectivity, associated with an ultrafast field-induced phase transition from a weakly polar phase (Cc) to a strongly polar phase (R3c) within 20 ps at 200 K. This phase transition was confirmed using X-ray powder diffraction and by electrical measurements which showed a decrease in the frequency dispersion of relative permittivity at low frequencies

Profile and correlates of injecting-related injuries and diseases among people who inject drugs in Australia

Introduction: People who inject drugs (PWID) commonly experience harms related to their injecting, many of which are consequences of modifiable drug use practices. There is currently a gap in our understanding of how certain injecting-related injuries and diseases (IRID) cluster together, and socio-demographic and drug use characteristics associated with more complex clinical profiles. Method: Surveys were conducted with 902 Australian PWID in 2019. Participants provided information regarding their drug use, and past month experience of the following IRID: artery injection, nerve damage, skin and soft tissue infection, thrombophlebitis, deep vein thrombosis, endocarditis, septic arthritis, osteomyelitis, and septicaemia. We performed a latent class analysis, grouping participants based on reported IRID and ran a class-weighted regression analysis to determine variables associated with class-membership. Results: One-third (34 %) of the sample reported any IRID. A 3-class model identified: 1) no IRID (73 %), moderate IRID (21 %), and 3) high IRID (6%) clusters. Re-using one`s own needles was associated with belonging to the high IRID versus moderate IRID class (ARRR = 2.38; 95 % CI = 1.04−5.48). Other factors, including daily injecting and past 6-month mental health problems were associated with belonging to moderate and high IRID classes versus no IRID class. Conclusion: A meaningful proportion of PWID reported highly complex IRID presentations distinguished by the presence of thrombophlebitis and associated with greater re-use of needles. Increasing needle and syringe coverage remains critical in addressing the harms associated with injecting drug use and expanding the capacity of low-threshold services to address less severe presentations might aid in reducing IRID amongst PWID

Iniciado projeto multiinstitucional de melhoramento de pêra.

o fato da pêra ser importada em larga escala pelo Brasil (para atender nada menos que 90% da demanda de consumo desta fruta!), associado à necessidade dos fruticultores de ampliarem o leque de alternativas de espécies para produção comercial, tem gerado novos desafios para a pesquisa agropecuária. Nesta linha, foi iniciado, em outubro de 2006, o projeto "Desenvolvimento de cultivares para a viabilização da cultura da pereira no Brasil", o qual trata de uma proposta de pesquisa que visa superar a deficiência de cultivares adaptadas e capazes de produzir em quantidade e qualidade suficientes e com regularidade. Pretende-se, em última análise, participar da construção de uma trajetória de modificação do quadro atual, onde o Brasil figura como maior importador mundial de pêra, de forma a garantir, para o futuro, auto-suficiência na produção desta fruta, mediante a viabilização da produção sustentável e competitiva.bitstream/item/200240/1/8650-2007-p.22.pd

COVID-19 Testing in a Weekly Cohort Study of Gay and Bisexual Men: The Impact of Health-Seeking Behaviors and Social Connection

Gay, bisexual, and other men who have sex with men (GBM) have developed community norms for regular HIV/STI testing. We investigated factors associated with self-reported COVID-19 testing in response to reported COVID-19 cases and public health restrictions. Participants responded to weekly cohort surveys between 10th May 2021 and 27th September 2021. We used the Andersen-Gill extensions to the Cox proportional hazards model for multivariable survival data to predict factors influencing COVID-19 testing. Mean age of the 942 study participants was 45.6 years (SD: 13.9). In multivariable analysis, GBM were more likely to report testing during periods of high COVID-19 caseload in their state of residence; if they were younger; university educated; close contact of someone with COVID-19; or reported coping with COVID-19 poorly. COVID-19 testing was higher among men who: were more socially engaged with other GBM; had a higher proportion of friends willing to vaccinate against COVID-19; and were willing to contact sexual partners for contact tracing. Social connection with other gay men was associated with COVID-19 testing, similar to what has been observed throughout the HIV epidemic, making community networks a potential focus for the promotion of COVID-19 safe practices

Com a genética vamos superar o desafio da produção de pêra?

A pêra é o principal item da pauta de importações de frutas frescas do Brasil. Em 2005, representou, de acordo com o Datafruta (Ibraf, 2006),102.558 t (46%) de um total de 224.495 ton e US$54,016,000 (43$125,634,000. Dados do MAPA (Brasil, 2006) mostram que, no período de 1996 a 2005, houve importação anual média de quase 120.000 ton de pêras, o que correspondeu a desembolso anual ao redor de US$ 60 milhões, para atender a 90% da demanda interna de consumo. Este quadro nos remete à trajetória da cultura da maçã no Brasil.bitstream/item/200091/1/7916-2006-p.2.pd

The biosynthesis of thymol, carvacrol, and thymohydroquinone in Lamiaceae proceeds via cytochrome P450s and a short-chain dehydrogenase

Thymol and carvacrol are phenolic monoterpenes found in thyme, oregano, and several other species of the Lamiaceae. Long valued for their smell and taste, these substances also have antibacterial and anti-spasmolytic properties. They are also suggested to be precursors of thymohydroquinone and thymoquinone, monoterpenes with anti-inflammatory, antioxidant, and antitumor activities. Thymol and carvacrol biosynthesis has been proposed to proceed by the cyclization of geranyl diphosphate to γ-terpinene, followed by a series of oxidations via p-cymene. Here, we show that γ-terpinene is oxidized by cytochrome P450 monooxygenases (P450s) of the CYP71D subfamily to produce unstable cyclohexadienol intermediates, which are then dehydrogenated by a short-chain dehydrogenase/reductase (SDR) to the corresponding ketones. The subsequent formation of the aromatic compounds occurs via keto–enol tautomerisms. Combining these enzymes with γ-terpinene in in vitro assays or in vivo in Nicotiana benthamiana yielded thymol and carvacrol as products. In the absence of the SDRs, only p-cymene was formed by rearrangement of the cyclohexadienol intermediates. The nature of these unstable intermediates was inferred from reactions with the γ-terpinene isomer limonene and by analogy to reactions catalyzed by related enzymes. We also identified and characterized two P450s of the CYP76S and CYP736A subfamilies that catalyze the hydroxylation of thymol and carvacrol to thymohydroquinone when heterologously expressed in yeast and N. benthamiana. Our findings alter previous views of thymol and carvacrol formation, identify the enzymes involved in the biosynthesis of these phenolic monoterpenes and thymohydroquinone in the Lamiaceae, and provide targets for metabolic engineering of high-value terpenes in plants

Parental supply of alcohol and alcohol consumption in adolescence: prospective cohort study

Background: Parents are a major supplier of alcohol to adolescents, yet there is limited research examining the impact of this on adolescent alcohol use. This study investigates associations between parental supply of alcohol, supply from other sources, and adolescent drinking, adjusting for child, parent, family and peer variables. Method: A cohort of 1927 adolescents was surveyed annually from 2010 to 2014. Measures include: consumption of whole drinks; binge drinking (>4 standard drinks on any occasion); parental supply of alcohol; supply from other sources; child, parent, family and peer covariates. Results: After adjustment, adolescents supplied alcohol by parents had higher odds of drinking whole beverages [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.33–2.45] than those not supplied by parents. However, parental supply was not associated with bingeing, and those supplied alcohol by parents typically consumed fewer drinks per occasion (incidence rate ratio 0.86, 95% CI 0.77–0.96) than adolescents supplied only from other sources. Adolescents obtaining alcohol from non-parental sources had increased odds of drinking whole beverages (OR 2.53, 95% CI 1.86–3.45) and bingeing (OR 3.51, 95% CI 2.53–4.87). Conclusions: Parental supply of alcohol to adolescents was associated with increased risk of drinking, but not bingeing. These parentally-supplied children also consumed fewer drinks on a typical drinking occasion. Adolescents supplied alcohol from non-parental sources had greater odds of drinking and bingeing. Further follow-up is necessary to determine whether these patterns continue, and to examine alcohol-related harm trajectories. Parents should be advised that supply of alcohol may increase children's drinking