Forest carbon stock development following extreme drought-induced dieback of coniferous stands in Central Europe: a CBM-CFS3 model application.

BACKGROUND: We analyze the forest carbon stock development following the recent historically unprecedented dieback of coniferous stands in the Czech Republic. The drought-induced bark-beetle infestation resulted in record-high sanitary logging and total harvest more than doubled from the previous period. It turned Czech forestry from a long-term carbon sink offsetting about 6% of the country's greenhouse gas emissions since 1990 to a significant source of CO2 emissions in recent years (2018-2021). In 2020, the forestry sector contributed nearly 10% to the country's overall GHG emissions. Using the nationally calibrated Carbon Budget Model of the Canadian Forest Sector (CBM-CFS3) at a regional (NUTS3) spatial resolution, we analyzed four scenarios of forest carbon stock development until 2070. Two critical points arise: the short-term prognosis for reducing current emissions from forestry and the implementation of adaptive forest management focused on tree species change and sustained carbon accumulation. RESULTS: This study used four different spruce forest dieback scenarios to assess the impact of adaptive forest management on the forest carbon stock change and CO2 emissions, tree species composition, harvest possibilities, and forest structure in response to the recent unprecedented calamitous dieback in the Czech Republic. The model analysis indicates that Czech forestry may stabilize by 2025 Subsequently, it may become a sustained sink of about 3 Mt CO2 eq./year (excluding the contribution of harvested wood products), while enhancing forest resilience by the gradual implementation of adaptation measures. The speed of adaptation is linked to harvest intensity and severity of the current calamity. Under the pessimistic Black scenario, the proportion of spruce stands declines from the current 43-20% by 2070, in favor of more suited tree species such as fir and broadleaves. These species would also constitute over 50% of the harvest potential, increasingly contributing to harvest levels like those generated by Czech forestry prior to the current calamity. The standing stock would only be recovered in 50 years under the optimistic Green scenario. CONCLUSION: The results show progress of adaptive management by implementing tree species change and quantify the expected harvest and mitigation potential in Czech forestry until 2070.

Buprenorphine/naloxone versus methadone and lofexidine in community stabilisation and detoxification: A randomised controlled trial of low dose short-term opiate-dependent individuals.

Buprenorphine/naloxone, methadone and lofexidine are medications with utility in the treatment of opiate withdrawal. We report the first randomised controlled trial to compare the effects of these two medications on withdrawal symptoms and outcome during opiate induction/stabilisation and detoxification. A double-blind randomised controlled trial was conducted in an outpatient satellite clinic of a specialist drug service. Eighty opiate dependent individuals meeting DSM-IV criteria for opiate dependence, using ⩽ ½ g heroin smoked/chased or » g heroin injected or ⩽ 30mg methadone, with ⩽ 3 years of opioid dependency, underwent a short-term opiate treatment programme involving induction/stabilisation on methadone 30mg or buprenorphine/naloxone 4mg/1mg, followed by detoxification (where the methadone group was assisted by lofexidine). The main outcome measures were urine drug screens for opiates and withdrawal and craving questionnaires. There were no overall differences in positive urine drug screens and drop-outs during any phase of the study. During induction/stabilisation, withdrawal symptoms subsided more slowly for buprenorphine/naloxone than for methadone, and craving was significantly higher in the buprenorphine/naloxone group ( p<0.05, 95% confidence interval -3.5, -0.38). During detoxification, withdrawal symptoms were significantly greater and the peak of withdrawal was earlier for the methadone/lofexidine group than the buprenorphine/naloxone group ( p<0.01, 95% confidence interval 3.0, 8.3). Methadone/lofexidine and buprenorphine/naloxone had comparable outcomes during rapid outpatient stabilisation and detoxification in low dose opiate users.

Valuing environmental health for informed policy-making.

BACKGROUND: Monetized environmental health impact assessments help to better evaluate the environmental burden of a wide range of economic activities. Apart from the limitations and uncertainties in physical and biological science used in such assessments, assumptions taken from economic valuation may also substantially influence subsequent policy-making considerations. AIM: This study attempts to demonstrate the impact of normative policy assumptions on quantified external costs using a case study of recently discussed variants of future coal mining and use of extracted coal in electricity and heat generation in the Czech Republic. METHODS: A bottom-up impact-pathway approach is used for quantification of external costs. Several policy perspectives are elaborated for aggregating impacts that differ in geographic coverage and in how valuation of quantified impacts is adjusted in a particular perspective. RESULTS: We find that the fraction of monetized external impacts taken into policy-making considerations may vary according to choice of decision perspective up to a factor of 10. CONCLUSION: At present there are virtually no hard rules for defining geographical boundaries or adjusting values for a summation of monetized environmental impacts. We, however, stress that any rigorous external cost assessment should, for instance in a separate calculation, take account of impacts occurring beyond country borders.

Ranking the harm of non-medically used prescription opioids in the UK.

A panel of nine experts applied multi-criteria decision analysis (MCDA) to determine the relative overall harm to users and harms to others of street heroin (injected and smoked) and eleven non-medically used prescription opioids. The experts assessed harm scores for each of the 13 opioids on each of 20 harm criteria, weighted the criteria and explored the resulting weighted harm scores for each opioid. Both forms of heroin scored very high: overall harm score of 99 for injected heroin and 72 for smoked heroin on a scale of 0-100. The main feature that distinguishes both forms of street heroin use is that their harm to others is more than five times that of the other eleven opioids. The overall harm score of fentanyl (including injection of fentanyl extracted from patches) and diamorphine (medically prescribed form of heroin) was 54 and 51, respectively, whereas that of orally used opioids ranged from 32 (pethidine) to 11 (codeine-containing pharmaceuticals). Injected street heroin, fentanyl and diamorphine emerged as most harmful to users, with the latter two very low in harm to others. Pethidine, methadone, morphine and oxycodone are also low in harm to others, while moderate in harm to users. We conclude that the overall harms of non-medically used prescription opioids are less than half that of injected street heroin. These data may give a basis for precautionary regulatory measures that should be considered if the rising trend in non-medical use of prescription opioids were to become evident in the UK.

Pharmacological strategies for detoxification.

Detoxification refers to the safe discontinuation from a substance of dependence and is distinct from relapse prevention. Detoxification usually takes between a few days and a few weeks to complete, depending on the substance being misused, the severity of dependence and the support available to the user. Psychosocial therapies alongside pharmacological treatments are essential to improve outcome. The dependencies considered in this overview are detoxification from opioids (with methadone, buprenorphine, α2-adrenoceptor agonists and adjunct medications), alcohol (with benzodiazepines, anti-glutamatergics and γ-aminobutyric acid (GABA)-ergic drugs), stimulants and cannabis (with no clear recommended pharmacological treatments), benzodiazepines (with dose tapering) and nicotine (with nicotine replacement therapy, antidepressants and partial agonists). Evidence is limited by a lack of controlled trials robust enough for review bodies, and more research is required into optimal treatment doses and regimes, alone and in combination.

Benzodiazepine dependence and its treatment with low dose flumazenil.

Globally benzodiazepines remain one of the most prescribed medication groups, especially in the primary care setting. With such high levels of prescribing it is not surprising that benzodiazepine dependence is common, cutting across all socioeconomic levels. Despite recognition of the potential for the development of iatrogenic dependence and the lack of any effective treatment, benzodiazepines continue to be widely prescribed in general practice. Conventional dependence management, benzodiazepine tapering, is commonly a protracted process over several weeks or months. It is often associated with significant withdrawal symptoms and craving leading to patient drop out and return to use. Accordingly, there is a worldwide need to find effective pharmacotherapeutic interventions for benzodiazepine dependence. One drug of increasing interest is the GABAA benzodiazepine receptor antagonist/partial agonist, flumazenil. Multiple bolus intravenous infusions of low dose flumazenil used either with or without benzodiazepine tapering can reduce withdrawal sequelae, and/or longer term symptoms in the months following withdrawal. Preliminary data suggest that continuous intravenous or subcutaneous flumazenil infusion for 4 days significantly reduces acute benzodiazepine withdrawal sequelae. The subcutaneous infusion was shown to be tissue compatible so the development of a longer acting (i.e. several weeks) depot flumazenil formulation has been explored. This could be capable of managing both acute and longer term benzodiazepine withdrawal sequelae. Preliminary in vitro water bath and in vivo biocompatibility data in sheep show that such an implant is feasible and so is likely to be used in clinical trials in the near future.

Single bright light exposure decreases sweet taste threshold in healthy volunteers.

INTRODUCTION: Bright light exposure can alter circulating serotonin levels, and alteration of available serotonin by acute selective serotonin reuptake inhibition significantly lowers sweet but not salt taste recognition thresholds. We tested the hypothesis that bright light exposure would increase sweet but not salt taste sensitivity in healthy adults. METHODS: Fourteen healthy volunteers were exposed to bright (10,000 lux) and dim (<20 lux) light for 30 min each, in counterbalanced order. Measures of taste perception (salt and sweet) and mood were determined at baseline, and before and after each light exposure period. RESULTS: Recognition thresholds for sucrose were significantly lower after bright but not dim light exposure. Thresholds for salt were unaffected by either condition. There were no significant changes in taste acuity, intensity or pleasantness for both the taste modalities and on visual analogue scales (VASs) for mood, anxiety, sleepiness and alertness, under either light condition. CONCLUSION: Brief bright light exposure reduces sweet but not salt taste recognition thresholds in healthy humans.

Opiate agonists and antagonists modulate taste perception in opiate-maintained and recently detoxified subjects.

Heroin addicts consume large quantities of refined sugars. This study investigated the effect of opiate use and antagonism on sweet taste in opiate-maintained drug users and detoxified former chronic opiate users, using a within-subject design. Seven opiate users received methadone and seven buprenorphine maintenance. Six detoxified subjects received naltrexone. Sucrose recognition thresholds and measurements of pleasantness and intensity were determined before and four hours after 1) a single dose of methadone or buprenorphine or 2) naltrexone. Control data were taken from a cohort of healthy volunteers including smokers. All measures of sweet and salt taste perception were significantly greater in opiate users and recently detoxified subjects compared to control subjects, with the exception of sweet pleasantness, which returned to control level after detoxification. Acute methadone administration reduced salt thresholds and unpleasantness to control levels. Increased sweet thresholds and salt unpleasantness in detoxified subjects were reversed by acute opioid antagonism, returning to control levels. These results suggest that opiate use and antagonism alters taste perception. Some of the alterations reverse on detoxification (sweet pleasantness), and others can be reversed by opioid antagonism (sweet threshold, salt unpleasantness). Changes in taste perception may underlie altered consumption of refined sugars in opiate users.

Rare and new etiological agents revealed among 178 clinical Aspergillus strains obtained from Czech patients and characterized by molecular sequencing.

A collection of 178 Aspergillus isolates, recovered from Czech patients, mostly from 2007-2011, was subjected to multilocus DNA sequence typing using the ITS region, ß-tubulin, and calmodulin genes. An unusually wide spectrum of etiologic agents that included 36 species of Aspergillus is discussed in the context of recent taxonomic and clinical reports. Invasive aspergillosis (IA), onychomycosis, and otitis externa were the predominant clinical entities. Five cases due to species newly proven as etiologic agents of human mycoses, as well as cases with unique clinical manifestations caused by unusual agents are discussed in more detail. Three species (i.e., A. insulicola, A. westerdijkiae and A. tritici) were identified as the confirmed etiologic agents of non-dermatophytic onychomycosis. Emericella rugulosa was recovered from a premature newborn with a fatal necrotising disseminated infection and is reported for only the second time as the cause of IA. Furthermore, we document the first infection due to A. calidoustus in a patient with chronic granulomatous disease. The infection manifested as a latent brain aspergilloma with an unusual clinical-laboratory finding. In addition to the well-known agents of human mycosis, several rarely isolated or poorly documented species were identified. An undescribed cryptic species related to A. versicolor was found to be common among isolates linked to proven and probable onychomycosis. An isolate representing A. fresenii, or an unnamed sister species, were causal agents of otomycosis. Three well defined, and tentative new species belonging to section Cervini, Candidi and Aspergillus (Eurotium spp.), were associated with cases of probable onychomycosis.

Opioid dependence.

INTRODUCTION: Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three stages to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final stage is relapse prevention. This treatment process contributes to recovery of the individual, which also includes improved overall health and wellbeing, as well as engagement in society. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimens.

Taste and weight: is there a link?

Investigations of the relations between taste perception and obesity have concentrated largely on sweet and bitter tastes, with little work on the "savory" tastes-salt and glutamate-and very little work on sour taste. This article briefly reviews current understanding of the relations between the ability to taste different tastes (ie, taste threshold for sweet, bitter, sour, salt, and umami) and body mass. Obese children and adolescents show a disturbance in some tastes, with reported reductions in sweet and salt thresholds. Observations on relations between sweet taste threshold and obesity are contradictory; literature discrepancies may depend on the techniques used to evaluate taste. Obese women, however, report higher intensities of monosodium glutamate perception. Taste thresholds have been reported to be raised (bitter and sour), lowered (salt), or unchanged (sweet) in obese adults. Taste perceptual changes (threshold, intensity) in obesity are complex and may be different in obese men and women and in adults and children. Very little is currently known about the relations between savory tastes-salt and umami-and body weight, and these areas merit further study.

Differential diagnosis of apneas in preterm infants.

Clinically relevant apneas, which are common in preterm infants, may adversely affect later neuropsychological condition in this group of patients. Pharmacotherapy to stimulate respiratory functions may be unsuccessful. Polygraphic recording may help in the differential diagnosis of these clinically relevant events. Twenty-nine preterm neonates born before 36 weeks of gestational age were examined using polygraphic recording (respiration--two channels, perioral electromyography, oxygen saturation, heart rate, electroencephalography, electrocardiography, electrooculography). The examination was ordered by the attending physician after an unsuccessful treatment of apnea by Aminophylline, and it should contribute to the clarification of the causes of these events. In the course of the polygraphic examinations, altogether 63 episodes were recorded during which the pulse oximeter alarm signal was set off. In 42 cases, the alarm signal was set off in events during which SaO(2) fell below 85%. In the remaining 21 cases, the alarm signal was set off in episodes during which early bradycardia below 90/min occurred. The onset of apnea was very often associated with the phasic increase of the perioral electromyography and with electroencephalography arousal reaction. Because of suspicion that these apneas may be triggered by episodes of gastroesophageal reflux, the interruption of the Aminophylline treatment and setting up an antireflux regimen were recommended. These therapeutic measures had a positive effect: The frequency of alarm signals decreased within 48 h by a statistically significant 50%. In cases where the pharmacotherapy of apnea by stimulation of respiratory functions is not successful, differential diagnostic analysis should be performed. Polygraphy may contribute to the clarification of the causes underlying clinically relevant apneas in a view of newly described polygraphic signs. It is feasible to suspect, based on these signs, that gastroesophageal reflux is the cause for clinically significant apneas in that case.

Opioid dependence.

INTRODUCTION: Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three approaches to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final aim is relapse prevention. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimes.

Opioid dependence.

INTRODUCTION: Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three approaches to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state, such as craving and mood, and independent of circumstances, such as finance, and physical location. The next stage is to withdraw (detox) from opioids. The final aim is relapse prevention. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: buprenorphine, clonidine, lofexidine, methadone, naltrexone, and ultra-rapid withdrawal.

Human taste thresholds are modulated by serotonin and noradrenaline.

Circumstances in which serotonin (5-HT) and noradrenaline (NA) are altered, such as in anxiety or depression, are associated with taste disturbances, indicating the importance of these transmitters in the determination of taste thresholds in health and disease. In this study, we show for the first time that human taste thresholds are plastic and are lowered by modulation of systemic monoamines. Measurement of taste function in healthy humans before and after a 5-HT reuptake inhibitor, NA reuptake inhibitor, or placebo showed that enhancing 5-HT significantly reduced the sucrose taste threshold by 27% and the quinine taste threshold by 53%. In contrast, enhancing NA significantly reduced bitter taste threshold by 39% and sour threshold by 22%. In addition, the anxiety level was positively correlated with bitter and salt taste thresholds. We show that 5-HT and NA participate in setting taste thresholds, that human taste in normal healthy subjects is plastic, and that modulation of these neurotransmitters has distinct effects on different taste modalities. We present a model to explain these findings. In addition, we show that the general anxiety level is directly related to taste perception, suggesting that altered taste and appetite seen in affective disorders may reflect an actual change in the gustatory system.

Quantitative topographic differentiation of the neonatal EEG.

OBJECTIVE: To test the discriminatory topographic potential of a new method of the automatic EEG analysis in neonates. A quantitative description of the neonatal EEG can contribute to the objective assessment of the functional state of the brain, and may improve the precision of diagnosing cerebral dysfunctions manifested by 'disorganization', 'dysrhythmia' or 'dysmaturity'. METHODS: 21 healthy, full-term newborns were examined polygraphically during sleep (EEG-8 referential derivations, respiration, ECG, EOG, EMG). From each EEG record, two 5-min samples (one from the middle of quiet sleep, the other from the middle of active sleep) were subject to subsequent automatic analysis and were described by 13 variables: spectral features and features describing shape and variability of the signal. The data from individual infants were averaged and the number of variables was reduced by factor analysis. RESULTS: All factors identified by factor analysis were statistically significantly influenced by the location of derivation. A large number of statistically significant differences were also established when comparing the effects of individual derivations on each of the 13 measured variables. Both spectral features and features describing shape and variability of the signal are largely accountable for the topographic differentiation of the neonatal EEG. CONCLUSIONS: The presented method of the automatic EEG analysis is capable to assess the topographic characteristics of the neonatal EEG, and it is adequately sensitive and describes the neonatal electroencephalogram with sufficient precision. SIGNIFICANCE: The discriminatory capability of the used method represents a promise for their application in the clinical practice.

Using [11C]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: clinical and preclinical studies.

Substitute methadone prescribing is one of the main modes of treatment for opioid dependence with established evidence for improved health and social outcomes. However, the pharmacology underpinning the effects of methadone is little studied despite controversies about dosing in relation to outcome. We therefore examined the relationship between methadone dose and occupation of opioid receptors in brain using the positron emission tomography (PET) radioligand [(11)C]diprenorphine in humans and rats. Eight opioid-dependent subjects stable on their substitute methadone (18-90 mg daily) had an [(11)C]diprenorphine PET scan at predicted peak plasma levels of methadone. These were compared with eight healthy controls. No difference in [(11)C]diprenorphine binding was found between the groups, with no relationship between methadone dose and occupancy. Adult male Sprague-Dawley rats that had been given an acute i.v. injection of methadone hydrochloride (0.35, 0.5, 0.7, or 1.0 mg kg(-1)) before [(11)C]diprenorphine showed a dose-dependent increase in biodistribution but no reduction in [(11)C]diprenorphine binding. We suggest that the lack of a dose-dependent relationship between methadone dose, either given chronically in human or acutely in rat, and occupancy of opioid receptor measured with [(11)C]diprenorphine PET is related to efficacy of this opioid agonist at very low levels of opioid receptor occupancy. This has implications for understanding the actions of methadone in comparison with other opioid drugs such as partial agonists and antagonists.

High doses of acyclovir: a new concept in the treatment of neonatal herpes simplex virus infection.

The authors present a case of a preterm newborn with congenital infection of herpes simplex virus type 2. The patient was treated with newly recommended high intravenous doses of acyclovir. It can be supposed that it reduces mortality, but the high morbidity continues to be a problem.

Functional connectivity analysis of the neural circuits of opiate craving: "more" rather than "different"?

We investigated the functional connectivity of brain regions activated during opiate craving. Previously we used recorded autobiographical scripts to induce opiate craving in 12 abstinent opiate-dependent subjects while they were undergoing positron emission tomography (PET) scanning using the regional cerebral blood flow (rCBF) tracer H2 15O. SPM99 was used to examine the connectivity patterns associated with the primary brain regions activated in response to drug-craving memories (anterior cingulate, AC) and correlated with opiate craving (orbitofrontal cortex, OFC). Two separate connectivity patterns were identified associated with the OFC and AC regions. The AC region was associated with activity in the left temporal region. The left OFC region activity correlated with activity in the right OFC, and left parietal and posterior insular regions. There was also a positive association with the hippocampus and brainstem. Both the AC and OFC regions showed a negative association with posterior visual areas. We suggest that the patterns of functional connectivity reflect the ability of drug-related stimuli to activate attentional and memory circuits to a greater degree than non-drug-related stimuli. This argues that neural circuits of dependence and craving are not specific "craving" or "addiction" brain regions but are "normal" circuits activated to a greater degree.