The effective use of land in Northeast China is of great significance for ensuring national food security and regional rural revitalization.In this study,based on the survey data collected from Jilin Province,Northeas...The effective use of land in Northeast China is of great significance for ensuring national food security and regional rural revitalization.In this study,based on the survey data collected from Jilin Province,Northeast China,we analyzed the vacancy rates of rural homesteads in suburban,outer suburban,and remote villages,as well as the withdrawal intention of rural-settled farmers,urbansettled farmers,and farmers with urban and rural dual residency from vacant homesteads.From the perspective of farmers’perceptions,this study constructed a theoretical framework of the influence mechanism of their withdrawal intention and analyzed such mechanism by constructing a structural equation model.The results indicated that:1)rural homestead vacancy rates increased with distance from the village to the city.2)rural-settled farmers showed a low withdrawal intention for vacant rural homesteads,followed by urban and rural dual-residence farmers,and urban-settled farmers showed the highest withdrawal intention.3)the relative importance of the factors influencing withdrawal intention is in the following order:policy awareness>interest perception>living environment perception>family characteristics.Finally,this study discussed the reformation of the homestead system and rural homestead transition in Northeast China,which can provide policy support to increase the potential of cultivated land and promote sustainable rural development and urban-rural coordination.展开更多
Phenibut(β-phenyl-γ-aminobutyric acid)is a psychoactive gamma-aminobutyric acid(GABA)analog marketed online as a nutritional and nootropic(cognition enhancing)supplement.Phenibut consumption poses a high risk of pot...Phenibut(β-phenyl-γ-aminobutyric acid)is a psychoactive gamma-aminobutyric acid(GABA)analog marketed online as a nutritional and nootropic(cognition enhancing)supplement.Phenibut consumption poses a high risk of potential abuse.Withdrawal from phenibut mimics benzodiazepine and alcohol withdrawal and can be dangerous.A number of approaches have been described for phenibut withdrawal,including protocols that include baclofen,but for inpatient and outpatient use.Here we describe a 30-year-old male who presented to an emergency department(ED)with insomnia,anxiety and palpitations after he stopped taking phenibut.展开更多
Two tests initiated by unscrammed control rod withdrawal were performed on the High Temperature GasCooled Reactor-Test Module(HTR-10) in November 2003 after the reactor achieved its full power, and the test conditions...Two tests initiated by unscrammed control rod withdrawal were performed on the High Temperature GasCooled Reactor-Test Module(HTR-10) in November 2003 after the reactor achieved its full power, and the test conditions represented a typical transient scenario of modular high-temperature reactors(HTRs), called pressurized loss of forced cooling, and anticipated transient without scram.Based on the test parameters, the HTR-10 thermal behaviors under the test conditions were studied with the help of the system analysis code THERMIX. The combination of the test results and the investigation results makes the HTR-10 safety potential better understood. Key phenomena, such as the helium natural circulation and the temperature redistribution in the reactor, were revealed. As the safety feature of most significance, there is a large margin between the maximum fuel temperature and its safety limit in each test. Temperatures of thermocouples in different components were calculated by THERMIX and compared with the test values. The applicability of the code was verified by good agreement obtained from the comparison.展开更多
Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events represent...Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.展开更多
Based on the Computable General Equilibrium (CGE) model and scenario analysis, the impacts of the U.S. withdrawal from the Paris Agreement on the carbon emission space and mitigation cost in China, European Union (EU)...Based on the Computable General Equilibrium (CGE) model and scenario analysis, the impacts of the U.S. withdrawal from the Paris Agreement on the carbon emission space and mitigation cost in China, European Union (EU), and Japan are assessed under Nationally Determined Contributions (NDCs) and 2 C scenarios due to the changed emission pathway of the U.S. The results show that, under the condition of constant global cumulative carbon emissions and a fixed burden-sharing scheme among countries, the failure of the U.S. to honor its NDC commitment to different degrees will increase the U.S. carbon emission space and decrease its mitigation cost. However, the carbon emission space of other parties, including China, EU, and Japan, will be reduced and their mitigation costs will be increased. In 2030, under the 2 C target, the carbon price will increase by 4.4e14.6 US$ t1 in China, by 9.7e35.4 US$ t1 in the EU, and by 16.0e53.5 US$ t1 in Japan. In addition, China, EU, and Japan will incur additional Gross Domestic Production (GDP) loss. Under the 2 C target, the GDP loss of China would increase by US$22.0e71.1 billion (equivalent to 16.4e53.1 US$ per capita), the EU's GDP loss would increase by US$9.4e32.1 billion (equivalent to 20.7e71.1 US$ per capita), and Japan's GDP loss will increase by US$4.1e13.5 billion (equivalent to 34.3e111.6 US$ per capita).展开更多
In this study, we consider the heat-induced withdrawal reflex caused by exposure to an electromagnetic beam. We propose a concise dose-response relation for predicting the occurrence of withdrawal reflex from a given ...In this study, we consider the heat-induced withdrawal reflex caused by exposure to an electromagnetic beam. We propose a concise dose-response relation for predicting the occurrence of withdrawal reflex from a given spatial temperature profile. Our model is distilled from sub-step components in the ADT CHEETEH-E model developed at the Institute for Defense Analyses. Our model has only two parameters: the activation temperature of nociceptors and the critical threshold on the activated volume. When the spatial temperature profile is measurable, the two parameters can be determined from test data. We connect this dose-response relation to a temperature evolution model for electromagnetic heating. The resulting composite model governs the process from the electromagnetic beam deposited on the skin to the binary outcome of subject’s reflex response. We carry out non-dimensionalization in the time evolution model. The temperature solution of the non-dimensional system is the product of the applied power density and a parameter-free function. The effects of physical parameters are contained in non-dimensional time and depth. Scaling the physical temperature distribution into a parameter-free function greatly simplifies the analytical solution, and helps to pinpoint the effects of beam spot area and applied power density. With this formulation, we study the theoretical behaviors of the system, including the time of reflex, effect of heat conduction, biological latency in observed reflex, energy consumption by the time of reflex, and the strategy of selecting test conditions in experiments for the purpose of inferring model parameters from test data.展开更多
Methylene blue (MB), a tricyclic phenothiazine drug, has been reported to enhance mitochondrial functions including mitochondrial respiration. By comparison, stress associated with abrupt ethanol withdrawal (EW) imped...Methylene blue (MB), a tricyclic phenothiazine drug, has been reported to enhance mitochondrial functions including mitochondrial respiration. By comparison, stress associated with abrupt ethanol withdrawal (EW) impedes mitochondrial functions. We investigated whether MB protects mitochondrial respiration and cell survival from EW stress through a key mitochondrial enzyme, cytochrome c oxidase (COX). We also investigated whether the MB’s protection involves the inhibition of an excitatory neurotransmitter, glutamate. Male rats were exposed to and withdrawn from ethanol-diet (7.5%, 5 weeks). MB (0.5 mg/kg, intraperitoneal) was injected for the last 5 days of ethanol-diet and on the first day of EW. Cerebellum was then harvested to measure mitochondrial respiration and COX expression using real-time XF respirometer and immunohistochemistry, respectively. Separately, HT22 cells (a murine hippocampal cell line) were exposed to and abruptly withdrawn for 4 hours from chronic ethanol (100 mM, 3 days). MB was administered during EW with or without a COX inhibitor (NaN3) or glutamate. Mitochondrial respiration, COX content, and cell viability were then assessed using real-time XF respirometer, an immunoblot method, and Calcein assay, respectively. MB attenuated the suppressing effects of EW on mitochondrial respiration, COX content, and cell survival. This protection was reduced after NaN3 or glutamate cotreatment. These results suggest that MB treatment help maintain mitochondrial respiratory and cellular integrity through COX-upregulation and glutamateinhibition upon EW stress. MB treatment may help identify mitochondrial mechanisms underlying hyperexcitatory CNS disorders.展开更多
To study steroid withdrawal in immunosuppresion after liver transplantation (LTx).Methods Fifty-eight consecutive patients undergoing primary LTx,under cyclosporine and steroid immunosuppresion,10 additional patients ...To study steroid withdrawal in immunosuppresion after liver transplantation (LTx).Methods Fifty-eight consecutive patients undergoing primary LTx,under cyclosporine and steroid immunosuppresion,10 additional patients treated with mycophemolate mofetil (MMF),were included in this study.If there was no evidence of rejection and the patient’s liver function tests were nearly normal,the steroid weaning process started 2 to 3 weeks after LTx.Results During a mean follow-up period of 9.3±5.5 months after LTx,54 patients survived and 4 died.Steroids could be withdrawn in 72.2% patients at 3rd month post-transplant,in 76.2% at 6th month and in 77.8% at first year,respectively.In 3 patients with rejection after steroid withdrawal,the steroid dose before withdrawal was given.After the rejection was reversed the steroid was withdrawn.Freedom from steroids was thus observed in 10 additional patients treated with MMF at 3rd to 4th month post-transplant.Conclusion Cyclosporine-based immunosuppression allows safe early steroid withdrawal in some patients of LTx.3 refs,1 tab.展开更多
Applying qualitative and quantitative methods, this article explains the driving forces behind U.S. President Donald Trump's decision to withdraw from the Paris Agreement, assesses the impacts of this withdrawal o...Applying qualitative and quantitative methods, this article explains the driving forces behind U.S. President Donald Trump's decision to withdraw from the Paris Agreement, assesses the impacts of this withdrawal on the compliance prospects of the agreement, and proposes how China should respond. The withdrawal undercuts the foundation of global climate governance and upsets the process of climate cooperation, and the impacts are manifold. The withdrawal undermines the universality of the Paris Agreement and impairs states' confidence in climate cooperation; it aggravates the leadership deficit in addressing global climate issues and sets a bad precedent for international climate cooperation. The withdrawal reduces other countries' emission space and raises their emission costs, and refusal to contribute to climate aid makes it more difficult for developing countries to mitigate and adapt to climate change. Cutting climate research funding will compromise the quality of future IPCC reports and ultimately undermine the scientific authority of future climate negotiations. China faces mounting pressure from the international community to assume global climate leadership after the U.S. withdraws, and this article proposes that China should reach the high ends of its domestic climate targets under the current Nationally Determined Contributions; internationally, China should facilitate the rebuilding of shared climate leadership, replacing the G2 with C5. Meanwhile, China needs to keep the U.S. engaged in climate cooperation.展开更多
Objective: To evaluate the effects of Oscimum sanctum L(O. sanctum), an important medicinal herb, on alcohol withdrawal syndrome in Wistar rats. Methods: Liquid diet with 7.2%, v/v ethanol was administered to the rats...Objective: To evaluate the effects of Oscimum sanctum L(O. sanctum), an important medicinal herb, on alcohol withdrawal syndrome in Wistar rats. Methods: Liquid diet with 7.2%, v/v ethanol was administered to the rats for 21 d. Control group animals received sucrose as an isocaloric liquid diet. After alcohol withdrawal, rats were examined at 6 th and 24 th hour for major withdrawal signs that included anxiety and hyper locomotor activity. Ethanol withdrawal anxiety was tested using elevated plus maze, light and dark model; the hyper locomotor activity using actophotometer. O. sanctum leaf extract(100, 200 and 300 mg/kg, oral) and diazepam(2 mg/kg, i.p) were administered to the treatment group animals 30 min before alcohol withdrawal estimation. Drug treatment was also given 30 min before the second observation at 24 th hour. On the last day of the protocol, rats were sacrificed by cervical dislocation liver, kidney and brain were isolated and preserved in formalin for further histopathological examination. Results: Findings from the present study revealed that O. Sanctum leaf extract treatment at doses 100, 200 and 300 mg/kg, oral had a significant protective effect on signs and symptoms of ethanol withdrawal in alcohol-dependent rats. However, no remarkable pathological and microscopic alterations were observed in histopathological examination. Conclusions: O. sanctum seems to be an active drug for the treatment of alcohol abstinence syndrome.展开更多
With an increase in population and economic development,water withdrawals are close to or even exceed the amount of water available in many regions of the world.Modelling water withdrawals could help water planners im...With an increase in population and economic development,water withdrawals are close to or even exceed the amount of water available in many regions of the world.Modelling water withdrawals could help water planners improve the efficiency of water use,water resources allocation,and management in order to alleviate water crises.However,minimal information has been obtained on how water withdrawals have changed over space and time,especially on a regional or local scale.This research proposes a data-driven framework to help estimate county-level distribution of water withdrawals.Using this framework,spatial statistical methods are used to estimate water withdrawals for agricultural,industrial,and domestic purposes in the Huaihe River watershed in China for the period 1978–2018.Total water withdrawals were found to have more than doubled,from 292.55×10^(8)m^(3) in 1978 to 642.93×10^(8)m^(3) in 2009,and decreased to 602.63×10^(8)m^(3) in 2018.Agricultural water increased from 208.17×10^(8)m^(3) in 1978 to 435.80×10^(8)m^(3) in 2009 and decreased to 360.84×10^(8)m^(3) in 2018.Industrial and domestic water usage constantly increased throughout the 1978–2018 period.In 1978,industrial and domestic demands were 20.35×10^(8)m^(3) and 60.04×10^(8)m^(3),respectively,and up until 2018,the figures were 105.58×10^(8)m^(3) and 136.20×10^(8)m^(3).From a spatial distribution perspective,Moran’s I statistical results show that the total water withdrawal has significant spatial autocorrelation during 1978–2018.The overall trend was a gradual increase in 1978–2010 with withdrawal beginning to decline in 2010–2018.The results of Getis-Ord G_(i)^(*)statistical calculations showed spatially contiguous clusters of total water withdrawal in the Huaihe River watershed during1978–2010,and the spatial agglomeration weakened from 2010 to 2018.This study provides a data-driven framework for assessing water withdrawals to enable a deeper understanding of competing water use among economic sectors as well as water withdrawal modelled with proper data resource and method.展开更多
Background:Gut microbiota plays a key role in health,immunity,digestion,and production in layers.Factors such as environment,diet,diseases,stress,and flock management significantly affect gut microbiota;however,it is ...Background:Gut microbiota plays a key role in health,immunity,digestion,and production in layers.Factors such as environment,diet,diseases,stress,and flock management significantly affect gut microbiota;however,it is not known how potential stressors such as intramuscular injections or feed withdrawal alter the composition of gut microbiota that result in increased the shedding level of foodborne pathogens.In the current study,the effects of intramuscular corticosterone injection and feed withdrawal were evaluated to understand their role in Salmonella Typhimurium shedding and changes in the composition of gut microbiota in layers.Results:Salmonella shedding was observed for 8 weeks post-infection.There was a significant increase in Salmonella Typhimurium count after intramuscular injection and feed withdrawal.The Salmonella infected and the negative control groups showed significant differences in the abundance of different genera in gut microbiota at week 1 and up to week 7 post infection.The infected group showed a significant reduction in alpha diversity of gut microbiota.Firmicutes reduced significantly(P<0.05)after intramuscular injection,while the feed withdrawal groups did not cause any significant changes in Proteobacteria-Firmicutes ratio.Furthermore,intramuscular injection resulted in a significant change in alpha diversity of gut microbiota.Conclusions:Exposure of chicks to relatively low dose of Salmonella Typhimurium can lead to persistent shedding in pullets.The Salmonella Typhimurium infection disrupted the gut microbiota composition immediately after infection.The potential stress of intramuscular injection and feed withdrawal significantly increased the Salmonella Typhimurium count in faeces.The intramuscular injection also resulted in a significant alteration of the Proteobacteria-Firmicutes ratio,which could increase the risk of dysbiosis.展开更多
Al-4.5wt.%Cu alloy has been directionally solidified at constant and abruptly changing withdrawal rates, respectively. The effects of the withdrawal rate on solidification microstructure, primary dendrite arm spacing(...Al-4.5wt.%Cu alloy has been directionally solidified at constant and abruptly changing withdrawal rates, respectively. The effects of the withdrawal rate on solidification microstructure, primary dendrite arm spacing(PDAS) and liquid solute distribution in front of the solid-liquid interface were investigated. The experimental results for the PDAS at a constant withdrawal rate agree well with the values calculated by the Hunt, Trivedi and Hunt-Lu models. At an abrupt change in the withdrawal rate, the maximum to minimum ratio of the PDAS at a given solidification parameter, i.e. λ1max/λ1min, is more than 2, and the PDAS values are remarkably history-dependent. Further, the liquid-solute distribution curve based on theoretical calculation shows that the larger the initial withdrawal rate is, the smaller the minimum of liquid solute concentration in front of the solid-liquid interface is after the abrupt change in withdrawal rate.展开更多
In recent years,the withdrawal of several batches of articles from international academic journals has negatively affected Chinese scholars.The Chinese government,the scientific community,and many scientific researche...In recent years,the withdrawal of several batches of articles from international academic journals has negatively affected Chinese scholars.The Chinese government,the scientific community,and many scientific researchers have made substantial efforts to rectify this problem.This Editorial reviews the mass withdrawal events as a whole;identifies their causes;and systematically investigates China’s policy adjustments,institutional arrangements,and regulatory mechanisms in response.We hope that,in addition to reminding authors to pay greater attention to avoiding withdrawals,this Editorial will provide guidance to help them conduct scientific research and present their achievements in a more standardized manner.展开更多
The objective of our study was to investigate whether the chronic administration of a low dose of nicotine can be followed by a withdrawal syndrome at cessation of nicotine delivery. Pre-vious studies showed various r...The objective of our study was to investigate whether the chronic administration of a low dose of nicotine can be followed by a withdrawal syndrome at cessation of nicotine delivery. Pre-vious studies showed various results, depend-ing in the doses of nicotine, species, ways of administration and behavioural paradigms, but all emphasized a withdrawal effect on some or all of the following spontaneous behaviours: grooming, rearing, body shake or tremor, body scratching, abdominal constriction, jumping. However, it is not clear which behaviour is ex-actly altered, as a global behavioural index is most frequently used. This is not clear either if anxiety modulates the behavioral expression of withdrawal or which factors contribute to its locomotors effect, if any. To distant-angle these processes, we scored each of these behaviours individually before nicotine exposure, during continuous nicotine delivery and at cessation of nicotine delivery after precipitated withdrawal by mecamylamine injection. We also measured locomotor activity and anxiety levels in the same animals. We used a low dose of nicotine (2.4 mg/kg/day as free base) that has been pre-viously shown to produce nicotinic receptors up-regulation, both in the brain and in blood cells. With such a low dose, nicotine withdrawal didn’t affect locomotion nor anxiety levels but increased the number of rearing, jumping, and marginally, body-scratching. Other behaviours, classically considered to contribute to with-drawal syndrome, were unaffected, e.g., groom- ing, body or forelimb shakes. Our results show that anxiety may be dissociated from the be-havioural withdrawal syndrome. Also, the se-verity of the syndrome produced by nicotine withdrawal is qualitatively and quantitatively different from the one induced by other drugs of abuse and also by the one produced by nicotine at higher doses.展开更多
The Global Fund has long been the largest international assistance in human immunodeficiency virus(HIV)responses for three Southeast Asian countries,including Myanmar,Laos,and Vietnam.However,it recently decided to re...The Global Fund has long been the largest international assistance in human immunodeficiency virus(HIV)responses for three Southeast Asian countries,including Myanmar,Laos,and Vietnam.However,it recently decided to reduce or withdraw its funding from countries not yet going through donor phase out,aiming to make these countries respond with their own resources.In examining whether these three countries are well-prepared to donor transition,we uncover potential challenges that will appear in their healthcare systems and especially in the prevention and control for vulnerable populations.By reviewing China's succesful experience in donor transition,we propose recommendations for these pre transition countries,in terms of program operation,budget allocation,and social stigmatization.展开更多
Objective: Sustained withdrawal is a sign of infant distress and may be determined by extreme conditions like organic pathology or relationship problems. The Alarm Distress Baby Scale is the best instrument to identif...Objective: Sustained withdrawal is a sign of infant distress and may be determined by extreme conditions like organic pathology or relationship problems. The Alarm Distress Baby Scale is the best instrument to identify withdrawal in infants between 2 and 24 months of age. The aim of this study was to assess the association between infant social withdrawal behavior and maternal pathology in the perinatal period. Method: The target sample of the study was 134 mother-child couples examined at the Policlinico Agostino Gemelli General Pediatric Outpatient Clinic and Psychiatric Outpatient Clinic, in Rome. We analyzed the relationship between withdrawal behavior and psychological and organic prenatal/postnatal pathology, using the Chi Square exact test. Results: When the mother suffers from both organic and psychological pathologies in the perinatal period, the risk of withdrawal is increased: the probability of infant withdrawal behavior is increased by maternal organic postnatal pathology by 14 times, by maternal psychological postnatal pathology by 9 times, and by maternal psychological postnatal depression, measured by Edinburgh Postnatal Depression Scale, by almost 4 times. Conclusion: Increased or sustained withdrawal reactions can be observed in unsatisfactory mother-child interaction. Maternal risk factors should be strictly considered in the pediatric clinical evaluation.展开更多
Antiepileptic drugs (AEDs), have demonstrated efficacy treating a number of acute conditions, encompassing a broad range of symptoms and syndromes, in addition to being first-line treatment for epilepsy. Clinically, s...Antiepileptic drugs (AEDs), have demonstrated efficacy treating a number of acute conditions, encompassing a broad range of symptoms and syndromes, in addition to being first-line treatment for epilepsy. Clinically, since their inception, AEDs have been used off-label for acute and chronic medical conditions, both as primary and as adjuvant therapies. In this review, we describe the observed clinical effectiveness of AEDs across a set of commonly encountered acute conditions in the general hospital: traumatic brain injury, pain, alcohol withdrawal. In describing the individual benefits and usages of specific agents, the applicability of these agents to other common neuropsychiatric conditions may be further explored.展开更多
Objective: Baclofen (β-p-chlorophenyl-GABA) selectively activates the GABAB subtype of γ-aminobutyric acid (GABA) receptors, a group of receptors known to provide inhibitory neurotransmission in the central nervous ...Objective: Baclofen (β-p-chlorophenyl-GABA) selectively activates the GABAB subtype of γ-aminobutyric acid (GABA) receptors, a group of receptors known to provide inhibitory neurotransmission in the central nervous system. Available for over thirty years in oral form for the treatment of skeletal muscle spasticity, its availability now includes continuous intrathecal infusion via an internally implanted pump. While ideal for long-term attenuation of symptoms, this treatment modality can also become disastrous should the pump empty and withdrawal subsequently ensue. Case Report: A 48-year-old male with a past medical history of T8 spinal cord injury from a motor vehicle crash originally presented with altered mental status. Because of resultant paraplegia and spasticity from his injuries, a neurosurgeon implanted an intrathecal baclofen pump three years prior to presentation with symptomatic relief. Further exploration revealed that he had missed his scheduled pump refill appointment and interrogation of his pump confirmed a completely empty reservoir. The patient endured a protracted hospital course that included rhabdomyolysis, acute renal failure, lactic acidosis, respiratory failure, and systemic inflammatory response syndrome. Treatment included benzodiazepines, dantrolene, aggressive hydration, opiates, and refill of his intrathecal baclofen pump. His mentation and ventilatory status improved with recovery from his critical illness and eventual discharge. Conclusions: Treatment of intrathecal baclofen withdrawal should focus on restoration of previous intrathecal baclofen levels by refill of the intrathecal pump. Adjuvant medications such as benzodiazepines, propofol, cyproheptadine, dantrolene, tizanidine, and opiates may prove crucial in helping with muscle spasticity while these levels are reestablished. A high index of suspicion, leading to timely initiation of proper treatment, may serve as the most important factor in successful recovery from this life-threatening syndrome.展开更多
Objective: One of the common misinterpretation be- liefs in some societies (especially eastern communities) is the using of opium can reduce serum glucose and lipids. Opium is a derivative from a plant family called P...Objective: One of the common misinterpretation be- liefs in some societies (especially eastern communities) is the using of opium can reduce serum glucose and lipids. Opium is a derivative from a plant family called Papaveracea and contains almost 80 types of alkaloids. Drug addiction causes physiological dependency and its withdrawal lead to some disorders. The aim of this study was to determine the effects of opium consumption and its withdrawal on some blood biochemical factors in addicted people. Methods: We enrolled fifty-six opium addicted people according to the especial criteria to this study. Biochemical blood parameter levels such as fasting blood sugar (FBS), urea, Creatinine (Cr), Aspartate transaminase (AST), Alanine transaminase (ALT) and Alkaline phosphatase (ALP) enzymes levels were measured and urine analysis was also performed before and 3 months after withdrawal. Data were analyzed by using SPSS software version 18 and a P < 0.05 was considered as significant. Results: our finding showed that opium withdrawal reduces FBS and increases AST but these changes were not significant. Nevertheless opium withdrawal significantly increased blood urea level (P < 0.0001). We didn’t find any significant difference in Cr, ALP, AST and Urea specific gravity (SG). Conclusion: According to the results of the current study we can concluded that opium increases FBS, which is in contrast to the most previous studies and withdrawal has opposite effects.展开更多
基金Under the auspices of Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDA28100405,XDA28020403)National Natural Science Foundation of China (No. 41771179, 42071275)+1 种基金Talents Training Project Supported by the Central Government for the Reform and Development of Local UniversitiesYoung Scientist Group Project of Northeast Institute of Geography and Agroecology,Chinese Academy of Sciences (No. 2022QNXZ02)
文摘The effective use of land in Northeast China is of great significance for ensuring national food security and regional rural revitalization.In this study,based on the survey data collected from Jilin Province,Northeast China,we analyzed the vacancy rates of rural homesteads in suburban,outer suburban,and remote villages,as well as the withdrawal intention of rural-settled farmers,urbansettled farmers,and farmers with urban and rural dual residency from vacant homesteads.From the perspective of farmers’perceptions,this study constructed a theoretical framework of the influence mechanism of their withdrawal intention and analyzed such mechanism by constructing a structural equation model.The results indicated that:1)rural homestead vacancy rates increased with distance from the village to the city.2)rural-settled farmers showed a low withdrawal intention for vacant rural homesteads,followed by urban and rural dual-residence farmers,and urban-settled farmers showed the highest withdrawal intention.3)the relative importance of the factors influencing withdrawal intention is in the following order:policy awareness>interest perception>living environment perception>family characteristics.Finally,this study discussed the reformation of the homestead system and rural homestead transition in Northeast China,which can provide policy support to increase the potential of cultivated land and promote sustainable rural development and urban-rural coordination.
文摘Phenibut(β-phenyl-γ-aminobutyric acid)is a psychoactive gamma-aminobutyric acid(GABA)analog marketed online as a nutritional and nootropic(cognition enhancing)supplement.Phenibut consumption poses a high risk of potential abuse.Withdrawal from phenibut mimics benzodiazepine and alcohol withdrawal and can be dangerous.A number of approaches have been described for phenibut withdrawal,including protocols that include baclofen,but for inpatient and outpatient use.Here we describe a 30-year-old male who presented to an emergency department(ED)with insomnia,anxiety and palpitations after he stopped taking phenibut.
基金supported by the Chinese National S&T Major Project(No.ZX069)
文摘Two tests initiated by unscrammed control rod withdrawal were performed on the High Temperature GasCooled Reactor-Test Module(HTR-10) in November 2003 after the reactor achieved its full power, and the test conditions represented a typical transient scenario of modular high-temperature reactors(HTRs), called pressurized loss of forced cooling, and anticipated transient without scram.Based on the test parameters, the HTR-10 thermal behaviors under the test conditions were studied with the help of the system analysis code THERMIX. The combination of the test results and the investigation results makes the HTR-10 safety potential better understood. Key phenomena, such as the helium natural circulation and the temperature redistribution in the reactor, were revealed. As the safety feature of most significance, there is a large margin between the maximum fuel temperature and its safety limit in each test. Temperatures of thermocouples in different components were calculated by THERMIX and compared with the test values. The applicability of the code was verified by good agreement obtained from the comparison.
文摘Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.
基金This study was supported by the 2017 National Natural Science Foundation Project “The Impacts of U.S. Withdrawal from Paris Agreement on Global Climate Governance and China's Response”.
文摘Based on the Computable General Equilibrium (CGE) model and scenario analysis, the impacts of the U.S. withdrawal from the Paris Agreement on the carbon emission space and mitigation cost in China, European Union (EU), and Japan are assessed under Nationally Determined Contributions (NDCs) and 2 C scenarios due to the changed emission pathway of the U.S. The results show that, under the condition of constant global cumulative carbon emissions and a fixed burden-sharing scheme among countries, the failure of the U.S. to honor its NDC commitment to different degrees will increase the U.S. carbon emission space and decrease its mitigation cost. However, the carbon emission space of other parties, including China, EU, and Japan, will be reduced and their mitigation costs will be increased. In 2030, under the 2 C target, the carbon price will increase by 4.4e14.6 US$ t1 in China, by 9.7e35.4 US$ t1 in the EU, and by 16.0e53.5 US$ t1 in Japan. In addition, China, EU, and Japan will incur additional Gross Domestic Production (GDP) loss. Under the 2 C target, the GDP loss of China would increase by US$22.0e71.1 billion (equivalent to 16.4e53.1 US$ per capita), the EU's GDP loss would increase by US$9.4e32.1 billion (equivalent to 20.7e71.1 US$ per capita), and Japan's GDP loss will increase by US$4.1e13.5 billion (equivalent to 34.3e111.6 US$ per capita).
文摘In this study, we consider the heat-induced withdrawal reflex caused by exposure to an electromagnetic beam. We propose a concise dose-response relation for predicting the occurrence of withdrawal reflex from a given spatial temperature profile. Our model is distilled from sub-step components in the ADT CHEETEH-E model developed at the Institute for Defense Analyses. Our model has only two parameters: the activation temperature of nociceptors and the critical threshold on the activated volume. When the spatial temperature profile is measurable, the two parameters can be determined from test data. We connect this dose-response relation to a temperature evolution model for electromagnetic heating. The resulting composite model governs the process from the electromagnetic beam deposited on the skin to the binary outcome of subject’s reflex response. We carry out non-dimensionalization in the time evolution model. The temperature solution of the non-dimensional system is the product of the applied power density and a parameter-free function. The effects of physical parameters are contained in non-dimensional time and depth. Scaling the physical temperature distribution into a parameter-free function greatly simplifies the analytical solution, and helps to pinpoint the effects of beam spot area and applied power density. With this formulation, we study the theoretical behaviors of the system, including the time of reflex, effect of heat conduction, biological latency in observed reflex, energy consumption by the time of reflex, and the strategy of selecting test conditions in experiments for the purpose of inferring model parameters from test data.
文摘Methylene blue (MB), a tricyclic phenothiazine drug, has been reported to enhance mitochondrial functions including mitochondrial respiration. By comparison, stress associated with abrupt ethanol withdrawal (EW) impedes mitochondrial functions. We investigated whether MB protects mitochondrial respiration and cell survival from EW stress through a key mitochondrial enzyme, cytochrome c oxidase (COX). We also investigated whether the MB’s protection involves the inhibition of an excitatory neurotransmitter, glutamate. Male rats were exposed to and withdrawn from ethanol-diet (7.5%, 5 weeks). MB (0.5 mg/kg, intraperitoneal) was injected for the last 5 days of ethanol-diet and on the first day of EW. Cerebellum was then harvested to measure mitochondrial respiration and COX expression using real-time XF respirometer and immunohistochemistry, respectively. Separately, HT22 cells (a murine hippocampal cell line) were exposed to and abruptly withdrawn for 4 hours from chronic ethanol (100 mM, 3 days). MB was administered during EW with or without a COX inhibitor (NaN3) or glutamate. Mitochondrial respiration, COX content, and cell viability were then assessed using real-time XF respirometer, an immunoblot method, and Calcein assay, respectively. MB attenuated the suppressing effects of EW on mitochondrial respiration, COX content, and cell survival. This protection was reduced after NaN3 or glutamate cotreatment. These results suggest that MB treatment help maintain mitochondrial respiratory and cellular integrity through COX-upregulation and glutamateinhibition upon EW stress. MB treatment may help identify mitochondrial mechanisms underlying hyperexcitatory CNS disorders.
文摘To study steroid withdrawal in immunosuppresion after liver transplantation (LTx).Methods Fifty-eight consecutive patients undergoing primary LTx,under cyclosporine and steroid immunosuppresion,10 additional patients treated with mycophemolate mofetil (MMF),were included in this study.If there was no evidence of rejection and the patient’s liver function tests were nearly normal,the steroid weaning process started 2 to 3 weeks after LTx.Results During a mean follow-up period of 9.3±5.5 months after LTx,54 patients survived and 4 died.Steroids could be withdrawn in 72.2% patients at 3rd month post-transplant,in 76.2% at 6th month and in 77.8% at first year,respectively.In 3 patients with rejection after steroid withdrawal,the steroid dose before withdrawal was given.After the rejection was reversed the steroid was withdrawn.Freedom from steroids was thus observed in 10 additional patients treated with MMF at 3rd to 4th month post-transplant.Conclusion Cyclosporine-based immunosuppression allows safe early steroid withdrawal in some patients of LTx.3 refs,1 tab.
基金This study was supported by the 2017 National Natural Science Foundation Project “The Impacts of U.S. Withdrawal from the Paris Agreement on Global Climate Governance and China's Response”.
文摘Applying qualitative and quantitative methods, this article explains the driving forces behind U.S. President Donald Trump's decision to withdraw from the Paris Agreement, assesses the impacts of this withdrawal on the compliance prospects of the agreement, and proposes how China should respond. The withdrawal undercuts the foundation of global climate governance and upsets the process of climate cooperation, and the impacts are manifold. The withdrawal undermines the universality of the Paris Agreement and impairs states' confidence in climate cooperation; it aggravates the leadership deficit in addressing global climate issues and sets a bad precedent for international climate cooperation. The withdrawal reduces other countries' emission space and raises their emission costs, and refusal to contribute to climate aid makes it more difficult for developing countries to mitigate and adapt to climate change. Cutting climate research funding will compromise the quality of future IPCC reports and ultimately undermine the scientific authority of future climate negotiations. China faces mounting pressure from the international community to assume global climate leadership after the U.S. withdraws, and this article proposes that China should reach the high ends of its domestic climate targets under the current Nationally Determined Contributions; internationally, China should facilitate the rebuilding of shared climate leadership, replacing the G2 with C5. Meanwhile, China needs to keep the U.S. engaged in climate cooperation.
基金supported by Science and Engineering Research Board(SERB)Department of Science and Technology,Government of India(SR/FT/LS–07/2012)
文摘Objective: To evaluate the effects of Oscimum sanctum L(O. sanctum), an important medicinal herb, on alcohol withdrawal syndrome in Wistar rats. Methods: Liquid diet with 7.2%, v/v ethanol was administered to the rats for 21 d. Control group animals received sucrose as an isocaloric liquid diet. After alcohol withdrawal, rats were examined at 6 th and 24 th hour for major withdrawal signs that included anxiety and hyper locomotor activity. Ethanol withdrawal anxiety was tested using elevated plus maze, light and dark model; the hyper locomotor activity using actophotometer. O. sanctum leaf extract(100, 200 and 300 mg/kg, oral) and diazepam(2 mg/kg, i.p) were administered to the treatment group animals 30 min before alcohol withdrawal estimation. Drug treatment was also given 30 min before the second observation at 24 th hour. On the last day of the protocol, rats were sacrificed by cervical dislocation liver, kidney and brain were isolated and preserved in formalin for further histopathological examination. Results: Findings from the present study revealed that O. Sanctum leaf extract treatment at doses 100, 200 and 300 mg/kg, oral had a significant protective effect on signs and symptoms of ethanol withdrawal in alcohol-dependent rats. However, no remarkable pathological and microscopic alterations were observed in histopathological examination. Conclusions: O. sanctum seems to be an active drug for the treatment of alcohol abstinence syndrome.
基金Under the auspices of the National Natural Science Foundation of China(No.71203200)the National Social Science Fund Project(No.20&ZD138)+1 种基金the National Science and Technology Platform Construction Project(No.2005DKA32300)the Major Research Projects of the Ministry of Education(No.16JJD770019)。
文摘With an increase in population and economic development,water withdrawals are close to or even exceed the amount of water available in many regions of the world.Modelling water withdrawals could help water planners improve the efficiency of water use,water resources allocation,and management in order to alleviate water crises.However,minimal information has been obtained on how water withdrawals have changed over space and time,especially on a regional or local scale.This research proposes a data-driven framework to help estimate county-level distribution of water withdrawals.Using this framework,spatial statistical methods are used to estimate water withdrawals for agricultural,industrial,and domestic purposes in the Huaihe River watershed in China for the period 1978–2018.Total water withdrawals were found to have more than doubled,from 292.55×10^(8)m^(3) in 1978 to 642.93×10^(8)m^(3) in 2009,and decreased to 602.63×10^(8)m^(3) in 2018.Agricultural water increased from 208.17×10^(8)m^(3) in 1978 to 435.80×10^(8)m^(3) in 2009 and decreased to 360.84×10^(8)m^(3) in 2018.Industrial and domestic water usage constantly increased throughout the 1978–2018 period.In 1978,industrial and domestic demands were 20.35×10^(8)m^(3) and 60.04×10^(8)m^(3),respectively,and up until 2018,the figures were 105.58×10^(8)m^(3) and 136.20×10^(8)m^(3).From a spatial distribution perspective,Moran’s I statistical results show that the total water withdrawal has significant spatial autocorrelation during 1978–2018.The overall trend was a gradual increase in 1978–2010 with withdrawal beginning to decline in 2010–2018.The results of Getis-Ord G_(i)^(*)statistical calculations showed spatially contiguous clusters of total water withdrawal in the Huaihe River watershed during1978–2010,and the spatial agglomeration weakened from 2010 to 2018.This study provides a data-driven framework for assessing water withdrawals to enable a deeper understanding of competing water use among economic sectors as well as water withdrawal modelled with proper data resource and method.
基金post graduate research scholarships from the Australian Eggs and the University of Adelaide。
文摘Background:Gut microbiota plays a key role in health,immunity,digestion,and production in layers.Factors such as environment,diet,diseases,stress,and flock management significantly affect gut microbiota;however,it is not known how potential stressors such as intramuscular injections or feed withdrawal alter the composition of gut microbiota that result in increased the shedding level of foodborne pathogens.In the current study,the effects of intramuscular corticosterone injection and feed withdrawal were evaluated to understand their role in Salmonella Typhimurium shedding and changes in the composition of gut microbiota in layers.Results:Salmonella shedding was observed for 8 weeks post-infection.There was a significant increase in Salmonella Typhimurium count after intramuscular injection and feed withdrawal.The Salmonella infected and the negative control groups showed significant differences in the abundance of different genera in gut microbiota at week 1 and up to week 7 post infection.The infected group showed a significant reduction in alpha diversity of gut microbiota.Firmicutes reduced significantly(P<0.05)after intramuscular injection,while the feed withdrawal groups did not cause any significant changes in Proteobacteria-Firmicutes ratio.Furthermore,intramuscular injection resulted in a significant change in alpha diversity of gut microbiota.Conclusions:Exposure of chicks to relatively low dose of Salmonella Typhimurium can lead to persistent shedding in pullets.The Salmonella Typhimurium infection disrupted the gut microbiota composition immediately after infection.The potential stress of intramuscular injection and feed withdrawal significantly increased the Salmonella Typhimurium count in faeces.The intramuscular injection also resulted in a significant alteration of the Proteobacteria-Firmicutes ratio,which could increase the risk of dysbiosis.
基金financially supported by the National Natural Science Foundation of China(No.50971101)the Specialized Research Fund for the Doctoral Program of Higher Education(No.20136102110014)
文摘Al-4.5wt.%Cu alloy has been directionally solidified at constant and abruptly changing withdrawal rates, respectively. The effects of the withdrawal rate on solidification microstructure, primary dendrite arm spacing(PDAS) and liquid solute distribution in front of the solid-liquid interface were investigated. The experimental results for the PDAS at a constant withdrawal rate agree well with the values calculated by the Hunt, Trivedi and Hunt-Lu models. At an abrupt change in the withdrawal rate, the maximum to minimum ratio of the PDAS at a given solidification parameter, i.e. λ1max/λ1min, is more than 2, and the PDAS values are remarkably history-dependent. Further, the liquid-solute distribution curve based on theoretical calculation shows that the larger the initial withdrawal rate is, the smaller the minimum of liquid solute concentration in front of the solid-liquid interface is after the abrupt change in withdrawal rate.
文摘In recent years,the withdrawal of several batches of articles from international academic journals has negatively affected Chinese scholars.The Chinese government,the scientific community,and many scientific researchers have made substantial efforts to rectify this problem.This Editorial reviews the mass withdrawal events as a whole;identifies their causes;and systematically investigates China’s policy adjustments,institutional arrangements,and regulatory mechanisms in response.We hope that,in addition to reminding authors to pay greater attention to avoiding withdrawals,this Editorial will provide guidance to help them conduct scientific research and present their achievements in a more standardized manner.
文摘The objective of our study was to investigate whether the chronic administration of a low dose of nicotine can be followed by a withdrawal syndrome at cessation of nicotine delivery. Pre-vious studies showed various results, depend-ing in the doses of nicotine, species, ways of administration and behavioural paradigms, but all emphasized a withdrawal effect on some or all of the following spontaneous behaviours: grooming, rearing, body shake or tremor, body scratching, abdominal constriction, jumping. However, it is not clear which behaviour is ex-actly altered, as a global behavioural index is most frequently used. This is not clear either if anxiety modulates the behavioral expression of withdrawal or which factors contribute to its locomotors effect, if any. To distant-angle these processes, we scored each of these behaviours individually before nicotine exposure, during continuous nicotine delivery and at cessation of nicotine delivery after precipitated withdrawal by mecamylamine injection. We also measured locomotor activity and anxiety levels in the same animals. We used a low dose of nicotine (2.4 mg/kg/day as free base) that has been pre-viously shown to produce nicotinic receptors up-regulation, both in the brain and in blood cells. With such a low dose, nicotine withdrawal didn’t affect locomotion nor anxiety levels but increased the number of rearing, jumping, and marginally, body-scratching. Other behaviours, classically considered to contribute to with-drawal syndrome, were unaffected, e.g., groom- ing, body or forelimb shakes. Our results show that anxiety may be dissociated from the be-havioural withdrawal syndrome. Also, the se-verity of the syndrome produced by nicotine withdrawal is qualitatively and quantitatively different from the one induced by other drugs of abuse and also by the one produced by nicotine at higher doses.
基金supported in part by the National Natural Science Foundation of China(Grant No.71904171)the Fundamental Research Funds for the Central Universities(Grant No.2020QNA7021)China Medical Board(Project No.202032).
文摘The Global Fund has long been the largest international assistance in human immunodeficiency virus(HIV)responses for three Southeast Asian countries,including Myanmar,Laos,and Vietnam.However,it recently decided to reduce or withdraw its funding from countries not yet going through donor phase out,aiming to make these countries respond with their own resources.In examining whether these three countries are well-prepared to donor transition,we uncover potential challenges that will appear in their healthcare systems and especially in the prevention and control for vulnerable populations.By reviewing China's succesful experience in donor transition,we propose recommendations for these pre transition countries,in terms of program operation,budget allocation,and social stigmatization.
文摘Objective: Sustained withdrawal is a sign of infant distress and may be determined by extreme conditions like organic pathology or relationship problems. The Alarm Distress Baby Scale is the best instrument to identify withdrawal in infants between 2 and 24 months of age. The aim of this study was to assess the association between infant social withdrawal behavior and maternal pathology in the perinatal period. Method: The target sample of the study was 134 mother-child couples examined at the Policlinico Agostino Gemelli General Pediatric Outpatient Clinic and Psychiatric Outpatient Clinic, in Rome. We analyzed the relationship between withdrawal behavior and psychological and organic prenatal/postnatal pathology, using the Chi Square exact test. Results: When the mother suffers from both organic and psychological pathologies in the perinatal period, the risk of withdrawal is increased: the probability of infant withdrawal behavior is increased by maternal organic postnatal pathology by 14 times, by maternal psychological postnatal pathology by 9 times, and by maternal psychological postnatal depression, measured by Edinburgh Postnatal Depression Scale, by almost 4 times. Conclusion: Increased or sustained withdrawal reactions can be observed in unsatisfactory mother-child interaction. Maternal risk factors should be strictly considered in the pediatric clinical evaluation.
文摘Antiepileptic drugs (AEDs), have demonstrated efficacy treating a number of acute conditions, encompassing a broad range of symptoms and syndromes, in addition to being first-line treatment for epilepsy. Clinically, since their inception, AEDs have been used off-label for acute and chronic medical conditions, both as primary and as adjuvant therapies. In this review, we describe the observed clinical effectiveness of AEDs across a set of commonly encountered acute conditions in the general hospital: traumatic brain injury, pain, alcohol withdrawal. In describing the individual benefits and usages of specific agents, the applicability of these agents to other common neuropsychiatric conditions may be further explored.
文摘Objective: Baclofen (β-p-chlorophenyl-GABA) selectively activates the GABAB subtype of γ-aminobutyric acid (GABA) receptors, a group of receptors known to provide inhibitory neurotransmission in the central nervous system. Available for over thirty years in oral form for the treatment of skeletal muscle spasticity, its availability now includes continuous intrathecal infusion via an internally implanted pump. While ideal for long-term attenuation of symptoms, this treatment modality can also become disastrous should the pump empty and withdrawal subsequently ensue. Case Report: A 48-year-old male with a past medical history of T8 spinal cord injury from a motor vehicle crash originally presented with altered mental status. Because of resultant paraplegia and spasticity from his injuries, a neurosurgeon implanted an intrathecal baclofen pump three years prior to presentation with symptomatic relief. Further exploration revealed that he had missed his scheduled pump refill appointment and interrogation of his pump confirmed a completely empty reservoir. The patient endured a protracted hospital course that included rhabdomyolysis, acute renal failure, lactic acidosis, respiratory failure, and systemic inflammatory response syndrome. Treatment included benzodiazepines, dantrolene, aggressive hydration, opiates, and refill of his intrathecal baclofen pump. His mentation and ventilatory status improved with recovery from his critical illness and eventual discharge. Conclusions: Treatment of intrathecal baclofen withdrawal should focus on restoration of previous intrathecal baclofen levels by refill of the intrathecal pump. Adjuvant medications such as benzodiazepines, propofol, cyproheptadine, dantrolene, tizanidine, and opiates may prove crucial in helping with muscle spasticity while these levels are reestablished. A high index of suspicion, leading to timely initiation of proper treatment, may serve as the most important factor in successful recovery from this life-threatening syndrome.
文摘Objective: One of the common misinterpretation be- liefs in some societies (especially eastern communities) is the using of opium can reduce serum glucose and lipids. Opium is a derivative from a plant family called Papaveracea and contains almost 80 types of alkaloids. Drug addiction causes physiological dependency and its withdrawal lead to some disorders. The aim of this study was to determine the effects of opium consumption and its withdrawal on some blood biochemical factors in addicted people. Methods: We enrolled fifty-six opium addicted people according to the especial criteria to this study. Biochemical blood parameter levels such as fasting blood sugar (FBS), urea, Creatinine (Cr), Aspartate transaminase (AST), Alanine transaminase (ALT) and Alkaline phosphatase (ALP) enzymes levels were measured and urine analysis was also performed before and 3 months after withdrawal. Data were analyzed by using SPSS software version 18 and a P < 0.05 was considered as significant. Results: our finding showed that opium withdrawal reduces FBS and increases AST but these changes were not significant. Nevertheless opium withdrawal significantly increased blood urea level (P < 0.0001). We didn’t find any significant difference in Cr, ALP, AST and Urea specific gravity (SG). Conclusion: According to the results of the current study we can concluded that opium increases FBS, which is in contrast to the most previous studies and withdrawal has opposite effects.
