Meta-analysis of cognitive function in Chinese first-episode schizophrenia: MATRICS Consensus Cognitive Battery (MCCB) profile of impairment

Background Compromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cognitive Battery (MCCB), it is not clear about the level and pattern of cognitive impairment among this population. Aim To provide a meta-analysis systematically analysing studies of neurocognitive function using MCCB in Chinese patients with FES. Methods An independent literature search of both Chinese and English databases up to 13 March 2019 was conducted by two reviewers. Standardised mean difference (SMD) was calculated using the random effects model to evaluate the effect size. Results 56 studies (FES=3167, healthy controls (HC)=3017) were included and analysed. No study was rated as 'high quality' according to Strengthening the Reporting of Observational Studies in Epidemiology. Compared with HCs, Chinese patients with FES showed impairment with large effect size in overall cognition (SMD=-1.60,95% Cl -1.82 to -1.38,厂=67%) and all seven cognitive domains, with the SMD ranging from -0.87 to -1.41. In nine MCCB subtests, patients with FES showed significant difference in Symbol Coding (SMD=-1.90), Trail Making Test (TMT)(SMD=-1.36), Continuous Performance Test-Identical Pairs (SMD=-1.33), Hopkins Verbal Learning Test (SMD=-1.24), Brief Visuospatial Memory Test (SMD=-1.18), Mazes (SMD=-1.16), Category Fluency (SMD=-1.01), Spatial Span (SMD=-0.69) and Mayer-Salovey-Caruso Emotional Intelligence Test (SMD=-0.38). Conclusions Our meta-analysis demonstrates that Chinese patients with FES show neurocognitive deficits across all seven MCCB cognitive domains and all nine subtests, particularly in two neurocognitive domains: speed of processing and attention/vigilance, with the least impairment shown in social cognition. Symbol Coding and TMT may be the most sensitive tests to detect cognitive deficit in Chinese patients with FES.

重复经颅磁刺激治疗抑郁症疗效及安全性的Meta分析（英文）

背景:重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)是一种新型的物理治疗技术,已经被广泛用于抑郁症的研究。尽管大量的临床实验发现相对于伪刺激,rTMS对抑郁症状有改善作用,但是由于rTMS治疗的频率、参数、部位等不同,因此研究结论仍不一致。目的:本研究系统评价中英文研究中rTMS联合抗抑郁药物在随机、双盲、伪刺激对照试验中对郁抑症状治疗的安全性及有效性,探索其中与疗效和安全性的可能相关因素。方法:利用关键词"抑郁""经颅磁刺激"查询中文数据库:万方、维普、中国知网,英文电子数据库:Pubmed、Web of Science、Embase、PsycInfo、Cochrane Library共8个数据库截止到2017年1月5日收录的rTMS治疗抑郁症的临床随机对照研究(randomized controlled trials,RCTs),利用Cochrane风险偏倚评估工具评估纳入研究的文献质量,利用RevMan5.3软件,根据研究组别对纳入的研究治疗效果及安全性进行统计分析。结果:共检索到9798篇文献,最终29篇文献纳入本研究,总样本量1659例,其中研究组样本838例,对照组样本821例,进行Meta分析后发现rTMS联合抗抑郁药物可改善抑郁症患者的抑郁症状(SMD=-0.84,95%CI=-1.19^-0.48)。纳入的研究中均无重大不良事件报道,Meta分析两组间脱落率差异无统计学意义(RR=1.27,95%CI:0.75~2.12,Z=0.89,p=0.37)。GRADE对主要结局指标的证据质量评价为中等水平。结论:抗抑郁药物联合rTMS治疗抑郁症状相对于伪刺激有一定的治疗优势,副反应轻微,可接受性好,研究间差异较大,有待大样本临床研究探索影响疗效的相关因素。

Efficacy and safety of repetitive transcranial magnetic stimulation for generalised anxiety disorder: A metaanalysis

Background Pharmacological and conventional nonpharmacological treatments are only moderately effective in treatingeneralised anxiety disorder(GAD).Recently,repetitive transcranial magnetic stimulation(rTMS)has attracted interest because of its potential therapeutic value.Aim To investigate the efficacy and safety of rTMS treatment for GAD.Methods Literature studies published in English or Chinese were screened in 10 electronic databases up to 5 December 2018.The included studies'bias risk was assessed using Cochrane risk of bias assessment tool.Meta-analysis was performed to compute the standardised mean difference(SMD)and risk ratio(RR)along with its 95%Cis through using RevMan V.5.3.Heterogeneity was inspected by I2 and the χ2 test.We performed subgroup analysis and meta-regression to investigate heterogeneity.We used funnel plot to assess publication bias.We used the GRADE approach to assess the whole quality of evidence.Results Twenty-one studies,with a total sample size of 1481,were analysed.The risk of bias in most studies included is moderate,the majority of which are lacking of blinding methods of treatment allocation.The treatment had beneficial effects in the rTMS group compared with the control group in mean anxiety score(SMD=-0.68;95%Cl-0.89 to-0.46).None of the 21 studies included here reported severe adverse events.As for dropout rates,there are no statistically significant differences between the two groups(RR 1.14,95%Cl 0.72 to 1.82)or adverse events(RR 0.95,95%Cl 0.77 to 1.18).No particular influence on the heterogeneity of any variable was observed.The risk of publication bias was low.According to the GRADE approach,the evidence levels of primary outcome(treatment effects)and secondary outcomes(acceptability and safety)were rated as‘medium’.Conclusion The use of rTMS combined with medication treatment may have a significant positive anti-anxiety effect on patients with GAD.However,we should interpret the results cautiously due to the relatively high heterogeneity of the meta-analysis.Future high-quality clinical trials are needed to confirm our results.

重复经颅磁刺激辅助治疗精神分裂症的幻听有效吗?(英文)

The experience of auditory hallucinations,especially verbal hallucinations,is a common psychotic symptom in persons with schizophrenia,but in about 30%of these individuals traditional treatment with antipsychotic medication is not effective inreducing the hallucinations.

Attenuated niacin-induced skin flush response in individuals with clinical high risk for psychosis

Background Im paired sesitwity of he soin Mlush response bo miacin is one of the most rpicated findngs in patents with schizoprenia Howewer.prior studies have usaly focused on postonset psychusis,and ll is knowm about the dinical high-risk(CHR)phase of niacin senstity in psychosis Aims To proftle and compare the miacin flush responsge among CHR individuals(converters and non-coverters)patients with frstepso schinophrenia(FES)and healty controls(HCs).Methods Sensivily 1o ftour concentralions (0.1-0001M)of aqueous methylnicotinate was tested in 105 CHR individuals,57 patients with FES and 52 HCs.CHR individuals were further grouped as converters and non converters according to the 2-year follow-up outcomes.Skin flush response scores were rated on a 4-point scale.Results Of the 105 CHR individuals,21 individuals were lost during the study,leaving 84 CHR individuals;16(19.0%)converted to full psychosis at 2 years of fllow-up.Flush response scores identifed in the CHR samples were characterised as modest degree levels,intermediate between those of HC individuals and patients with FES.The flush responses in the CHR group mimicked the responses observed in the FES group at higher concentrations(0.01 M,0.1 M)and longer time points(15 min,20min);however,these became comparable vith the responses in the HC group at the shorter time points and at lower concentr ations.The converters exhibited lower mean flush response scores than the non-converters.Conclusions Attenuated niacin-induced flushing emerged during the early phase of psychosis.New devices should be developed and verified for objective quantification of skin responses in the CHR population.

Prevalence and dynamic features of psychological issues among Chinese healthcare workers during the COVID-19 pandemic:a systematic review and cumulative meta-analysis

Background The COVID-19 pandemic has placed tremendous pressure on healthcare workers who are at the frontline in the battle against it,causing various forms of psychological distress.Aims To outline the prevalence and dynamic changing features of medical workers’psychological issues and to review the related national policies during the COVID-19 pandemic in China.Methods We systematically searched for studies on the psychological states of Chinese medical staff from 1 January 2020 to 8 May 2020.The aggregate prevalence of each psychological issue was calculated and plotted to observe the changes over time.Policies on psychological support for medical staff during the pandemic were reviewed to explore their link to the prevalence of psychological problems.Results In total,26 studies were included in this study.A total of 22062 medical workers were surveyed from 31 January to 27 February 2020.Medical staff exhibited a substantial prevalence of anxiety symptoms,depression symptoms,stress-related symptoms and sleep problems during the survey period,with aggregate prevalence rates of 27.0%,26.2%,42.1%and 34.5%,respectively.Cumulative meta-analyses revealed that the prevalence of psychological distress peaked at the beginning of the pandemic and subsequently exhibited a slow downward trend.Conclusion Chinese medical staff displayed significant psychological disturbance during the outbreak of the COVID-19 pandemic,which was especially severe at the early stage.Implementing supportive policies may help alleviate ongoing psychological problems in healthcare workers.

Altered heartbeat perception sensitivity associated with brain structural alterations in generalised anxiety disorder

Background Palpitation is a common complaint in generalised anxiety disorder(GAD).Brain imaging studies have Investigated the neural mechanism of heartbeat perception in healthy volunteers.This study explored the neuroanatomical differences of altered heartbeat perception in patients with GAD using structural MRI.Aims Based on the strong somatic-interoceptive symptoms in GAD,we explored the regional structural brain abnormalities involved in heartbeat perception in patients with GAD.Methods This study was applied to the a priori regions using neuroanatomical theories of heartbeat perception,including the insula,anterior cingulate cortex,supplementary motor area and prefrontal cortex.A total of 19 patients with GAD and 19 healthy control subjects were enrolled.We used the FMRIB Software Library voxel-based morphometry software for estimating the grey matter volume of these regions of interest and analysed the correlation between heartbeat perception sensitivity and the volume of abnormal grey matter.Results Patients with GAD showed a significantly decreased volume of grey matter in their left medial prefrontal cortex,right orbital frontal cortex and anterior cingulate cortex.The grey matter volume of the left medial prefrontal cortex negatively correlated with heartbeat perception sensitivity in patients with GAD.Conclusions It should be the first study that shows heartbeat perception is associated with brain structure in GAD.Our findings suggest that the frontal region may play an important role in aberrant heartbeat perception processing in patients with GAD,and this may be an underlying mechanism resulting in the abnormal cardiovascular complaints in GAD.This is hypothesised as a'top-down'deficiency,especially in the medial prefrontal cortex.This will provide the foundation for a more targeted region for neuromodulation intervention in the future.

Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

Background Disrupted white matter(WM)microstructure has been commonly identified in youth at clinical high risk(CHR)for psychosis.Several lines of evidence suggest that fatty acids,especially unsaturated fatty acids(UFAs),might play a crucial role in the WM pathology of early onset psychosis.However,evidence linking UFA and WM microstructure in CHR is quite sparse.Aims We investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls(HC).Methods Plasma fatty acids were assessed and diffusion tensor imaging(DTI)data were performed with tract-based spatial statistics(TBSS)analysis for 66 individuals at CHR for psychosis and 70 HC.Results Both the global and regional diffusion measures showed significant between-group differences,with decreased fractional anisotropy(FA)but increased mean diffusivity(MD)and radial diffusivity(RD)found in the CHR group compared with the HC group.On top of that,we found that in the HC group,plasma arachidic acid showed obvious trend-level associations with higher global FA,lower global MD and lower global RD,which regionally spread over the corpus callosum,right anterior and superior corona radiata,bilateral anterior and posterior limb of the internal capsule,and bilateral superior longitudinal fasciculus.However,there were no associations between global WM measures and any UFA in the CHR group.Conversely,we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group.Conclusions Compared with the HC group,CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA,with a neuroprotective effect found in the HC group but not in the CHR group.Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group,highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.

Relationships between selfreflectiveness and clinical symptoms in individuals during pre-morbid and early clinical stages of psychosis

Background Self-reflectiveness,one dimension of cognitive insight,plays a protective role in an individual’s mental state.Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness.Aims This study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis.Methods A total of 181 subjects,including individuals with attenuated positive symptoms(APS,n=122)and patients with first-episode psychosis(FEP,n=59),completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale.All subjects were classified into three groups according to their level of selfreflectiveness:low level(LSR,n=59),medium level(MSR,n=67)and high level(HSR,n=55).Both linear and nonlinear relationships between self-reflectiveness and clinical symptoms were explored.Results More individuals with APS were classified into the MSR group,while more patients with FEP were classified into the LSR group.The LSR group demonstrated less awareness of illness than the MSR and HSR groups,more stereotyped thinking and poorer impulse control but less anxiety than the MSR group,and lower levels of blunted affect and guilt feelings than the HSR group.The MSR group demonstrated lower stereotyped thinking than the HSR group.Compared to the LSR group,the MSR group had increased selfreflectiveness,improved awareness of illness,decreased stereotyped thinking,and better impulse control,but increased feelings of guilt.The HSR group showed increased stereotyped thinking when compared to the MSR group,but the other variables did not change significantly between these two groups.Overall,self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness,a U-shaped relationship with stereotyped thinking and poor impulse control,and an almost linear relationship with anxiety and guilt feelings.Conclusions Self-reflectiveness demonstrates complex relationships with clinical symptoms and fails to exert significant positive effects when reaching a certain high level.

Biological mechanisms and clinical efficacy of sulforaphane for mental disorders

Current clinical management of major mental disorders,such as autism spectrum disorder,depression and schizophrenia,is less than optimal.Recent scientific advances have indicated that deficits in oxidative and inflammation systems are lessthanoptimal.Recentscientific advances have indicated extensively involved in the pathogenesis of these disorders. These findings have led to expanded considerations for treatment.Sulforaphane(SFN)is a dietary phytochemical extracted from cruciferous vegetables.It is an effective activator of the transcription factor nuclear erythroid-2 like factor-2,which can upregulate multiple antioxidants and protect neurons against various oxidative damages.On the other hand,it can also significantly reduce inflammatory response to pathological states and decrease the damage caused by the immune response via the nuclear factor-kB pathway and other pathways.In this review,we introduce the biological mechanisms of SFN and the pilot evidence from its clinical trials of major mental disorders,hoping to promote an increase in psychiatric clinical studies of SFN.

Altered attentive bias towards interpersonal communication information across phases of schizophrenia: an eye-tracking study

Background Eye movement abnormality in schizophrenia has been studied for several decades.However,patient differences in eye movements across phases of schizophrenia from eye-tracking studies have not been well documented.Aims This pilot study used eye-tracking technology to investigate attentive bias towards interpersonal communication information across different clinical phases of schizophrenia.Methods This study included 78 persons at clinical high risk(CHR)for schizophrenia,68 first-episode(FEZ)patients,and 39 chronically ill patients from the Shanghai At Risk for Psychosis Extending Project(SHARP Extending cohort)as well as 74 healthy controls(HCs).The experiment was an unguided-viewing task composed of 24 trials showing three types of pictures which varied in the degree of interpersonal communication.Type 1 was a scenery picture without people,type 2 was a picture with four people not communicating,and type 3 was a picture with four people communicating.We used two measures:(1)initial fixation duration and(2)total fixation duration.Results A ratio for both measures was calculated between measures for pictures with more or less interpersonal communication.The ratio of initial fixation duration for pictures with people communicating versus pictures with people not communicating was lowest in chronically ill patients(0.13(0.34))compared with HCs(0.31(0.36)),FEZ patients(0.31(0.46)),and CHR patients(0.36(0.42)).The difference in the ratios of initial fixation duration for type 2 and type 3 pictures was also significant for female participants(HCs vs chronically ill patients,t=2.706,p=0.009;CHR patients vs chronically ill patients,t=4.079,p<0.001).In addition,the ratio of initial fixation duration on pictures with people not communicating versus pictures without people negatively correlated with participants’high-risk symptoms(r=−0.35,p=0.002)among the CHR group and also correlated with the negative symptom subscore on the Positive and Negative Syndrome Scale(PANSS)among chronically ill patients(r=−0.33,p=0.037).The ratio of initial fixation duration between type 1 and type 3 pictures was associated with PANSS negative symptoms only in female patients with schizophrenia(r=−0.46,p=0.004).Conclusions These findings suggest an altered attentive bias towards pictures with a high degree of interpersonal communication information across different clinical phases in schizophrenia.The ratio of initial attentive orienting was associated with negative symptoms in female patients.

Abnormal neural oscillations in clinical high risk for psychosis:a magnetoencephalography method study

Background Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks.Abnormal neural oscillations have been discovered in patients with schizophrenia.However,there is limited evidence available on abnormal spontaneous neural oscillations in clinical high risk for psychosis(CHR-P).The brain signals recorded by the magnetoencephalography(MEG)technique are not to be disrupted by the skull and scalp.Methods In this study,we applied the MEG technique to record the resting-state neural activities in CHR-P.This was followed by a detailed MEG analysis method including three steps:(1)preprocessing,which was band-pass filtering based on the 0.5-60Hz frequency range,removal of 50Hz power frequency interference,and removal of electrocardiography(ECG)and electrooculography(EOG)artefacts by independent component analysis;(2)time-frequency analysis,a multitaper time-frequency transformation based on the Hanning window,and(3)source localisation.an exact low-resolution brain electromagnetic tomography.The method was verified by comparing aparticipant with CHR-P with a healthy control during the MEG recordings with an eyes-closed resting state.Results Experimental results show that the neural oscillations in CHR-P were significantly abnormal in the theta frequency band(4-7Hz)and the delta frequency band(1-3Hz).Also,relevant brain regions were located in the left occipital lobe and left temporo-occipital junction for the theta band and in the right dorsolateral prefrontal lobe and near orbitofrontal gyrus for the delta band.Conclusions Abnormal neural oscillations based on specific frequency bands and corresponding brain sources may become biomarkers for high-risk groups.Further work will validate these characteristics in CHR-P cohorts.

Reduced temporal activation during a verbal fluency test in clinical high risk of psychosis: a functional near-infrared spectroscopy-based study

Background Clinical high risk(CHR)of psychosis is a state in which positive symptoms cause the subjects distress but do not approach a severity level that fulfils the criteria for a psychotic episode.CHR exhibits cognitive deficits;however,the underlying neurobiological mechanisms remain unclear.This study aimed to investigate whether brain activation measured by the levels of oxygenated hemoglobin(oxy-Hb)in CHR subjects could be correlated with cognitive deficits.Methods Fifty-eight CHR individuals who fulfilled the criteria for attenuated positive syndrome as specified in the Structured Interview for Prodromal Syndrome(SIPS)and the Scale of Prodromal Syndrome(SOPS)and 58 age-and sex-matched healthy participants were included in the study.All subjects completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia(MATRICS)Consensus Cognitive Battery(MCCB)that includes tests measuring attention,verbal memory,verbal fluency,executive function,and general intelligence.Functional near-infrared spectroscopy(fNIRS)was used to measure the level of oxy-Hb in the dorsolateral prefrontal and frontotemporal cortices.Results We observed significantly decreased oxy-Hb levels in channel 32(located in the right superior temporal gyrus,rSTG)within the CHR individuals compared with that in the healthy controls(HCs)(t=−3.44,Bonferroni-corrected p=0.002),indicating lower brain activity.A significant positive correlation was observed between task-relatedβvalues and working memory in the CHR group(r=0.35,p=0.008).Conclusions The brain activation of rSTG is abnormal among subjects at clinicial high risk for psychosis.This abnormality is probably associated with the neural mechanisms of deficits in the working memory during the early stage of psychosis.

Clinical high risk for psychosis provides new opportunities for schizophrenia intervention strategies

Schizophrenia is a chronic lifelong illness that is associated with huge healthcare burdens for society and healthcare systems,and even more so for ill individuals and their families.It is characterised clinically by problems in multiple domains,including cognition,motivation,thinking,brain function,social functioning,and mood.Many of these difficulties precede the formal diagnosisof schizophreniaor a related disorder such as schizoaffective disorder.Psychosis usually develops in adolescence or early adulthood,after many of these clinical problems have already started,and eventually leads to the formal diagnosis of the illness.

Artificial intelligence-assisted niacin skin flush screening in early psychosis identification and prediction

Schizophrenia is a devastating mental disorder affecting 20 million people worldwide.Early diagnosis is crucial for disease management and improvement in prognosis,and diagnostic biomarkerscan serveasobjective indicators for the early screening of the disease.Based on the observation of diminished flush responses to niacin in patients with schizophrenia Horrobin proposed anoninvasive niacin skin flush screening for schizophrenia.

Different levels of facial expression recognition in patients with firstepisode schizophrenia:A functional MRI study

Background The impairment of facial expression recognition has become a biomarker for early identification of first-episode schizophrenia, and this kind of research is increasing.Aims To explore the differences in brain area activation using different degrees of disgusted facial expression recognition in antipsychotic-na?ve patients with firstepisode schizophrenia and healthy controls.Methods In this study, facial expression recognition tests were performed on 30 first-episode, antipsychoticna?ve patients with schizophrenia(treatment group) and 30 healthy subjects(control group) with matched age, educational attainment and gender. Functional MRI was used for comparing the differences of the brain areas of activation between the two groups.Results The average response time difference between the patient group and the control group in the ‘high degree of disgust' facial expression recognition task was statistically significant(1.359(0.408)/2.193(0.625), F=26.65, p<0.001), and the correct recognition rate of the treatment group was lower than that of the control group(41.05(22.25)/59.84(13.91, F=19.81, p<0.001). Compared with the control group, the left thalamus, right lingual gyrus and right middle temporal gyrus were negatively activated in the patients with first-episode schizophrenia in the ‘high degree of disgust' emotion recognition, and there was a significant activation in the left and right middle temporal gyrus and the right caudate nucleus. However, there was no significant activation difference in the ‘low degree of disgust' recognition.Conclusions In patients with first-episode schizophrenia, the areas of facial recognition impairment are significantly different in different degrees of disgust facial expression recognition.

Euphoric effect induced by zolpidem:a case study of magnetoencephalography

Initially,zolpidem,a non-benzodiazepine hypnotic agent,was considered to have fewer adverse reactions than traditional benzodiazepines.However,after zolpidem was approved for medical use,an increasing number of case reports have described abuse or dependence complications.We were especially interested in the cases of dependence that presented a paradoxical‘euphoric’effect of zolpidem.This article reports the case of a female zolpidem-dependent patient who presented with 6 years of daily use of 400-1400 mg of zolpidem.She reported subjective effects of euphoria,intense craving and the inability to stop drug ingestion.Her diagnoses were zolpidem dependence and a depressive episode induced by substance abuse.To explore the neural mechanisms of the euphoric effect caused by high-dose zolpidem,we performed repeated magnetoencephalography(MEG)recordings.Before undergoing detoxification,her MEG results indicated that cerebellar electrical signal activation increased when taking high zolpidem doses.However,the prefrontal and parietal lobes’electrical signal activity showed a tendency to recover to a normal state as the withdrawal time progressed to completion.This case suggests that the cerebellum plays a role in the euphoria induced by high zolpidem doses and provides clues for further research.

Concept,Grouping and Subgrouping of Ecological Technology

Although modern technology has an important role in human economic and social development,it can result in significant ecological damage.Thus,research has begun to focus on so-called"ecological technologies"to repair the degraded land and fragmented ecological environment and build a green mode of production and development.However,the concept of"ecological technology"is currently ill-defined,given the many different research fields involved.Therefore,here we divide ecological technologies into broad versus narrow technologies in terms of their impact on economic and social development and the related needs of production and ecological governance.We redefine each concept and clarify their aims and extensions,before further dividing them into three groups and seven subgroups,and clarifying the functions of each.The grouping and subgrouping of ecological technology will lay a foundation for the technology selection,collocation,implementation,promotion,monitoring and evaluation of ecological engineering planning and design.