颅内外血管旁路移植术治疗慢性缺血性脑血管病的随访研究

目的探讨颅内外血管旁路移植术对慢性缺血性脑血管病患者预防卒中的作用。方法回顾性分析首都医科大学宣武医院于2000年10月—2009年10月间因慢性缺血性脑血管病行颅内外血管旁路移植术217例患者的临床资料,并随访患者术后的血管造影、临床症状等资料及氙CT检测脑血流的改善情况。结果①217例患者平均年龄（42±13）岁,其中男131例（60．4％）,女86例（39．6％）。所有患者术前6个月内均存在脑缺血症状,包括短暂性脑缺血发作117例（53．9％）、可逆性神经功能缺损37例（17．1％）、完全性卒中63例（29．0％）。所有患者术前接受血流动力学评价,显示受累血管区局部脑血流量降低。②术前血管造影显示,烟雾病62例（28．6％）,一侧颈动脉闭塞72例（33．2％）,单侧大脑中动脉闭塞57例（26．3％）,介入治疗困难的颈动脉或大脑中动脉重度狭窄患者26例（12．0％）。③术后脑血管造影显示,388个吻合口中,380个通畅,通畅率为98．0％（380／388）。围手术期9例（4．1％）患者出现颅内血肿,1例（0．5％）因颅内血肿引发脑疝死亡。④217例患者中,10例患者失访,失访率4．6％。其中172例患者平均随访时间（38±18）个月,81例患者于手术后1年临床症状完全消失。⑤共50例患者术后1个月接受氙CT定量检测脑血流,显示患侧局部脑血流量较术前明显改善（t=3．312,P〈0．05）。结论通过对慢性缺血性脑血管病患者行颅内外血管旁路移植术后的中长期临床随访,显示颅内外血管旁路移植术对血流动力学性慢性缺血性脑血管病患者具有较好的疗效。     

颅内外血管架桥术治疗缺血性脑血管病疗效的再评价

目的 对颅内外血管架桥术治疗缺血性脑血管病的疗效进行再评价。 方法 对30例经正规内科治疗后仍有颈内动脉系统缺血症状的患者,进行了颞浅动脉-大脑中动脉吻合术,并对术后患者的脑血流改善情况及临床情况进行了分析。 结果 术前患者均为一过性缺血发作神经性缺损(TIA),可逆性缺血性神经障碍(RIND)和不典型脑缺血症状,术前CT,MRI检查无大面积脑梗死,SPECT·rCBF均有脑血流减低区。术后血管造影显示吻合口通畅率为86.7％,术后局部脑血流改善率为70％,随访仅发现2例患者有2次TIA,无完全性卒中发生,术前有轻度神经功能障碍的8例患者,术后均有不同程度的恢复。 结论颞浅动脉-大脑中动脉吻合术可预防颈内动脉系统血流动力学障碍性脑缺血发展成完全性卒中。     

氙CT指导脑血运重建术治疗症状性前循环动脉狭窄及闭塞

目的 探讨氙CT脑血流灌注成像技术在脑血运重建术前及疗效评估中的作用。方法 回顾性分析15例症状性前循环供血动脉粥样硬化性狭窄或闭塞患者的临床资料,其中行血管内支架置入术8例、颈内动脉内膜切除术1例和颞浅动脉-大脑中动脉旁路移植术6例,对比术前与术后2周内氙CT检测的局部脑血流量(r CBF)及术后6个月改良Rankin量表(mRS)评分。结果 (1)12例术前靶血管远端血流灌注异常患者平均r CBF值为(30±10)ml/(100 g·min),术后为(32±14)ml/(100 g·min),与术前比较差异有统计学意义(P=0.044);3例术前靶血管远端血流灌注正常患者平均r CBF值为(48±6)ml/(100 g·min),术后平均r CBF值为(50±7)ml/(100 g·min),与术前比较差异无统计学意义(P0.05)。(2)术后mRS评分改善8例,稳定7例。15例患者术后mRS评分为[1(0,3)]分,与术前[3(1,3)]分比较,差异有统计学意义(P0.05)。随访期间无一例新发神经功能障碍。结论 血运重建术可改善术前存在血流动力学障碍的症状性前循环供血动脉狭窄或闭塞患者的靶血管远端局部脑血流灌注及神经功能缺损症状,而术前氙CT脑血流灌注成像灌注异常可能较灌注正常患者获益更多。     

症状性脑动脉狭窄介入治疗的疗效观察

目的评价症状性脑动脉狭窄血管内支架成形术的安全性及近远期疗效。方法回顾性分析2009年—2010年在我院行颅内外动脉支架成形术的10例症状性脑动脉狭窄病人,就手术安全性及术后近远期临床疗效进行分析。结果本组10例病人,手术成功率达100%,8例病人术后症状消失,2例术后症状好转。随访4个月~18个月,所有病人无卒中临床复发,支架内均无血栓形成或内膜增厚。结论血管内支架成形术治疗症状性脑动脉狭窄比较安全,近期疗效较好,其远期疗效有待于进一步继续追踪观察。     

ICVD患者血管内支架成形术后脑CT灌注成像结果分析

目的从影像学角度评价血管内支架成形术治疗缺血性脑血管病(ICVD)的临床效果,探讨脑CT灌注成像检查的重要性及必要性。方法对19例因颅内外动脉狭窄导致的ICVD患者行颅内外血管内支架成形术,颈内动脉放置支架15枚、大脑中动脉M1段放置支架4枚。术前及术后1周内行脑CT灌注成像检查,记录相对脑血流量(r CBF)、相对脑血容量(r CBV)、相对平均通过时间(r MTT)。结果与术前比较,19例患者术后r CBF升高、r MTT降低(P<0.05),r CBV差异无统计学意义。结论血管内支架成形术可明显改善ICVD的脑血流灌注,CT灌注成像检查是评价血管内支架成形术手术效果的可靠方法。     

缺血性脑卒中脑血管狭窄支架治疗临床效果观察

目的研究缺血性卒中血管狭窄患者支架治疗的临床疗效。方法选取2013年1月至2013年12月本院收治的缺血性脑卒中血管狭窄患者64例,根据随机数表法分为观察组和对照组,每组32例。对照组患者仅接受内科保守治疗,观察组患者在对照组治疗基础上选择颅内外狭窄血管进行支架治疗。观察两组患者治疗前后血管狭窄情况、症状及体征变化情况、神经功能缺损评分(NIHSS评分)。结果治疗后两组患者的血管狭窄情况明显改善,观察组患者血管狭窄率(9.38%)显著低于对照组(40.63%)。差异有统计学意义(P0.05);治疗后两组患者头痛、头晕、肢体乏力、视物模糊、肌力等均得到改善,观察组患者改善情况优于对照组(P0.05);治疗后两组患者的NIHSS评分均有所降低,观察组患者NIHSS评分显著低于对照组(P0.05)。观察组患者手术成功率100%,无患者死亡,术中无脑卒中发生、支架移位与脱载,术后2 d CT血管造影(CAT)和经颅多普勒超声(TCD)检查显示血流动力学参数改善,术后脑血流量、脑血容量增多,达峰时间缩短,所有患者放置支架手术成功。结论对缺血性卒中颅内外血管狭窄患者采取支架治疗,可明显改善患者的血管狭窄程度、神经功能缺损程度及临床症状。     

颞浅动脉-大脑中动脉旁路移植术治疗闭塞性脑血管病的临床效果观察

目的观察颞浅动脉-大脑中动脉旁路移植术(STA-MCA)治疗闭塞性脑血管病的临床疗效。方法选取2010—2015年海口市人民医院收治的行STA-MCA的闭塞性脑血管病患者19例,比较患者手术前后脑血流量、血流通过时间及改良Rankin量表(mRS)评分。结果 19例患者均成功完成手术,术后7~10 d出院。PCT检查结果示术后患者健侧脑血流量、血流通过时间与术前比较,差异无统计学意义(P0.05);患侧脑血流量高于术前,血流通过时间短于术前(P0.05)。术前患者患侧脑血流量低于健侧,血流通过时间长于健侧(P0.05);术后患者患侧脑血流量、血流通过时间与健侧比较,差异无统计学意义(P0.05)。术后患者mRS评分低于术前(P0.05)。结论STA-MCA可有效改善闭塞性脑血管病患者脑部血流动力学及神经功能,临床效果较好。     

螺旋CT灌注成像在脑胶质瘤术前分级与术后疗效评价中的应用

对30例脑胶质瘤患者于术前、术后分别行CT灌注成像,测量术前病灶局部脑血流量(rCBF)、局部脑血容量(rCBV)及术后病灶区、对侧正常脑组织区域的脑血流量(CBF)、脑血容量(CBV).结果显示,术前脑胶质瘤随肿瘤级别的增高病变区rCBV升高,P<0.01;术后复发者,病变区CBF、CBV较未复发者及对侧正常脑组织区域升高,P均<0.01;未复发者,病变区CBF、CBV较对侧正常脑组织区域低,P均<0.05.认为CT灌注成像能较好地对胶质瘤进行术前分级,而且有助于术后疗效评价.     

高分辨率磁共振成像指导下血管腔内成形术在非急性期症状性颅内大动脉闭塞中的应用

目的评估在高分辨率磁共振成像(HR-MRI)指导下应用血管腔内成形术开通症状性非急性期闭塞颅内大动脉的可行性、安全性和临床疗效。方法回顾性分析2017年6月至2019年12月大连医科大学附属第一医院介入治疗科连续收治的症状性颅内大动脉亚急性及慢性闭塞患者31例的临床资料,全部患者使用HR-MRI对闭塞段管腔和斑块位置进行评估,明确闭塞性质(血栓或管壁实质性闭塞),获取颅内动脉斑块分布以及与穿支动脉开口位置之间的关系。根据评估结果筛选出26例患者,采用血管腔内成形术进行再通治疗,评价手术技术成功率、围手术期并发症及术后临床和影像学的随访效果,采用改良Rankin量表(mRS)评估患者的预后。结果 26例手术患者中,22例闭塞血管成功开通;4例开通失败,其中1例为颈内动脉C6段闭塞,2例为椎动脉颅内段闭塞,1例为基底动脉闭塞,术中均因导丝难以通过闭塞段而终止手术。术中发生并发症2例,均为无症状性末梢栓塞事件,无围手术期出血并发症及死亡患者。22例成功开通患者中位随访时间12(3,21)个月,无死亡及失访病例,中位mRS评分为1(1,3),无新发卒中及短暂性脑缺血发作;2例发生无症状性支架再狭窄,无不良反应及不良后果发生。4例手术失败患者中位随访时间11(3,18)个月,无死亡及失访患者,中位mRS评分为2(2,3),1例新发卒中,2例发生短暂性脑缺血发作。结论对于非急性期症状性颅内大动脉闭塞患者,经过HR-MRI对闭塞段的闭塞长度、病变性质和潜在腔隙等进行评价,结合其他临床情况,筛选合适病例,实施血管腔内成形术治疗安全可行,短期内能够改善患者的缺血症状,降低再发卒中率,远期疗效尚需长期随访证实。     

脑血管造影评估在血管内支架成形术治疗脑供血动脉狭窄中的价值

目的探讨脑血管造影评估在血管内支架成形术治疗脑供血动脉狭窄中的价值。方法对105例症状性脑缺血发作患者进行术前全脑血管造影，对相关影像学信息进行全面评估，根据评估结果对136支狭窄血管行血管内支架成形术，术后不同时期进行脑血管造影随访。结果70处血管狭窄恢复正常血管直径，54处残余狭窄〈20％，7处残余狭窄为50％～80％。5例因支架不能输送到位而放弃手术；术中血栓保护伞完全被封堵1例。患者术前症状均有不同程度缓解。70例患者获得术后1～36个月的脑血管造影随访，颈动脉再狭窄2例，椎动脉起始部再狭窄6例，颅内动脉再狭窄6例。结论 术前充分评估脑血管造影结果并据此制定个体化治疗策略是保证血管内支架成形术安全性的前提。     

A clinical study in elderly patients with Parkinson's disease using MRI and SPECT--Parkinson's disease and the lacunar state]

Parkinson's disease (PD) is often associated with dementia in elderly patients, and sometimes PD coexists with senile dementia of the Alzheimer type (SDAT) or cerebrovascular disease (CVD) in the elderly. However, since there are few previous clinical studies on the coincidence of, or relationship between PD and CVD, the authors evaluated these aspects in 34 elderly patients with PD using MRI and SPECT. All the patients were over 70 years old. The diagnosis of PD was based on the presence of three symptoms (resting tremor, cogwheel rigidity and bradikinesia) which are characteristic of PD, and the effectiveness of L-DOPA therapy. We therefore believe that patients with vascular Parkinsonism were excluded from our study. In 34 cases, 24 (71%) had MRI evidence of CVD (mainly the lacunar state). In the 10 cases who had no CVD, 2 (20%) had severe dementia and the decrease of regional cerebral blood flow (rCBF) in the temporal and parietal lobes bilaterally correlated with the SPECT findings commonly found in SDAT. A comparison of the rCBF and the results of Hasegawa's dementia score (HDS) (verbal intelligence score) was made between the patients with PD associated with CVD and the patients with PD who had no CVD and no SPECT findings which correlated with SDAT. The rCBF in the frontal lobes and the results of the HDS of the former group were significantly lower than those of the latter. As mentioned above, elderly patients with PD often had CVD, leading to dementia.(ABSTRACT TRUNCATED AT 250 WORDS)     

神经精神狼疮患者局部脑血流灌注显像的临床研究

目的 观察神经精神狼疮患者脑血流改变,探讨神经精神狼疮患者局部脑血流灌注(rCBF)显像的临床意义.方法 20例神经精神狼疮患者(NPSLE组)、20例无神经精神表现的狼疮患者(SLE组)和20名年龄相当的健康志愿者(健康组)行单光子发射计算机断层(SPECT)rCBF显像,并划取感兴趣区作半定量分析得半定量(HQ)值.比较各组SPECT rCBF显像结果,并对HQ结果进行分析.同时20例神经精神狼疮患者行CT/磁共振成像(MRI)显像并与rCBF显像进行对比.结果 NPSLE组患者rCBF显像均阳性100%,其中19例局部脑血流降低,1例局部脑血流增加;20例患者CT/MRI头部显像阳性4例(20%),同rCBF显像相比差异有统计学意义(P＜0.01).SLE组患者rCBF显像阳性1例(5%),表现为局部脑血流降低.20名健康志愿者rCBF显像未见异常.NPSLE组患者rCBF显像病灶主要分布在颞叶(36%)、额叶(18%).其颞叶、额叶HQ值与SLE对照组和健康对照组比较,差异有统计学意义(P＜0.01和P＜0.05). 结论 rCBF显像灵敏度高,对早期诊断和治疗神经精神狼疮有重要意义.神经精神狼疮患者rCBF显像多表现为局部脑血流降低,好发部位为大脑中动脉供血区,以颞叶、额叶多见.     

Usefulness of Tc-99m ECD brain SPECT to evaluate the effects of methylprednisolone pulse therapy in lupus erythematosus with brain involvement: a preliminary report

Methylprednisolone pulse therapy (MPT) was introduced to avoid life-threatening complications in systemic lupus erythematosus (SLE) with brain manifestations. However, its efficacy in SLE patients remains uncertain and needs to be objectively evaluated. In this study, technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect regional cerebral blood flow (rCBF) in SLE patients with normal brain magnetic resonance imaging (MRI) findings. Twelve female SLE patients with neuropsychiatric symptoms were enrolled in this study. All patients had normal brain MRI and abnormal Tc-99m ECD brain SPECT findings. The Tc-99m ECD brain SPECT studies were performed 2 weeks after MPT. Pre- and post-MPT serum levels of anticardiolipin antibodies (ACA) and antiribosomal P antibodies (anti-P) were also measured. Before MPT, four patients had positive ACA and seven had positive anti-P. After MPT, all 12 patients demonstrated negative serologic findings and no neuropsychiatric symptoms. After MPT, ten patients showed complete recovery and two showed partial recovery of rCBF in the follow-up Tc-99m ECD brain SPECT images. This imaging is a logical and objective tool for measuring the effects of MPT in SLE patients with brain involvement by the determination of rCBF changes.     

Cerebral Blood Flow in Patients With Peritoneal Dialysis by an Easy Z‐Score Imaging System for Brain Perfusion Single‐Photon Emission Tomography

Cognitive impairment has long been recognized as a complication of chronic kidney disease. However, there is little information available regarding regional cerebral blood flow (rCBF) in patients with peritoneal dialysis (PD). Therefore, we evaluated rCBF using brain single photon emission computed tomography (SPECT). We conducted a cross‐sectional study in our hospital. Eighteen consecutive PD patients who could visit the hospital by themselves without any history of stroke were examined by Technetium‐99 m‐labeled ethylcrysteinate dimer brain SPECT. An easy Z‐score imaging system (eZIS) was used to compare rCBF in PD patients with those in age‐matched healthy controls. We also evaluated cognitive dysfunction with the mini‐mental state examination (MMSE) questionnaire. Only one patient showed an MMSE score of 18 points, and the remaining 14 patients were considered as normal (MMSE ≥ 27), and three patients were considered to have mild cognitive impairment (24 ≤ MMSE ≤ 26). In all patients, rCBF in the posterior cingulated gyri, precunei, and parietal cortices was significantly decreased. The ratio of the reduction of rCBF in each region relative to that of rCBF across the whole brain correlated positively with the PD duration (r = 0.559; P < 0.05). The serum β2‐microglobulin level was significantly higher in patients who had a higher ratio of rCBF reduction compared with those with lower ratios. In conclusion, all PD patients in the present study had decreased rCBF irrespective of MMSE scores.     

A comparison of the effects of citalopram and moclobemide on resting brain perfusion in social anxiety disorder

Introduction: The serotonin specific reuptake inhibitor (SSRI) citalopram and the reversible mono-amine oxidase-A inhibitor (RIMA) moclobemide have both been used successfully for the treatment of social anxiety disorder (SAD). In this study we investigate the effects of these compounds on resting brain function using single photon emission computed tomography (SPECT). Methods: Subjects meeting DSM-IV criteria for SAD underwent regional cerebral blood flow (rCBF) SPECT using Tc-HMPAO at baseline and after 8 weeks of treatment with either citalopram or moclobemide. Using statistical parametric mapping brain SPECT studies were analysed to determine the effects of treatment on rCBF, to compare the effects of citalopram and moclobemide, and to detect correlations between changes in rCBF and clinical response. Results: Subjects received citalopram (n=17) or moclobemide (n=14) as therapy. Subjects in both treatment groups demonstrated a significant improvement of SAD symptoms as measured by the Liebowitz Social Anxiety Scale total score. All subjects demonstrated a decrease in rCBF in the insulae post therapy. Subjects receiving citalopram had decreased superior cingulate rCBF after therapy compared to those receiving moclobemide. Conclusion: Both SSRI's and RIMA's decreased rCBF in the insulae during treatment of SAD; an effect that may be consistent with the role of these regions in processing internal somatic cues evoked by emotional stimuli. Citalopram had a greater effect on superior cingulate perfusion, an effect that is consistent with evidence of high levels of 5-HT transporters in this region.     

Stroke in coronary artery bypass graft surgery: an analysis of the CASS experience. The participants in the Coronary Artery Surgery Study.

An analysis of the Coronary Artery Surgery Registry (CASS) was performed to determine the occurrence of stroke after coronary artery bypass surgery in patients entered into the Coronary Artery Surgery Study Registry. Of the 10,098 patients having coronary artery bypass surgery at the Coronary Artery Surgery Study participating sites during the period July 1974 through May 1979, a total of 348 patients (or 3.4%) sustained a stroke during the first year after coronary bypass surgery. Fifty-nine strokes occurred on the day of surgery, and an additional 129 strokes occurred during hospitalization for coronary bypass surgery. Thus, 188 patients (1.9%) of the entire surgical group sustained a stroke during initial hospitalization for coronary artery bypass surgery. Logistic regression analysis was used to predict stroke on the day of surgery, during the hospitalization for surgery, and during the first year after surgery. The most powerful predictors of stroke on the day of coronary artery bypass surgery were: 1) older age (n = less than 0.0001); 2) use of alpha-adrenergic drugs after bypass (n = 0.0001); and 3) longer duration of cardiopulmonary bypass (n = 0.002). For those strokes occurring at least 1 day after coronary artery bypass but during the initial hospitalization, age and duration of cardiopulmonary bypass were the most powerful predictors of stroke. An analysis of predictors of stroke within 1 yr after hospital dismissal for initial coronary bypass surgery revealed that the most powerful predictor was a history of previous cerebrovascular disease (n less than 0.0001) and a history of hypertension (n less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Negative symptoms and regional cerebral blood flow in patients with schizophrenia: a single photon emission computed tomography study

There have been few functional imaging studies of negative symptoms in schizophrenia during the resting state, particularly in Asian patients with schizophrenia. The aim of this study was to evaluate the relationship between regional cerebral flood flow (rCBF) and negative symptoms, and to discuss the association between severity and subgroups of negative symptoms and rCBF. Sixteen patients with chronic schizophrenia were evaluated for negative symptoms using the Scale for the Assessment of Negative Symptoms (SANS), and brain single photon emission computed tomography (SPECT) imaging to assess rCBF during the resting state. Results were assessed using Spearman's correlation analysis. Total SANS scores were significantly negatively correlated with bilateral hypofrontality, especially in the left orbital frontal and bilateral superior frontal areas. Subscores for attention were significantly negatively correlated with the left lower frontal-temporal area and the right cerebellum. Subscores for anhedonia had a negative correlation with the right hemisphere. Subscores for affect were negatively correlated with rCBF in the bilateral prefrontal and bilateral superior frontal areas. There were no associations between rCBF and SANS in alogia and avolition. These results support the notion that frontal lobe dysfunction in schizophrenia is associated with negative symptoms. The left anterior hemisphere may play an important role in attention deficit. These relationships between negative symptoms and neuroanatomy require further clarification.     

Early somatosensory evoked potentials in cerebrovascular ischemic diseases. III. Correlations with age, sex, clinical data, EEG, emission and transmission computed tomography

Short latency SEP were investigated in 140 patients suffering from various cerebrovascular ischemic disease (CVD). CCT,AR and number of cortical phases of each stimulation side, as well as AR left to right side (AR l/r) were correlated to patient's age and sex, to diagnosis and vascular supply, to clinical symptoms, duration between stroke and investigation, SPECT, TCT and EEG. Significant correlations were found between CCT and diagnosis, vascular supply, clinical symptoms, duration, SPECT and TCT findings. CCT was prolonged in patients with completed stroke, MID, ischemia of the A.C.M., sensomotor hemiparesis or monoparesis of the upper extremity and lesions in SPECT and TCT located within thalamus and/or postcentral gyrus. Decreased perfusion in SPECT was only of statistical significance when it was combined with clinical symptoms and/or lesions in TCT. Significant correlations were found between AR l/r and all variables except age and sex. Differences in sub-groups corresponded to those found for the CCT. AR was lower at the affected side. Deviations of AR were also found in patients with focal lesions both in the EEG and in the TCT. Significant correlations were found between number of phases, clinical findings and SPECT, but no correlation was seen to TCT. Patients with CVD showed significant abnormalities of CCT and AR only in cases presenting neurological deficit and structural lesion in TCT. The abnormalities were more prominent in patients with an interval stroke-investigation over one year. No abnormalities were seen in patients with reversible symptomatology investigated after cessation of symptoms. A direct correlation may be suspected between number of phases and tracer uptake in SPECT.     

Abnormal regional cerebral blood flow in primary antiphospholipid antibody syndrome patients with normal magnetic resonance imaging findings. A preliminary report

Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in primary antiphospholipid antibody syndrome (PAPS) patients. The patients had mild neuropsychiatric manifestations and normal brain magnetic resonance imaging (MRI) findings in this preliminary study. Fifteen such female PAPS patients were examined with Tc-99m ECD brain SPECT in order to evaluate the rCBF. In addition, serum anti-cardiolipin antibodies (ACA) and lupus anticoagulant (LA) were simultaneously measured for comparison. RESULTS: (a) Tc-99m ECD brain SPECT revealed hypoperfusion brain lesions in 12 (80%) of the PAPS patients. Pariental lobes were the most commonly involved areas. (b) 11 (73%) and 9 (60%) cases had positive ACA and positive LA, respectively. In addition, ACA and LA results were correlated to the Tc-99m ECD brain SPECT findings. Tc-99m ECD brain SPECT is a sensitive tool for detecting abnormal rCBF in PAPS patients with mild neuropsychiatric manifestations and normal brain MRI findings.