Recovery and Quality of Life in Patients with Ruptured Cerebral Aneurysms




Subarachnoid hemorrhage (SAH) secondary to ruptured cerebral aneurysm is a common and frequently devastating condition with a high mortality and morbidity among survivors. The purpose of this study was to conduct a long-term follow-up of SAH patients, assess the changes in functional outcomes, describe quality of life (QOL), and determine its predictors 3.6 years after the hemorrhage.


The study design is an exploratory, descriptive correlational design.


Results were collected from a sample of 113 SAH survivors treated in our institution over a 2-year period (January 2006 until December 2007). We collected data on early and long-term functional outcomes and compared the differences. The health-related QOL was measured using the Polish version of The Short Form – 36 Health Survey Questionnaire (SF-36v2). Multivariable logistic regression was derived to define independent predictors of the QOL.


The mean follow-up time was 3.6 years. Sixty-six percent of patients had improvement in functional outcomes and among previously employed people 56% returned to work. QOL deteriorated in 24% of patients with the most affected dimension of Physical Role. Factors that predict good QOL are male gender, younger age, good economic/professional status, lack of physical handicaps, rehabilitation in a professional center, subjective improvement in health status, and absence of headaches or physical decline.

Conclusions and Clinical Relevance

Recovery process in SAH patients is dynamic and progresses over time. Since physical handicaps and low economic status significantly reduce the quality of life, an effort should be made to provide intensive rehabilitation and to encourage SAH survivors to return to work.


Subarachnoid hemorrhage (SAH) secondary to ruptured cerebral aneurysm is a common and frequently devastating condition affecting 6–10 people per 100,000 per year (Bederson et al., 2009). Due to enormous progress in the diagnostic techniques and new treatment strategies in recent years, the case-fatality rates have decreased by 17% during the last three decades, but still remain unacceptably high (Hop, Rinkel, Algra, & van Gijn, 1997; Nieuwkamp et al., 2009). Among survivors, one-third of patients are disabled in the first month after the acute SAH (Hop, Rinkel, Algra, & van Gijn, 1998; Nieuwkamp et al., 2009). However, recovery continues and with time, the percentage of disabled patients significantly decreases (Greebe, Rinkel, Hop, Visser-Meily, & Algra, 2010; Hop, Rinkel, Algra, & van Gijn, 2001; Hop et al., 1998). It is an encouraging perspective especially for healthcare workers who are particularly involved in the process of patients' rehabilitation. After initial neurosurgery, the complete recovery of patients requires team of skilled nurses, multiple physical, occupational and language therapists, and family caregivers.

The concept of recovery as a dynamic process is an important one also from an economic point of view. The economic burden of SAH includes the direct costs of providing medical care to patients and the indirect costs associated with loss of productivity. In the United States, the lifetime economic healthcare cost of an individual affected by the SAH was calculated as $228,030 (the highest among all stroke subtypes) with 58% accounted for indirect cost. The aggregate lifetime costs for all individuals affected by SAH in the United States in 1 year has been calculated as $ 5.6 billion (Taylor et al., 1996). Therefore, decreasing long-term disability of these patients will have a considerable impact on healthcare economy.

A good general and neurological condition of the patient does not mean that the recovery is totally complete. In the neurosurgical literature, the outcomes of the SAH patients are commonly divided into two groups: favorable and unfavorable. The outcomes are determined on available scales: Glasgow Outcome Scale (GOS) or modified Rankin Scale (mRS). A favorable outcome is determined by independence in daily activities and absence or presence of only minor neurological deficits. However, independence in daily life or lack of neurological deficits does not necessarily imply full physical, psychological, and social function of the patient, which is better defined by quality of life (QOL) questionnaires. In a study on the QOL in patients 4 months after SAH, only 19% of patients who were independent had no significant reduction in QOL. Twelve months after SAH, the number of these patients increased to 30% (Hop et al., 1998, 2001).

The aim of our study was to conduct a long-term follow-up of SAH patients who underwent surgical treatment and assess the changes in functional outcomes. We also described the QOL of these patients and determined its predictors 3 years after hemorrhage.

Material and methods

Patients and procedure

This study was approved by the Ethics Committee of Wroclaw Medical University and was conducted in the Department of Neurosurgery. One hundred sixty-three patients with SAH due to ruptured cerebral aneurysm admitted to our center, and treated by surgical clipping between January 2006 and December 2007, were found in our database. Thirty-one patients died during their hospitalization, thus, 132 survivors were eligible for the study. The patients were invited by a telephone call or a letter to participate in the study. They were asked to arrive for an appointment with their families or caregivers. Of the 132 patients, 113 responded to an invitation and were included. Nineteen patients did not participate in the study for various reasons: six died (the deaths were not directly related to SAH), six could not be contacted and seven refused to participate.


To assess the outcomes, we applied three commonly used scales, which are easy to administer and measure the degree of disability or dependence in the daily activities. GOS is a 5-point and mRS is a 6-point handicap scale. The Karnofsky scale (KS) runs from 100 to 0, with a standard interval of 10, where 100 is a perfect health and 0 is death.

The quality of life was evaluated using the Polish version of The Short Form – 36 Health Survey Questionnaire (SF-36v2) consisting of 36 items (Żołnierczyk-Zreda, Wrześniewski, & Bugajska, 2009). It measures eight health-related domains: Physical Function – PF (10 items), Physical Role – (role limitations because of physical health problems) – PR (4 items), Physical Pain – PP (2 items), General Health perception – GH (5 items), Vitality – VT (4 items), Social Function – SF (2 items), Emotional Role (role limitations because of emotional problems) – ER (3 items), and general Mental Health – MH (5 items). The direct score in the different domains is based on a scale that ranges from 0 (maximum reduction in QOL) to 100 (no reduction in QOL). Additionally, we assessed physical and mental component summary measures (PCS, MCS).

Data collection

All questionnaires were administrated in a face-to-face interview by the research team that included a neurosurgeon, a psychologist, a physiotherapist, and a nurse. Patients and family members or caregivers were interviewed together. They were asked questions related to clinical history, comorbidities, current health problems, changes in social and economic status. Each patient underwent neurological exam and assessment using the mRS, GOS, and KS scales. The SF-36v2 questionnaire was administered next. If the patient was unable to understand or answer the questions, they were directed to the family members or caregivers.

Data analysis

We collected the early (at the time of discharge from the hospital) and long-term outcomes (at the time of the study) as assessed by the mRS, GOS, and KS scales and we compared differences. We evaluated the improvement in patients' functional outcome in the period between discharge and the study visit. A “significant improvement” was the change in GOS or mRS of 1 degree or higher, a “slight improvement” was the change in KS of 10 or 20 points, without a change in the GOS score. To compare the differences in the outcomes, we used nonparametric Wilcoxon Rank Sum test.

We assessed the QOL, using as a reference the Polish population data (Żołnierczyk-Zreda et al., 2009). The decline in QOL was established if the direct score was one standard deviation below the mean. Next, we investigated the variables predicting QOL in SAH patients. The variables were divided into several groups: the variables related to a patient (age, sex, comorbidities, the economic and professional status), the variables related to an aneurysm (location, size, multiplicity), the variables related to SAH (the clinical status on admission assessed using the Hunt-Hess [H-Hs] and World Federation of Neurosurgical Surgeons Grading System for Subarachnoid Hemorrhage [WFNS] scales, the extension of SAH assessed using the Fisher's grade), the outcome variables (the physical handicap assessed using mRS or GOS, the presence of neurological deficits such as hemiparesis or aphasia) and others (the permanent changes in the patient's health status after SAH, rehabilitation in professional center after discharge, gradual health improvement). Multivariable linear regression was used to identify the association of the described variables with patients' QOL. In total, ten multivariable linear regressions were performed, one for each dimension of the SF-36, and additionally two for PCS and MCS.


The study group consisted of 113 SAH patients, 76 of which were women. The mean age was 54.2 with a range 21–71 years. The mean follow-up period was 3.6 years. The demographic and clinical characteristics of the patients are presented in Table 1.

Table 1. Demographic and clinical characteristics of patients with hemorrhage
Characteristic n percent
Age, median (years)54.2 ± 11.57 
Female sex7667.2
Size, mean (mm)9.1 ± 6.3 
Hunt-Hess grade
Fisher grade

At the time of discharge, 36 patients (32%) had neurological deficits: hemiparesis (14 patients), aphasia (4 patients), hemiparesis with aphasia (16 patients), and the oculomotor nerve paresis (2 patients). At the time of follow-up, 22 patients (19%) had neurological deficits: hemiparesis (7 patients), aphasia (4 patients), hemiparesis with aphasia (10 patients), and the oculomotor nerve paresis (1 patient). In 14 patients neurological deficits resolved completely; this represents 39% of all the patients with deficits. Eighteen of the 22 patients with residual neurological deficits demonstrated significant improvement in neurological symptoms, compared to the symptoms at the time of hospital discharge.

Despite the decrease in neurological deficits, 47 patients (41.5%) had a significant decline in physical capacity, 36 patients (32%) had a fresh memory deficits, 25 patients (22%) had intense and disabling headaches, 8 patients (7%) had personality changes, 3 patients (2.6%) had psychomotor retardation, 2 patients (1.7%) had intellectual deficits, 2 patients (1.7%) had anxiety disorders, 2 patients (1.7%) had vertigo, and one patient (0.8%) had epilepsy.

After discharge from hospital, 38 patients (33%) received continuing physical and occupational therapy; however, many of them did not receive services because of their lack of availability and high cost.

When patients were asked to define their main current complaints and health problems, 65 patients did not have any, 31 patients reported a new health problem, which was not present before SAH and 17 patients reported symptoms associated with chronic diseases that already existed before SAH (Table 2). Of the 113 patients, 73 (65%) assessed their health status as good, 33 (29%) as average, and 7 (6%) as poor.

Table 2. Patients' symptoms resulting from hemorrhage and associated chronic diseases
Patients' symptomsn, percent
None65 (57.5%)
Symptoms resulting from hemorrhage31 (27.4%)
Reduction in life independence8
Memory deficits6
Anxiety disorders2
Physical decline1
Symptoms associated with chronic diseases17 (15.1%)
Spine degenerative disease5
Kidney failure1
Heart failure1
Circulatory failure1

In the study group of 113 patients, 36 patients were retired, 34 patients were receiving work disability insurance provided by government, due to post-SAH disability, and 43 has returned to work. Among the previously employed 77 patients, 56% returned to work. Thirty-seven patients described their economic status as good, 57 patients as average, and 19 as poor.

Outcomes comparison

The early and long-term outcomes determined by using GOS, mRS, and KS scales are presented in Table 3. We noted an improvement in the functional outcomes in the period between discharge from the hospital and the study time in 75 (66%) patients. A significant improvement occurred in 39 patients (34%). In 29 patients, GOS has improved from 4 to 5 points, in two patients from 3 to 5 points, in seven patients from 3 to 4 points, and in one patient from 2 to 3 points. A slight improvement in the outcomes (10–20 points in KS) occurred in 36 patients (32%). The Wilcoxon Rank Sum test revealed a statistically significant improvement in long-term outcomes compared to early outcomes (p < .001).

Table 3. Early and long-term outcomes assessed by Glasgow Outcome Scale (GOS), modified Rankin Scale (mRS), and Karnofsky scale (KS)
ScalesEarly outcomes n = 113Long-term outcomes n = 113

Quality of life assessment

The analysis of QOL domains revealed that Physical Role was the most affected with 35.5% of patients reporting decline, followed by Emotional Role (30.5% of patients affected), Physical Function (23.7% affected), Physical Pain (23.7% affected), and General Health (23.7% affected). The least affected were Vitality, Social Function, and Mental Health with 22%, 18.6%, and 16.9% of patients affected, respectively (Figure 1).

Figure 1.

Percent of patients reporting a decline in quality of life. Physical Function (PF), Physical Role (PR), Physical Pain (PP), General Health (GH), Vitality (VT), Social Function (SF), Emotional Role (ER), Mental Health (MH)

Quality of life predictors

The results of the multiple regression analyses are presented in Table 4. Patients' demographics are strong predictors of QOL in different dimensions. A male gender is associated with a better QOL especially in physical domains such as Physical Function and Physical Pain but also in General Health perception. Age over 60 years is a negative predictive factor for both physical and mental domains (Physical Function, General Health perception, Vitality). Poor economic status is associated with decrease in QOL in 5 dimensions: Physical Function, Physical Pain, General Health perception, Vitality, and Mental Health. Among the variables related to aneurysms and SAH, only a high Fisher's grade (3 and 4) on admission had a negative predictive value for Physical Function and Emotional Role. Physical handicaps such as hemiparesis or aphasia are associated with high mRS score and predict poor QOL, whereas high GOS scores predict better QOL (improved Physical Function, Physical Pain, General Health perception, Social Function, Emotional Role, Mental Health). The permanent changes in patients' health status that occur after SAH such as physical decline and persistent headaches have negative predictive value for all dimensions of QOL. Any improvement in patients' health status is associated with better QOL in mental domains (Vitality, Mental Health). Intensive rehabilitation in a professional center has a positive predictive value for Physical Function, Physical Role, General Health perception, and Social Function.

Table 4. Quality of life (QOL) predictor variables (multiple linear regression analysis); R2 – coefficient of determination; β – regression coefficient, GOS – Glasgow Outcome Scale
Domain (SF-36)VariablesR2βp-value
Physical Function (PF)Male gender0.640.38.004
Advanced age −0.77<.001
High GOS (4;5) on discharge 1.75<.001
Hemiparesis on discharge −0.12.015
Physical decline −0.12.039
Poor economic status −0.30.003
Rehabilitation in professional center 0.17.025
Physical Role (PR)Physical decline0.28−0.35.006
High Fisher grade (3;4) −0.51.018
Rehabilitation in professional center 1.45<.001
Physical Pain (PP)Male gender0.380.34.005
Hemiparesis on discharge −0.25.032
Headache −0.47<.001
Social security −0.360.015
General Health (GH)Male gender0.460.36.013
Advanced age −0.50.018
High GOS (4;5) on discharge 1.05.001
Physical decline −0.17.020
Poor economic status −0.31.006
Rehabilitation in professional center 0.51.022
Vitality (VT)Advanced age0.33−0.26.040
Health improvement 0.29.028
Headache −0.29.026
Physical decline −0.30.018
Poor economic status −0.28.028
Social Function (SF)High GOS (4;5) on discharge0.340.39.001
Physical decline -0.38.003
Rehabilitation in professional center 0.240.045
Emotional Role (ER)High Rankin (4;5) on discharge 0.28−0.29.007
Physical decline −0.27.017
High Fisher grade (3;4) −0.45.012
Mental Health (MH)Chronic comorbidities0.43−0.30.024
Health improvement 0.24.032
High GOS (4;5) on discharge 0.52.000
Headache −0.25.057
Social security −0.29.008
Physical summary measures (PCS)Male gender0.490.33.002
Advanced age −0.47<.001
Hemiparesis −0.46<.001
Headache 0.31.005
Physical decline −0.240.022
Rehabilitation in professional center 0.28.017
Mental summary measures (MCS)High GOS (4;5) on discharge0.420.80<.001
Physical decline −0.11.032
Poor economic status −0.09.03

Key Practice Points

  • Subarachnoid hemorrhage (SAH) secondary to ruptured cerebral aneurysm is a common and frequently devastating condition with high mortality and morbidity rate. Residual physical and mental disability in survivors is a serious social and economic problem.
  • The recovery process of these patients is dynamic and progresses over time which is an encouraging perspective especially for healthcare workers such as nurses, multiple physical, occupational and language therapists and family caregivers, who are particularly involved in the process of patients' rehabilitation.
  • A good general and neurological condition of patient does not mean that the recovery is totally complete. Independence in daily life or lack of neurological deficits does not necessarily imply full physical, psychological, and social function of the patient, which is better defined by quality of life and determined by gender, age, physical condition, and economic factors.
  • As physical handicaps and low economic status significantly reduce the quality of life, a collaborative effort of healthcare workers should be made to provide intensive rehabilitation and to encourage SAH survivors to return to work.


Although there are reports on QOL in stroke survivors, research on QOL in a subgroup of stroke patients, such as SAH patients is still lacking (Leach, Gall, Dewey, Macdonell, & Thrift, 2011; Secrest & Thomas, 1999, 2007). The long-term follow-up of SAH patients is essential to establish effectiveness of new treatment strategies, understand coping mechanisms of patients with life-threatening illnesses and find the factors that could be targeted to improve the outcomes and QOL (van Gijn & Rinkel, 2001; Katati et al., 2007). This knowledge is particularly important for nurses and many healthcare workers such as physical, occupational and speech therapists, and also family members and caregivers who are closely involved in the long process of patient's recovery.

In our study, after a 3.6-year follow-up, 66% of patients showed improvement, which is very encouraging. Thirty-four percent of patients had considerable improvement and 32% had slight improvement. In total, 83% of survivors had good outcome evaluated in GOS scale. Other authors reported similar good outcomes in long-term follow-up. Malmivaara, Juvela, Hernesniemi, Lappalainen, and Siironen (2012) reported 75% of patients with good outcomes in a 10-year period. Wong et al. (2011) reported 73% of patients with good outcomes after a 6-month follow-up. Hop et al. (2001) reported that 50% of patients improved at least by one point on the mRS between 4 and 18 months after the hemorrhage. Similarly, in the study of Greebe et al. (2010) between 4 months and 5 years after the hemorrhage, half of the survivors showed an improvement on the mRS of at least one point. The improvement of the functional outcome was parallel to the improvement of QOL. However, there was no further improvement in the functional outcome between 5 and 12.5 years after SAH, and even a slight decline, which was associated with increasing age and comorbidities. Despite the reduction in physical functioning, QOL improved over this period, which indicates the adaptation of patients to the conditions of life after SAH. Such an improvement in a subjective well-being as a result of psychological adaptation has been described in other patients with chronic conditions (Kempen, Ormel, Brilman, & Relyveld, 1997).

Social rehabilitation and return to work is a major issue for individuals who survive SAH. Passier, Visser-Meily, and Rinkel (2011) found that 61.4% of patients returned to work, but only 35.2% resumed their work completely. Other studies also indicated that the proportion of patients who resumed their previous professional status, despite the continuous improvement of the functional outcome and QOL, is indeed low. The authors emphasize that the scores on the Sickness Impact Profile of the patients with mRS Grade 0 did not differ markedly from the scores of the reference population, with the exception of the subcategory “work” (Hop et al., 2001; Ogden, Utley, & Mee, 1997). However, in our study, 56% of previously employed patients returned to work. In the study of McKenna, Willison, Phil, Lowe, and Neil-Dwyer (1989) most of employed patients returned to work within 3 months and of the 31% of patients who found their work capacity reduced, only 4% attributed this change to SAH. Carter, Buckley, Ferraro, Rordorf, and Ogilvy (2000) reported that 67% of patients returned to a full-time status. According to Malmivaara et al. (2012) 63% of patients returned to work and 10 years later, 36% were still working and 27% had retired because of age, only 24% reported that they do not work because of SAH.

It is important that functional outcomes defined by commonly used scales (GOS, mRS) may considerably differ from the outcomes in QOL. Recovery to an independent physical state does not necessarily mean that QOL is satisfactory. In the study of Hop et al. only 19% of patients who were independent 4 months after the SAH had no significant reduction in QOL. Re-evaluation of this cohort at 18 months after the SAH showed that the outcome had improved and 31% of patients had no reduction in QOL (Hop et al., 2001). This indicates that the recovery after SAH is a dynamic process and progresses over time. The improvement in the functional outcomes is parallel to the improvement in QOL. According to Meyer et al. (2012) the QOL was significantly decreased in SAH patients compared to general population at 3 month and at 1 year, but showed improvement over time. In the study of Katati et al. (2007) 4 months after the hemorrhage, 42.9% of patients had deterioration in QOL. Our study showed that in a 3.6-year follow-up, 23.7% of patients had deterioration in QOL. According to published data, after 10-year follow-up, overall QOL of SAH patients was similar to that of general population (Malmivaara et al., 2012).

The data from our study confirm that all dimensions of QOL are affected, but Physical Function and Emotional Role are affected the most. This indicates that the state of patients' physical and emotional health strongly interferes with their daily life activities and work. Hackett and Anderson (2000), who evaluated the QOL one year after SAH, reached the similar conclusion. Our patients' Mental Health was less affected, which was in contrast to the study of Katati et al. (2007), who reported almost half of their patients suffering from depression, anxiety and loss of control over their behavior and emotions. The other authors found that the main QOL domains affected were Physical Function, Social Function, and Physical Role (Hop et al., 2001; Wong et al., 2011).

We assessed the early and long-term outcomes by the GOS, mRS, and KS scales, which are widely used for neurosurgical patients, with generally high interrater reliability (79–95%) and accepted rates of validity (Anderson, Housley, Jones, Slattery, & Miller, 1993; Banks & Marotta, 2007; Levin et al., 2001). These scales were very helpful to demonstrate the patient's recovery as a dynamic process. However, several limitations have been noted. On the scales of this type, a favorable outcome means that a patient has no or only minor focal neurological deficit and is independent in activities of daily life. However, it does not necessarily mean that the patient's recovery is totally complete. Such scales are insensitive to subtle improvements in the patient's status, fail to reflect the multidimensional nature of a patient's deficits and overemphasize physical disability, rather than cognitive and neurobehavioral problems. They were never intended as an instrument for documenting and describing individual patient's recovery patterns (Anderson et al., 1993; Kim, Haney, & Van Ginhoven, 2005). For that reason, we used SF-36 to better define the exact physical, psychological, and social function of a patient (Kim et al., 2005). The reliability of the eight scales of SF-36 has been estimated using both internal consistency and test-retest methods. With rare exceptions, published reliability statistics exceeded the minimum standard of 0.70, with most of them exceeding 0.80. Studies to date have yielded content, concurrent, criterion, construct, and predictive evidence of validity of SF-36 (Żołnierczyk-Zreda et al., 2009).

Another objective of our study was to identify the predictors of QOL in patients 3.6 years after SAH. We found that among demographic variables, the best predictors were age, sex, economic, and professional status. Males and younger patients have a better QOL, especially in the domains related to physical activity. This finding was confirmed by other studies, showing that men have a better QOL than women after SAH. Women reported more depressions and more symptoms of fatigue, less energy and less ability to work. However, other authors found no significant differences pertaining to age (Katati et al., 2007; Passier et al., 2012; Wik, Lindegaard, & Brunborg, 2005). Katati et al. (2007) stated that the age was the predictor in only one dimension that of Physical Function with patients older than 60 years having a physically more limited life. In contrast, Hütter et al. (1999) stated that the age is an important factor of future QOL. Poor economic status, that is a dependence on the government's disability payments, decreases QOL in the domains related to both physical and mental activity. It seems, therefore, that the QOL of SAH patients could be improved by intensive rehabilitation and returning to work.

The variables related to an aneurysm (location, size, multiplicity) did not affect the QOL. Among the SAH-related variables, we found that the extent of SAH (assessed in the Fisher's grade) is a predictor of QOL. According to Cedzich and Roth (2005) neither the H-Hs scale nor the Fisher's grade is a predictor of future QOL; however, Hütter et al. (1999) stated the opposite. Katati et al. (2007) found WFNS as a strong predictor of QOL.

The outcome variables such as the physical handicap, the neurological deficits and the others such as the permanent changes in the patient's health status, rehabilitation in a professional center and gradual health improvement are strong predictors of QOL in SAH patients. Physical handicaps and changes in the patient's health status such as physical decline and headaches have a negative impact on the QOL in the domains related to both physical and mental activity. A subjective and even a small improvement in the health status as well as rehabilitation in professional centers predict better QOL. A recent meta-analysis showed that only one of the traditional variables studied (patient age, sex, neurologic state on admission, severity of bleeding, physical disability, cognitive impairment, time between injury and psychosocial assessment) namely physical disability, had any notable effect on QOL (Noble & Schenk, 2010). Similarly, Hop et al. (1998, 2001) described the relationship between QOL and the degree of physical disability and found mRS to be a key prognostic factor. In addition, Katati et al. (2007) showed that the best predictors of QOL are mRS scale and the patient's gender. Being a man and the absence of physical disability predict a better QOL. Cedzich and Roth (2005) found the correlation between GOS and QOL and Leach et al. (2011) confirmed that physical disability is a strong predictor and it could be targeted to improve QOL of SAH patients. It is important to emphasize again that continuing therapy provided by qualified personnel in an appropriate rehabilitation center has enormous implications for long-term recovery, outcome, and later function of patients in society.


Recovery process in SAH patients is dynamic and progresses over time. Long-term outcomes are relatively good with 56% of previously employed patients returning to work. Persistent physical disability and low socioeconomic status significantly reduce the QOL. Therefore, healthcare resources should be allocated on intensive rehabilitation in professional centers and effort to return the patients to work.


The authors thank Anna Usowicz, MD, and Golde Dudell, MD, from Childrens' Hospital Oakland and Research Institute for their cooperation and assistance in editing the article.

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