Abstract TP332: Multi-Institutional Validation of the NAG Scale for Predicting Hematoma Expansion in Acute Intracerebral Hemorrhage Patients

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Kenichi Sakuta ◽  
Takeo Sato ◽  
Teppei Komatsu ◽  
Kenichiro Sakai ◽  
Hidetaka Mitsumura ◽  
...  

Background and Purpose: Early hematoma expansion (HE) is seen in about 30% of intracerebral hemorrhage (ICH) patients, but detecting those patients with high risk of HE is challenging. The NAG scale was previously published as the simple predictive scale for HE in acute ICH patients. Multi-institutional validation for utility of the scale was the aim of this study. Methods: We retrospectively reviewed consecutive primary ICH patients, who were admitted between September 2016 and December 2018 to Jikei University Hospital or Kashiwa Hospital, Japan. NAG scale is consist of 3 factors based on examination on admission; NIHSS ≥10, Anticoagulant agents use, Glucose ≥133 mg/dl, with 1 point assigned for each parameter. Patients received an initial non-contrast computed tomography (CT) scan within 24 hours from symptom onset, and underwent follow-up CT scans at 6 hours, 24 hours, and 7 days after admission. The HE was defined as an increment in hemorrhage volume >33% or an absolute increase >6 mL on follow-up CT scans. Poor prognosis was defined as modified Rankin Scale 4-6 at discharge. We performed logistic regression analysis and receiver operating characteristic curves to determine discrimination ability of the score. Results: A total of 142 patients (96 men; median age 64 years; median NIHSS 11) were included in our study, and HE was observed in 38 patients (27%). Higher NAG sores were related to HE (P<0.001), poor prognosis (P<0.001), and in-hospital death (P<0.001). The C statistic was 0.72 (95% confidence interval [CI], 0.63-0.82) for HE, 0.67 (95% CI, 0.58-0.76) for poor prognosis, and 0.85 (95% CI, 0.74-0.95) for in-hospital death. Multivariate logistic regression analysis with known risk factors showed the NAG scale was the independent factor for HE (Odds ratio, 2.95; 95% CI, 1.57-5.52; P = 0.001). Conclusion: Multi-institutional validation of the NAG scale showed good discrimination.

2021 ◽  
Vol 16 (1) ◽  
pp. 703-710
Author(s):  
Yuhang Mu ◽  
Boqi Hu ◽  
Nan Gao ◽  
Li Pang

Abstract This study investigates the ability of blood neutrophil-to-lymphocyte ratio (NLR) to predict acute organophosphorus pesticide poisoning (AOPP). Clinical data of 385 patients with AOPP were obtained within 24 h of admission, and NLR values were calculated based on neutrophil and lymphocyte counts. The patients were divided into two groups – good and poor – based on prognosis. Poor prognosis included in-hospital death and severe poisoning. The factors affecting prognosis were analyzed by logistic regression analysis, and the prognostic value of NLR was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that NLR levels, serum cholinesterase, and creatinine levels were good predictors of AOPP. Multivariate logistic regression analysis showed that high NLR was an independent risk factor for severe poisoning (adjusted odds ratio [AOR], 1.13; 95% CI, 1.10–1.17; p < 0.05) and in-hospital mortality (AOR, 1.07; 95% CI, 1.03–1.11; p < 0.05). NLR values >13 and >17 had a moderate ability to predict severe poisoning and in-hospital mortality, respectively (AUC of 0.782 [95% CI, 0.74–0.824] and 0.714 [95% CI, 0.626–0.803], respectively). Our results show that high NLR at admission is an independent indicator of poor prognosis in AOPP and can be used to optimize treatment and manage patients.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Shahram Majidi ◽  
Basit Rahim ◽  
Sarwat I Gilani ◽  
Waqas I Gilani ◽  
Malik M Adil ◽  
...  

Background: The temporal evolution of intracerebral hematomas and perihematoma edema in the ultra-early period on computed tomographic (CT) scans in patients with intracerebral hemorrhage (ICH) is not well understood. We aimed to investigate hematoma and perihematoma changes in “neutral brain” models of ICH. Methods: One human and 6 goat cadaveric heads were used as “neutral brains” to provide physical properties of the brain without any biological activity or new bleeding. ICH was induced by slow injection of 4 ml of fresh blood into the right basal ganglia of the goat brains. Similarly, 20 ml of fresh blood was injected deep into the white matter of the human cadaver head in each hemisphere. Serial CT scans of the heads were performed at 0, 1, 3, and 5 hours after inducing ICH. Analyze software (AnalyzeDirect, Overland Park, KS) was used to measure hematoma and perihematoma hypodensity volumes in the baseline and follow up CT scans. Results: The initial hematoma volumes of 11.6 ml and 10.5 ml in the right and the left hemispheres of the human cadaver brain gradually decreased to 6.6 ml and 5.4 ml at 5 hours, showing 43% and 48% retraction of hematoma, respectively. The volume of the perihematoma hypodensity in the right and left hemisphere increased from 2.6 ml and 2.2 ml in the 1 hour follow up CT scans to 4.9 ml and 4.4 ml in the 5 hour CT scan, respectively. Hematoma retraction was also observed in all six ICH models in the goat brains. The mean ICH volume in the goat heads was decreased from 1.49 ml in the baseline CT scan to 1.01 ml in the 5 hour follow up CT scan showing 29.6% hematoma retraction. Perihematoma hypodensity was visualized in 70% of ICH in goat brains, with an increasing mean hypodensity volume of 0.4 ml in the baseline CT scan to 0.8 ml in the 5 hour follow up CT scan. Conclusion: Our study demonstrated that substantial hematoma retraction and perihematoma hypodensity occurs in intracerebral hematomas in the absence of any new bleeding or biological activity of the surrounding brain. Such observations suggest that active bleeding is underestimated in patients with no or small hematoma expansion and our understanding of perihematoma hypodesity needs to be reconsidered.


2020 ◽  
Author(s):  
Bo You ◽  
Zi Chen Yang ◽  
Yu Long Zhang ◽  
Yu Chen ◽  
Yun Long Shi ◽  
...  

Abstract BackgroundAcute kidney injury (AKI) is a morbid complication and the main cause of multiple organ failure and death in severely burned patients. The objective of this study was to explore the epidemiological characteristics, the risk factors, and impact of both early and late AKIs, respectively.MethodsThis retrospective study was performed with prospectively collected data of severely burned patients from the Institute of Burn Research in Southwest Hospital during 2011-2017. AKI was diagnosed according to Kidney Disease Improving Global Outcomes (KDIGO) criteria (2012), and it was divided into early and late AKIs depending on its onset time (within the first 3 days or >3 days post burn). The baseline characteristics, clinical data, and outcomes of the three groups (early AKI, late AKI and non-AKI) were compared using logistic regression analysis. Mortality predictors of patients with AKI were assessed.ResultsA total of 637 patients were included in analysis. The incidence of AKI was 36.9% (early AKI 29.4%, late AKI 10.0%). The mortality of patients with AKI was 32.3% (early AKI 25.7%, late AKI 56.3%), and that of patients without AKI was 2.5%. AKI was independently associated with obviously increased mortality of severely burned patients [early AKI, OR = 12.98 (6.08-27.72); late AKI, OR = 34.02 (15.69-73.75)]. Multiple logistic regression analysis revealed that age, gender, total burn surface area (TBSA), full-thickness burns of TBSA, chronic comorbidities (hypertension or/and diabetes), hypovolemic shock of early burn, and tracheotomy were independent risk factors for both early and late AKIs. However, sepsis was only a risk factor for late AKI. Decompression escharotomy was a protective factor for both AKIs. ConclusionsAKI remains prevalent and is associated with high mortality in severely burned patients. Compared with early AKI, late AKI has a lower occurrence rate, but greater severity and worse prognosis,is a devastating complication. Late AKI is a poor prognosis sign in severe burns.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sara Fernandes ◽  
Beatriz Donato ◽  
Adriana Paixão Fernandes ◽  
Luís Falcão ◽  
Mário Raimundo ◽  
...  

Abstract Background and Aims Anemia is a well-know complication of Chronic Kidney Disease (CKD) and it seems to contribute for deterioration of kidney function. Experimental data suggest that anemia produces hypoxia of tubular cells which leads to tubulointerstitial damage resulting on CKD progression. Other mechanism described is that red blood cells have antioxidant properties that prevent the damage of tubulointerstitial cells and glomerulosclerosis from oxidative stress. There aren’t many observational studies that evaluated the association between anemia and progression of CKD. Therefore, our aim was to evaluate the association of anemia and CKD progression and its association outcomes in an outpatient ND-CKD population. Method We conduct a retrospective, patient-level, cohort analysis of all adult ND-CKD patients evaluated in an outpatient nephrology clinic over a 6 years period. The follow up time was at least 12 months. Anemia was defined according to the WHO definition (hemoglobin [hb] &lt; 13.0 g/dL in men and 12.0 g/dL in women). Progression of CKD was defined by one of the following criteria: decline in eGFR (CKD-EPI) superior to 5 ml/min/1.73 m2/year; duplication of serum creatinine or the need renal replacement therapy. Demographics and clinical data were also accessed. Results Out of 3008 patients referred to the nephrology clinic, 49.9% had anemia (mean age 71.9±15.9 years; 50.4% male; 92% white; mean follow-up time of 2.3±1.2 years). The mean Hb was 11.8 ±1.9 g/dL. Important cardiovascular comorbidities in patients with anemia were arterial hypertension (86.7%), obesity (65.5%), Diabetes Mellitus (DM) (52%) and dyslipidemia (46%). In univariate analysis, mortality was associated with anemia (36.9 vs 13.0%, p&lt;0.001), obesity (30.1 vs 21.8%, p&lt;0.001) and DM (30.1 vs 21.1%, p&lt;0.001). Of the patients with anemia, 738 met the criteria for CKD progression. In univariate analysis, CKD progression was associated with anemia (49.6 vs 43.9%, p=0.002), male gender (49.5 vs 43.6% p= 0.001); DM (49.6 vs 44.8 % p=0.009) and hypertension (47.9 vs 42.3% p=0.0018). In multivariate logistic regression analysis, anemia emerged was an independent predictor of CKD progression (OR 1.435, CI 95% 1.21-1.71, p&lt;0,001). Comparing hb values intervals (hb ≤10g/dl; hb10-12 g/dL; hb ≥12 g/dL), in the multivariate logistic regression analysis, hb ≤10g/dl was not associated with CKD progression and hb value between 10-12 g/dL was associated (OR 1,486, CI 95% 1.23-1.80, p&lt;0,001), when compared with the group with hb ≥12g/dL. In multivariate logistic regression analysis, the independent predictors of mortality were: older age (OR per 1 year increase: 1.048, 95% CI 95% 1.04-1.06, p&lt;0.001); arterial hypertension (OR 0.699 CI 95% 0.51-0.96, p=0.0029); obesity (OR 0.741, CI 95% 0.60-0.91, p=0.004) and hb value (OR per 1 g/dL decrease: 1.301, CI 95% 1.23-1.38, p&lt;0.001). Cardiovascular events were correlated with Hb levels between 10-12 g/dL (univariate analysis: OR 2.021, CI 95% 1.27-3.22, P=0.003), but not with the group with hb≤10 g/dL (univariate analysis: OR 1.837, CI 95% 0.96-3.51, P=0.066), having the group with hb ≥12g/dL was reference. Anemia was strongly associated with hospitalizations (multivariate logistic regression analysis: OR per 1 g/dL of Hb decrease: 1.256 CI 95% 1.12-1.32 p&lt;0.001), and this strong association was also observed on the groups with hb hb≤10 g/dL (multivariate logistic regression analysis: OR 3.591 CI 95% 32.67-4.84 p&lt;0.001) and between 10-12 g/dL (multivariate logistic regression analysis: OR 1.678 CI 95% 1.40-2.02, p&lt;0.001) Conclusion Our study suggests that anemia, at first consultation, increases the risk for rapid CKD progression and global mortality. This study could guide us on the development of futures studies in order to prove if anemia correction can slow the progression of CKD.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Masatomo Miura ◽  
Yoichiro Nagao ◽  
Makoto Nakajima ◽  
Seigo Shindo ◽  
Kuniyasu Wada ◽  
...  

Background: In acute ischemic stroke (AIS) patients due to intracranial atherosclerosis-related occlusions (ICAS-O), despite successful reperfusion with mechanical thrombectomy (MT), unexpected early reocclusion sometimes occurs and worsens clinical outcome. We investigated prevalence, outcomes, and predictors of early reocclusion within 48 hours of MT in AIS due to ICAS-O. Methods: In 557 consecutive AIS patients who underwent MT from January, 2016 to March, 2019 in two stroke centers, 71 patients due to ICAS-O were retrospectively evaluated. We divided them into two groups: patients with early reocclusion and those without. Clinical and angiographical findings and outcomes were compared between the 2 groups. Multivariable logistic regression analysis was used to investigate predictors of early reocclusion after MT. Results: Of 71 patients (aged 72 ± 10 years; 23 women; median NIHSS score, 15), early reocclusion was observed in 11 (15%). The first procedure for recanalization was stent retriever in 25 patients (35%), Penumbra system in 25 patients (35%), and balloon angioplasty in 21 patients (30%). Of these, 63 patients (88%) received rescue therapy (balloon angioplasty, 50; intracranial stenting, 13). In the early reocclusion group, more number of intraprocedural reocclusion (median [IQR], 3 [2-3] vs. 1 [0-1], p < 0.001), a higher rate of remaining stenosis on the final angiography (67.6 ± 5.9% vs 57.3 ± 15.9%, p = 0.044), and a higher rate of procedure-related adverse events (27% vs 5%, p = 0.043) were observed compared to the other group. On logistic regression analysis, a total number of intraprocedural reocclusion was independently associated with early reocclusion (odds ratio, 31.4; 95% confidence interval, 2.6-375.2). Early reocclusion was related to a low rate of favorable outcome at 90 days (modified Rankin Scale ≤ 2, 9% vs 54%, p = 0.007). Conclusions: In AIS patients due to ICAS-O, early reocclusion within 48 hours was not rare and associated with unfavorable outcome. Patients with repeated intraprocedural reocclusion are at high risk for early reocclusion; they might need follow-up angiographical assessment and intensive antithrombotic treatment.


2017 ◽  
Vol 11 (12) ◽  
pp. 323-331 ◽  
Author(s):  
Diego Castini ◽  
Simone Persampieri ◽  
Sara Cazzaniga ◽  
Giulia Ferrante ◽  
Marco Centola ◽  
...  

Background: With this study, we sought to identify patient characteristics associated with clopidogrel prescription and its relationship with in-hospital adverse events in an unselected cohort of ACSs patients. Materials and Methods: We studied all consecutive patients admitted at our institution for ACSs from 2012 to 2014. Patients were divided into two groups based on clopidogrel or novel P2Y12 inhibitors (prasugrel or ticagrelor) prescription and the relationship between clopidogrel use and patient clinical characteristics and in-hospital adverse events was evaluated using logistic regression analysis. Results: The population median age was 68 years (57–77 year) and clopidogrel was prescribed in 230 patients (46%). Patients characteristics associated with clopidogrel prescription were older age, female sex, non-ST-elevation ACS diagnosis, the presence of diabetes mellitus and anemia, worse renal and left ventricular functions and a higher Killip class. Patients on clopidogrel demonstrated a significantly higher incidence of in-hospital mortality (4.8%) than prasugrel and ticagrelor-treated patients (0.4%), while a nonstatistically significant trend emerged considering bleeding events. However, on multivariable logistic regression analysis female sex, the presence of anemia and Killip class were the only variables independently associated with in-hospital death. Conclusion: Patients treated with clopidogrel showed a higher in-hospital mortality. However, clinical variables associated with its use identify a population at high risk for adverse events and this seems to play a major role for the higher in-hospital mortality observed in clopidogrel-treated patients.


2002 ◽  
Vol 32 (4) ◽  
pp. 595-607 ◽  
Author(s):  
K. BARKOW ◽  
W. MAIER ◽  
T. B. ÜSTÜN ◽  
M. GÄNSICKE ◽  
H.-U. WITTCHEN ◽  
...  

Background. Studies that examined community samples have reported several risk factors for the development of depressive episodes. The few studies that have been performed on primary care samples were mostly cross-sectional. Most samples had originated from highly developed industrial countries. This is the first study that prospectively investigates the risk factors of depressive episodes in an international primary care sample.Methods. A stratified primary care sample of initially non-depressed subjects (N = 2445) from 15 centres from all over the world was examined for the presence or absence of a depressive episode (ICD-10) at the 12 month follow-up assessment. The initial measures addressed sociodemographic variables, psychological/psychiatric problems and social disability. Logistic regression analysis was carried out to determine their relationship with the development of new depressive episodes.Results. At the 12-month follow-up, 4·4% of primary care patients met ICD-10 criteria for a depressive episode. Logistic regression analysis revealed that the recognition by the general practitioner as a psychiatric case, repeated suicidal thoughts, previous depressive episodes, the number of chronic organic diseases, poor general health, and a full or subthreshold ICD-10 disorder were related to the development of new depressive episodes.Conclusions. Psychological/psychiatric problems were found to play the most important role in the prediction of depressive episodes while sociodemographic variables were of lower importance. Differences compared with other studies might be due to our prospective design and possibly also to our culturally different sample. Applied stratification procedures, which resulted in a sample at high risk of developing depression, might be a limitation of our study.


2021 ◽  
Vol 23 (2) ◽  
pp. 168-174
Author(s):  
O. А. Koziolkin ◽  
A. A. Kuznietsov

The aim of the study was to evaluate the diagnostic and prognostic value of serum hepcidin concentration in patients with acute spontaneous supratentorial intracerebral hemorrhage (SSICH). Materials and methods. Prospective cohort study of 88 patients with acute SSICH receiving the conservative therapy was conducted. Level of neurological deficit was evaluated using the Full Outline of UnResponsiveness Scale, the Glasgow Coma Scale and the National Institute of Health Stroke Scale. Computed tomography was performed to detect an intracerebral hemorrhage volume (ICHV), secondary intraventricular hemorrhage volume (SIVHV) and total volume of intracranial hemorrhage (TVICH). Laboratory blood samples were taken within 24 hours of hospitalization. Hepcidin levels, serum iron concentrations and total iron-binding capacity were determined, followed by calculations of transferrin saturation coefficient. Early neurological deterioration (END) and unfavorable variants of the acute period of SSICH (lethal outcome, modified Rankin score 4-5 on the 21st day of the disease) were considered as endpoints. Statistical processing of the obtained results included a correlation analysis, logistic regression analysis and ROC-analysis. Results. It was identified, that serum hepcidin level in the patients with SSICH was correlated with ICHV (R = 0.44, P ˂ 0.01), SIVHV (R = 0.45, P ˂ 0.01) and TVICH (R = 0.57, P ˂ 0.01). Hepcidin serum concentrations in the patients with ICHV >30 ml exceeded the value of those in cases of ICHV ≤30 ml by 69.0 % (P ˂ 0.0001). Serum levels of hepcidin were significantly higher in the patients with an unfavorable course and outcome of the disease in the acute period on the 1st day of admission (P ˂ 0.0001). Informative multipredictor models were developed via multiple logistic regression analysis, which include hepcidin values coupled with clinical and neurovisualization findings and are predictive of lethal and unfavorable acute period functional outcomes (AUC = 0,93, P ˂ 0.0001). Conclusions. The level of serum hepcidin in patients with acute SSICH is associated with the severity of cerebral lesions. The integration of serum hepcidin concentration with clinical and neuroimaging findings in the structure of multipredictor logistic regression models allows to determine the vital and functional prognosis of the acute period of SSICH with an accuracy of >85 %


2017 ◽  
Vol 127 (2) ◽  
pp. 249-254 ◽  
Author(s):  
Robert M. Starke ◽  
Justin M. Cappuzzo ◽  
Nicholas J. Erickson ◽  
Jonathan H. Sherman

OBJECTIVECystic lesions of the pineal gland are most often uncomplicated benign lesions with typical MRI characteristics. The authors aimed to study pineal lesion characteristics on MRI to better distinguish benign pineal cysts from other pineal region malignancies as well as to determine which characteristics were predictive of the latter malignancies. They also aimed to study risk factors predictive of hydrocephalus or malignancy in patients harboring these lesions.METHODSThe authors performed a retrospective review of a prospectively compiled database documenting the outcomes of patients with suspected pineal cysts on MRI who had presented in the period from 1998 to 2004. Inherent patient and lesion characteristics were assessed in a univariate logistic regression analysis to predict the following dependent variables: development of hydrocephalus, biopsy-confirmed malignancy, and intervention. Possible inherent patient and lesion characteristics included age, sex, T1 and T2 MRI signal pattern, contrast enhancement pattern, presence of cyst, presence of blood, complexity of lesion, presence of calcification, and duration of follow-up. Inherent patient and lesion characteristics that were predictive in the univariate analysis (p < 0.15) were included in the multivariable logistic regression analysis.RESULTSOf the 79 patients with benign-appearing pineal cysts, 26 (33%) were male and 53 (67%) were female, with a median age of 38 years (range 9–86 years). The median cyst radius was 5 mm (range 1–20 mm). Two patients (2.5%) had evidence of calcifications, 7 (9%) had multicystic lesions, and 25 (32%) had some evidence of contrast enhancement.The median follow-up interval was 3 years (range 0.5–13 years). Seven patients (9%) had an increase in the size of their lesion over time. Eight patients (10%) had a hemorrhage, and 11 patients (14%) developed hydrocephalus. Nine (11%) received ventriculoperitoneal shunts for the development of hydrocephalus, and 12 patients (16%) were found to have malignancies following biopsy or resection. In the multivariate analysis, contrast enhancement on MRI (OR 1.6, 95% CI 2.86–74.74, p = 0.013) and hemorrhage (OR 26.9, 95% CI 3.4–212.7, p = 0.022) were predictive of hydrocephalus. Increasing lesion size and hydrocephalus were near perfect predictors of malignancy and thus were removed from multivariate analysis. In addition, contrast enhancement on MRI (OR 8.8, 95% CI 2.0–38.6, p = 0.004) and hemorrhage (OR 6.8, 95% CI 1.1–40.5, p = 0.036) were predictive of malignancy.CONCLUSIONSAlthough cystic abnormalities of the pineal gland are often benign lesions, they are frequently monitored over time, as other pineal region pathologies may appear similarly on MRI. Patients with growing lesions, contrast enhancement, and hemorrhage on MRI are more likely to develop hydrocephalus and have malignant pathology on histological examination and should therefore be followed up with serial MRI with a lower threshold for neurosurgical intervention.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Xiaoying Yao ◽  
Magdy Selim ◽  
Ye Xu ◽  
Erica Siwila-Sackman

Background: Early identification of intracerebral hemorrhage (ICH) patients at risk of significant hematoma expansion (SHE) could facilitate the selection of appropriate patients who are likely to benefit from therapies aiming to minimize ICH growth. Nomograms have been proved to have superior individualized disease-related risk estimations of given outcomes. This study aims to develop a normogram that can be performed during the hyperacute phase to predict the risk of SHE in patients with spontaneous ICH. Methods: We reviewed clinical, laboratory, and radiological data from 237 patients diagnosed with spontaneous ICH who had baseline head CT within 12 hours of symptom onset and follow-up CT during the following 72 hours. SHE was defined as an absolute increase in ICH volume > 6ml or an increase greater than 33% from baseline to follow-up CT. To construct the nomogram, we performed logistic regression analyses to determine the predictors of SHE. Each predictor was assigned a point in the graphic interface of a nomogram, and the points were summed up to determine the predicted probability of SHE for a specific ICH patient. Results: SHE occurred in 74 patients (31.2%). The final model to predict SHE, presented as a nomogram, included: time from onset to baseline CT scan (< 3h vs 3-12h), dementia, current smoking, antiplatelet use, serum creatinine level, Glasgow Comma Scale score, and presence of subarachnoid hemorrhage on baseline CT. The model had satisfactory discrimination ability with a bootstrap corrected c index of 0.77 (95% CI, 0.75-0.82) and good calibration. The in-hospital mortality was higher in patients with SHE (42% vs. 15%; p <0.001). Conclusion: We developed and internally validated a novel nomogram model which accurately predicts the possibility of SHE based on seven easily obtainable parameters. This could be useful for treatment decision and stratification. External validation of our nomogram is warranted before its application to other populations.


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