Assess Bone Changes Research Articles

Bone loss-related factors in tissue and bone level dental implants: a systematic review of clinical trials.

Dental implants are popular for dental rehabilitation after tooth loss. The goal of this systematic review was to assess bone changes around bone-level and tissue-level implants and the possible causes. Electronic searches of PubMed, Google Scholar, Scopus, and Web of Science, and a hand search limited to English language clinical trials were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines up to September 2020. Studies that stated the type of implants used, and that reported bone-level changes after insertion met the inclusion criteria. The risk of bias was also evaluated. A total of 38 studies were included. Eighteen studies only used bone-level implants, 10 utilized tissue-level designs and 10 observed bone-level changes in both types of implants. Based on bias assessments, evaluating the risk of bias was not applicable in most studies. There are vast differences in methodologies, follow-ups, and multifactorial characteristics of bone loss around implants, which makes direct comparison impossible. Therefore, further well-structured studies are needed.

Bone Changes in the Condylar Process of the Mandible in Computed Tomography Images and Cephalogram in a Female Patient during a Growth Spurt Treated with a Removable Functional Appliance.

Introduction Functional treatment is the type of treatment preferred in young patients with lateral bite because it leads to simultaneous improvement of occlusion and facial profile. Objective The aim of this study is to assess bone changes within the condylar process of the mandible and to associate them with the changes observed in the analysis of lateral cephalograms and in the patient's occlusion. Materials and Methods Cone beam tomography of the temporomandibular joint, lateral radiogram of the skull, was performed at the beginning of treatment and after one year of therapy. Changes in cephalometric radiograms were evaluated by analyzing them and shown by making superimposition and staining layers. For the purpose of assessing bone changes within the condylar process, digital 3D solids of these processes were generated using data from computed tomography. Results Correction towards Angle's dental class I, overjet reduction from 8 mm to 3 mm, and improvement of the patient's profile were obtained. A rotation of the occlusal plane and improvement in an ANB by 1° and in the WITS measurement by 2.7 mm were observed. A growth of the condylar processes “backwards” and “upwards” was also observed, as well as a change of their shape and volume. Conclusions The obtained results suggest that the patient's significant improvement in occlusal conditions is due to posterior growth stimulation of the condylar processes of the mandible. The results confirm the validity of using this treatment technique in the case of growing children with complete posterior occlusion.

Detecting bone changes along dental implants, after immediate or delayed loading, using digital subtraction on cropped panoramic radiographs. A prospective clinical trial with minimum 3-year follow up

Aim The aim of this study was to assess bone changes along implants after immediate or delayed loading, using subtractions of digital images originated from cropped panoramic radiographs and visual evaluation. Materials and methods Eleven patients received 4 Ankylos implants interforaminal in the mandible. In 7 patients the implants were loaded immediately and 4 followed delayed loading. All patients were restored with a telescopic overdenture with Syncone abutments. From each patient 3 panoramic radiographs (PRs) were obtained: upon delivery of the restoration (T1), 6 months later (T2) and after 3 years (T3). 33 implants were finally selected. The radiographs were analyzed using the Emago® Software. The grey scale values were measured either manually (Stage A) or automatically (Stage B) in six areas (neck, middle and apex; both mesially and distally) along the implants’ sides to evaluate the bone density during clinical function. Images were also visually evaluated by five observers to detect bone changes at the cervical implant area. Results Strong positive correlation between the two stages (A and B) was found in all 3 examinations (Pearson’s r 0.84-0.98). The t-test showed no statistically significant differences in grey level values between immediate and delayed loading (p<0.05) and no statistically significant changes in the visual evaluation among implants undergoing either immediately or delayed loading (p<0.05). Conclusions Emago® is a valuable method for bone level assessment around implants’ neck. The grey value measurements of the bone adjacent to the implants that have been loaded either immediately or delayed do not significantly differ after 3 years of fuction. The visual assessment of the PRs images supports these findings.

Evaluation of the effect of systemic omega-3 polyunsaturated fatty acids on post-orthodontic relapse in a rabbit model

Introduction: Long term stability is the major goal of orthodontic treatment. Hence, a series of safe pharmacological agents have been investigated to increase osteoblastic activity around orthodontically moved teeth to help in retention and stability of their correction. Aim of the study: To evaluate the effect of systemic administration of Omega-3 fatty acids on post-orthodontic relapse, and to histologically assess bone changes concurrent with its administration in rabbits. Materials and Methods: Thirty two adult albino male rabbits were divided equally and randomly into two groups. Each group received NiTi coil springs installed on mandibular first molars and ligated to anterior incisors. Omega-3 or Saline were given from day one of orthodontic tooth movement (OTM) till end of relapse period by oral gavage. After 21 days of active OTM, appliances were removed from both groups to allow orthodontic relapse (OR); then amount and percentage of relapse were measuredon days 21, 28 and 42. Animals were sacrificed for histomorphometric analysis of alveolar bone remodeling. Results: A significant difference in relapse percentage was found on the third week of OR with means (66.04 ± 6.01 %) and (75.22 ± 13.61%) for experimental and control groups, respectively. Histomorphometric analysis showed a significant reduction in the area of active bone-resorptive lacunae and a significant increase in newly formed bone area related to omega-3 group. Conclusions: A strong evidence of the osteoblastic simulative effect of Omega-3 had been found with decreased percentage of OR after OTM.

Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis.

ObjectiveThe degradation of articular cartilage, which characterises osteoarthritis (OA), is usually paired with excessive bone remodelling, including subchondral bone sclerosis, cysts, and osteophyte formation. Experimental models of OA are widely used to investigate pathogenesis, yet few validated methodologies for assessing periarticular bone morphology exist and quantitative measurements are limited by manual segmentation of micro-CT scans. The aim of this work was to chart the temporal changes in periarticular bone in murine OA by novel, automated micro-CT methods.MethodsOA was induced by destabilisation of the medial meniscus (DMM) in 10-week old male mice and disease assessed cross-sectionally from 1- to 20-weeks post-surgery. A novel approach was developed to automatically segment subchondral bone compartments into plate and trabecular bone in micro-CT scans of tibial epiphyses. Osteophyte volume, as assessed by shape differences using 3D image registration, and by measuring total epiphyseal volume was performed.ResultsSignificant linear and volumetric structural modifications in subchondral bone compartments and osteophytes were measured from 4-weeks post-surgery and showed progressive changes at all time points; by 20 weeks, medial subchondral bone plate thickness increased by 160±19.5 μm and the medial osteophyte grew by 0.124±0.028 μm3. Excellent agreement was found when automated measurements were compared with manual assessments.ConclusionOur automated methods for assessing bone changes in murine periarticular bone are rapid, quantitative, and highly accurate, and promise to be a useful tool in future preclinical studies of OA progression and treatment. The current approaches were developed specifically for cross-sectional micro-CT studies but could be applied to longitudinal studies.

Physical activity, bone mass and muscle strength in children

Physical activity, bone mass and muscle strength in children

Radiodiagnosis of osteonecrosis of the mandible following radiation therapy

The paper describes a case of mandibular osteonecrosis in a patient who has received a radiotherapy cycle for tongue cancer. It deals with estimating the capacities of radiodiagnostic techniques to detect local tissue responses manifesting as radionecrosis after radiotherapy. To assess bone changes, clinical and laboratory examinations and comprehensive radiodiagnosis were made, which could validly evaluate the bone structures and soft tissues, determine the degree of injury, and identify complications. X-ray studies established that when evaluating the bone tissue, multislice computed tomography (MSCT) and cone-beam computed tomography (CBCT) were comparable in their diagnostic efficiency; however, MSCT was of greater informative value for the detection of soft tissue changes. CBCT may be successfully used during and after jaw osteonecrosis treatment as a control technique to evaluate its efficiency.

AB0742 Which Patients Have Erosive Psoriatic Arthropathy?

BackgroundThe term of erosive arthritis is borrowed from rheumatoid arthritis and is needed for complete evaluation of a patient with PA (Psoriatic Arthritis). Plain radiography is still the gold standard...

Application of sub-regional analysis to bone mineral density of the lower limb from whole body DXA scans

Bone mineral density at spine and hip is widely used to diagnose osteoporosis. Certain conditions cause changes in bone density at other sites, particularly in the lower limb, with fractures occurring in non-classical locations. Bone density changes at these sites would be of interest for diagnosis and treatment. We describe an application, based on an existing software option for Hologic scanners, which allows reproducible measurement of bone density at six lower limb sites (upper femur, mid-femur, lower femur; upper leg, mid-leg, lower leg). In 30 unselected subjects, referred for bone density, precision (CV%) measured on 2 occasions, separated by repositioning, ranged from 1.7% (mid-femur) to 4.5% at the lowest leg site. Intra-operator precision, measured by three operators on ten subjects on three occasions, was between 1.0% and 2.9%, whilst inter-operator precision was between 1.0% and 3.6%, according to region. These values compare well with those at the spine and upper femur, and in the literature. There was no evidence that this operator agreement improved between occasions 1 and 3. This technique promises to be useful for assessing bone changes at vulnerable sites in the lower limb, in diverse pathological states and in assessing response to treatment.

Effect of Temperature on Bone Tissue: Histological Changes

The analysis of burned human remains has been of great interest among forensic anthropologists largely due to the difficulty that their recovery, classification, reconstruction, and identification present. The main purpose of this analysis is to present histological methodology for the interpretation of bones altered by thermal processes. We include analyses of the microscopic changes among bones exposed to different temperatures, with the goal of establishing categories of histological morphology in relation to fire temperature. Samples of bone (ilium) were exposed systematically to controlled temperatures. Analysis of the resulting histological changes has allowed the formation of a clear four-stage classification of the alterations observed. This classification should prove useful in assessing bone changes in relation to temperature of exposure, particularly in cases where this temperature was previously not known.

Evaluation of bone changes in the temporomandibular joint using cone beam CT

The aim of this study was to assess bone changes and mobility in temporomandibular joints (TMJs) using cone beam CT (CBCT) in a population sample in Recife, PE, Brazil. The TMJ images of patients treated by a radiologist at a private dental radiology service over a period of 1 year were retrieved from the computer database and assessed using a computer with a 21-inch monitor and the iCAT Cone Beam 3D Dental Imaging System Workstation program (Imaging Sciences International, Hatfield, PA). The Pearson χ(2) test was used to analyse the differences in percentage of bone changes among the categories of mobility (p ≤ 0.05). The McNemar test was used to compare the presence of bone changes in TMJs on the right and left sides (p ≤ 0.05). An adjusted logistic regression model was used to assess the effect of age and gender on the occurrence of bone changes (p ≤ 0.05). Bone changes were present in 227 (71%) patients. Age group and gender showed a statistically significant association with presence of bone changes (p ≤ 0.05). There was no significant difference between the right and left sides (p = 0.556) and in condylar mobility (p = 0.925) with regard to the presence of degenerative bone changes. There is a high prevalence of degenerative bone alteration in TMJs, which is more frequent in women and mostly located in the condyle. The prevalence of degenerative bone changes increases with age. There is no correlation between condylar mobility and the presence of degenerative bony changes in TMJs.

Hard tissue alterations after socket preservation: an experimental study in the beagle dog

The aim of the following experimental study was to assess bone changes in the horizontal and vertical dimension when using different socket preservation procedures. In five beagle dogs the distal roots of the 3rd and 4th premolar were extracted without elevation of a mucoperiosteal flap and the following treatments were assigned: Tx 1: The extraction socket was filled with BioOss Collagen (Geistlich Biomaterials, Wolhusen, Switzerland) and interrupted sutures were applied.: Tx 2: The extraction socket was filled with BioOss Collagen (Geistlich Biomaterials, Wolhusen, Switzerland) and a free gingival graft was sutured to cover the socket.: Tx 3: The extraction socket was left with its blood clot and interrupted sututes were applied.: Four month after surgery the dogs were sacrificed and from each extraction site two histological sections were selected for histometric analysis. The following parameters were evaluated: (1) the vertical dimension was determined by placing a horizontal line on the lingual bone wall. Then, the distance from this line to the buccal bone wall was measured. (2) The horizontal dimension was assessed at three different areas measured from the top of the lingual crest: 1 mm (Value 1), 3 mm (Value 3) and 5 mm (Value 5). The mean vertical loss of the buccal bone plate for the Tx 1 group was 2.8+/-0.2 mm. The Tx 2 group showed vertical loss of 3.3+/-0.2 mm. The Tx 3 group demonstrated 3.2+/-0.2 mm of mean vertical loss. The horizontal dimension of the alveolar process was 4.4+/-0.3/6.1+/-0.2/7.2+/-0.1 mm at the three different levels for the Tx 1 group. The Tx 2 group depicted bone dimensions of 4.8+/-0.2/6.0+/-0.2/7.1+/-0.1 mm. The horizontal dimension of the Tx 3 group was 3.7+/-0.3/6.2+/-0.2/7.0+/-0.1 mm. When the results from the horizontal measurements were tested with the analysis of variance (ANOVA), a clear significance could be found in particular for Value 1 mm between the test groups Tx 1 and Tx 2 and the control group (Tx 3) (P<0.001). Furthermore the mean of treatment 1 (Tx 1) was slightly significantly lower than of treatment 2 (Tx 2) (P<0.05). The findings from the present study disclose that incorporation of BioOss Collagen into the extraction socket has only limited impact on the subsequent biologic process with particular respect to the buccal bone plate. The horizontal measurement of the alveolar ridge depicted that the loss of the buccal bone plate was replaced to a certain amount by newly generated bone guided by the BioOss Collagen scaffold. It seems that the mechanical stability provided by BioOss Collagen and furthermore by a free gingival graft could act as a placeholder preventing the soft tissue from collapsing.

Serum Cross-Linked N-Terminal Telopeptide of Type I Collagen for Evaluation of Renal Osteodystrophy in Hemodialysis Patients

Background: Useful markers of bone resorption are needed for hemodialysis patients with renal osteodystrophy. This study investigated the use of a new immunoassay for cross-linked N-terminal telopeptide of type 1 collagen to assess bone changes in hemodialysis patients. Methods: Radial bone mineral density was examined in 178 hemodialysis patients at baseline and after 12 months. Serum levels of N-terminal telopeptide and other markers were measured. Results: The annual percent change of radial bone mineral density was negatively correlated with the levels of N-terminal telopeptide, intact osteocalcin, tartrate-resistant acid phosphatase, bone-specific alkaline phosphatase, and intact parathyroid hormone. The annual percent change of radial bone mineral density showed a stronger correlation with N-terminal telopeptide levels than with the other markers, except for intact parathyroid hormone. Also, intact parathyroid hormone and N-terminal telopeptide levels showed a stronger correlation than that of either tartrate-resistant acid phosphatase or cross-linked carboxyterminal telopeptide of type 1 collagen with intact parathyroid hormone. Conclusion: Serum N-terminal telopeptide may be the most useful bone resorption marker in renal osteodystrophy and its use combined with bone formation markers may improve the management of this condition.

Bone Biopsy as a Diagnostic Tool in the Assessment of Renal Osteodystrophy

When renal disease develops, mineral and vitamin D homeostasis is disrupted, resulting in diverse modifications in bone cells, bone structure and the rate of bone turnover. In end stage renal failure (ESRF) when patients require chronic maintenance dialysis, nearly all of them have abnormal bone histology known as renal osteodystrophy (ROD). Moreover, survival rates of patients on dialysis have increased because of therapeutic improvement and the resultant increase in duration of dialysis has led to a further rise in renal osteodystrophy. Because metabolic bone disease can produce fractures, bone pain, and deformities late in the course of the disease, prevention and early treatment are essential. Serum PTH and various bone markers are commonly used to assess bone changes in ESRF patients, but the diagnosis of underlying bone disease is still rather uncertain. To date, bone biopsy is the most powerful and informative diagnostic tool to provide precise information on the type and severity of renal osteodystrophy, and on the presence and amount of aluminum and strontium deposited in the bone. Bone biopsy is not only useful in clinical settings but also in research to assess the effects of therapies on bone. Although considered an invasive procedure, bone biopsy has been proven to be safe and free from major complications, but the operator's experience and skill is important in further minimizing morbidity. Alternatives to bone biopsy continue to be sought, but the non-invasive bone markers have not been proven to be sufficient in diagnostic performance related to bone turnover, mineralization process and bone cell abnormality. Hence, transiliac bone biopsy remains the gold standard for the diagnosis of renal osteodystrophy.

Does Protein Intake During Weight Loss Affect Bone Mineral Content and Density?

0695 Although the effects of weight loss on bone have not been extensively examined, it is theorized that weight loss has adverse effects on bone health. Moreover, the impact of dietary protein on bone status during weight loss remains unclear. PURPOSE: To evaluate the effects of dietary weight loss regimens varying in macronutrient content on bone mineral content (BMC) and density (BMD) of the whole body (WB), proximal femur (PF) and lumbar spine (LS). METHODS: Fifty-two (21M, 31F), middleaged (M ± SD; 47.9 ± 7.2 y), overweight individuals (BMI = 33.7 ± 4.5 kg/m2) were randomized to a 4-month lifestyle physical activity program and isocaloric (females = 1700 kcal/day and males = 1900 kcal/day) diet consisting of either: A) higher protein (PRO; 1.6 g/kg-day or ∼ 30% protein, 40% carbohydrate and 30% fat) OR B) higher carbohydrate (CARB; 0.8g/kg-day or ∼15% protein, >55% carbohydrate and 30% fat). Body composition and bone measures were acquired using dual energy x-ray absorptiometry (DXA; Hologic 4500A). RESULTS: Weight loss was not statistically different between PRO and CARB (−8.8 ± 4.7 vs.−7.1 ± 4.1 kg, p = 0.16), however, there was a strong trend for greater WB fat loss (−6.0 ± 3.2 vs. −4.5 ± 2.4 kg, p = 0.07) and trunk fat loss (−3.7 ± 2.1 vs. −2.8 ± 1.5 kg, p = 0.05) in PRO. No group or time effect was apparent for WB BMC or BMD. Total PF and PF neck BMD decreased in the total group (−0.6 ± 2.0%, p = 0.03; −0.9 ± 3.0%, p = 0.02) with no group effect. In contrast, PRO significantly increased LS BMC (3.7 ± 4.2 vs. 1.5 ± 3.8%, p = 0.03) and BMD (3.0 ± 3.8 vs. 0.9 ± 2.0%, p = 0.01) compared to CARB. Although no significant change in LS area occurred (p = 0.98), a significant negative relation existed between changes in LS BMC and changes in WB fat, mineral free lean and trunk fat mass (range = −0.37 to −0.48, p < 0.01). Coupled with the divergent effects of weight loss on PF and LS, measurement artifact cannot be discounted. CONCLUSION: Although it appears that weight loss diets higher in protein confer increases in bone health indices, measurement error cannot be dismissed. Additional studies investigating A) the effect of protein intake during weight loss on bone health and B) the accuracy of fan-beam DXA in assessing bone changes during weight loss states are warranted. Supported by National Cattleman's Beef Association

Hormonal therapies and osteoporosis.

Osteoporosis, now defined as a disease characterized by low bone mass and a microarchitectural deterioration of bone tissue leading to enhanced bone fragility and fracture risk, is a major public health problem. Classic hormonal therapies to prevent and treat osteoporosis associated with menopause have recently been questioned due to the risk/benefit ratio of prolonged treatment. There is a critical need for safe and effective alternative therapeutics for this disease. Nonhuman primates have been used as models to assess bone changes associated with estrogen deficiency because their trabecular and cortical bone remodeling processes, monthly menstrual cycles, and reproductive-hormone patterns are similar to those of humans. The ovariectomized nonhuman primate has become the preferred model in which to study effects on bone remodeling, particularly with regard to bone mass, architecture, and strength, in fulfillment of studies required by international guidelines for the development of antiosteoporotic drugs. The nonhuman primate is amenable to several methodologies that assess bone quantity and quality, including dual energy x-ray absorptiometry (DXA), quantitative computed tomography (QCT), histology, static and dynamic histomorphometry, and biomechanical testing, as well as assays developed for clinical use, which serve as biomarkers of bone metabolic processes. The use of the nonhuman primate model in the assessment of osteoporosis therapeutics, both hormonal (sex steroids and their analogues, parathyroid hormone) and nonhormonal (bisphosphonates), has provided valuable information on the safety and efficacy as well as the mechanisms of bone loss associated with estrogen deficiency that is directly applicable to the human situation.

Influence of age, sex, and growth variables on phalangeal quantitative ultrasound measures: a study in healthy children and adolescents.

Skeletal status by phalangeal quantitative osteosonography (DBM Sonic BP-IGEA) was examined in 1227 healthy children (641 boys and 586 girls) aged 3-16 years. Aims of the study were to evaluate some physical parameters pertaining to the ultrasound transmission crossing the phalanx in a school-age population and to relate these values to age, sex, and growth variables. A correlation was found between AD-SoS (amplitude-dependent speed of sound) and BTT (bone transmission time) and, age, height, weight, and pubertal stage, respectively. No correlation existed between FWA (fast wave amplitude) and SDy (dynamics of the ultrasound signal) and age, height, weight, pubertal stage, and BMI, respectively. AD-SoS increased in boys until 7-8 years of age. Thereafter a plateau was reached up to age 12-13 years, when a rapid increase was observed corresponding to pubertal growth rate acceleration. In girls, AD-SoS increased with age up to 10-11 years with a steeper increase at the time of puberty starting about 2 years earlier than in boys. BTT presented a similar trend. Mean AD-SoS values increased from Tanner pubertal stages 1 to 2 and from stage 3 to 4 in both sexes. Significantly higher mean AD-SoS values in stages 2, 3, and 4 were observed in girls as compared to boys. Mean BTT values increased significantly from stage 1 to 5 in girls and from 1 to 4 in boys. QUS technology showed the ability to assess bone changes in the growing bone.

Vitamin D Status and Nonhemiplegic Bone Mass in Patients Following Stroke.

To assess bone changes in hemiplegic stroke patients, vitamin D status and bone density on hemiplegic and intact sides of sunlight deprived stroke patients were evaluated. Sera were collected from 88 hemiplegic stroke patients and 34 controls. The sera were assayed for 25-hydroxyvitamin D (25-OHD) and 1, 25 dihydroxyvitamin D (1, 25-[OH]2D). Bone density was measured bilaterally from radiographs of the hands using computed X-ray densitometry (CXD) and the Z-score of bone mineral density was calculated. Serum 25-OHD and 1, 25-[OH]2D concentrations were significantly lower in patients (11.5 +/- 5.4 ng/mL, 23.1 +/- 10.3 pg/mL) than in controls (21.6 +/- 3.1 ng/mL, 49.6 +/- 9.2 pg/mL) (P < .0001). The patients' Z-scores for osteopenia were lower on the hemiplegic side than on the nonhemiplegic side. Even on the intact side, the Z-scores were significantly lower as compared to controls. In addition to the strong positive correlation between the Z-scores on the hemiplegic side and degree of hemiplegia, the Z-scores on both sides in patients correlated positively with the serum 25-OHD concentration. These results suggest that vitamin D deficiency and disuse can cause osteopenia on the hemiplegic side and may increase the risk of hip fracture. In addition, it was demonstrated that hypovitaminosis D decreased bone mass on the nonhemiplegic side. This hypovitaminosis D might be corrected readily by the routine use of vitamin D supplements.

Ultrasound densitometry: Comparison with dual energy X-ray absorptiometry to assess bone changes early after menopause

Ultrasound densitometry: Comparison with dual energy X-ray absorptiometry to assess bone changes early after menopause

Digital subtraction radiography in assessing bone changes in periodontal defects following guided tissue regeneration

19 patients with a total of 23 periodontal lesions were selected for the study. Following flap-elevation, an occlusive membrane (Gore Tex) adjusted to the size and shape of the lesion was applied. The membrane was removed 4-6 weeks later by a 2nd operation. Clinical attachment levels were measured and intraoral radiographs taken prior to surgery, and 6 and 12 months postoperatively. The root length and marginal bone level were measured on paper drawings of the teeth magnified (15x) from the conventional radiographs. The radiographs were digitized for analysis of the subtraction images between the preoperative and the 6- and 12-month postoperative images. Clinical attachment gain was seen in 78% of the teeth after 6 months and 70% after 12 months. Bone gain was recorded in 56% and 22% after 6 months and in 44% and 66% after 12 months by conventional and digital subtraction radiography, respectively. The bone level measurements on conventional radiographs differed significantly (p = 0.001) between the preoperative and 6-month postoperative, but not between the 6- and 12-month, (p = 0.29) conventional radiographs. There was no significant relationship between the clinical measurements and the assessments of bone changes on conventional radiographs (r = 0.28, p = 0.25), while a stronger relationship was observed between assessment of clinical attachment gain and assessment of bone changes on the subtraction images (r = 0.58, p = 0.01).