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Background: This study evaluated, as a snapshot, the variability in quantification and image quality (IQ) of the clinically utilized PET [18F]FDG whole-body protocols in Finland using a NEMA/IEC IQ phantom permanently filled with 68Ge. Methods: The phantom was imaged on 14 PET-CT scanners, including a variety of models from two major vendors. The variability of the recovery coefficients (RCmax, RCmean and RCpeak) of the hot spheres as well as percent background variability (PBV), coefficient of variation of the background (COVBG) and accuracy of corrections (AOC) were studied using images from clinical and standardized protocols with 20 repeated measurements. The ranges of the RCs were also compared to the limits of the EARL 18F standards 2 accreditation (EARL2). The impact of image noise on these parameters was studied using averaged images (AVIs). Results: The largest variability in RC values of the routine protocols was found for the RCmax with a range of 68% and with 10% intra-scanner variability, decreasing to 36% when excluding protocols with suspected cross-calibration failure or without point-spread-function (PSF) correction. The RC ranges of individual hot spheres in routine or standardized protocols or AVIs fulfilled the EARL2 ranges with two minor exceptions, but fulfilling the exact EARL2 limits for all hot spheres was variable. RCpeak was less dependent on averaging and reconstruction parameters than RCmax and RCmean. The PBV, COVBG and AOC varied between 2.3–11.8%, 9.6–17.8% and 4.8–32.0%, respectively, for the routine protocols. The RC ranges, PBV and COVBG were decreased when using AVIs. With AOC, when excluding routine protocols without PSF correction, the maximum value dropped to 15.5%. Conclusion: The maximum variability of the RC values for the [18F]FDG whole-body protocols was about 60%. The RC ranges of properly cross-calibrated scanners with PSF correction fitted to the EARL2 RC ranges for individual sphere sizes, but fulfilling the exact RC limits would have needed further optimization. RCpeak was the most robust RC measure. Besides COVBG, also RCs and PVB were sensitive to image noise. [ABSTRACT FROM AUTHOR]

Abstract Background Hip resurfacing arthroplasty (HRA) is considered a bone-preserving procedure and may eliminate proximal femoral stress shielding and osteolysis. However, in addition to implant-related stress-shielding factors, various patient-related factors may also have an effect on bone mineral density (BMD) of the proximal femur in patients with HRA. Thus, we studied the effects of stem-neck angle, demographic variables, and physical functioning on the BMD of the proximal femur in a one-year follow-up. Methods Thirty three patients (9 females and 24 males) with a mean (SD) age of 55 (9) years were included in the study. BMD was measured two days and 3, 6, and 12 months postoperatively and 10 regions of interest (ROI) were used. Stem-neck angle was analyzed from anteroposterior radiographs. Results Three months postoperatively, BMD decreased in six out of 10 regions of interest (ROI) on the side operated on and in one ROI on the control side (p < 0.05) compared to the second postoperative day. At 12 months, BMD had increased in 7 ROIs on the operated side and one ROI on the control side (all p < 0.001). Correlation was found between the stem-neck angle and BMD in ROIs 2, 3, 7, and 9 (r = 0.36 - 0.61). In multiple regression analysis, stem-neck angle, age, sex, body mass index, and walking distance did not explain the BMD changes. Conclusions After an early drop, the BMD of the upper femur was restored and even exceeded the preoperative level at one year follow-up. From a clinical standpoint, the changes in BMD in these HRA patients could not be explained by stem-neck angle or patient related factors.

Background: This study evaluated, as a snapshot, the variability in quantification and image quality (IQ) of the clinically utilized PET [ 18 F]FDG whole-body protocols in Finland using a NEMA/IEC IQ phantom permanently filled with 68 Ge., Methods: The phantom was imaged on 14 PET-CT scanners, including a variety of models from two major vendors. The variability of the recovery coefficients (RC max , RC mean and RC peak ) of the hot spheres as well as percent background variability (PBV), coefficient of variation of the background (COV BG ) and accuracy of corrections (AOC) were studied using images from clinical and standardized protocols with 20 repeated measurements. The ranges of the RCs were also compared to the limits of the EARL 18 F standards 2 accreditation (EARL2). The impact of image noise on these parameters was studied using averaged images (AVIs)., Results: The largest variability in RC values of the routine protocols was found for the RC max with a range of 68% and with 10% intra-scanner variability, decreasing to 36% when excluding protocols with suspected cross-calibration failure or without point-spread-function (PSF) correction. The RC ranges of individual hot spheres in routine or standardized protocols or AVIs fulfilled the EARL2 ranges with two minor exceptions, but fulfilling the exact EARL2 limits for all hot spheres was variable. RC peak was less dependent on averaging and reconstruction parameters than RC max and RC mean . The PBV, COV BG and AOC varied between 2.3-11.8%, 9.6-17.8% and 4.8-32.0%, respectively, for the routine protocols. The RC ranges, PBV and COV BG were decreased when using AVIs. With AOC, when excluding routine protocols without PSF correction, the maximum value dropped to 15.5%., Conclusion: The maximum variability of the RC values for the [ 18 F]FDG whole-body protocols was about 60%. The RC ranges of properly cross-calibrated scanners with PSF correction fitted to the EARL2 RC ranges for individual sphere sizes, but fulfilling the exact RC limits would have needed further optimization. RC peak was the most robust RC measure. Besides COV BG , also RCs and PVB were sensitive to image noise., (© 2023. The Author(s).)

Therapeutic angiogenesis induced by gene therapy is a promising approach to treat patients suffering from severe coronary artery disease. In small experimental animals, adeno-associated viruses (AAVs) have shown good transduction efficacy and long-term transgene expression in heart muscle and other tissues. However, it has been difficult to achieve cardiac-specific angiogenic effects with AAV vectors. We tested the hypothesis whether AAV2 gene transfer (1 × 10 13  vg) of vascular endothelial growth factor B (VEGF-B186) together with immunosuppressive corticosteroid treatment can induce long-term cardiac-specific therapeutic effects in the porcine ischemic heart. Gene transfers were delivered percutaneously using direct intramyocardial injections, improving targeting and avoiding direct contact with blood, thus reducing the likelihood of immediate immune reactions. After 1- and 6-month time points, the capillary area was analyzed, myocardial perfusion reserve (MPR) was measured with radiowater positron emission tomography ([ 15 O]H 2 O-PET), and fluorodeoxyglucose ([ 18 F]FDG) uptake was used to evaluate myocardial viability. Clinical chemistry and immune responses were analyzed using standard methods. After 1- and 6-month follow-up, AAV2-VEGF-B186 gene transfer failed to induce angiogenesis and improve myocardial perfusion and viability. Here, we show that inflammatory responses attenuated the therapeutic effect of AAV2 gene transfer by significantly reducing successful transduction and long-term gene expression despite the efforts to reduce the likelihood of immune reactions and the use of targeted local gene transfer methods., (© 2022. The Author(s).)

Vascular endothelial growth factor B (VEGF-B) is an interesting therapeutic candidate for coronary artery disease. However, it can also cause ventricular arrhythmias, potentially preventing its use in clinics. We cloned VEGF-B isoforms with different receptor binding profiles to clarify the roles of VEGFR-1 and Nrp-1 in angiogenesis and to see if angiogenic properties can be maintained while avoiding side effects. VEGF-B constructs were studied in vivo using adenovirus (Ad)-mediated intramyocardial gene transfers into the normoxic and ischemic porcine heart (n = 51). It was found that the unprocessed isoform VEGF-B186R127S is as efficient angiogenic growth factor as the native VEGF-B186 in normoxic and ischemic heart. In addition, AdVEGF-B186R127S increased myocardial perfusion reserve by 22% in ischemic heart without any side effects. AdVEGF-B127 (VEGFR-1 and Nrp-1 ligand) and AdVEGF-B109 (VEGFR-1 ligand) did not induce angiogenesis. Thus, VEGF-B186 is angiogenic only before its proteolytic processing to VEGF-B127. Only the VEGF-B186 C-terminal fragment was associated with arrhythmias., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Background: Spinal surgeries are the leading causes for patient settlement issues. Recent European Medical Device Regulations aims to reduce complications by enforcing that surgical tools are validated before clinical use. Human cadavers are favored in preclinical use, but due to anatomic variance, decay, and scarce supply, alternative synthetic and animal models are used. This study evaluates the fidelity and validity of porcine models in training and assessment of microsurgical decompressive techniques in the lumbar spine., Methods: Anatomic dimensions of 10 human and 5 young pig spines were assessed from computed tomography images. Novel "en bloc" fresh-frozen ex vivo porcine model tissues' fidelity and validity for decompressive surgery was evaluated by 3 expert neurosurgeons, in comparison with other models., Results: The pigs' anatomic dimensions were on average 11% smaller than in humans. The pigs' L4-L5 was most alike humans, and the highest similarity was in lamina and spinous process widths, and the skin to posterior longitudinal ligament distance. Dimensional variability was higher in humans (F = 19.06-0.56, P < 0.05). The pigs' tissues were felt as good as living patients and better than cadavers for skin, fascia, bone, facets, ligamentum flavum, and dura, but poor for vessels (experts' intraclass correlation coefficient = 0.696-0.903). The pig models' validity for assessing drills' adverse features (friction, jitter, heating, and soft tissue trauma) was reported to be unanimously excellent., Conclusion: Pigs are representative for assessing microsurgical decompression techniques in the lower lumbar spine. The novel "en bloc" pig model can be an asset for industries and clinicians during assessment and training of new spinal techniques., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The suggested association between severe obstructive sleep apnea (OSA) and risk of Alzheimer's disease (AD) needs further study. Only few recent reports exist on associations between brain amyloid-β (Aβ) burden and severe OSA in middle-aged patients., Objective: Examine the possible presence of cortical Aβ accumulation in middle-aged patients with severe OSA., Methods: We performed detailed multimodal neuroimaging in 19 cognitive intact patients (mean 44.2 years) with severe OSA (Apnea-Hypopnea Index >30 h-1). Known etiological factors for possible Aβ accumulation were used as exclusion criteria. Aβ uptake was studied with [11C]-PiB-PET, glucose metabolism with [18F]-FDG-PET, and structural imaging with 3.0T MRI., Results: When analyzed individually, in [11C]-PiB-PET a substantial number (∼32%) of the patients exhibited statistically significant evidence of increased cortical Aβ uptake based on elevated regional Z-score values, mostly seen bilaterally in the precuneus and posterior cingulum regions. Cortical glucose hypometabolism in [18F]-FDG-PET was seen in two patients. MRI did not show structural changes suggestive of AD-related pathology., Conclusion: Increased [11C]-PiB uptake was seen in middle-aged cognitively intact patients with severe OSA. These findings are similar to those described in cognitive unimpaired older OSA patients. The changes in cortical Aβ uptake suggest that severe OSA itself may predispose to alterations related to AD already in middle-age. Aβ clearance may be compromised without simultaneous evidence of metabolic or structural alterations. The results emphasize the importance of early diagnostics and proper treatment of severe OSA in cognitively intact middle-aged subjects, possibly diminishing the individual risk for later cognitive dysfunction.

Aim: Cardiac resynchronization therapy (CRT) is a treatment for patients with end-stage heart failure. However, two-thirds of the patients are nonresponders. Evaluation of left ventricular mechanical dyssynchrony may help in finding patients who will benefit from CRT. Dyssynchrony can be evaluated by the phase analysis method in myocardial perfusion imaging (MPI) or with cardiac ultrasound. The aim of this study was to investigate the reproducibility of phase analysis parameters in MPI and echocardiographic parameters in the evaluation of left ventricular mechanical dyssynchrony. In particular, the influence of BMI on reproducibility was studied., Methods and Results: Twenty-one patients underwent an ECG-gated MPI scan. Acquisition was repeated after the rest image. The patients were also studied twice with transthoracic echocardiography. Of MPI phase analysis parameters bandwidth, histogram SD and entropy% were highly reproducible in the pooled population: Cronbach's α 0.927-0.967 and intraclass correlation (ICC) 0.868-0.967, (P<0.001 for all). However, the reproducibility of bandwidth and SD was poorer in patients with BMI≥29 kg/m group (α 0.203 and -0.055; ICC 0.106 and -0.027, NS for both) than in those with BMI<29 kg/m (α 0.984 and 0.980; ICC 0.968 and 0.961, P<0.001 for both). In contrast, BMI had no obvious influence on the reproducibility of global longitudinal strain in echocardiography., Conclusion: Parameters reflecting mechanical dyssynchrony were found to be well reproducible. However, this study indicates that phase analysis results may be less reproducible in patients with high BMI, whereas global longitudinal strain in echocardiography seems to be less critical for a patient's BMI.

Purpose: We aimed to provide comprehensive data on and reference values for cardiorespiratory fitness, respiratory function and hemodynamic responses during and after maximal cycle ergometer test in children., Methods: The participants were a population sample of 140 children (69 girls) aged 9-11 years. Heart rate (HR) and systolic blood pressure (SBP) were measured from pre-exercise rest to the end of recovery. Respiratory gases were measured directly by the breath-by-breath method. Peak workload, HR changes, peak oxygen uptake (VO2), peak oxygen pulse (O2 pulse), peak respiratory exchange ratio (RER) and the lowest ratio of ventilation and carbon dioxide output (VE/VCO2) during the exercise test in girls and boys were presented according to their distributions in 5 categories., Results: HR decreased more during 4-min recovery in boys than in girls (76 vs. 67 beats/min, p < 0.001), whereas SBP decrease was similar in boys and girls (30 vs. 22 mmHg, p = 0.66). Boys had a higher peak VO2 per weight [51.9 vs. 47.6 ml/kg/min, p < 0.001] and per lean mass [67.3 vs. 63.0 ml/kg/min, p < 0.001] than girls. Peak O2 pulse per lean mass was higher in boys than in girls (0.34 vs. 0.31 ml/kg/beat, p < 0.001). There was no difference in the lowest VE/VCO2 during the test between boys and girls (28 vs. 29, p = 0.18)., Conclusions: The indicators of cardiorespiratory fitness were better in boys than in girls. These data enable the evaluation of cardiorespiratory function during and after maximal exercise test and the detection of children with abnormal values.

Objective and Methods: We compared InBody720 segmental multifrequency bioimpedance analysis (SMF-BIA) with Lunar Prodigy Advance dual-energy X-ray absorptiometry (DXA) in assessment of body composition among 178 predominantly prepubertal children. Segmental agreement analysis of body compartments was carried out, and inter-relationships of anthropometric and other measures of body composition were defined. Moreover, the relations of different reference criteria for excess body fat were evaluated., Results: The prevalence of excess body fat varies greatly according to the used criteria. Intraclass and Pearson's correlations between SMF-BIA and DXA were >0·92 in total body and >0·74 in regional measures. SMF-BIA underestimated percentage body fat (%BF) and fat mass (FM), and overestimated lean mass (LM) and percentage LM with significant offset trend bias. Higher adiposity increased offsets, and overall agreement was poorer in girls. On average, %BF offsets (girls/boys) and limits of agreement (LA) were 3·9/1·6% [(-)1·4-9·2%/(-)3·4-6·7%]. Interestingly percentage offsets of fat content (%BF: 18·9/10·1%, FM: 18·8/11·1%) showed no significant bias trends indicating that the corresponding absolute methodological offset depends on the amount of fat content. The smallest percentage offset was found with LM: 4·3/0·1%, referring offset (LA) of 0·88/0·03 kg (±2·05/±1·71 kg). Correspondingly, segmental LM had poorer agreement than total body LM. All anthropometrics except for the waist-to-hip ratio showed strong correlations (r = 0·76-0·95) with abdominal and total body fat., Conclusion: Segmental multifrequency bioimpedance analysis is precise enough for total-LM analysis and had also sufficient trueness for total body composition analysis to be used in epidemiological purposes. There is need to generate scientifically and clinically relevant criteria and reference values for excess body fat., (© 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

A real-time ultrasound measurement system for tablet compression monitoring is introduced. The measurement system was tested in actual manufacturing environment and found to be capable of measuring the ultrasound response of the tabletting process from bulk to tablet. The tablet sets were compressed and the ultrasound measurements were conducted as implemented in eccentric single station tabletting apparatus in through transmission geometry. The speed of sound and ultrasound spectrum was measured during dynamic compression for microcrystalline cellulose/paracetamol tablets. The ultrasound system introduced in this study was found to be suitable for tabletting process monitoring as the mechanical properties of compressed tablets can be estimated during compression using the ultrasound system. In addition, it was found that the ultrasound was sensitive to the mixing time of magnesium stearate and the concentration of paracetamol. Thus, ultrasound measurements made during the compression can be used to monitor the tablet formation process., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Hip resurfacing arthroplasty (HRA) is considered a bone-preserving procedure and may eliminate proximal femoral stress shielding and osteolysis. However, in addition to implant-related stress-shielding factors, various patient-related factors may also have an effect on bone mineral density (BMD) of the proximal femur in patients with HRA. Thus, we studied the effects of stem-neck angle, demographic variables, and physical functioning on the BMD of the proximal femur in a one-year follow-up., Methods: Thirty three patients (9 females and 24 males) with a mean (SD) age of 55 (9) years were included in the study. BMD was measured two days and 3, 6, and 12 months postoperatively and 10 regions of interest (ROI) were used. Stem-neck angle was analyzed from anteroposterior radiographs., Results: Three months postoperatively, BMD decreased in six out of 10 regions of interest (ROI) on the side operated on and in one ROI on the control side (p<0.05) compared to the second postoperative day. At 12 months, BMD had increased in 7 ROIs on the operated side and one ROI on the control side (all p<0.001). Correlation was found between the stem-neck angle and BMD in ROIs 2, 3, 7, and 9 (r=0.36-0.61). In multiple regression analysis, stem-neck angle, age, sex, body mass index, and walking distance did not explain the BMD changes., Conclusions: After an early drop, the BMD of the upper femur was restored and even exceeded the preoperative level at one year follow-up. From a clinical standpoint, the changes in BMD in these HRA patients could not be explained by stem-neck angle or patient related factors.

An ultrasound measurement system for tablet defect detection is introduced. The measurement system was implemented in an eccentric single station tabletting apparatus, where ultrasound transducers were placed inside the upper and lower punches. These instrumented punches were then used to measure the speed of sound and ultrasound attenuation values in both intact and defective tablets made from dibasic calcium phosphate, microcrystalline cellulose and lactose monohydrate. Ultrasound attenuation was found to be a very sensitive method to discriminate defective tablets from intact ones. In addition, it was found that the determined ultrasound attenuation was different between all three materials used in this study, which indicates that different materials could be distinguished from one another by this detection method., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The strength as well as the acoustic properties of trabecular bone are determined by its structure and composition. Consequently, tissue structure and compositional properties also affect the ultrasound propagation in bone. The diagnostic potential of ultrasound has not been fully exploited in clinical quantitative ultrasound devices. The aim of this study was to investigate the ability of quantitative ultrasound pulse-echo imaging, conducted over a broad range of frequencies (1 to 5 MHz), to predict the mechanics, composition and microstructure of trabecular bone. Ultrasound reflection and backscatter parameters correlated significantly with the ultimate strength of the trabecular bone and the bone volume fraction (r=0.76-0.90, n=20, p<0.01). Ultrasound backscatter associated significantly (independently of bone structure or mineral content) with the collagen content of the bone matrix (r=0.75, r(adjusted)=0.66, p<0.01). Interestingly, the applied ultrasound frequency seemed to relate the sensitivity of ultrasound backscatter to different properties of trabecular bone. At frequencies ranging from 1 to 3.5 MHz, the ultrasound backscatter associated significantly with the tissue mechanical and structural parameters. At 5MHz, the composition of the bone matrix was a more significant determinant of the measured backscatter. This study provides useful information for optimizing the use of pulse-echo measurements, and thereby further emphasizes the diagnostic potential of the ultrasound backscatter measurements of trabecular bone.

The composition of bone marrow is influenced by many factors, such as age and diseases. The present numerical study investigates the contribution of marrow on the acoustic measurements of trabecular bone. Cylindrical bone samples (n = 11), extracted from three anatomical sites of human cadaver knees, were imaged with a high-resolution microtomography (microCT). Three-dimensional finite difference time domain (FDTD) models (Wave 3000 Pro 2.2, Cyberlogic Inc., NY, USA) were created using the segmented microCT images of each sample. First, we evaluated the effect of voxel size on the computer resource requirements, morphological parameters and acoustic simulations. Second, the effect of bone marrow on ultrasonic measurements was assessed. The simulations were repeated with two voxel sizes before and after substitution of bone marrow (i.e., fat) with water. The voxel size of the FDTD mesh controlled the fine structure of the modeled calcified matrix and significantly affected the simulation results. However, present simulations showed that the effect of bone marrow on ultrasound parameters can be reliably simulated with the applied voxel sizes of 72 and 90 microm. Ultrasound attenuation and speed were found (p < 0.01) to decrease and increase, respectively, when bone marrow was substituted with water. Moreover, reflection from the surface of the sample increased (p < 0.01) and backscatter from internal structures decreased (p < 0.01) after removal of marrow. The effect of bone marrow on the acoustic properties was stronger in samples with low bone volume fraction. The present results indicate that the amount and quality of bone marrow significantly influence the acoustic properties of trabecular bone. Possible interindividual differences in the composition of bone marrow may increase uncertainty in clinical ultrasound diagnostics of osteoporosis. Importantly, the effect is most significant in osteoporotic low-density bone.

Quantitative ultrasound has been suggested for screening of osteoporosis. Most commercial ultrasound devices are based on the through-transmission measurement of calcaneus, which is not a typical fracture site. In contrast to through-transmission measurements, reflection and backscattering measurements may be conducted at typical fracture sites such as vertebra and proximal femur. At these regions, soft tissues overlying bones affect reliability of the measurements. In this study, a novel dual-frequency ultrasound (DFUS) pulse-echo technique is introduced for reduction of the errors induced by soft tissues. First, DFUS was validated using elastomer samples. For further validation, human trabecular bone samples (n = 25) covered with heterogeneous soft tissues were measured at frequencies of 2.25 MHz and 5.0 MHz. The DFUS technique reduced (p < 0.01) the mean error induced by soft tissue from 58.6% to -4.9% and from 127.4% to 23.8% in broadband ultrasound backscattering and integrated reflection coefficient (at 5.0 MHz), respectively. To conclude, the DFUS, being the first ultrasound technique capable of determination of the composition and thickness of the soft tissue overlying the bone, may enhance the accuracy of clinical ultrasound measurements. Thereby, DFUS shows a significant clinical potential.

Mechanical properties of bone are determined not only by bone mineral density (BMD), but also by tissue trabecular structure and organic composition. Impedance spectroscopy has shown potential to diagnose trabecular bone BMD and strength, however, the relationships between organic composition and electrical and dielectric properties have not been systematically investigated. To investigate these issues organic composition of 26 human trabecular bone samples harvested from the distal femur and proximal tibia was determined and compared with relative permittivity, loss factor, conductivity, phase angle, specific impedance and dissipation factor measured at wide range (50 Hz to 5 MHz) of frequencies. A strong linear correlation was found between the relative permittivity at 1.2 MHz and trabecular bone fat content (r = -0.85, p<0.01, n=26). On the other hand, relative permittivity measured at 200 Hz served as a good predictor of water content (r = 0.83). Phase angle, specific impedance and especially conductivity were strongly related to the trabecular bone dry density and water content (|r| > or = 0.69). Variation in bone tissue collagen content was strongly related to the relative permittivity measured at 1.2 MHz (r = 0.64), but only moderately to other parameters. Glycosaminoglycan content showed no significant relations with any investigated electrical parameters. The present study indicates that if the trabecular bone composition is known, the relationships presented in this study could facilitate calculation of current field distribution, e.g. during electrical stimulation of osteogenesis. On the other hand, our results suggest that permittivity measured at low (<1 kHz) or high (>100 kHz) frequencies could be used, e.g. during implant surgery, for prediction of trabecular bone water or fat contents, respectively.

In osteoporosis, changes in tissue composition and structure reduce bone strength and expose it to fractures. The current primary diagnostic technique, i.e., dual energy X-ray absorptiometry, measures areal bone mineral density (BMD) but provides no direct information on trabecular structure or organic composition. Although still poorly characterized, ultrasound techniques may bring about information on bone composition and structure. In this study, relationships of 2.25-MHz ultrasound speed, attenuation, reflection and backscattering with composition of human trabecular bone (n=26) were characterized experimentally, as well as by using numerical analyses. We also determined composition of the trabecular sample (fat and water content, bone volume fraction) and that of the calcified matrix (mineral, proteoglycan and collagen content of trabeculae). In experimental analyses, bone volume fraction and mineral content of the calcified matrix were the only determinants of BMD. Further, bone volume fraction served as the strongest determinant of ultrasound parameters (r=0.51-0.87). In numerical simulations, density and mechanical properties of the calcified matrix systematically affected ultrasound speed, attenuation, reflection and backscattering. However, partial correlation coefficients revealed only low associations(|r|

Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine has recently been shown to be capable of inducing antibodies to H. influenzae in infants. In an evaluation of its clinical efficacy, 60,000 children were enrolled in an open trial in Finland. Children born on odd-numbered days between October 1, 1985, and September 30, 1986, received the vaccine at 3, 4, 6, and 14 months; those born on even-numbered days served as controls. The geometric mean antibody titer measured in a cohort of 99 children rose from a prevaccination level of 0.08 microgram per milliliter at three months of age to 0.42 microgram per milliliter at seven months. Only minor adverse reactions were reported. Up to February 1987, two cases of invasive H. influenzae infection had occurred among the children who had received three doses of vaccine, whereas 12 cases had occurred among the controls (P = 0.0005 by Poisson one-tailed test). The rate of short-term (average follow-up time, five months) protection provided by this conjugate vaccine in infancy was thus 83 percent.