How many glomerular profiles must be measured to obtain reliable estimates of mean glomerular areas in human renal biopsies?

The objective of this study was to investigate the number of glomerular profiles that are required for accurate estimates of mean profile area in a renal biopsy series. Slides from 384 renal biopsies from one center were reviewed. They contained a median of seven glomerular profiles or of four profiles without sclerosis. Profile areas were measured using stereologic point counting. The true individual mean for each biopsy was calculated and the true population mean for groups of biopsies derived. Individual and population random sample means then were calculated from a random sampling of profiles in each biopsy and were compared with true means for the same biopsies. The effect on the true population means of the entire group of biopsies was also assessed, as the minimum number of glomerular profiles that were required for inclusion was changed. In a single biopsy, random sampling of >= 10 profiles without exclusions and of eight profiles or more without sclerosis reliably estimated the true mean areas. In a group of 30 biopsies, random sampling of five or more glomeruli per biopsy reliably estimated the true population mean. In the aggregate series, inclusion of all 384 biopsies produced the most robust true population mean; the reliability of the estimates decreased as the numbers of eligible biopsies diminished with increasing requisite minimum numbers of profiles per biopsy. We conclude that, while >= 10 profiles might be needed for reliable area estimates in a single biopsy, far fewer profiles per biopsy can suffice when groups of biopsies are studied. In analyses of groups of biopsies, all available biopsies should be used without consideration of the number of glomerular profiles in each. Stipulation of a specific minimum number of glomeruli in each biopsy for inclusion reduces the power of analyses because fewer biopsies are available for evaluation.

High- and low-volume resistance training similarly enhances functional performance in older adults

It is well known that resistance training improves muscle strength in older adults and may enhance or preserve functional performance. However, it is unclear if the volume of work undertaken in the elderly alters the response in functional performance. PURPOSE: To investigate the effect of a high- versus low-volume resistance training program on functional performance in older adults. METHODS: Thirty-two healthy men and women aged 65-78 years were randomly assigned to either a single-set (SS, n = 16) or 3-set (MS, n = 16) progressive resistance training program for 20 weeks. Groups trained 2 days per week using machine weights at 8 repetitions maximum (8-RM) for 7 upper and lower body exercises. Muscle strength was assessed by the 1-RM and functional performance by a battery of tests (repeated chair rise, usual and fast 6-m walk, 6-m backwards walk, floor rise to standing, stair climb, and 400-m walk time). RESULTS: Twenty-eight subjects completed the study. There was no difference between groups at baseline in muscle strength or functional performance. Whole body muscle strength significantly increased in both groups with greater gains in the 3-set group (MS 32.9 ± 3.1%; SS 18.6 ± 2.7%, mean ± SE; P < 0.01). Significant improvement (time effect, P < 0.01) occurred for both groups in the chair rise (MS 13.6 ± 3.2%; SS 10.2 ± 3.0%), 6-m backwards walk (MS 14.9 ± 3.3%; SS 14.3 ± 4.2%), stair climb (MS 6.4 ± 2.8%; SS 7.7 ± 3.1%) and 400-m walk (MS 7.4 ± 1.4%; SS 3.9 ± 1.2%). There were no interaction (group × time) effects for functional performance and no differences by sex. CONCLUSION: Resistance training that utilizes either a singleset or 3-set regimen may significantly and similarly improve functional performance in community-dwelling older adults. Enhancement of functional performance may prolong independence and improve quality of life. ©2004The American College of Sports Medicine

Estimation of ocular volume from axial length

Background/aims - To determine which biometric parameters provide optimum predictive power for ocular volume. Methods - Sixty-seven adult subjects were scanned with a Siemens 3-T MRI scanner. Mean spherical error (MSE) (D) was measured with a Shin-Nippon autorefractor and a Zeiss IOLMaster used to measure (mm) axial length (AL), anterior chamber depth (ACD) and corneal radius (CR). Total ocular volume (TOV) was calculated from T2-weighted MRIs (voxel size 1.0 mm3) using an automatic voxel counting and shading algorithm. Each MR slice was subsequently edited manually in the axial, sagittal and coronal plane, the latter enabling location of the posterior pole of the crystalline lens and partitioning of TOV into anterior (AV) and posterior volume (PV) regions. Results - Mean values (±SD) for MSE (D), AL (mm), ACD (mm) and CR (mm) were −2.62±3.83, 24.51±1.47, 3.55±0.34 and 7.75±0.28, respectively. Mean values (±SD) for TOV, AV and PV (mm3) were 8168.21±1141.86, 1099.40±139.24 and 7068.82±1134.05, respectively. TOV showed significant correlation with MSE, AL, PV (all p<0.001), CR (p=0.043) and ACD (p=0.024). Bar CR, the correlations were shown to be wholly attributable to variation in PV. Multiple linear regression indicated that the combination of AL and CR provided optimum R2 values of 79.4% for TOV. Conclusion - Clinically useful estimations of ocular volume can be obtained from measurement of AL and CR.

Cenozoic global ice volume and temperature simulations over the past 40 million years

Variations in global ice volume and temperature over the Cenozoic era have been investigated with a set of one-dimensional (1-D) ice-sheet models. Simulations include three ice sheets representing glaciation in the Northern Hemisphere, i.e. in Eurasia, North America and Greenland, and two separate ice sheets for Antarctic glaciation. The continental mean Northern Hemisphere surface-air temperature has been derived through an inverse procedure from observed benthic d18O records. These data have yielded a mutually consistent and continuous record of temperature, global ice volume and benthic d18O over the past 35 Ma. The simple 1-D model shows good agreement with a comprehensive 3-D ice-sheet model for the past 3 Ma. On average, differences are only 1.0°C for temperature and 6.2 m for sea level. Most notably, over the 35 Ma period, the reconstructed ice volume-temperature sensitivity shows a transition from a climate controlled by Southern Hemisphere ice sheets to one controlled by Northern Hemisphere ice sheets. Although the transient behaviour is important, equilibrium experiments show that the relationship between temperature and sea level is linear and symmetric, providing limited evidence for hysteresis. Furthermore, the results show a good comparison with other simulations of Antarctic ice volume and observed sea level.

Progression of left atrial volume index in a population at risk for heart failure:a substudy of the STOP-HF (St Vincent's Screening TO Prevent Heart Failure) trial

AIMS: Limited data are available concerning the evolution of the left atrial volume index (LAVI) in pre-heart failure (HF) patients. The aim of this study was to investigate clinical characteristics and serological biomarkers in a cohort with risk factors for HF and evidence of serial atrial dilatation.

METHODS AND RESULTS: This was a prospective substudy within the framework of the STOP-HF cohort (NCT00921960) involving 518 patients with risk factors for HF electively undergoing serial clinical, echocardiographic, and natriuretic peptide assessment. Mean follow-up time between assessments was 15 ± 6 months. 'Progressors' (n = 39) were defined as those with serial LAVI change ≥3.5 mL/m(2) (and baseline LAVI between 20 and 34 mL/m(2)). This cut-off was derived from a calculated reference change value above the biological, analytical, and observer variability of serial LAVI measurement. Multivariate analysis identified significant baseline clinical associates of LAVI progression as increased age, beta-blocker usage, and left ventricular mass index (all P < 0.05). Serological biomarkers were measured in a randomly selected subcohort of 30 'Progressors' matched to 30 'Non-progressors'. For 'Progressors', relative changes in matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase 1 (TIMP1), and the TIMP1/MMP9 ratio, markers of interstitial remodelling, tracked with changes in LAVI over time (all P < 0.05).

CONCLUSION: Accelerated LAVI increase was found to occur in up to 14% of all pre-HF patients undergoing serial echocardiograms over a relatively short follow-up period. In a randomly selected subcohort of 'Progressors', changes in LAVI were closely linked with alterations in MMP9, TIMP1, and the ratio of these enzymes, a potential aid in highlighting this at-risk group.

Multiple training interventions significantly improve reproducibility of PET/CT-based lung cancer radiotherapy target volume delineation using an IAEA study protocol

BACKGROUND AND PURPOSE: To assess the impact of a standardized delineation protocol and training interventions on PET/CT-based target volume delineation (TVD) in NSCLC in a multicenter setting.

MATERIAL AND METHODS: Over a one-year period, 11 pairs, comprised each of a radiation oncologist and nuclear medicine physician with limited experience in PET/CT-based TVD for NSCLC from nine different countries took part in a training program through an International Atomic Energy Agency (IAEA) study (NCT02247713). Teams delineated gross tumor volume of the primary tumor, during and after training interventions, according to a provided delineation protocol. In-house developed software recorded the performed delineations, to allow visual inspection of strategies and to assess delineation accuracy.

RESULTS: Following the first training, overall concordance indices for 3 repetitive cases increased from 0.57±0.07 to 0.66±0.07. The overall mean surface distance between observer and expert contours decreased from -0.40±0.03 cm to -0.01±0.33 cm. After further training overall concordance indices for another 3 repetitive cases further increased from 0.64±0.06 to 0.80±0.05 (p=0.01). Mean surface distances decreased from -0.34±0.16 cm to -0.05±0.20 cm (p=0.01).

CONCLUSION: Multiple training interventions improve PET/CT-based TVD delineation accuracy in NSCLC and reduces interobserver variation.

Evaluation of biomaterials with and without platelet-rich plasma: a histometric study using beagle dogs

Aim: To compare the alveolar bone repair process using biomaterial in dogs with and without the incorporation of platelet-rich plasma. Methods: Six beagles were used. Bilateral extractions of the three mandibular premolars were performed. Bio-Gen® was applied in the first alveolus, the clot was maintained in the second alveolus and Genox® was applied to the third alveolus. PRP was added to all alveoli on the left side only. The dogs were submitted to euthanasia after 30, 60 and 90 days and submitted to histological analysis for the determination of mean area of new bone formation. Tukey’s post test was used in the statistical analysis. Results: Significant increase in bone formation occurred in Bio-Gen® + PRP when compared with the other groups at 30 and 90 days. In the evaluation at 60 days, no statistically significant differences among the groups were found. Conclusions: The Bio-Gen® biomaterial led to the best bone repair and the combination of platelet-rich plasma accelerated the repair process.

Levels of dioxin-like PCBs in low-volume serum samples of male patients attending fertility clinics

An accurate and easy method for the extraction, cleanup, and HRGC-HRMS analysis of dioxin-like PCBs (DL-PCBs) in low-volume serum samples (1 mL) was developed. Serum samples were extracted several times using n-hexane and purified by acid washing. Recovery rates of labeled congeners ranged from 70 to 110 % and the limits of detection were below 1 pg/g on lipid basis. Although human studies are limited and contradictory, several studies have shown that DL-PCBs can have adverse effects on the male reproductive system. In this way, the present method was applied to 21 serum samples of male patients attending fertility clinics. The total levels obtained for the patients ranged from 6.90 to 84.1 pg WHO-TEQ/g lipid, with a mean value of 20.3 pg WHO-TEQ/g lipid. The predominant PCBs (the sum of PCB 118, 156, and 105) contributed 67 % to the mean concentration of total DL-PCBs in the samples analyzed.

Volume, intensity, and timing of muscle power potentiation are variable

Whereas muscle potentiation is consistently demonstrated with evoked contractile properties, the potentiation of functional and physiological measures is inconsistent. The objective was to compare a variety of conditioning stimuli volumes and intensities over a 15-min recovery period. Twelve volleyball players were subjected to conditioning stimuli that included 10 repetitions of half squats with 70% of 1-repetition maximum (RM) (10 × 70), 5 × 70, 5 × 85, 3 × 85, 3 × 90, 1 × 90, and control. Jump height, power, velocity, and force were measured at baseline, 1, 3, 5, 10, and 15 min. Data were analysed with a 2-way repeated measure ANOVA and magnitude-based inferences. The ANOVA indicated significant decreases in jump height, power, and velocity during recovery. This should not be interpreted that no potentiation occurred. Each dependent variable reached a peak at a slightly different time: peak jump height (2.8 ± 2.3 min), mean power (3.6 ± 3.01 min), peak power (2.5 ± 1.8 min), and peak velocity (2.5 ± 1.8 min). Magnitude-based inference revealed that both the 5 × 70 and 3 × 85 protocol elicited changes that exceeded 75% likelihood of exceeding the smallest worthwhile change (SWC) for peak power and velocity. The 10 × 70 and the 5 × 70 had a substantial likelihood of potentiating peak velocity and mean power above the SWC, respectively. Magnitude-based inferences revealed that while no protocol had a substantial likelihood of potentiating the peak vertical jump, the 5 × 70 had the most consistent substantial likelihood of increasing the peak of most dependent variables. We were unable to consistently predict if these peaks occurred at 1, 3, or 5 min poststimulation, though declines after 5 min seems probable.

Inhibition of nitro-oxidative stress attenuates pulmonary and systemic injury induced by high-tidal volume mechanical ventilation

Mechanisms contributing to pulmonary and systemic injury induced by high tidal volume (VT) mechanical ventilation are not well known. We tested the hypothesis that increased peroxynitrite formation is involved in organ injury and dysfunction induced by mechanical ventilation. Male Sprague-Dawley rats were subject to low- (VT, 9 mL/kg; positive end-expiratory pressure, 5 cmH2O) or high- (VT, 25 mL/kg; positive end-expiratory pressure, 0 cmH2O) VT mechanical ventilation for 120 min, and received 1 of 3 treatments: 3-aminobenzamide (3-AB, 10 mg/kg, intravenous, a poly adenosine diphosphate ribose polymerase [PARP] inhibitor), or the metalloporphyrin manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP, 5 mg/kg intravenous, a peroxynitrite scavenger), or no treatment (control group), 30 min before starting the mechanical ventilation protocol (n = 8 per group, 6 treatment groups). We measured mean arterial pressure, peak inspiratory airway pressure, blood chemistry, and gas exchange. Oxidation (fluorescence for oxidized dihydroethidium), protein nitration (immunofluorescence and Western blot for 3-nitrotyrosine), PARP protein (Western blot) and gene expression of the nitric oxide (NO) synthase (NOS) isoforms (quantitative real-time reverse transcription polymerase chain reaction) were measured in lung and vascular tissue. Lung injury was quantified by light microscopy. High-VT mechanical ventilation was associated with hypotension, increased peak inspiratory airway pressure, worsened oxygenation; oxidation and protein nitration in lung and aortic tissue; increased PARP protein in lung; up-regulation of NOS isoforms in lung tissue; signs of diffuse alveolar damage at histological examination. Treatment with 3AB or MnTMPyP attenuated the high-VT mechanical ventilation-induced changes in pulmonary and cardiovascular function; down-regulated the expression of NOS1, NOS2, and NOS3; decreased oxidation and nitration in lung and aortic tissue; and attenuated histological changes. Increased peroxynitrite formation is involved in mechanical ventilation-induced pulmonary and vascular dysfunction.

A second order control-volume finite-element least-squares strategy for simulating diffusion in strongly anisotropic media

An unstructured mesh �nite volume discretisation method for simulating di�usion in anisotropic media in two-dimensional space is discussed. This technique is considered as an extension of the fully implicit hybrid control-volume �nite-element method and it retains the local continuity of the ux at the control volume faces. A least squares function recon- struction technique together with a new ux decomposition strategy is used to obtain an accurate ux approximation at the control volume face, ensuring that the overall accuracy of the spatial discretisation maintains second order. This paper highlights that the new technique coincides with the traditional shape function technique when the correction term is neglected and that it signi�cantly increases the accuracy of the previous linear scheme on coarse meshes when applied to media that exhibit very strong to extreme anisotropy ratios. It is concluded that the method can be used on both regular and irregular meshes, and appears independent of the mesh quality.