Glomerular filtration rate estimation for carboplatin dosing in patients with gynaecological cancers.

BACKGROUND: Carboplatin remains integral for treatment of gynaecological malignancies and dosing is based on glomerular filtration rate (GFR). Measurement via radiotracer decay [nuclear medicine GFR (nmGFR)] is ideal. However, this may be unavailable. Therefore GFR is often estimated using formulae that have not been validated in patients with cancer and/or specifically for gynaecological malignancies, leading to debate over optimal estimation. Suboptimal GFR estimation may affect efficacy or toxicity. METHODS: We surveyed several UK National Health Service Trusts to assess carboplatin dosing practise. We then explored single-centre accuracy, bias and precision of various formulae for GFR estimation, relative to nmGFR, before validating our findings in an external cohort. RESULTS: Across 18 Trusts, there was considerable heterogeneity in GFR estimation, including the formulae used [Cockcroft-Gault (CG) versus Wright], weight adjustment and area under the curve (AUC; 5 versus 6). We analysed 274 and 192 patients in two centres. Overall, CamGFR v2 (a novel formula for GFR estimation developed at Cambridge University Hospitals NHS Foundation Trust) excelled, showing the highest accuracy and precision. This translated into accuracy of hypothetical carboplatin dosing; nmGFR-derived carboplatin dose fell within 20% of the Cam GFR v2-derived dose in 86.5% and 87% of patients across the cohorts. Among the CG formula and its derivatives, using adjusted body weight in those with body mass index ≥25 kg/m2 [CG-adjusted body weight (CG-AdBW)] was optimal. The Wright and unadjusted CG estimators performed most poorly. CONCLUSIONS: When compared with nmGFR assessment, accuracy, bias and precision varied widely between GFR estimators, with the newly developed Cam GFR v2 and CG-AdBW performing best. In general, weight (or body surface area)-adjusted formulae excelled, while the unadjusted CG and Wright formulae or the use of AUC6 (versus nmGFR AUC5) produced risk of significant overdose. Thus, individual centres should validate their GFR estimation methods. In the absence of validation, CG-AdBW or CamGFR v2 is likely to perform well while unadjusted CG/Wright formulae or AUC6 dosing should be avoided.

Experimental and theoretical study of rhenium radioisotopes production for manufacturing of new compositional radiopharmaceuticals.

Rhenium therapeutic radioisotopes, namely rhenium-186 and 188, are radionuclides that have been used in combination with various ligands to provide different radiopharmaceuticals for the treatment of different diseases for many years. Each of these radioisotopes has its own special attributes, which make it appropriate to destroy special-sized tumors. High energy, long range beta particles in 188Re can give this certainty that large tumors can be eradicated with high efficiency. On the other hand, 186Re with low energy, short range beta particles is adequate item to ruin small tumors with minimum side effects and high yield. Thus, each of these radioisotopes has features that can cover just part of the treatment individually. So we thought accompanying 186Re and 188Re must have the best outcome to treat tumors with various sizes. Irradiating natural rhenium with neutrons has this potential to produce parallel 186Re and 188R together. We are looking for investigating whether the natural rhenium irradiation, in addition the concurrent production of these radioisotopes, gives us the appropriate radioactivity values to produce compositional radiopharmaceuticals? In this research, the experimental and theoretical assessments of 186Re and 188R simultaneous production to reach compositional radiopharmaceutical by natural rhenium irradiation in the Tehran research reactor, as well as the type and amount of produced impurities have been investigated. The results showed that experimental data are in good agreement with theoretical calculations. The maximum relative error in data has been calculated 8%. The results showed that, in the simultaneous production 186Re and 188R via the natural rhenium irradiation method, the amounts of impurities are trivial compared to the main products, and the activities of main products are properly enough to produce compositional radiopharmaceuticals.

Eccentric exercise induces spatial changes in the mechanomyographic activity of the upper trapezius muscle.

In this study, we hypothesized that the recordings of multichannel mechanomyography (MMG) of the upper trapezius muscle would reveal spatially dependent manifestations in the presence of delayed onset muscle soreness occurring 24 hours after eccentric exercise (ECC). Sixteen participants performed high-intensity eccentric exercises (5 sets of 10 eccentric contractions at 100% of max elevation force) targeting the upper trapezius on their dominant side. Twelve accelerometers were attached to record MMG activity during submaximal exercise consisting of static and dynamic arm flexion and abduction. Measurements were taken before and 24 hours after ECC. Average rectified value (ARV), percentage of determinism (% DET), and recurrence (% REC) of the MMG signals were computed to estimate the level of muscular activity and the magnitude of regularity of the MMG. The ARV, % REC, and % DET maps revealed heterogeneous MMG activity of the upper trapezius 24 hours after ECC when compared with before. Increased ARV, % REC, and % DET were found 24 hours after ECC when compared with before. The study provides new key information on how a single muscle responds to ECC. Our findings suggest that multichannel MMG and nonlinear analyses may detect muscular and musculo-tendinous alterations due to ECC.

Demonstration of a 120° hybrid based simplified coherent receiver on SOI for high speed PON applications.

We demonstrate the first simplified coherent receiver using a 120° hybrid on silicon-on-insulator (SOI) for high speed PON applications. This coherent receiver integrates an inverse taper edge coupler for the received signal, a vertical grating coupler for the local oscillator input, a polarization splitter and rotator (PSR), a 120° hybrid based on a 3×3 multimode interference (MMI) coupler, and three germanium photodetectors. We achieved 25 Gbit/s two-level pulse amplitude modulation (PAM-2) transmission over 30 km standard single mode fiber (SMF) in the C-band without any digital signal processing (DSP) (e.g., pre-emphasis, pulse shaping, equalization, nonlinearity compensation) and dispersion compensation (e.g., optical or digital) either at the transmitter or at the receiver. The requirements for frequency and phase locking of the local oscillator (LO) were avoided due to the use of intensity modulated signals. Receiver sensitivities of -23.70 dBm, -20.30 dBm, and -15.10 dBm are achieved at a bit error rate (BER) below the hard-decision forward error correction (HD-FEC) threshold (i.e., 3.8 × 10-3) in back-to-back (B2B), after 21 km and 30 km, respectively. We also demonstrate 25 Gbit/s PAM-4 transmission achieving receiver sensitivities of -15.30 dBm, -13.90 dBm, and -9.50 dBm below the HD-FEC threshold in B2B, after 10.5 km and 21 km, respectively.

Reduced complexity of force and muscle activity during low level isometric contractions of the ankle in diabetic individuals.

BACKGROUND: This study evaluated the structure and amount of variability of surface electromyography (sEMG) patterns and ankle force data during low-level isometric contractions in diabetic subjects with different degrees of neuropathy. METHODS: We assessed 10 control subjects and 38 diabetic patients, classified as absent, mild, moderate, or severe neuropathy, by a fuzzy system based on clinical variables. Multichannel sEMG (64-electrode matrix) of tibialis anterior and gastrocnemius medialis muscles were acquired during isometric contractions at 10%, 20%, and 30% of the maximum voluntary contraction, and force levels during dorsi- and plantarflexion were recorded. Standard deviation and sample entropy of force signals were calculated and root mean square and sample entropy were calculated from sEMG signals. Differences among groups of force and sEMG variables were verified using a multivariate analysis of variance. FINDINGS: Overall, during dorsiflexion contractions, moderate and severe subjects had higher force standard deviation and moderate subjects had lower force sample entropy. During plantarflexion, moderate subjects had higher force standard deviation and all diabetic subjects had lower entropy. Tibialis anterior presented higher root mean square in absent group and lower entropy in mild subjects. For gastrocnemius medialis, entropy was higher in severe and lower in moderate subjects. INTERPRETATION: Diabetic neuropathy affects the complexity of the neuromuscular system during low-level isometric contractions, reducing the system's capacity to adapt to challenging mechanical demands. The observed patterns of neuromuscular complexity were not associated with disease severity, with the majority of alterations recorded in moderate subject.

The effects of transportation stress on Japanese quail (Coturnix Coturnix japonica) fed corn-based diet in comparison with wheat-based diet supplemented with xylanase and phytase.

Harvesting, handling and transporting quails to the slaughterhouses, other farms and laboratories might covertly reduce their welfare. The aim of this study was to evaluate the effects of two major sources of energy in poultry nutrition on reducing transportation stress in Japanese quail (Coturnix Coturnix japonica). Male quails (n = 60) were divided into two groups. The first group was fed corn-based diet, and the second was fed wheat-based diet supplemented with xylanase and phytase. At the end of the experiment (day 35), quails were subjected to 80 km of transportation. Immediately on arrival and after 24 h, heterophil counts, lymphocyte counts and H:L ratios were measured. On arrival, H counts were lower, L counts were higher, and H:L ratios were lower for corn-fed group. After 24 h, wheat-fed group showed lower increment of H counts, greater increment of L counts and also decrement of H:L ratios rather than corn-fed group which showed increment of H:L ratios. However, these ratios were still lower in corn-fed group. Results indicate that corn-based diets can help Japanese quail to better resist transportation stress, although it seems that feeding wheat-based diets supplemented with xylanase and phytase could have positive effects for coping better with stress after journeys.

Inter-subject variability of muscle synergies during bench press in power lifters and untrained individuals.

The purpose of the study was to elucidate the role of expertise on muscle synergies involved in bench press. Ten expert power lifters (EXP) and nine untrained participants (UNT) completed three sets of eight repetitions at 60% of three repetition maximum in bench press. Muscle synergies were extracted from surface electromyography data of 21 bench press cycles using non-negative matrix factorization algorithm. The synergy activation coefficient represents the relative contribution of the muscle synergy to the overall muscle activity pattern, while the muscle synergy vector represents the relative weighting of each muscle within each synergy. Describing more than 90% of the variability, two muscle synergies reflected the eccentric and concentric phase. The cross-correlations (ρ(max)) for synergy activation coefficient 2 (concentric phase) were 0.83 [0.71;0.88] and 0.59 [0.49;0.77] [Median ρ(max) (25th;75th percentile)] (P = 0.001) in UNT and EXP, respectively. Median correlation coefficient (ρ) for muscle synergy vector 2 was 0.15 [-0.08;0.46] and 0.48 [0.02;0.70] (P = 0.03) in UNT and EXP, respectively. Thus, EXP showed larger inter-subject variability than UNT in the synergy activation coefficient during the concentric phase, while the muscle synergy vectors were less variable in EXP. This points at the importance of a specialized neural strategy in elite bench press performance.

Effects of two recovery procedures after a football game on sensory and biochemical markers.

AIM: The aim of this study was to investigate recovery processes on pressure pain sensitivity and blood indicators in professional football players after three different post-game training modalities: standard recovery training, no physical activity, delayed onset muscle soreness reduction training. METHODS: Eleven male football field players participated in the present study. The experiment was performed in three sessions over three weeks after three football league games. The procedure was composed of the following assessments included in each session: measurement of pain pressure threshold, creatine kinase activity and myoglobin (Mb) concentration before, 24 and 48 hours after game. RESULTS: In standard recovery training there was no full recovery in deep structure sensitivity of the frontal thigh muscles at 48 hours after game (P=0.008). In the no physical activity session, sensitivity returned to its level before game. On the contrary, in the delayed onset muscle soreness reduction training sensitivity decreased 48 hours after game (P<0.001). Creatine kinase activity decreased significantly from 24 hours to 48 hours in session with no activity and delayed onset muscle soreness reduction training (P<0.05). None of the recovery methods had an influence on Mb concentration. CONCLUSION: The present study points towards a potent effect of delayed onset muscle soreness reduction training on recovery after a football game.

Natural radioactivity in surface soil samples from dwelling areas in Tehran city, Iran.

The study was carried out to determine radioactivity concentrations in surface soil samples of the city of Tehran and associated potential radiological hazards. The natural radionuclide ((226)Ra, (232)Th and (40)K) contents were determined for 50 locations throughout the geological surface formations in a representative area in the city of Tehran, Iran, using high-resolution gamma-spectrometric analysis. The range of activity concentrations of (226)Ra, (232)Th and (40)K in the soil from the studied areas varies from 30.5±0.6 to 45.4±0.9, 27.3±0.5 to 57.1±1.1 and 328.0±4.6 to 768.5±13.4 Bq kg(-1) with overall mean values of 38.8±0.7, 43.4±0.8 and 555.1±8.9 Bq kg(-1), respectively. The mean radium equivalent activity, external hazard index, internal hazard index to quantify the internal exposure to radon and its daughter products, as well as the gamma activity concentration index for each sample are 143.6±4.6 Bq kg(-1), 0.39, 0.49 and 0.53, respectively. The average estimated radium equivalent is comparable with reported values for many countries in the world. Therefore, these areas may not pose radiological risks to the inhabitants due to harmful effects of the ionising radiation from the natural radioactivity in soil. The calculated average external and internal hazard indexes were found to be less than unity, as a recommended safe level. Estimates of the measured radionuclide content have been made for calculating the absorbed dose rate in the outdoor air at 1 m above the ground level. The absorbed dose rates resulting from those concentrations ranged from 48.1 to 88.7 nGy h(-1). Assuming a 20 % occupancy factor proposed by UNSCEAR, 2000, the corresponding effective dose rates in outdoor air equivalent to the population were calculated to be between 0.06 and 0.11 mSv y(-1). The measurement results and calculated values obtained from this study indicate that the dwelling areas in Tehran city, Iran, have background radioactivity levels within natural limits.

Principle component analysis of exposure variation analysis during computer work at presence of delayed onset muscle soreness.

Eleven healthy volunteers took part in three sessions where computer work was performed for 10 min in each session. The recordings were made on two consecutive days. After the first session, the subjects underwent a series of high intensity eccentric exercises of shoulder elevation to induce muscle soreness. The second session was performed immediately after the exercises and third session 24 hours after the exercise. Surface electromyography (EMG) of descending and ascending trapezius, deltoideus anterior and serratus anterior was recorded. Exposure variation analysis (EVA) centroid and marginal distribution was computed. Principle component analysis (PCA) was performed on both cases. Describing more than 80% of variance, first eight components for EVA marginal distributions and first four ones for EVA centroid were picked to be investigated. The sole EVA amplitude levels played a practically significant role to describe the variation in EVA marginal distribution. However, a significant pattern of load redistribution to superficial muscles was not found. This may suggest investigating the role of deep muscles in redistribution of load during computer work in response to high level eccentric contractions.

Inverse relationship between the complexity of midfoot kinematics and muscle activation in patients with medial tibial stress syndrome.

Medial tibial stress syndrome is a common overuse injury characterized by pain located on the medial side of the lower leg during weight bearing activities such as gait. The purpose of this study was to apply linear and nonlinear methods to compare the structure of variability of midfoot kinematics and surface electromyographic (SEMG) signals between patients with medial tibial stress syndrome and healthy controls during gait. Fourteen patients diagnosed with medial tibial stress syndrome and 11 healthy controls were included from an orthopaedic clinic. SEMG from tibialis anterior and the soleus muscles as well as midfoot kinematics were recorded during 20 consecutive gait cycles. Permuted sample entropy and permutation entropy were used as a measure of complexity from SEMG signals and kinematics. SEMG signals in patients with medial tibial stress syndrome were characterized by higher structural complexity compared with healthy controls (p<0.001) while it was the opposite for the midfoot kinematics (p=0.01). Assessing the complexity of midfoot kinematics and SEMG activation pattern enabled a precise characterization of gait in patients with medial tibial stress syndrome. The reported inverse relationship in foot kinematics and SEMG complexity most likely point towards separated control processes governing gait variability.

Measurement of the hyperelastic properties of ex vivo brain tissue slices.

The elastic and hyperelastic properties of brain tissue are of interest to the medical research community as there are several applications where accurate characterization of these properties is crucial for an accurate outcome. The linear response is applicable to brain elastography, while the non-linear response is of interest for surgical simulation programs. Because of the biological differences between gray and white matter, it is reasonable to expect a difference in their mechanical properties. The goal of this work is to characterize the elastic and hyperelastic properties of the brain gray and white matter. In this method, force-displacement data of these tissues were acquired from 25 different brain samples using an indentation apparatus. These data were processed with an inverse problem algorithm using finite element method as the forward problem solver. Young's modulus and the hyperelastic parameters corresponding to the commonly used Polynomial, Yeoh, Arruda-Boyce, and Ogden models were obtained. The parameters characterizing the linear and non-linear mechanical behavior of gray and white matters were found to be significantly different. Young's modulus was 1787±186 and 1195±157Pa for white matter and gray matter, respectively. Among hyperelastic models, due to its accuracy, fewer parameters and shorter computational time requirements, Yeoh model was found to be the most suitable. Due to the significant differences between the linear and non-linear tissue response, we conclude that incorporating these differences into brain biomechanical models is necessary to increase accuracy.

Changes in the spatio-temporal organization of the trapezius muscle activity in response to eccentric contractions.

We hypothesized changes in the spatial organization of the trapezius muscle electromyographic (EMG) activity after a shoulder eccentric exercise. The rate of perceived exertion (RPE), the size of the soreness area, maximum force and, EMG from the upper, middle and lower trapezius were recorded. Root mean square (RMS), mean frequency (MNF) and normalized mutual information (a measure of functional connectivity between muscle sub-divisions) were computed during submaximal dynamic and static contractions performed before, immediately after and 24 h after exercise. Immediately after exercise, RPE, soreness area, RMS from the upper and middle trapezius and normalized mutual information among upper-middle sub-divisions increased while MNF decreased for the middle trapezius (P<0.05). After 24 h, the maximum force decreased. RMS from the upper trapezius and normalized mutual information among upper-middle trapezius sub-divisions were higher than before exercise. MNF values increased from immediately after to 24 h after for the upper and lower trapezius (P<0.05). The current results underlined changes in the spatio-temporal organization of the trapezius in response to shoulder eccentric exercise. The observed changes in EMG temporal and spectral contents and the enhanced sub-division coupling underlined the functional role of spatial variations of the EMG activity during muscle fatigue and in the presence of delayed-onset muscle soreness.

Preparation and quality control of ¹77Lu-[tris(1,10-phenanthroline) lutetium(III)] complex for therapy.

The ¹77Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (¹77Lu-PQ3) was prepared successfully with high radiochemical purity (> 99%). Lu-177 chloride was obtained by thermal neutron flux (4 × 10¹³ n.cm⁻².s⁻¹) of natural Lu2(NO3)3 sample, dissolved in acidic media. The radiochemical yield was checked by measuring the radiochemical purity of the (177)Lu-PQ complex by ITLC (10 mM DTPA, pH = 5, as mobile phase). The final complex solution was injected intravenously into wild-type male rats and bio-distribution of the complex was checked for up to 48 hours. The dose limiting organs were shown to be the reticulu-endothelial system. The bio-distribution of the labelled compounds in tumour-bearing animals is under investigation.

Transcutaneous electrical nerve stimulation (TENS) in the symptomatic management of chronic prostatitis/chronic pelvic pain syndrome: a placebo-control randomized trial.

OBJECTIVE: The aim of the study was to investigate the therapeutic efficacy of transcutaneous electrical nerve stimulation (TENS) in the symptomatic management of chronic prostatitis pain/chronic pelvic pain syndrome. DESIGN: A pretest, posttest randomized double blind design was used in data collection. PARTICIPANT: Twenty-four patients diagnosed with chronic prostatitis- category IIIA and IIIB of the National Institute of Health Chronic Pain (NIH-CP) were referred for physiotherapy from the Urology department. INTERVENTION: Pre treatment pain level was assessed using the NIH-CP (pain domain) index. The TENS group received TENS treatment, 5 times per week for a period of 4 weeks (mean treatment frequency, intensity, pulse width and duration of 60 Hz, 100 microS, 25 mA and 20 minutes respectively). The Analgesic group received no TENS treatment but continued analgesics; the Control group received no TENS and Analgesic but placebo. All subjects were placed on antibiotics throughout the treatment period. OUTCOME MEASURES: Post-treatment pain level was also assessed using NIH-CP pain index. RESULT: Findings of the study revealed significant effect of TENS on chronic prostatitis pain at p < 0.05. CONCLUSION: TENS is an effective means of non-invasive symptomatic management of chronic prostatitis pain.

Transcutaneous electrical nerve stimulation (TENS) in the symptomatic management of chronic prostatitis/chronic pelvic pain syndrome: a placebo-control randomized trial

OBJECTIVE: The aim of the study was to investigate the therapeutic efficacy of transcutaneous electrical nerve stimulation (TENS) in the symptomatic management of chronic prostatitis pain/chronic pelvic pain syndrome. DESIGN: A pretest, posttest randomized double blind design was used in data collection. PARTICIPANT: Twenty-four patients diagnosed with chronic prostatitis- category IIIA and IIIB of the National Institute of Health Chronic Pain (NIH-CP) were referred for physiotherapy from the Urology department. Intervention: Pre treatment pain level was assessed using the NIH-CP (pain domain) index. The TENS group received TENS treatment, 5 times per week for a period of 4 weeks (mean treatment frequency, intensity, pulse width and duration of 60Hz, 100µS, 25mA and 20 minutes respectively). The Analgesic group received no TENS treatment but continued analgesics; the Control group received no TENS and Analgesic but placebo. All subjects were placed on antibiotics throughout the treatment period. Outcome measures: Post-treatment pain level was also assessed using NIH-CP pain index. RESULT: Findings of the study revealed significant effect of TENS on chronic prostatitis pain at p < 0.05. CONCLUSION: TENS is an effective means of non-invasive symptomatic management of chronic prostatitis pain.

A non-rigid image registration technique for 3D ultrasound carotid images using a "twisting and bending" model.

Atherosclerosis at the carotid bifurcation resulting in cerebral emboli is a major cause of ischemic stroke. Most strokes associated with carotid atherosclerosis can be prevented by lifestyle/dietary changes and pharmacological treatments if identified early by monitoring carotid plaque changes. Sensitive monitoring of plaque changes in volume and morphology requires that 3D ultrasound (US) images of carotid plaque obtained at different time points be registered and evaluated for change. This registration technique should be non-rigid, since different head positions in image acquisitions cause relative bending and torsion in the neck, producing non-linear deformations between the images. We modeled the movement of the neck using a "twisting and bending model" with only six parameters for non-rigid registration. We used a Mutual Information (MI) based image similarity measure with the Powell optimization method as they have been used effectively in US image registration applications. For evaluation of our algorithm, we acquired 3D US carotid images from three subjects at two different head positions to simulate images acquired at different times. Then, we registered each image set using our "twisting bending model" based non-rigid registration algorithm. We calculated the Mean Registration Error (MRE) between the segmented vessel surfaces in the target image and the registered image using a distance-based error metric. We repeated the experiment with only rigid registration to compare the capabilities of the proposed algorithm in improving registration of 3D carotid US images. The average registration error was 1.03+/-0.23 mm using our non-rigid registration technique, while it was 1.50+/-0.50 mm when we applied the rigid registration alone.

The role of the IGF-I receptor in the regulation of matrix metalloproteinases, tumor invasion and metastasis.

The breakdown of the extracellular matrix (ECM) by proteinases is an essential step in the process of cancer invasion and metastasis. Malignant progression is frequently associated with upregulated production and/or activity of one or several ECM degrading proteinases. Prominent among them are the matrix metalloproteinases (MMPs). The MMPs constitute a family of structurally related, zinc-dependent endopeptidases collectively capable of degrading essentially all the components of the extracellular matrix. At present, 23 members of the human MMP gene family are known. The increased expression and/or activity of one or more members of this family have been documented in essentially all human malignancies and some have been implicated in the process of angiogenesis. Prominent among those are MMP-2 and MT1-MMP, two metalloproteinases that form a cell membrane-associated complex leading to MMP-2 activation and ECM proteolysis. Here, we review our data that identified the type 1 insulin-like growth factor receptor (IGF-IR) as a regulator of tumor invasion and the synthesis of MT1-MMP and MMP-2 and report on the signal transduction pathways that mediate this regulation. These findings are discussed in the context of a broader review of the role of the IGF-IR/IGF axis in the regulation of tumor invasion and metastasis.