Cylindrical ionization chamber response in static and dynamic 6 and 15 MV photon beams.

Purpose.To investigate the response of the CC13 ionization chamber under non-reference photon beam conditions, focusing on penumbra and build-up regions of static fields and on dynamic intensity-modulated beams.Methods. Measurements were performed in 6 MV 100 × 100, 20 × 100, and 20 × 20 mm2static fields. Monte Carlo calculations were performed for the static fields and for 6 and 15 MV dynamic beam sequences using a Varian multi-leaf collimator. The chamber was modelled using EGSnrc egs_chamber software. Conversion factors were calculated by relating the absorbed dose to air in the chamber air cavity to the absorbed dose to water. Correction and point-dose correction factors were calculated to quantify the conversion factor variations.Results. The correction factors for positions on the beam central axis and at the penumbra centre were 0.98-1.02 for all static fields and depths investigated. The largest corrections were obtained for chamber positions beyond penumbra centre in the off-axis direction. Point-dose correction factors were 0.54-0.71 at 100 mm depth and their magnitude increased with decreasing field size and measurement depth. Factors of 0.99-1.03 were obtained inside and near the integrated penumbra of the dynamic field at 100 mm depth, and of 0.92-0.94 beyond the integrated penumbra centre. The variations in the ionization chamber response across the integrated dynamic penumbra qualitatively followed the behaviour across penumbra of static fields.Conclusions. Without corrections, the CC13 chamber was of limited usefulness for profile measurements in 20-mm-wide fields. However, measurements in dynamic small irregular beam openings resembling the conditions of pre-treatment patient quality assurance were feasible. Uncorrected ionization chamber response could be applied for dose verification at 100 mm depth inside and close to large gradients of dynamically accumulating high- and low-dose regions assuming 3% tolerance between measured and calculated doses.

Unloader bracing in osteoarthritis of the knee - Is there a direct effect on the damaged cartilage?

BACKGROUND: Unloading knee braces represent a conservative treatment option for non-pharmalogical management of unicompartmental osteoarthritis of the knee. Though there is consensus on the clinical effectiveness of unloading, the effect mechanism of bracing remains part of a debate. Our study was designed to assess the effect of unloader bracing on damaged cartilage via MRI cartilage mappings. METHODS: Fourteen patients (7 female, 7 male, mean age 43.1 ± 9.4 years) with unicompartmental cartilage wear in knees with varus or valgus malalignment were enrolled. Clinical scores, radiographs and MR-graphic properties (T2/T2* mapping, T1 Delayed Gadolinium Enhanced MRI of the cartilage (dGEMRIC) mapping, high-resolution PDw sequences) of knee cartilage were recorded before and three months after brace use. RESULTS: Bracing the knees for a mean of 14.4 ± 2.0 weeks (range 11 to 18 weeks) resulted in significant pain reduction (VAS changed from 5.9 ± 2.0 to 2.0 ± 1.3, p < 0.001) and improvement in knee function (KOOS increased from 42.1 ± 22.7 to 64.8 ± 18.7, p < 0.001). In the affected cartilage regions T2 relaxation times significantly decreased from 56.1 ± 11.4 ms to 46.5 ± 11.2 ms (p < 0.05). No changes in T1-dGEMRIC and T2* relaxation times, thickness or the extent of the damaged cartilage area could be detected. CONCLUSIONS: Our results suggest, that unloader bracing improves the biochemical properties of the damaged cartilage by increasing collagen and proteoglycan concentration as well as decreasing the cartilage edema.

Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS.

HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors - synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.

Radiosensitivity: Gender and Order of Administration of G-CSF, An Experimental Study in Mice.

To elucidate the potential influence of stimulating bone marrow before cell-cycle-dependent irradiation, we sought to determine overall survival in mice receiving total-body irradiation (TBI) when administered granulocyte stimulating factor (G-CSF) at different time points. Gender differences were also studied. C57/BL/6J mice, aged 9-14 weeks, received 8 Gy TBI in a perspex cage using a linear accelerator. In each of five different experiments, three groups were studied: 1. one control group receiving TBI only; 2. one group treated with filgrastim [500 lg/kg subcutaneously/intraperitoneally (s.c./i.p.)] the day before TBI, followed by daily filgrastim injections postirradiation (1-5 days); and 3. one group treated with daily filgrastim injections only post-TBI (1-5 days). Each experimental group included male and female mice. Survival of the mice was monitored daily, and mice were euthanized when their condition deteriorated. A total of 293 mice were monitored for at least 37 days post-TBI. Control mice that received 8 Gy TBI showed a significant gender difference, with a median survival of 22 days in females and 17 days in males. Addition of G-CSF, irrespective of pre- or postirradiation, significantly improved survival, but in males the improvement was significantly better when G-CSF was not given before TBI. Improved survival in females was independent of the order of administration of GCSF. Multiple filgrastim injections were more effective than a single injection, and s.c. administration was not better than i.p. In conclusion, these findings indicate that male mice are more sensitive to TBI than females. Filgrastim improved survival in both genders irrespective of whether given pre- or postirradiation, but in males the improvement was significantly less if an injection was given before irradiation. These results suggest that, to prevent toxicity most effectively, GCSF should not be given before cytotoxic therapy. While a completely different experimental model was used here, these results may also be extrapolated to indicate that endocrine cell-cycle suppression therapy should not be given before or during cytotoxic therapy of hormone-dependent tumors (e.g., breast and prostate cancer), thus a reduction in the efficacy of cell-cycle-dependent therapy can be prevented.

Behavioural responses of krill and cod to artificial light in laboratory experiments.

Most fishes and crustaceans respond to light, and artificial light sources may therefore be an efficient stimulus to manipulate behaviours in aquatic animals. It has been hypothesised that the catch efficiency of pots could be increased if prey, for example krill, can be attracted into the pots providing a visual stimulus and a source of live bait. To find which light characteristics are most attractive to krill, we tested the effects of light intensity and wavelength composition on Northern krill's (Meganyctiphanes norvegica) behavioural response to an artificial light source. The most attractive individual wavelength was 530 nm (green light), while broadband (425-750 nm) white light was an equally attractive light source. The intensity of the emitted light did not appear to have a direct effect on attraction to the light source, however it did significantly increase swimming activity among the observed krill. The most promising light stimuli for krill were tested to determine whether they would have a repulsive or attractive effect on cod (Gadus morhua); These light stimuli appeared to have a slightly repulsive, but non-significant, effect on cod. However, we suggest that a swarm of krill attracted to an artificial light source may produce a more effective visual stimulus to foraging cod.

Size-dependent social attraction and repulsion explains the decision of Atlantic cod Gadus morhua to enter baited pots.

The present study tested whether the presence of already retained fishes inside baited fish pots acted as a social attraction and affected the entrance probability of Atlantic cod Gadus morhua in a fjord in northern Norway. Video analysis revealed that the probability of an entrance initially increased with the presence of low numbers of fishes inside the pot, but subsequently decreased at a critical number of caught fishes. The critical number was dependent on the size of the G. morhua attempting to enter. This demonstrates that social attraction and repulsion play a role in G. morhua pot fishing and has important implications for the capture efficiency of fisheries executed with pots.

Seasonal variation in male alternative reproductive tactics.

Genetic parentage analyses reveal considerable diversity in alternative reproductive behaviours (e.g. sneaking) in many taxa. However, little is known about whether these behaviours vary seasonally and between populations. Here, we investigate seasonal variation in male reproductive behaviours in a population of two-spotted gobies (Gobiusculus flavescens) in Norway. Male two-spotted gobies guard nests, attract females and care for fertilized eggs. We collected clutches and nest-guarding males early and late in the breeding season in artificial nests and used microsatellite markers to reconstruct parentage from a subset of offspring from each nest. We hypothesized that mating, reproductive success and sneaking should be more prevalent early in the breeding season when competition for mates among males is predicted to be higher. However, parentage analyses revealed similar values of mating, reproductive success and high frequencies of successful sneaking early (30% of nests) and late (27% of nests) in the season. We also found that multiple females with eggs in the same nest were fertilized by one or more sneaker males, indicating that some males in this population engage in a satellite strategy. We contrast our results to previous work that demonstrates low levels of cuckoldry in a population in Sweden. Our results demonstrate marked stability in both the genetic mating system and male alternative reproductive tactics over the breeding season. However, sneaking rates may vary geographically within a species, likely due to local selection influencing ecological factors encountered at different locations.

Size Dependent Male Reproductive Tactic in the Two-Spotted Goby (Gobiusculus flavescens).

Male investment in testes and sperm duct gland in the polygamous nest breeding two-spotted goby Gobiusculus flavescens (Fabricius) was investigated in relation to time in reproductive season and individual physical parameters. This small teleost fish is most likely the most abundant species found along the rocky shores of the North East Atlantic. The two-spotted goby has a single reproductive season, during which nest-caring males can raise several clutches of offspring. According to the literature the males are on average larger than the females. Here we report for the first time a population showing a reversal of this trend, with males on average being smaller than females, a difference likely caused by a large proportion of small males. Early in the breeding season these small males have typical sneaker characters, with relatively large testes and small seminal duct glands compared to the larger dominant territorial males. The presence of these two alternative male reproductive tactics is confirmed by histological studies, which shows the presence of sperm in the sperm duct glands (SDG) of smaller males, but not in the SDG of intermediate and larger males. To our knowledge, males with typical sneaker characters have not been reported in earlier studied populations of two-spotted goby. Interestingly we found that testes investment declined significantly over the course of the breeding season, and that this reduction was significantly more pronounced in small compared to the large males. Further, a significant increase in seminal duct gland (SDG) mass was observed for the smaller males over the breeding season. We propose that this indicates a possible shift in mating tactic by smaller males from a parasitic to a nest-holding tactic over the course of the breeding season. Thus, the observed size dependent plasticity in investment in SDG over time suggests that the reproductive tactic of G. flavescens is conditional, and possibly influenced by mate availability and male--male competition.

Opposite selection on behavioural types by active and passive fishing gears in a simulated guppy Poecilia reticulata fishery.

This study assessed whether fishing gear was selective on behavioural traits, such as boldness and activity, and how this was related with a productivity trait, growth. Female guppies Poecilia reticulata were screened for their behaviour on the shy-bold axis and activity, and then tested whether they were captured differently by passive and active fishing gear, here represented by a trap and a trawl. Both gears were selective on boldness; bold individuals were caught faster by the trap, but escaped the trawl more often. Boldness and gear vulnerability showed weak correlations with activity and growth. The results draw attention to the importance of the behavioural dimension of fishing: selective fishing on behavioural traits will change the trait composition of the population, and might eventually affect resilience and fishery productivity.

An insight into the reproductive biology of the bearded goby Sufflogobius bibarbatus.

Preliminary results obtained from histological analyses of the male reproductive organs, supplemented with field and behavioural data, indicate that Sufflogobius bibarbatus, a small, slow growing gobiid exhibiting low fecundity, which plays an important role in the food web off Namibia, where large areas of the shelf are hypoxic, spawns demersally. Large males defend benthic nests, possibly at the edge of the hypoxic shelf. Male reproductive strategy appears to be flexible, and tentative evidence to suggest that polygyny and sneaking may also occur is presented.

The wand versus traditional injection for mandibular nerve block in children and adolescents: perceived pain and time of onset.

PURPOSE: The purpose of this study was to compare the perception of pain and time of onset in relation to mandibular alveolar nerve block administered by a computerized anesthesia delivery system (ie, The Wand) and a traditional anesthesia system (ie, the syringe). METHODS: This study was conducted according to a split-mouth design, with both types of injections being given to all patients. Subjects consisted of 33 patients between 7 and 18 years of age requiring local anesthesia for dental restorations in both sides of the mandible. All patients were blindfolded, and the sound from the Wand machine was activated during both types of administration. Topical analgesic was placed in the area of the injection site in all cases. Pain ratings were obtained using a 10-point visual analog scale (VAS). Time of onset was measured, from withdrawal of the needle to numbness of the lower lip was reported. RESULTS: The computerized anesthesia delivery system resulted in significantly lower pain ratings than the traditional syringe. No difference could be found in time of onset between the 2 methods. CONCLUSIONS: Mandibular alveolar block analgesia seems to be less painful when using The Wand than when using a traditional syringe.

Parental investment of male two-spotted goby, Gobiusculus flavescens (Fabricius).

The trade-off between parental care and feeding was studied in the male two-spotted goby (Gobiusculus flavescens F.). Two temperatures, 8.5 degrees C and 13.0 degrees C, were used, with five replicates at each temperature, in order to determine whether temperature influenced parental behaviour. In each replicate, two males and four females were introduced to an aquarium, where the males chose between two nests and courted the females. In each replicate, one male spawned. After spawning, the males guarded the eggs until hatching. The guarding males' behaviour was recorded with a video camera twice a day (15 min each time), once before and once after they were fed. The male's condition (c-factor) was calculated at the start of the experiment and after egg hatching. The eggs were spawned in an artificial nest (half of a PVC tube), and attached to the nest in a single layer. The areas with eggs (representing brood size) were marked after spawning and the fry counted after hatching (which was used to calculate area hatched). Numbers of prey eaten (plankton) and number of aggressive encounters between the guarding male and the other fishes were recorded. Time spent in the nest and time used on fertilisation, fanning and cleaning were estimated and related to egg age, brood size, hatching success, temperature and food availability (no food or food).The results showed that feeding (expected to influence future reproduction) decreased and parental expenditure (current reproduction) increased, as the eggs developed (became closer to independence). Parental expenditure was significantly higher at 13.0 degrees C than at 8.5 degrees C, presumably due to higher oxygen demands by the eggs, and a greater risk of egg-infections. The c-factor of the males guarding eggs decreased over time, in contrast to the non-guarding males' c-factor. Guarding males' aggressiveness decreased as the eggs got older, but increased just before hatching. A possible explanation for this could be the decreasing intrusion by the non-guarding male and females caused by high aggressive behaviour by the guarding male early in the brood cycle. The exploitation of the nest (percentage of total nest area covered by eggs) seemed to determine the amount of parental expenditure and loss of condition, while brood size (area of eggs) had no effect.

The nontoxic tripeptide glycyl-prolyl-glycine amide inhibits the replication of human immunodeficiency virus type 1.

OBJECTIVE: To determine whether short peptides corresponding to the RGPGR motif of the V3 loop of gp 120 have anti-human immunodeficiency virus type 1 (anti-HIV-1) activity. DESIGN/METHODS: Short peptides were tested against the HIV-1 laboratory strains and clinical isolates. RESULTS: The tripeptide glycyl-prolyl-glycine amide (GPG-NH2) inhibited the replication of both laboratory strains and 47 clinical isolates, including 19 strains that were resistant to other drugs or that were from patients with failing therapy. The 50% inhibitory concentrations values were 2.7 to 37 microM. Phenotypic change of two isolates from nonsyncytia-inducing to syncytia-inducing did not change their sensitivity to GPG-NH2. The tripeptide added to the antiviral effect of both zidovudine and ritonavir. CONCLUSIONS: The tripeptide GPG-NH2 is a nontoxic compound that inhibits the replication of HIV-1 by an apparently new mode of action. Glycyl-prolyl-glycine-NH2 might prove useful by itself or as a lead compound for the treatment of drug-resistant HIV-1. Glycyl-prolyl-glycine-NH2 is currently undergoing phase I/II human clinical trials in Sweden.

Radio-and chemotoxicity in mice during hypothermia.

BACKGROUND: The influence of hypothermia induced by chlorpromazine (10-15 mg/kg given intra-peritoneally) on the survival from radiation and chemotherapy exposure in C57B1-mice, with or without tumour inoculation, was studied. MATERIALS AND METHODS: The mice were exposed to either whole body irradiation (8 Gy), or doxorubicin (15 or 17.5 mg/kg i.p.), or cisplatin (20 mg/kg i. p.) and followed to ensuing death. The control mice maintained a rectal temperature of 38 degres C while those receiving chlorpromazine developed moderate hypothermia of 28 degrees C or 36 degrees C, dependent on the ambient temperature. RESULTS: Hypothermia of 28 degrees C protected the mice from radiation-induced death and acute doxorubicin toxicity, with males gaining more protection than females. The effects appeared dependent on temperature, not on chlorpromazine. Hypothermia protected the mice from acute cisplatin toxicity and increased the anti-tumour effects in both genders. Chlorpromazine itself did not cause toxicity, neither did it change the natural course of tumour progression. CONCLUSION: Hypothermia of 28 degrees C induced by chlorpromazine profoundly reduces radiation, doxorubicin-and cisplatin-induced toxicity in mice with males benefiting more than females. The hypothermia itself, not the chlorpromazine, was responsible for these effects. The anti-neoplastic activity was not compromised; rather, it was enhanced, particularly for cisplatin.

Influence of sulphuric acid contaminants on Fricke dosimetry.

The sulphuric acid used for the preparation of the Fricke dosimeter solution may contain trace impurities that can affect the yield of ferric ions. Two methods, pre-irradiation or oxidation with hydrogen peroxide, have been proposed to reduce the influence of these impurities. Fricke users sometimes omit this treatment. In the present work Fricke solutions prepared from six different brands and qualities of sulphuric acid were compared in order to study any influences of the acid on the ferric ion yield. It was shown that the use of analytical grade sulphuric acid from one manufacturer resulted in a reduction of the ferric ion yield of about 5% at an absorbed dose of approximately 20 Gy. If this solution were to be used for an absolute dose determination together with epsilon(m) G values from the literature the absorbed dose would be underestimated by the same amount.

Steroid profiles determined by capillary electrochromatography, laser-induced fluorescence detection and electrospray-mass spectrometry.

Macroporous, monolithic capillary electrochromatography (CEC) columns, featuring a hydrophobic stationary phase, have been applied to the separations of steroids with good column efficiency. Using isocratic and gradient elution runs, mixtures of neutral or conjugated steroids could be resolved. While dansylated ketosteroids were detectable through laser-induced fluorescence at attomole levels, the CEC columns coupled to electrospray-ion-trap mass spectrometry featured femtomole detection limits.

Calibration of plane-parallel chambers and determination of p(wall) for the NACP and Roos chambers for 60Co gamma-ray beams.

Procedures for the calibration and use of plane-parallel ionization chambers in high-energy electron and photon beams have been given in the international code of practice IAEA TRS-381. In the present work, plane-parallel ionization chambers of the type PTW-34001 Roos and Scanditronix NACP02 have been calibrated using two N(K)-based procedures. For the NACP chamber the difference between the N(D,air) chamber factors determined in an electron beam and in a 60Co gamma-ray beam, respectively, is of the same magnitude as the experimental uncertainty. Results for the PTW Roos chambers, however, do not agree, in accordance with recent findings of other authors. The value determined in a 60Co gamma-ray beam is questioned and the reason for the discrepancy assigned to the correction factor for the perturbation due to the chamber wall, p(wall). New values of p(wall) have been experimentally determined by comparing absorbed dose measurements based on air-kerma and absorbed dose to water calibration procedures. A new p(wall) factor for the Roos chamber in 60Co gamma-ray beams in water (1.009+/-0.6%) was derived as the weighted average of the different determinations. The value is not significantly higher than the p(wall) factor given in TRS-381 (1.003+/-1.5%), but the combined standard uncertainty is reduced. The chamber to chamber variation for six commercial PTW Roos chambers and a Roos prototype was found to be very small.

Deletion of the GPG motif in the HIV type 1 V3 loop does not abrogate infection in all cells.

The three amino acids glycine, proline, and glycine (GPG) constitute a conserved motif at the center of the V3 loop of HIV-1 surface glycoprotein 120. It has been indicated that deletion of this GPG motif is lethal for viral infectivity and abrogates the ability of the virus to form syncytia. In the present work, we studied the effects of GPG deletion on viral infectivity, cell tropism, syncytium formation, and initiation of apoptosis by constructing a mutant provirus based on the infectious clone pBRu-2. Successful infection and replication of GPG-deleted virus were detected in MT-2 cells, although the mutant virus showed lower infectivity. Infection could also be observed in the C8166, C91-PL, Molt-3, and THP-1 cell lines, and in PBMC-derived dendritic cells (DCs), but not in CEM-SS, HUT78, H9, Jurkat, and U937 cell lines or in PBMCs. Mutant virus also induced syncytia and apoptosis in the MT-2 cells. An intact GPG motif is probably necessary for unimpaired induction of fusion in some HIV-1-permissive cells. However, once the virus enters the cells, the GPG sequence does not seem to be indispensable for syncytium formation or apoptosis induction in MT-2 cells. Our data also imply that cell surface molecules other than CD4 and CXCR4 may be involved in entry of the GPG-deleted virus.

Experimental study on the influence of the central electrode in Farmer-type ionization chambers.

In the IAEA TRS-381 protocol, k(cel) and p(cel) account for the central electrode perturbation during the air kerma chamber calibration and the in-phantom measurements. The values of these correction factors are based mainly on Monte Carlo simulations. In the present work experimental data on k(cel) and p(cel) for the NE-2571 chamber is provided, relative to a graphite electrode. In addition, the relative influence of the 3 mm diameter A-150 central electrode of the NE-2581 chamber is studied. The experimentally determined value of k(cel) for a 1 mm aluminium electrode is 1.008 +/- 0.2%, and of p(cel) in photon and electron beams 0.993 +/- 0.2% and 0.997 +/- 0.2% respectively. The experimental data and the Monte Carlo simulations agree to within 0.2%. No significant influence of the A-150 central electrode diameter on the absorbed dose determination is shown.