Dark matter local density determination: recent observations and future prospects.

This report summarises progress made in estimating the local density of dark matter (ρDM,⊙), a quantity that is especially important for dark matter direct detection experiments. We outline and compare the most common methods to estimateρDM,⊙and the results from recent studies, including those that have benefited from the observations of the ESA/Gaia satellite. The result of most local analyses coincide within a range ofρDM,⊙≃0.4-0.6GeVcm-3=0.011-0.016M⊙/pc3, while a slightly lower range ofρDM,⊙≃0.3-0.5GeVcm-3=0.008-0.013M⊙/pc3is preferred by most global studies. In light of recent discoveries, we discuss the importance of going beyond the approximations of what we define as the ideal Galaxy (a steady-state Galaxy with axisymmetric shape and a mirror symmetry across the mid-plane) in order to improve the precision ofρDM,⊙measurements. In particular, we review the growing evidence for local disequilibrium and broken symmetries in the present configuration of the Milky Way, as well as uncertainties associated with the galactic distribution of baryons. Finally, we comment on new ideas that have been proposed to further constrain the value ofρDM,⊙, most of which would benefit from Gaia's final data release.

Alpha emitter radium-223 and survival in metastatic prostate cancer.

BACKGROUND: Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. METHODS: In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. RESULTS: At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. CONCLUSIONS: In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).

Phenotypic variation within a clonal lineage of Phytophthora infestans infecting both tomato and potato in Nicaragua.

Late blight caused by Phytophthora infestans (Mont.) de Bary is a constraint to both potato and tomato crops in Nicaragua. The hypothesis that the Nicaraguan population of P. infestans is genotypically and phenotypically diverse and potentially subdivided based on host association was tested. A collection of isolates was analyzed using genotypic markers (microsatellites and mitochondrial DNA haplotype) and phenotypic markers (mating type, virulence, and fungicide sensitivity). The genotypic analysis revealed no polymorphism in 121 of 132 isolates of P. infestans tested. Only the Ia haplotype and the A2 mating type were detected. Most of the tested isolates were resistant to metalaxyl. The virulence testing showed variation among isolates of P. infestans. No evidence was found of population differentiation among potato and tomato isolates of P. infestans based on the genotypic and phenotypic analysis. We conclude that the Nicaraguan population of P. infestans consists of a single clonal lineage (NI-1) which belongs to the A2 mating type and the Ia mitochondrial DNA haplotype. Moreover, based on the markers used, this population of P. infestans does not resemble the population in countries from which potato seed is imported to Nicaragua or the population in neighboring countries. The data presented here indicate that the NI-1 clonal lineage is the primary pathogen on both potato and tomato, and its success on both host species is unique in a South American context.

Occupational radiation exposure in health care facilities.

BACKGROUND: Radiation, which is used extensively to diagnose and treat human diseases, poses an occupational health risk for the concerned health workers. Personal dosimetry is an important tool to monitor occupational radiation exposures. OBJECTIVE: This study was conducted to reveal and to describe the situation of occupational radiation exposure monitoring among staffs in different health care facilities in Nepal. METHODS: A cross-sectional study was performed among the 35 Health Care Facilities. Information about types and number of X-ray procedures performed, types and number of personnel involved, workload and the availability of personal dosimetry service were collected. RESULTS: Six Health Care Facilities had personal dosimetry service available for a total of 149 personnel. Of a total of nearly one million X-ray procedures performed in the 35 Health Care Facilities in 2007, 76 percent was performed by non-monitored personnel. The majority of the facilities performing high dose procedures, like catheterisation, angiography and intestinal barium procedures did not offer personal dosimetry for the involved personnel. CONCLUSION: There are a limited number of personnel being monitored with personal dosimetry. There are no regulatory dose limits for occupationally exposed staff. Thus, there is an urgent need to establish a national radiation protection authority to regulate the use of radiation in Nepal.

Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer.

Herein, we describe a novel approach in the search for prostate cancer biomarkers, which relies on the transcriptome within tumour exosomes. As a proof-of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3 and TMPRSS2:ERG the in exosomes isolated from urine of patients, showing the potential for diagnosis and monitoring cancer patients status.

Assessing doses to interventional radiologists using a personal dosimeter worn over a protective apron.

BACKGROUND: Interventional radiologists receive significant radiation doses, and it is important to have simple methods for routine monitoring of their exposure. PURPOSE: To evaluate the usefulness of a dosimeter worn outside the protective apron for assessments of dose to interventional radiologists. MATERIAL AND METHODS: Assessments of effective dose versus dose to dosimeters worn outside the protective apron were achieved by phantom measurements. Doses outside and under the apron were assessed by phantom measurements and measurements on eight radiologists wearing two routine dosimeters for a 2-month period during ordinary working conditions. Finger doses for the same radiologists were recorded using thermoluminescent dosimeters (TLD; DXT-RAD Extremity dosimeters). RESULTS: Typical values for the ratio between effective dose and dosimeter dose were found to be about 0.02 when the radiologist used a thyroid shield and about 0.03 without. The ratio between the dose to the dosimeter under and outside a protective apron was found to be less than 0.04. There was very good correlation between finger dose and dosimeter dose. CONCLUSION: A personal dosimeter worn outside a protective apron is a good screening device for dose to the eyes and fingers as well as for effective dose, even though the effective dose is grossly overestimated. Relatively high dose to the fingers and eyes remains undetected by a dosimeter worn under the apron.

Measurements of finger doses in x-ray guided surgery, nuclear medicine and research.

The Norwegian Radiation Protection Authority has performed measurements of finger doses to nuclear medicine staff exposed to 99Tc(m), researchers handling 32P, surgeons performing X-ray guided orthopaedic surgery and surgeons and radiologists performing X-ray guided endovascular treatment of abdominal aortic aneurysms (AAA). Calibrations were done with X-ray qualities N-40, N-60 and N-300 and with the beta source 90Sr + 90Y. Annual doses were estimated for the nuclear medicine staff and the orthopaedic surgeons. The mean annual finger dose to nuclear medicine staff exposed to 99Tc(m) was estimated to be 18.8 mSv, and the mean annual finger dose to surgeons performing X-ray guided orthopaedic surgery was 13.7 mSv. The surgeons and radiologists performing X-ray guided endovascular treatment of AAA received a mean finger dose of 0.35 mSv per treatment. The majority of researchers handling 32P received no finger dose at all, and the maximum reading was 1.65 mSv. All occupational groups received finger doses well below the annual finger dose limit of 500 mSv.

Inspection of cardiology departments in Norway: are they making it great in radiation protection?

Staff involved in interventional cardiology receive the highest occupational doses in Norway, and skin burns of patients have been reported. To identify the level of radiation protection (RP) for patients and staff, and compliance with the RP regulation, the Norwegian Radiation Protection Authority carried out inspections. The inspections were conducted (2013-14) as quality system reviews, based on document reviews, interviews, on-site inspections and observations of interventional procedures. The inspections revealed that most of the hospitals had non-compliances according to the RP regulation. Most deviations were associated with education in RP and follow-up of patients who had received high radiation doses. Lack of systematic optimisation of procedures and estimation of eye lens doses to evaluate the risk for cataracts were also common. Inspections turned out to increase the awareness of RP in cardiology and are identified as an effective tool for improving RP.

Are leukocytes involved in the human chorionic gonadotropin-induced increase in testicular vascular permeability?

Adult male rats were given a single sc injection of human CG (hCG). The volume density of polymorphonuclear leukocytes (PMNs) located in blood vessels or in the interstitial space was determined by morphometry. The volume of testicular interstitial fluid (IF) was also measured. hCG in doses from 50-800 IU increased the IF volume 8 h after treatment and resulted in migration of PMN into the interstitial space. In contrast, treatment with 12.5 IU hCG, although increasing intratesticular testosterone to about 50% of the maximal value, did not increase the volume of IF, and no leukocytes appeared in the interstitial space. Treatment with 50 IU hCG sc increased the volume of IF at 8, 16, and 32 h after treatment. The increase in IF volume, which is a reliable estimator of changes in the vascular permeability, was preceded by an intravascular accumulation of PMNs. Four hours after hCG treatment, there was a 6-fold increase in the volume density of intravascular PMNs. Later, leukocytes migrated into the interstitial space reaching a maximal concentration 8 h after hCG treatment (at that time 6.4 +/- 0.7 X 10(-5) of the total testis volume was composed of leukocytes). The number of interstitial PMNs declined thereafter and by 32 h they were no longer observed. It is suggested that leukocytes could be involved in mediating the hCG-induced increase in vascular permeability in the testis.

Little anticholinergic effect of E-10-hydroxynortriptyline compared with nortriptyline in healthy subjects.

Six healthy male subjects were randomly given nortriptyline (NT) (25 and 50 mg) and placebo in a double-blind, crossover study. An NT dose of 50 mg (but not 25 mg) clearly reduced saliva flow (P less than 0.05) and was therefore used for comparison with the major and active metabolite of NT, E-10-hydroxynortriptyline (E-10-OH-NT). Equimolar doses of both compounds (and placebo) were randomly given to eight healthy male subjects in another double-blind, crossover study aimed to assess the reduction of saliva flow. NT significantly depressed saliva flow compared with both placebo (P less than 0.01) and E-10-OH-NT (P less than 0.05). By contrast, there was no difference between E-10-OH-NT and placebo. This study confirms previous indications that the anticholinergic effect of E-10-OH-NT is considerably less than that of the parent drug NT.

High-precision conformal radiotherapy (HPCRT) of prostate cancer--a new technique for exact positioning of the prostate at the time of treatment.

PURPOSE: Biopsies taken 2 years after radiotherapy of localized prostate cancer indicate residual tumor cells in 20-60% of cases, and the prognosis for these patients is unfavorable. More precise methods of localization of the prostate are desirable to increase the dose to the prostate tumor and minimize the volume of adjacent sensitive tissues that are currently included in the planning target volume. We have sought a method to more accurately locate the prostate at the time of treatment, allowing a reduction of the volume of rectum and bladder included in the high dose region during dose escalation. METHODS AND RESULTS: We have developed a new technique using a special urethral catheter (patent pending), containing markers that can be visualized by the radiotherapy machine for accurate positioning of the prostate. The catheter is used throughout the treatment planning procedure and the isocenter is placed on one of the markers. On the treatment couch the markers are visualized on port-films and with portal imaging immediately before dose delivery. A beam-center-marker on the accelerator makes it possible to adjust the isocenter position to within 1 mm, giving very high precision, independent of external fixation. The technique involves a simple patient setup. The method has been tested in five patients with conventional dose level (70 Gy) and in 24 patients in the first Scandinavian dose escalation study with external beam radiotherapy. No increase in acute side-effects was observed. CONCLUSION: With the new high precision conformal radiotherapy (HPCRT) technique we have developed a technique that allows us to increase the dose to the prostate without excessive side effects. The method reduces the uncertainties in prostate localization, is easy to handle, and feasible in routine treatment.

Combined castration and fractionated radiotherapy in an experimental prostatic adenocarcinoma.

PURPOSE: The present study using the Dunning R3327-PAP rat prostatic adenocarcinoma model was designed to study the effect on tumor growth of castration prior to or after irradiation with 20-25 Gy as compared with either irradiation or castration alone. METHODS AND MATERIALS: Rats were bilaterally orchidectomized. During the irradiation procedure the nonanesthetized animals were held in a metallic frame with a strong cotton net and they were observed by means of a video camera. The suboptimal irradiation dose was given once daily with a 4-MeV linear accelerator, 4-5 Gy/fraction, during 5 consecutive days. Tumor volumes and rat weights were followed. At the end point of the study the animals were sacrificed and the tumors were morphometrically analyzed. RESULTS: The combination of irradiation and castration delayed tumor regrowth better than irradiation alone with the same suboptimal dose. Castration before irradiation delayed tumor regrowth more efficiently than castration after irradiation. However, castration alone delayed tumor regrowth even more effectively than suboptimal irradiation doses combined with castration. CONCLUSIONS: In combination with suboptimal irradiation neoadjuvant androgen deprivation was more inhibitory to rat prostatic adenocarcinoma regrowth than adjuvant androgen deprivation. Irradiation with suboptimal doses combined with castration may cause an earlier relapse to androgen-independent tumor growth than castration alone.

Relationship between human chorionic gonadotrophin-induced changes in testicular microcirculation and the formation of testicular interstitial fluid.

The relationship between testicular vascular permeability and testicular microcirculation as measured by laser Doppler flowmetry was studied in adult rats. In untreated control animals there was an oscillatory testicular blood-flow pattern with a frequency of 10.6 +/- 0.8 pulses/min and the amount of testicular interstitial fluid (IF) collected was 61.5 +/- 2.2 microliter/g testis. Treatment of the rats with 25-200 i.u. human chorionic gonadotrophin (hCG) s.c. 8 h before the experiment resulted in a change in the testicular flow pattern from pulsatile to continuous and an increase in IF volume. Treatment with hCG (50 i.u., s.c.) changed the testicular blood-flow pattern from oscillatory to continuous 4, 8 and 16 h after treatment. The flow pattern returned to being pulsatile 32 h after treatment with hCG. The IF information was increased at those times when the blood-flow pattern was continuous. No effects on blood flow or IF formation were observed with 12.5 i.u. hCG s.c. The present study shows a dose- and time-dependent covariation between the increase in testicular IF volume and the disappearance of the pulsatile flow in testicular microcirculation. It appears that a continuous flow pattern favours the transport of fluid from blood vessels to the interstitium.

Effects of oestradiol-17 beta on testicular microcirculation in rats.

The effect of oestradiol-17 beta on testicular microcirculation in intact and hypophysectomized rats was studied before and after treatment with human chorionic gonadotrophin (hCG). Treatment of intact rats with oestradiol-17 beta for 5 days did not influence vasomotion but decreased testicular interstitial fluid volume (IFV). Treatment of intact rats with 50 IU hCG 8 h before the experiment began induced an increase in testicular IFV, abolished vasomotion and increased the accumulation of polymorphonuclear leucocytes in the testicular venules and interstitium. These changes were unaffected by pretreatment with oestradiol-17 beta, despite the decreased testosterone production. However, pretreatment with oestradiol-17 beta potentiated the hCG-induced migration of polymorphonuclear leucocytes to the interstitium. The interstitial fluid volume and number of polymorphonuclear leucocytes in blood vessels were decreased in hypophysectomized rats, and vasomotion was abolished. Daily treatment with 5 IU hCG increased the IFV and the number of polymorphonuclear leucocytes in blood vessels, and preserved vasomotion. Treatment of hypophysectomized rats with oestradiol-17 beta decreased testosterone production but did not influence basal IFV, vasomotion or the changes in IFV and vasomotion induced by 5 IU hCG. The present study shows that the regulation of testicular vascular permeability and vasomotion may not be directly related to testicular steroidogenesis, and that oestrogens are probably not involved as a mediator of the hCG-induced changes in testicular microcirculation.

Predictive value of bcl-2 immunoreactivity in prostate cancer patients treated with radiotherapy.

BACKGROUND AND PURPOSE: Recent experimental evidence suggests that overexpression of bcl-2, a protein functioning by blocking apoptosis, may influence the treatment outcome in human tumours, including prostate cancer. To test the clinical implications of this hypothesis, tumours from patients with prostate cancer treated with external beam radiotherapy were investigated for bcl-2 immunoreactivity (IR) and correlated with prognosis and treatment outcome. MATERIALS AND METHODS: Bcl-2 IR was evaluated in archival tumour specimens obtained through transurethral resection from 42 patients with localized prostate cancer (T0-T4, N0 and M0). Bcl-2 IR expression was related to stage, grade and cancer-specific survival. Specimens were obtained prior to administrating routine radiotherapy for all patients. RESULTS: Bcl-2 IR was present in 19/42 (45%) tumours. The bcl-2-positive patients had a significantly longer cancer-specific survival than the bcl-2-negative patients (10.3 versus 3.4 years, P<0.04). At follow-up (7-19 years), nine patients were still alive, 26 patients had died of prostate cancer and seven patients had died of other causes. CONCLUSIONS: This study indicates that pre-treatment bcl-2 overexpression is related to a favourable outcome in prostate cancer treated with radiotherapy. Low bcl-2 along with a high stage may be a predictor of poor prognosis and these patients might benefit from additional treatment.

Leucocytes mediate the hCG-induced increase in testicular venular permeability.

Human chorionic gonadotrophin (hCG) treatment of adult male rats induces microvascular changes in the testis consisting of abolished vasomotion, an accumulation of leucocytes in postcapillary venules and increased vascular permeability. To study the role of leucocytes, rats were made leucopenic with a specific antineutrophil serum (ANS). Testicular interstitial fluid volume was decreased in leucopenic rats. Leucopenic rats also failed to show an hCG-induced increase in venular permeability as in saline-treated rats. The normally pulsatile blood flow pattern (vasomotion) persisted in leucopenic rats but was abolished after hCG treatment both in saline-treated and leucopenic rats. Plasma testosterone concentration after hCG treatment was not affected by elimination of circulating polymorphonuclear (PMN) leucocytes. It is concluded that PMN leucocytes mediate in part the hCG-induced increase in testicular venular permeability but not the hCG-induced inhibition of vasomotion.

Distribution of estramustine in the BT4C rat glioma model.

Estramustine (EaM), a carbamate ester of 17beta-estradiol and nor-nitrogen mustard, is a cytotoxic compound with antitumoral effect in malignant glioma in vitro and in vivo . However, knowledge of the pharmacokinetics of EaM in experimental glioma is limited. The objective of this study was therefore to investigate further the distribution of EaM in the BT4C rat glioma model. Assessment of EaM uptake and distribution was performed by quantitative whole-body autoradiography. In addition, the uptake of EaM and its metabolites estromustine (EoM), estradiol, and estrone were analyzed by gas chromatography. EaM was taken up from the circulation and was found to be the main product in glioma tissue. Whole-body autoradiography after [14C]-EaM administration revealed a strong 14C label simultaneously in tumor and normal brain tissue at 0.5 h after drug administration. In tumor tissue, sustained high levels of 14C label were detected at 12 h after drug administration. In contrast to the tumor, radioactivity in normal brain tissue rapidly leveled off, indicating a retention of radioactivity in the tumor. The tumor/brain radioactivity ratio reached a peak of 4.5 at 12 h after drug administration. High levels of 14C label were also found in pulmonary tissue. By gas chromatography, EoM was found to be the main metabolite in plasma. However, EaM reached higher levels in tumor tissue, with the mean tumor/plasma ratio being 11.7 as compared with 2.0 for EoM. Only low plasma levels of the estrogen metabolites were detected. In conclusion, EaM is taken up in the BT4C rat glioma tissue and is retained in the tumor as compared with normal brain tissue and plasma. EaM showed a greater selectivity for tumor tissue, exhibiting a high tumor/plasma ratio as compared with EoM. The distribution pattern after administration of EaM, as evaluated by both whole-body autoradiography and gas chromatography, supports the earlier suggestion that the uptake is related to a protein with EaM-binding characteristics.

Tumor blood flow and the cytotoxic effects of estramustine and its constituents in a rat glioma model.

OBJECTIVE: Estramustine (EaM) is a conjugate of nor-nitrogen mustard (NNM) and 17 beta-estradiol (E2) that has cytotoxic and radiosensitizing effects on experimental malignant glioma. Its mechanism of action is only partly understood. To further investigate the mechanism in vivo, the effects on tumor blood flow (TBF) and tumor growth were analyzed. METHODS: TBF was measured by radioactive microspheres, and tumor growth was measured by weight. Apoptosis was evaluated by in situ end labeling and gel electrophoresis. The effects of the constituents NNM and E2 were also evaluated. RESULTS: EaM increased TBF to 153.8 ml/100 g/min after 3 days and to 153.9 ml/100 g/min after 10 days of treatment, compared with 94.0 ml/100 g/min in untreated controls. Cerebral blood flow did not change after EaM treatment. NNM increased TBF but also showed a tendency to increase cerebral blood flow. E2 increased TBF, whereas cerebral blood flow was unchanged. EaM resulted in a rapid reduction in tumor weight from 230 mg in untreated animals to 146 mg after 3 days of treatment. EaM induced an early transient fragmentation of deoxyribonucleic acid in glioma but not in the normal brain. Neither NNM nor E2 affected tumor weight. CONCLUSION: EaM increases TBF in the BT4C rat glioma model with a concomitant rapid antitumoral effect. The increase in TBF could partially be induced by an estrogen-like action of EaM, but the rapid cytotoxic effect of the drug is obviously attributed to the intact EaM compound. This cytotoxic effect might be attributable to the induction of programmed cell death.

Guidance levels in the Nordic countries: a preliminary report for selected interventional procedures.

The Nordic radiation protection authorities have already published recommended guidance levels for patient doses for six conventional radiological examinations. Over the past two years a similar protocol has been in progress for three interventional procedures. Measurements have been performed in 22 different hospitals in the Nordic countries on patients in the weight range 40-100 kg. The selected procedures are percutaneous transluminal coronary angioplasty (PTCA), percutaneous transluminal angioplasty (PTA) and endoscopic retrograde cholangio- and pancreatio-graphy (ERCP). A total of 281 PTCA procedures, 304 PTA procedures and 147 ERCP procedures are included in the study. The results from this survey are presented as a first attempt to set guidance levels.

How 'do's' and 'dont's' can be of significant importance in radiation protection: a case report.

The Norwegian Radiation Protection Authority (NRPA) was contacted by a cardiology department because of a suspicious radiation burn on a patient. The patient had undergone two bi-ventricular pacemaker implantations and the lesion was recognised as radiation dermatitis. The NRPA sent sets of thermoluminescense dosemeters to the department to measure the skin dose on eight successive patients undergoing bi-ventricular pacemaker implantations. The average maximum entrance surface dose for the eight patients was 5.3 Gy, ranging from 2.0 to 13.1 Gy. A site audit was performed during a procedure, with the aim to observe the general skills in radiation protection. Based on the findings in the audit, a few very simple 'Do's' and 'Don'ts' were highlighted in a meeting directly after the audit. After the audit, dose measurements were performed on six new patients showing an average maximum entrance surface dose of 0.4 Gy, ranging from 0.2 to 0.8 Gy. The aim of this work was to illustrate the dose reductions that are possible to achieve with a very few basic advices, especially when the operator has suboptimal competence.