Estimation of Radiation Dosimetry for 68Ga-HBED-CC (PSMA-11) in Patients with Suspected Recurrence of Prostate Cancer

Introduction This study was performed to estimate the human radiation dosimetry for [68Ga]Ga-HBED-CC (PSMA-11) (68Ga PSMA-11). Methods Under an RDRC-approved research protocol, we evaluated the biodistribution and pharmacokinetics of 68Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical [11C]acetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0–10 min post-injection with the pelvis in the field-of-view. Whole-body images were acquired, pelvis-to-head, at 15, 60, and 90-min post-injection. Additional images of the pelvis were acquired at 40-min and 115-min, and voided urine collected from each subject at 48-min and 120-min post-injection. Radiation dosimetry estimates were calculated from these data using the OLINDA software package. Results Renal uptake was high and relatively invariant, ranging from 11% to 14% of the injected dose between 15 and 90-min post-injection. Radioactivity collected in the voided urine accounted for 14% of the injected dose over a period of 120-min. Lymph nodes and skeletal metastases suspicious for prostate cancer recurrence were detected in a greater number of patients using 68Ga PSMA-11 than using 11C-acetate. Conclusion Kidneys are the critical organ following 68Ga PSMA-11 administration, receiving an estimated dose of 0.413 mGy/MBq. Advances in knowledge and implications for patient care This study confirms that the kidneys will be the critical organ following intravenous administration of 68Ga PSMA-11, and provided data consistent with the expectation that 68Ga PSMA-11 will be superior to [11C]acetate for defining sites of recurrence in prostate cancer patients presenting with biochemical relapse

Cosmological spacetimes balanced by a scale covariant scalar field

A scale invariant, Weyl geometric, Lagrangian approach to cosmology is explored, with a a scalar field phi of (scale) weight -1 as a crucial ingredient besides classical matter \cite{Tann:Diss,Drechsler:Higgs}. For a particularly simple class of Weyl geometric models (called {\em Einstein-Weyl universes}) the Klein-Gordon equation for phi is explicitly solvable. In this case the energy-stress tensor of the scalar field consists of a vacuum-like term Lambda g_{mu nu} with variable coefficient Lambda, depending on matter density and spacetime geometry, and of a dark matter like term. Under certain assumptions on parameter constellations, the energy-stress tensor of the phi-field keeps Einstein-Weyl universes in locally stable equilibrium. A short glance at observational data, in particular supernovae Ia (Riess ea 2007), shows interesting empirical properties of these models.Comment: 28 pages, 1 figure, accepted by Foundations of Physic

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

[68Ga]Ga-P16-093 as a PSMA-Targeted PET Radiopharmaceutical for Detection of Cancer: Initial Evaluation and Comparison with [68Ga]Ga-PSMA-11 in Prostate Cancer Patients Presenting with Biochemical Recurrence

Purpose: This study was undertaken to evaluate radiation dosimetry for the prostate-specific membrane antigen targeted [68Ga]Ga-P16-093 radiopharmaceutical, and to initially assess agent performance in positron emission tomography (PET) detection of the site of disease in prostate cancer patients presenting with biochemical recurrence. Procedures: Under IND 133,222 and an IRB-approved research protocol, we evaluated the biodistribution and pharmacokinetics of [68Ga]Ga-P16-093 with serial PET imaging following intravenous administration to ten prostate cancer patients with biochemical recurrence. The recruited subjects were all patients in whom a recent [68Ga]Ga-PSMA-11 PET/X-ray computed tomography (CT) exam had been independently performed under IND 131,806 to assist in decision-making with regard to their clinical care. Voided urine was collected from each subject at ~ 60 min and ~ 140 min post-[68Ga]Ga-P16-093 injection and assayed for Ga-68 content. Following image segmentation to extract tissue time-activity curves and corresponding cumulated activity values, radiation dosimetry estimates were calculated using IDAC Dose 2.1. The prior [68Ga]Ga-PSMA-11 PET/CT exam (whole-body PET imaging at 60 min post-injection, performed with contrast-enhanced diagnostic CT) served as a reference scan for comparison to the [68Ga]Ga-P16-093 findings. Results: [68Ga]Ga-P16-093 PET images at 60 min post-injection provided diagnostic information that appeared equivalent to the subject's prior [68Ga]Ga-PSMA-11 scan. With both radiopharmaceuticals, sites of tumor recurrence were found in eight of the ten patients, identifying 16 lesions. The site of recurrence was not detected with either agent for the other two subjects. Bladder activity was consistently lower with [68Ga]Ga-P16-093 than [68Ga]Ga-PSMA-11. The kidneys, spleen, salivary glands, and liver receive the highest radiation exposure from [68Ga]Ga-P16-093, with estimated doses of 1.7 × 10-1, 6.7 × 10-2, 6.5 × 10-2, and 5.6 × 10-2 mGy/MBq, respectively. The corresponding effective dose from [68Ga]Ga-P16-093 is 2.3 × 10-2 mSv/MBq. Conclusions: [68Ga]Ga-P16-093 provided diagnostic information that appeared equivalent to [68Ga]Ga-PSMA-11 in this limited series of ten prostate cancer patients presenting with biochemical recurrence, with the kidneys found to be the critical organ. Diminished tracer appearance in the urine represents a potential advantage of [68Ga]Ga-P16-093 over [68Ga]Ga-PSMA-11 for detection of lesions in the pelvis

Poor newborn care practices - a population based survey in eastern Uganda

BACKGROUND: Four million neonatal deaths are estimated to occur each year and almost all in low income countries, especially among the poorest. There is a paucity of data on newborn health from sub-Saharan Africa and few studies have assessed inequity in uptake of newborn care practices. We assessed socioeconomic differences in use of newborn care practices in order to inform policy and programming in Uganda. METHODS: All mothers with infants aged 1-4 months (n = 414) in a Demographic Surveillance Site were interviewed. Households were stratified into quintiles of socioeconomic status (SES). Three composite outcomes (good neonatal feeding, good cord care, and optimal thermal care) were created by combining related individual practices from a list of twelve antenatal/essential newborn care practices. Multiple logistic regression analysis was used to identify determinants of each dichotomised composite outcome. RESULTS: There were low levels of coverage of newborn care practices among both the poorest and the least poor. SES and place of birth were not associated with any of the composite newborn care practices. Of newborns, 46% had a facility delivery and only 38% were judged to have had good cord care, 42% optimal thermal care, and 57% were considered to have had adequate neonatal feeding. Mothers were putting powder on the cord; using a bottle to feed the baby; and mixing/replacing breast milk with various substitutes. Multiparous mothers were less likely to have safe cord practices (OR 0.5, CI 0.3 - 0.9) as were mothers whose labour began at night (OR 0.6, CI 0.4 - 0.9). CONCLUSION: Newborn care practices in this setting are low and do not differ much by socioeconomic group. Despite being established policy, most neonatal interventions are not reaching newborns, suggesting a "policy-to-practice gap". To improve newborn survival, newborn care should be integrated into the current maternal and child interventions, and should be implemented at both community and health facility level as part of a universal coverage strategy

Genetic identification of cytomegaloviruses in a rural population of Côte d'Ivoire.

BACKGROUND: Cytomegaloviruses (CMVs) are herpesviruses that infect many mammalian species, including humans. Infection generally passes undetected, but the virus can cause serious disease in individuals with impaired immune function. Human CMV (HCMV) is circulating with high seroprevalence (60-100 %) on all continents. However, little information is available on HCMV genoprevalence and genetic diversity in subsaharan Africa, especially in rural areas of West Africa that are at high risk of human-to-human HCMV transmission. In addition, there is a potential for zoonotic spillover of pathogens through bushmeat hunting and handling in these areas as shown for various retroviruses. Although HCMV and nonhuman CMVs are regarded as species-specific, potential human infection with CMVs of non-human primate (NHP) origin, shown to circulate in the local NHP population, has not been studied. FINDINGS: Analysis of 657 human oral swabs and fecal samples collected from 518 individuals living in 8 villages of Côte d'Ivoire with generic PCR for identification of human and NHP CMVs revealed shedding of HCMV in 2.5 % of the individuals. Determination of glycoprotein B sequences showed identity with strains Towne, AD169 and Toledo, respectively. NHP CMV sequences were not detected. CONCLUSIONS: HCMV is actively circulating in a proportion of the rural Côte d'Ivoire human population with circulating strains being closely related to those previously identified in non-African countries. The lack of NHP CMVs in human populations in an environment conducive to cross-species infection supports zoonotic transmission of CMVs to humans being at most a rare event

Acute LPS sensitization and continuous infusion exacerbates hypoxic brain injury in a piglet model of neonatal encephalopathy.

Co-existing infection/inflammation and birth asphyxia potentiate the risk of developing neonatal encephalopathy (NE) and adverse outcome. In a newborn piglet model we assessed the effect of E. coli lipopolysaccharide (LPS) infusion started 4 h prior to and continued for 48 h after hypoxia on brain cell death and systemic haematological changes compared to LPS and hypoxia alone. LPS sensitized hypoxia resulted in an increase in mortality and in brain cell death (TUNEL positive cells) throughout the whole brain, and in the internal capsule, periventricular white matter and sensorimotor cortex. LPS alone did not increase brain cell death at 48 h, despite evidence of neuroinflammation, including the greatest increases in microglial proliferation, reactive astrocytosis and cleavage of caspase-3. LPS exposure caused splenic hypertrophy and platelet count suppression. The combination of LPS and hypoxia resulted in the highest and most sustained systemic white cell count increase. These findings highlight the significant contribution of acute inflammation sensitization prior to an asphyxial insult on NE illness severity

Patents and Industrialisation. An Historical Overview of the British Case, 1624-1907

A Report to the Strategic Advisory Board on Intellectual Property Policy (SABIP), U

Hypothermia is not therapeutic in a neonatal piglet model of inflammation-sensitized hypoxia-ischemia.

BACKGROUND: Perinatal inflammation combined with hypoxia-ischemia (HI) exacerbates injury in the developing brain. Therapeutic hypothermia (HT) is standard care for neonatal encephalopathy; however, its benefit in inflammation-sensitized HI (IS-HI) is unknown. METHODS: Twelve newborn piglets received a 2 µg/kg bolus and 1 µg/kg/h infusion over 52 h of Escherichia coli lipopolysaccharide (LPS). HI was induced 4 h after LPS bolus. After HI, piglets were randomized to HT (33.5 °C 1-25 h after HI, n = 6) or normothermia (NT, n = 6). Amplitude-integrated electroencephalogram (aEEG) was recorded and magnetic resonance spectroscopy (MRS) was acquired at 24 and 48 h. At 48 h, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive brain cell death, microglial activation/proliferation, astrogliosis, and cleaved caspase-3 (CC3) were quantified. Hematology and plasma cytokines were serially measured. RESULTS: Two HT piglets died. aEEG recovery, thalamic and white matter MRS lactate/N-acetylaspartate, and TUNEL-positive cell death were similar between groups. HT increased microglial activation in the caudate, but had no other effect on glial activation/proliferation. HT reduced CC3 overall. HT suppressed platelet count and attenuated leukocytosis. Cytokine profile was unchanged by HT. CONCLUSIONS: We did not observe protection with HT in this piglet IS-HI model based on aEEG, MRS, and immunohistochemistry. Immunosuppressive effects of HT and countering neuroinflammation by LPS may contribute to the observed lack of HT efficacy. Other immunomodulatory strategies may be more effective in IS-HI. IMPACT: Acute infection/inflammation is known to exacerbate perinatal brain injury and can worsen the outcomes in neonatal encephalopathy. Therapeutic HT is the current standard of care for all infants with NE, but the benefit in infants with coinfection/inflammation is unknown. In a piglet model of inflammation (LPS)-sensitized HI, we observed no evidence of neuroprotection with cooling for 24 h, based on our primary outcome measures: aEEG, MRS Lac/NAA, and histological brain cell death. Additional neuroprotective agents, with beneficial immunomodulatory effects, require exploration in IS-HI models