Good practices for 68Ga radiopharmaceutical production

Background: The radiometal gallium-68 (Ga-68) is increasingly used in diagnostic positron emission tomography (PET), with Ga-68-labeled radiopharmaceuticals developed as potential higher-resolution imaging alternatives to traditional Tc-99m agents. In precision medicine, PET applications of Ga-68 are widespread, with Ga-68 radiolabeled to a variety of radiotracers that evaluate perfusion and organ function, and target specific biomarkers found on tumor lesions such as prostate-specific membrane antigen, somatostatin, fibroblast activation protein, bombesin, and melanocortin. Main body: These Ga-68 radiopharmaceuticals include agents such as [Ga-68]Ga-macroaggregated albumin for myocardial perfusion evaluation, [Ga-68]Ga-PLED for assessing renal function, [Ga-68]Ga-t-butyl-HBED for assessing liver function, and [Ga-68]Ga-PSMA for tumor imaging. The short half-life, favourable nuclear decay properties, ease of radiolabeling, and convenient availability through germanium-68 (Ge-68) generators and cyclotron production routes strongly positions Ga-68 for continued growth in clinical deployment. This progress motivates the development of a set of common guidelines and standards for the Ga-68 radiopharmaceutical community, and recommendations for centers interested in establishing Ga-68 radiopharmaceutical production. Conclusion: This review outlines important aspects of Ga-68 radiopharmacy, including Ga-68 production routes using a Ge-68/Ga-68 generator or medical cyclotron, standardized Ga-68 radiolabeling methods, quality control procedures for clinical Ga-68 radiopharmaceuticals, and suggested best practices for centers with established or upcoming Ga-68 radiopharmaceutical production. Finally, an outlook on Ga-68 radiopharmaceuticals is presented to highlight potential challenges and opportunities facing the community

Antiferroelectric liquid crystal mixture without smectic layer shrinkage at the direct sma* - smca* transition

We report results of x-ray, optic, electro-optic, and dielectric investigations on an antiferroelectric liquid- crystal mixture exhibiting a direct second-order phase transition between the Sm-A* and Sm-Ca* phases with virtually no shrinkage in the smectic layer spacing. The birefringence measurements and texture observations suggest that the phase transition follows the diffuse cone model of Adrian de Vries, which explains the constant layer spacing. The antiferroelectric nature of the tilted phase is verified by the presence of twin polarization reversal peaks in the current response and by the absence of strong absorptions in the dielectric spectrum. The threshold for switching this phase to the synclinic, ferroelectric state is sharp and occurs at a very low voltage

Collision Dynamics and Solvation of Water Molecules in a Liquid Methanol Film

Environmental molecular beam experiments are used to examine water interactions with liquid methanol films at temperatures from 170 K to 190 K. We find that water molecules with 0.32 eV incident kinetic energy are efficiently trapped by the liquid methanol. The scattering process is characterized by an efficient loss of energy to surface modes with a minor component of the incident beam that is inelastically scattered. Thermal desorption of water molecules has a well characterized Arrhenius form with an activation energy of 0.47{\pm}0.11 eV and pre-exponential factor of 4.6 {\times} 10^(15{\pm}3) s^(-1). We also observe a temperature dependent incorporation of incident water into the methanol layer. The implication for fundamental studies and environmental applications is that even an alcohol as simple as methanol can exhibit complex and temperature dependent surfactant behavior.Comment: 8 pages, 5 figure

Papaverine effects on PGI2 and TXA2 release from the canine vascular wall

Operative manipulation of blood vessels might lead to spasm, thereby destroying the endothelial cell function: the spasm can be prevented by the vasodilator papaverine. To study if this was mediated via the prostanoid pathway the following investigation was undertaken: canine jugular veins and carotid arteries were dissected with or without papaverine. Vessel segments were then perfused with Hank's balanced salt solution for five times 15 min. Prostacyclin was measured as the stable degradation product 6-keto-PGF1[alpha] and thromboxane as TXB2, by radioimmunoassay. Control arterial segments' 6-keto-PGF1[alpha] release was initially 129.5 + 20.1 pg/mm2/15 min, and 29.7 + 10.4 after 60 min (p2/15 min (p125I tracer. When using 3H tracer including absorption of free antigen to dextran coated charcoal, papaverine displaced the free tracer giving artificially low values. There was no effect of papaverine given intraoperatively on the TXB2 release, neither from arteries nor from veins. In another experiment the vessel wall tension was examined and the cyclooxygenase inhibitor diclofenac did not inhibit the vasodilating effect of papaverine. It is concluded that the vasodilating effect of papaverine is not mediated via prostacyclin release and that the vasodilating effect does not influence the prostacyclin release from arteries or veins. Finally, papaverine interacts with the 3H assay by displacing the antigen-antibody complex.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29961/1/0000323.pd

Binary classification of spoken words with passive elastic metastructures

Many electronic devices spend most of their time waiting for a wake-up event: pacemakers waiting for an anomalous heartbeat, security systems on alert to detect an intruder, smartphones listening for the user to say a wake-up phrase. These devices continuously convert physical signals into electrical currents that are then analyzed on a digital computer -- leading to power consumption even when no event is taking place. Solving this problem requires the ability to passively distinguish relevant from irrelevant events (e.g. tell a wake-up phrase from a regular conversation). Here, we experimentally demonstrate an elastic metastructure, consisting of a network of coupled silicon resonators, that passively discriminates between pairs of spoken words -- solving the wake-up problem for scenarios where only two classes of events are possible. This passive speech recognition is demonstrated on a dataset from speakers with significant gender and accent diversity. The geometry of the metastructure is determined during the design process, in which the network of resonators ('mechanical neurones') learns to selectively respond to spoken words. Training is facilitated by a machine learning model that reduces the number of computationally expensive three-dimensional elastic wave simulations. By embedding event detection in the structural dynamics, mechanical neural networks thus enable novel classes of always-on smart devices with no standby power consumption.Comment: 13 pages, 9 figure

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (<i>Xiphophorus helleri</i>) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

Pain in the lumbar, thoracic or cervical regions: do age and gender matter? A population-based study of 34,902 Danish twins 20–71 years of age

Background. It is unclear to what extent spinal pain varies between genders and in relation to age. It was the purpose of this study to describe the self-reported prevalence of 1) pain ever and pain in the past year in each of the three spinal regions, 2) the duration of such pain over the past year, 3) pain radiating from these areas, and 4) pain in one, two or three areas. In addition, 5) to investigate if spinal pain reporting is affected by gender and 6) to see if it increases gradually with increasing age. Method. A cross-sectional survey was conducted in 2002 on 34,902 twin individuals, aged 20 to 71 years, representative of the general Danish population. Identical questions on pain were asked for the lumbar, thoracic and cervical regions. Results. Low back pain was most common, followed by neck pain with thoracic pain being least common. Pain for at least 30 days in the past year was reported by 12%, 10%, and 4%, respectively. The one-yr prevalence estimates of radiating pain were 22% (leg), 16% (arm), and 5% (chest). Pain in one area only last year was reported by 20%, followed by two (13%) and three areas (8%). Women were always more likely to report pain and they were also more likely to have had pain for longer periods. Lumbar and cervical pain peaked somewhat around the middle years but the curves were flatter for thoracic pain. Similar patterns were noted for radiating pain. Older people did not have pain in a larger number of areas but their pain lasted longer. Conclusion. Pain reported for and from the lumbar and cervical spines was found to be relatively common whereas pain in the thoracic spine and pain radiating into the chest was much less common. Women were, generally, more likely to report pain than men. The prevalence estimates changed surprisingly little over age and were certainly not more common in the oldest groups, although the pain was reported as more long-lasting in the older group

Genome analysis and comparative genomics of a Giardia intestinalis assemblage E isolate

<p>Abstract</p> <p>Background</p> <p><it>Giardia intestinalis </it>is a protozoan parasite that causes diarrhea in a wide range of mammalian species. To further understand the genetic diversity between the <it>Giardia intestinalis </it>species, we have performed genome sequencing and analysis of a wild-type <it>Giardia intestinalis </it>sample from the assemblage E group, isolated from a pig.</p> <p>Results</p> <p>We identified 5012 protein coding genes, the majority of which are conserved compared to the previously sequenced genomes of the WB and GS strains in terms of microsynteny and sequence identity. Despite this, there is an unexpectedly large number of chromosomal rearrangements and several smaller structural changes that are present in all chromosomes. Novel members of the VSP, NEK Kinase and HCMP gene families were identified, which may reveal possible mechanisms for host specificity and new avenues for antigenic variation. We used comparative genomics of the three diverse <it>Giardia intestinalis </it>isolates P15, GS and WB to define a core proteome for this species complex and to identify lineage-specific genes. Extensive analyses of polymorphisms in the core proteome of <it>Giardia </it>revealed differential rates of divergence among cellular processes.</p> <p>Conclusions</p> <p>Our results indicate that despite a well conserved core of genes there is significant genome variation between <it>Giardia </it>isolates, both in terms of gene content, gene polymorphisms, structural chromosomal variations and surface molecule repertoires. This study improves the annotation of the <it>Giardia </it>genomes and enables the identification of functionally important variation.</p

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0