Cooperative Jahn-Teller Distortion in PrO2

We report neutron diffraction data on single crystal PrO2 which reveal a cooperative Jahn-Teller distortion at TD = 120 +/- 2 K. Below this temperature an internal distortion of the oxygen sublattice causes the unit cell of the crystallographic structure to become doubled along one crystal axis. We discuss several possible models for this structure. The antiferromagnetic structure below TN = 13.5 K is found to consist of two components, one of which shares the same doubled unit cell as the distorted crystallographic structure. We also present measurements of the magnetic susceptibility, the specific heat capacity and the electrical conductivity of PrO2. The susceptibility data show an anomaly at a temperature close to TD. From the specific heat capacity data we deduce that the ground state is doubly degenerate, consistent with a distortion of the cubic local symmetry. We discuss possible mechanisms for this. The conductivity shows an activated behaviour with an activation energy Ea = 0.262 +/- 0.003 eV.Comment: 12 pages, 14 figures, 2 tables. Additional suggested structure in v

Experimental Investigation of the Nature of the Knee in the Primary Cosmic Ray Energy Spectrum with the GAMMA experiment

We present preliminary results obtained by a novel difference method for the study of the nature of the knee in the energy spectrum of the primary cosmic radiation. We have applied this method to data from the GAMMA experiment in Armenia. The analysis provides evidence for the possible existence of a nearby source of primary cosmic rays in the Southern hemisphere.Comment: 17 pages, 5 figure

Behavioural interventions for primary and secondary dysmenorrhoea

Background: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition with considerable morbidity. The behavioural approach assumes that psychological and environmental factors interact with, and influence, physiological processes. Behavioural interventions for dysmenorrhoea may include both physical and cognitive procedures and focus on both physical and psychological coping strategies for dysmenorrhoeic symptoms rather than modification of any underlying organic pathology. Objectives: To determine the effectiveness of any behavioural interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or conventional medical treatments for example non-steroidal anti-inflammatory drugs (NSAIDs). Search strategy: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2005), Cochrane Central Register of Controlled Trials (CENTRAL on The Cochrane Library, Issue 2, 2005), MEDLINE (1966 to April 2005), EMBASE (1980 to April 2005), Social Sciences Index (1980 to April 2005), PsycINFO (1972 to April 2005) and CINAHL (1982 to April 2005) and reference lists of articles. Selection criteria: Randomised controlled trials comparing behavioural interventions with placebo or other interventions in women with dysmenorrhoea. Data collection and analysis: Two authors independently assessed trial quality and extracted data. Main results: Five trials involving 213 women were included. Behavioural intervention vs control: One trial of pain management training reported reduction in pain and symptoms compared to a control. Three trials of relaxation compared to control reported varied results, two trials showed no difference in symptom severity scores however one trial reported relaxation was effective for reducing symptoms in menstrual sufferers with spasmodic symptoms. Two trials reported less restriction in daily activities following treatment with either relaxation of pain management training compared to a control. One trial also reported less time absent from school following treatment wit pain management training compared to a control. Behavioural intervention vs other behavioural interventions: Three trials showed no difference between behavioural interventions for the outcome of improvement in symptoms. One trial showed that relaxation resulted in a decrease in the need for resting time compared to the relaxation and imagery. Authors' conclusions: There is some evidence from five RCTs that behavioural interventions may be effective for dysmenorrhoea however results should be viewed with caution as they varied greatly between trials due to inconsistency in the reporting of data, small trial size, poormethodological quality and age of the trials

Ab initio calculations of the hydrogen bond

Recent x-ray Compton scattering experiments in ice have provided useful information about the quantum nature of the interaction between H$_2$O monomers. The hydrogen bond is characterized by a certain amount of charge transfer which could be determined in a Compton experiment. We use ab-initio simulations to investigate the hydrogen bond in H$_2$O structures by calculating the Compton profile and related quantities in three different systems, namely the water dimer, a cluster containing 12 water molecules and the ice crystal. We show how to extract estimates of the charge transfer from the Compton profiles.Comment: 16 pages, 7 figures, to appear in Phys. Rev.

An immunotherapy survivor population: health-related quality of life and toxicity in patients with metastatic melanoma treated with immune checkpoint inhibitors

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Purpose The immune checkpoint inhibitors (ICIs) have resulted in subgroups of patients with metastatic melanoma achievinghigh-quality durable responses. Metastatic melanoma survivors are a new population in the era of cancer survivorship. The aimofthis study was to evaluate metastatic melanoma survivors in terms of health-related quality of life (HRQoL), immune-relatedadverse events (irAEs) and exposure to immunosuppressive agents in a large single centre in the UK.Methods We defined the survivor population as patients with a diagnosis of metastatic melanoma who achieved a durableresponse to an ICI and had been followed-up for a minimum of 12 months from initiation of ICI without disease progression.HRQoL was assessed using SF-36. Electronic health records were accessed to collect data on demographics, treatments, irAEsand survival. HRQoL data was compared with two norm-based datasets.Results Eighty-four metastatic melanoma survivors were eligible and 87% (N = 73) completed the SF-36. ICI-related toxicity ofany grade occurred in 92%of patients and 43%had experienced a grade 3 or 4 toxicity. Almost half (49%) of the patients requiredsteroids for the treatment of ICI-related toxicity, whilst 14% required treatment with an immunosuppressive agent beyondsteroids.Melanoma survivors had statistically significant lower HRQoL scores with regard to physical, social and physical rolefunctioning and general health compared with the normative population. There was a trend towards inferior scores in patientswith previous exposure to ipilimumab compared with those never exposed to ipilimumab.Conclusions Our results show that metastatic melanoma survivors have potentially experienced significant ICI-related toxicityand experience significant impairments in specific HRQoL domains. Future service planning is required to meet this population’sunique survivorship needs.Peer reviewe

Search for EAS radio-emission at the Tien-Shan shower installation at a height of 3340 m above sea level

The complex EAS installation of the Tien Shan mountain cosmic ray station which is situated at a height of 3340 m above sea level includes the scintillation and Cherenkov detectors of charged shower particles, an ionization calorimeter and a set of neutron detectors for registering the hadronic component of the shower, and a number of underground detectors of the penetrative EAS component. Now it is intended to expand this installation with a promising method for detecting the radio-emission generated by the particles of the developing shower. The facility for radio-emission detection consists of a three crossed dipole antennae, one being set vertically, and another two – mutually perpendicularly in a horizontal plane, all of them being connected to a three-channel radio-frequency amplifier of German production. By the passage of an extensive air shower, which is defined by a scintillation shower detector system, the output signal of antenna amplifier is digitized by a fast multichannel DT5720 ADC of Italian production, and kept within computer memory. The further analysis of the detected signal anticipates its operation according to a special algorithm and a search for the pulse of radio-emission from the shower. A functional test of the radio-installation is made with artificial signals which imitate those of the shower, and with the use of a N1996A type wave analyzer of Agilent Technologies production. We present preliminary results on the registration of extensive air shower emission at the Tien Shan installation which were collected during test measurements held in Summer 2016

Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model

BACKGROUND: Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. METHODOLOGY/PRINCIPLE FINDINGS: EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). CONCLUSIONS/SIGNIFICANCE: Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of EGFR-targeted, doxorubicin-loaded minicells for effective treatment of human patients with recurrent glioblastoma

Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice.

Oxidized phospholipids (OxPL) are ubiquitous, are formed in many inflammatory tissues, including atherosclerotic lesions, and frequently mediate proinflammatory changes 1 . Because OxPL are mostly the products of non-enzymatic lipid peroxidation, mechanisms to specifically neutralize them are unavailable and their roles in vivo are largely unknown. We previously cloned the IgM natural antibody E06, which binds to the phosphocholine headgroup of OxPL, and blocks the uptake of oxidized low-density lipoprotein (OxLDL) by macrophages and inhibits the proinflammatory properties of OxPL2-4. Here, to determine the role of OxPL in vivo in the context of atherogenesis, we generated transgenic mice in the Ldlr-/- background that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter. E06-scFv was secreted into the plasma from the liver and macrophages, and achieved sufficient plasma levels to inhibit in vivo macrophage uptake of OxLDL and to prevent OxPL-induced inflammatory signalling. Compared to Ldlr-/- mice, Ldlr -/- E06-scFv mice had 57-28% less atherosclerosis after 4, 7 and even 12 months of 1% high-cholesterol diet. Echocardiographic and histologic evaluation of the aortic valves demonstrated that E06-scFv ameliorated the development of aortic valve gradients and decreased aortic valve calcification. Both cholesterol accumulation and in vivo uptake of OxLDL were decreased in peritoneal macrophages, and both peritoneal and aortic macrophages had a decreased inflammatory phenotype. Serum amyloid A was decreased by 32%, indicating decreased systemic inflammation, and hepatic steatosis and inflammation were also decreased. Finally, the E06-scFv prolonged life as measured over 15 months. Because the E06-scFv lacks the functional effects of an intact antibody other than the ability to bind OxPL and inhibit OxLDL uptake in macrophages, these data support a major proatherogenic role of OxLDL and demonstrate that OxPL are proinflammatory and proatherogenic, which E06 counteracts in vivo. These studies suggest that therapies inactivating OxPL may be beneficial for reducing generalized inflammation, including the progression of atherosclerosis, aortic stenosis and hepatic steatosis

Latest results of the Tunka Radio Extension (ISVHECRI2016)

The Tunka Radio Extension (Tunka-Rex) is an antenna array consisting of 63 antennas at the location of the TAIGA facility (Tunka Advanced Instrument for cosmic ray physics and Gamma Astronomy) in Eastern Siberia, nearby Lake Baikal. Tunka-Rex is triggered by the air-Cherenkov array Tunka-133 during clear and moonless winter nights and by the scintillator array Tunka-Grande during the remaining time. Tunka-Rex measures the radio emission from the same air-showers as Tunka-133 and Tunka-Grande, but with a higher threshold of about 100 PeV. During the first stages of its operation, Tunka-Rex has proven, that sparse radio arrays can measure air-showers with an energy resolution of better than 15\% and the depth of the shower maximum with a resolution of better than 40 g/cm\textsuperscript{2}. To improve and interpret our measurements as well as to study systematic uncertainties due to interaction models, we perform radio simulations with CORSIKA and CoREAS. In this overview we present the setup of Tunka-Rex, discuss the achieved results and the prospects of mass-composition studies with radio arrays.Comment: proceedings of ISVHECRI2016 conferenc

Banana root and soil health project - Australia

The banana plant forms an adventitious root system that is dependent on soil physical, chemical and biological properties to function efficiently. A pot experiment demonstrated that increasing soil compaction was able to significantly reduce the weight of banana roots and shoots. However, in the presence of Radopholus similis the effects of soil compaction were obscured, due to the significant reduction in root weight caused by the nematode. The use of a basic set of soil quality indicators that can be readily used by farmers, was linked to soil nematode indicators to determine relationships between soil properties. In a survey of banana fields in North Queensland, different diameter root classes were affected differently by changing soil properties. Banana roots greater than 5 mm diameter were positively correlated with aggregate stability and negatively correlated with soil bulk density. Banana roots less than 1 mm were positively correlated with electrical conductivity. Specific interactions between soil properties become apparent as crop production systems become more uniform. This allows farmers to prioritise management options to improve the most deficient soil health indicators. The addition of organic amendments is one possible method of correcting degrading soils. The use of amendments with high carbon contents, such as grass hay, banana trash and lucerne hay, were able to significantly suppress R. similis in the roots of banana plants relative to untreated soil. Due to banana production being located near environmentally sensitive areas there is an increasing need to monitor and modify soil management practices. However, this needs to be linked with a framework that allows the integration of all soil components with a system to allow continual improvement in soil management to allow banana production to have minimal impact on the surrounding environment