A compact low energy proton source.

A low energy proton source for non-neutral plasma experiments was developed. Electrons from a hot filament ionize H2 gas inside a geometrically compensated Penning trap to produce protons via dissociative ionization. A rotating wall electric field destabilizes the unwanted H2+ and H3+ generated in the process while concentrating protons at the center of the trap. The source produces bunches of protons with relatively low ion contamination (5.5% H2+ and 15.5% H3+), with energy tunable from 35 to 300 eV.

Aviation-Related Impacts on Ultrafine Particle Number Concentrations Outside and Inside Residences near an Airport.

Jet engine exhaust is a significant source of ultrafine particles and aviation-related emissions can adversely impact air quality over large areas surrounding airports. We investigated outdoor and indoor ultrafine particle number concentrations (PNC) from 16 residences located in two study areas in the greater Boston metropolitan area (MA, USA) for evidence of aviation-related impacts. During winds from the direction of Logan International Airport, that is, impact-sector winds, an increase in outdoor and indoor PNC was clearly evident at all seven residences in the Chelsea study area (∼4-5 km from the airport) and three out of nine residences in the Boston study area (∼5-6 km from the airport); the median increase during impact-sector winds compared to other winds was 1.7-fold for both outdoor and indoor PNC. Across all residences during impact-sector and other winds, median outdoor PNC were 19 000 and 10 000 particles/cm3, respectively, and median indoor PNC were 7000 and 4000 particles/cm3, respectively. Overall, our results indicate that aviation-related outdoor PNC infiltrate indoors and result in significantly higher indoor PNC. Our study provides compelling evidence for the impact of aviation-related emissions on residential exposures. Further investigation is warranted because these impacts are not expected to be unique to Logan airport.

The ASACUSA antihydrogen and hydrogen program: results and prospects.

The goal of the ASACUSA-CUSP collaboration at the Antiproton Decelerator of CERN is to measure the ground-state hyperfine splitting of antihydrogen using an atomic spectroscopy beamline. A milestone was achieved in 2012 through the detection of 80 antihydrogen atoms 2.7 m away from their production region. This was the first observation of 'cold' antihydrogen in a magnetic field free region. In parallel to the progress on the antihydrogen production, the spectroscopy beamline was tested with a source of hydrogen. This led to a measurement at a relative precision of 2.7×10-9 which constitutes the most precise measurement of the hydrogen hyperfine splitting in a beam. Further measurements with an upgraded hydrogen apparatus are motivated by CPT and Lorentz violation tests in the framework of the Standard Model Extension. Unlike for hydrogen, the antihydrogen experiment is complicated by the difficulty of synthesizing enough cold antiatoms in the ground state. The first antihydrogen quantum states scan at the entrance of the spectroscopy apparatus was realized in 2016 and is presented here. The prospects for a ppm measurement are also discussed.This article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.

In-beam measurement of the hydrogen hyperfine splitting and prospects for antihydrogen spectroscopy.

Antihydrogen, the lightest atom consisting purely of antimatter, is an ideal laboratory to study the CPT symmetry by comparison with hydrogen. With respect to absolute precision, transitions within the ground-state hyperfine structure (GS-HFS) are most appealing by virtue of their small energy separation. ASACUSA proposed employing a beam of cold antihydrogen atoms in a Rabi-type experiment, to determine the GS-HFS in a field-free region. Here we present a measurement of the zero-field hydrogen GS-HFS using the spectroscopy apparatus of ASACUSA's antihydrogen experiment. The measured value of νHF=1,420,405,748.4(3.4) (1.6) Hz with a relative precision of 2.7 × 10-9 constitutes the most precise determination of this quantity in a beam and verifies the developed spectroscopy methods for the antihydrogen HFS experiment to the p.p.b. level. Together with the recently presented observation of antihydrogen atoms 2.7 m downstream of the production region, the prerequisites for a measurement with antihydrogen are now available within the ASACUSA collaboration.

Speech and communication in Parkinson's disease: a cross-sectional exploratory study in the UK.

OBJECTIVE: To assess associations between cognitive status, intelligibility, acoustics and functional communication in PD. DESIGN: Cross-sectional exploratory study of functional communication, including a within-participants experimental design for listener assessment. SETTING: A major academic medical centre in the East of England, UK. PARTICIPANTS: Questionnaire data were assessed for 45 people with Parkinson's disease (PD), who had self-reported speech or communication difficulties and did not have clinical dementia. Acoustic and listener analyses were conducted on read and conversational speech for 20 people with PD and 20 familiar conversation partner controls without speech, language or cognitive difficulties. MAIN OUTCOME MEASURES: Functional communication assessed by the Communicative Participation Item Bank (CPIB) and Communicative Effectiveness Survey (CES). RESULTS: People with PD had lower intelligibility than controls for both the read (mean difference 13.7%, p=0.009) and conversational (mean difference 16.2%, p=0.04) sentences. Intensity and pause were statistically significant predictors of intelligibility in read sentences. Listeners were less accurate identifying the intended emotion in the speech of people with PD (14.8% point difference across conditions, p=0.02) and this was associated with worse speaker cognitive status (16.7% point difference, p=0.04). Cognitive status was a significant predictor of functional communication using CPIB (F=8.99, p=0.005, η2 = 0.15) but not CES. Intelligibility in conversation sentences was a statistically significant predictor of CPIB (F=4.96, p=0.04, η2 = 0.19) and CES (F=13.65, p=0.002, η2 = 0.43). Read sentence intelligibility was not a significant predictor of either outcome. CONCLUSIONS: Cognitive status was an important predictor of functional communication-the role of intelligibility was modest and limited to conversational and not read speech. Our results highlight the importance of focusing on functional communication as well as physical speech impairment in speech and language therapy (SLT) for PD. Our results could inform future trials of SLT techniques for PD.

Aviation Emissions Impact Ambient Ultrafine Particle Concentrations in the Greater Boston Area.

Ultrafine particles are emitted at high rates by jet aircraft. To determine the possible impacts of aviation activities on ambient ultrafine particle number concentrations (PNCs), we analyzed PNCs measured from 3 months to 3.67 years at three sites within 7.3 km of Logan International Airport (Boston, MA). At sites 4.0 and 7.3 km from the airport, average PNCs were 2- and 1.33-fold higher, respectively, when winds were from the direction of the airport compared to other directions, indicating that aviation impacts on PNC extend many kilometers downwind of Logan airport. Furthermore, PNCs were positively correlated with flight activity after taking meteorology, time of day and week, and traffic volume into account. Also, when winds were from the direction of the airport, PNCs increased with increasing wind speed, suggesting that buoyant aircraft exhaust plumes were the likely source. Concentrations of other pollutants [CO, black carbon (BC), NO, NO2, NOx, SO2, and fine particulate matter (PM2.5)] decreased with increasing wind speed when winds were from the direction of the airport, indicating a different dominant source (likely roadway traffic emissions). Except for oxides of nitrogen, other pollutants were not correlated with flight activity. Our findings point to the need for PNC exposure assessment studies to take aircraft emissions into consideration, particularly in populated areas near airports.

The Impact of Dietary Factors on Glycemic Control, Insulin Sensitivity and Secretion in the First Years after Diagnosis of Diabetes.

BACKGROUND: Dietary factors play an important role in the prevention of diabetes mellitus. We tested the hypothesis that dietary factors related to diabetes onset also associate with its progression, i. e., early time courses of insulin sensitivity and secretion in both type 1 and type 2 diabetes. METHODS: In a prospective observational study, well-controlled recent-onset diabetes patients (n=127) underwent detailed metabolic characterization within the first year after diagnosis. A follow-up was conducted 2 years after the first examination. Insulin secretion and sensitivity were assessed by intravenous glucose tolerance testing. Baseline food consumption was analyzed by a food propensity questionnaire. Multivariate linear regression analysis was used to assess associations between consumption frequencies at baseline with metabolic changes during the first 2 years. RESULTS: Within the first 2 years, metabolic control did not change in patients with type 1 and type 2 diabetes on average. In type 1 diabetes, an increased consumption frequency of refined grains by one time/day at baseline associated with higher HbA1c by 0.60% (95% CI: 0.04; 1.16), P=0.04 after 2 years compared to baseline. In type 2 diabetes, an increased consumption frequency of meat/meat products by one time/day at baseline associated with lower beta-cell adaptation index (-7.25% (95% CI: -13.16; -0.93), P=0.03) after adjustment for age, sex, BMI, and changes of BMI and glucose-lowering medication. CONCLUSION: Dietary factors associate with the initial course of diabetes. Reduced consumption of refined grains in type 1 diabetes and of meat products in type 2 diabetes may contribute to preservation of insulin secretion and sensitivity.

Roles of Cognitive Status and Intelligibility in Everyday Communication in People with Parkinson's Disease: A Systematic Review.

BACKGROUND: Communication is fundamental to human interaction and the development and maintenance of human relationships and is frequently affected in Parkinson's disease (PD). However, research and clinical practice have both tended to focus on impairment rather than participation aspects of communicative deficit in PD. In contrast, people with PD have reported that it is these participation aspects of communication that are of greatest concern to them rather than physical speech impairment. OBJECTIVE: To systematically review the existing body of evidence regarding the association between cognitive status and/or intelligibility and everyday communication in PD. METHODS: Five online databases were systematically searched in May 2015 (Medline Ovid, EMBASE, AMED, PsycINFO and CINAHL) and supplementary searches were also conducted. Two reviewers independently evaluated retrieved records for inclusion and then performed data extraction and quality assessment using standardised forms. Articles were eligible for inclusion if they were English-language original peer-reviewed research articles, book chapters or doctoral theses investigating the associations between at least one of cognitive status and level of intelligibility impairment and an everyday communication outcome in human participants with PD. RESULTS: 4816 unique records were identified through database searches with 16 additional records identified through supplementary searches. 41 articles were suitable for full-text screening and 15 articles (12 studies) met the eligibility criteria. 10 studies assessed the role of cognitive status and 9 found that participants with greater cognitive impairment had greater everyday communication difficulties. 4 studies assessed the role of intelligibility and all found that participants with greater intelligibility impairment had greater everyday communication difficulties, although effects were often weak and not consistent. CONCLUSIONS: Both cognitive status and intelligibility may be associated with everyday communicative outcomes in PD. The contribution of intelligibility to everyday communication appears to be of small magnitude, suggesting that other factors beyond predominantly motor-driven impairment-level changes in intelligibility may play an important role in everyday communication difficulties in PD.

Hypoxia-activated chemotherapeutic TH-302 enhances the effects of VEGF-A inhibition and radiation on sarcomas.

BACKGROUND: Human sarcomas with a poor response to vascular endothelial growth factor-A (VEGF-A) inhibition and radiation therapy (RT) have upregulation of hypoxia-inducible factor 1α (HIF-1α) and HIF-1α target genes. This study examines the addition of the hypoxia-activated chemotherapy TH-302 to VEGF-A inhibition and RT (a.k.a. trimodality therapy). METHODS: Trimodality therapy was examined in two xenograft models and in vitro in tumour endothelial cells and sarcoma cell lines. RESULTS: In both mouse models, VEGF-A inhibition and radiation showed greater efficacy than either therapy alone in slowing sarcoma growth. When TH-302 was added, this trimodality therapy completely blocked tumour growth with tumours remaining dormant for over 3 months after cessation of therapy. Trimodality therapy caused 2.6- to 6.2-fold more endothelial cell-specific apoptosis than bimodality therapies, and microvessel density and HIF-1α activity were reduced to 11-13% and 13-20% of control, respectively. When trimodality therapy was examined in vitro, increases in DNA damage and apoptosis were much more pronounced in tumour endothelial cells compared with that in sarcoma cells, especially under hypoxia. CONCLUSIONS: The combination of TH-302, VEGF-A inhibition, and RT is highly effective in preclinical models of sarcoma and is associated with increased DNA damage and apoptosis in endothelial cells and decreased HIF-1α activity.

MicroRNA-124 expression counteracts pro-survival stress responses in glioblastoma.

Glioblastomas are aggressive adult brain tumors, characterized by inadequately organized vasculature and consequent nutrient and oxygen (O2)-depleted areas. Adaptation to low nutrients and hypoxia supports glioblastoma cell survival, progression and therapeutic resistance. However, specific mechanisms promoting cellular survival under nutrient and O2 deprivation remain incompletely understood. Here, we show that miR-124 expression is negatively correlated with a hypoxic gene signature in glioblastoma patient samples, suggesting that low miR-124 levels contribute to pro-survival adaptive pathways in this disease. As miR-124 expression is repressed in various cancer types (including glioblastoma), we quantified miR-124 abundance in normoxic and hypoxic regions in glioblastoma patient tissue, and investigated whether ectopic miR-124 expression compromises cell survival during tumor ischemia. Our results indicate that miR-124 levels are further diminished in hypoxic/ischemic regions within individual glioblastoma patient samples, compared with regions replete in O2 and nutrients. Importantly, we also show that increased miR-124 expression affects the ability of tumor cells to survive under O2 and/or nutrient deprivation. Moreover, miR-124 re-expression increases cell death in vivo and enhances the survival of mice bearing intracranial xenograft tumors. miR-124 exerts this phenotype in part by directly regulating TEAD1, MAPK14/p38α and SERP1, factors involved in cell proliferation and survival under stress. Simultaneous suppression of these miR-124 targets results in similar levels of cell death as caused by miR-124 restoration. Importantly, we further demonstrate that SERP1 reintroduction reverses the hypoxic cell death elicited by miR-124, indicating the importance of SERP1 in promoting tumor cell survival. In support of our experimental data, we observed a significant correlation between high SERP1 levels and poor patient outcome in glioblastoma patients. Collectively, among the many pro-tumorigeneic properties of miR-124 repression in glioblastoma, we delineated a novel role in promoting tumor cell survival under stressful microenvironments, thereby supporting tumor progression.

In-trap spectroscopy of charge-bred radioactive ions.

In this Letter, we introduce the concept of in-trap nuclear decay spectroscopy of highly charged radioactive ions and describe its successful application as a novel spectroscopic tool. This is demonstrated by a measurement of the decay properties of radioactive mass A=124 ions (here, ^{124}In and ^{124}Cs) in the electron-beam ion trap of the TITAN facility at TRIUMF. By subjecting the trapped ions to an intense electron beam, the ions are charge bred to high charge states (i.e., equivalent to the removal of N-shell electrons), and an increase of storage times to the level of minutes without significant ion losses is achieved. The present technique opens the venue for precision spectroscopy of low branching ratios and is being developed in the context of measuring electron-capture branching ratios needed for determining the nuclear ground-state properties of the intermediate odd-odd nuclei in double-beta (ßß) decay.

Fatty acids modulate cytokine and chemokine secretion of stimulated human whole blood cultures in diabetes.

Fatty acids, uric acid and glucose are thought to contribute to subclinical inflammation associated with diabetes mellitus. We tested whether co-incubation of free fatty acids and uric acid or glucose influences the secretion of immune mediators from stimulated human whole blood in vitro. Fresh whole blood samples from 20 healthy subjects, 20 patients with type 1 diabetes and 23 patients with type 2 diabetes were incubated for 24 h with palmitic acid (PAL), linolenic acid (LIN) or eicosapentaenoic acid (EPA) alone or together with elevated concentrations of uric acid or glucose. Concentrations of proinflammatory cytokines interleukin (IL)-1ß, IL-2, IL-12(p70), IL-18, IFN-γ, of regulatory cytokines IL-4, IL-10, IL-17 and chemokine CCL2 (MCP-1) were measured by multiplex-bead technology from supernatants. Co-incubation of fatty acids with uric acid resulted in a significant reduction of IL-10, IL-12(p70), IFN-γ and CCL2 (MCP-1) concentrations in supernatants compared to incubation with uric acid alone (P < 0·0001). In contrast, IL-18 was up-regulated upon co-stimulation with fatty acids and uric acid. Similarly, co-incubation of fatty acids with glucose diminished secretion of IL-10, IFN-γ and CCL2 (monocyte chemotactic protein-1), while IL-8 was up-regulated (P < 0·001). Samples from healthy and diabetic subjects did not differ after adjustment for age, sex, body mass index and diabetes type. All three fatty acids similarly influenced whole blood cytokine release in vitro and modulated uric acid or glucose-stimulated cytokine secretion. Although the ω-3-fatty acid EPA showed slightly stronger effects, further studies are required to elaborate the differential effects of PAL, LIN and EPA on disease risk observed previously in epidemiological studies.

An unexpectedly low oscillator strength as the origin of the Fe XVII emission problem.

Highly charged iron (Fe(16+), here referred to as Fe XVII) produces some of the brightest X-ray emission lines from hot astrophysical objects, including galaxy clusters and stellar coronae, and it dominates the emission of the Sun at wavelengths near 15 ångströms. The Fe XVII spectrum is, however, poorly fitted by even the best astrophysical models. A particular problem has been that the intensity of the strongest Fe XVII line is generally weaker than predicted. This has affected the interpretation of observations by the Chandra and XMM-Newton orbiting X-ray missions, fuelling a continuing controversy over whether this discrepancy is caused by incomplete modelling of the plasma environment in these objects or by shortcomings in the treatment of the underlying atomic physics. Here we report the results of an experiment in which a target of iron ions was induced to fluoresce by subjecting it to femtosecond X-ray pulses from a free-electron laser; our aim was to isolate a key aspect of the quantum mechanical description of the line emission. Surprisingly, we find a relative oscillator strength that is unexpectedly low, differing by 3.6σ from the best quantum mechanical calculations. Our measurements suggest that the poor agreement is rooted in the quality of the underlying atomic wavefunctions rather than in insufficient modelling of collisional processes.

New precision mass measurements of neutron-rich calcium and potassium isotopes and three-nucleon forces.

We present precision Penning trap mass measurements of neutron-rich calcium and potassium isotopes in the vicinity of neutron number N=32. Using the TITAN system, the mass of 51K was measured for the first time, and the precision of the (51,52)Ca mass values were improved significantly. The new mass values show a dramatic increase of the binding energy compared to those reported in the atomic mass evaluation. In particular, 52Ca is more bound by 1.74 MeV, and the behavior with neutron number deviates substantially from the tabulated values. An increased binding was predicted recently based on calculations that include three-nucleon (3N) forces. We present a comparison to improved calculations, which agree remarkably with the evolution of masses with neutron number, making neutron-rich calcium isotopes an exciting region to probe 3N forces.

The on-line charge breeding program at TRIUMF's Ion Trap For Atomic and Nuclear Science for precision mass measurements.

TRIUMF's Ion Trap for Atomic and Nuclear science (TITAN) constitutes the only high precision mass measurement setup coupled to a rare isotope facility capable of increasing the charge state of short-lived nuclides prior to the actual mass determination in a Penning trap. Recent developments around TITAN's charge breeder, the electron beam ion trap, form the basis for several successful experiments on radioactive isotopes with half-lives as low as 65 ms and in charge states as high as 22+.

Loss of the Birt-Hogg-Dubé tumor suppressor results in apoptotic resistance due to aberrant TGFß-mediated transcription.

Birt-Hogg-Dubé (BHD) syndrome is an inherited cancer susceptibility disease characterized by skin and kidney tumors, as well as cystic lung disease, which results from loss-of-function mutations in the BHD gene. BHD is also inactivated in a significant fraction of patients with sporadic renal cancers and idiopathic cystic lung disease, and little is known about its mode of action. To investigate the molecular and cellular basis of BHD tumor suppressor activity, we generated mutant Bhd mice and embryonic stem cell lines. BHD-deficient cells exhibited defects in cell-intrinsic apoptosis that correlated with reduced expression of the BH3-only protein Bim, which was similarly observed in all human and murine BHD-related tumors examined. We further demonstrate that Bim deficiency in Bhd(-/-) cells is not a consequence of elevated mTOR or ERK activity, but results instead from reduced Bim transcription associated with a general loss of TGFß-mediated transcription and chromatin modifications. In aggregate, this work identifies a specific tumor suppressive mechanism for BHD in regulating TGFß-dependent transcription and apoptosis, which has implications for the development of targeted therapies.

First use of high charge states for mass measurements of short-lived nuclides in a Penning trap.

Penning trap mass measurements of short-lived nuclides have been performed for the first time with highly charged ions, using the TITAN facility at TRIUMF. Compared to singly charged ions, this provides an improvement in experimental precision that scales with the charge state q. Neutron-deficient Rb isotopes have been charge bred in an electron beam ion trap to q=8-12+ prior to injection into the Penning trap. In combination with the Ramsey excitation scheme, this unique setup creating low energy, highly charged ions at a radioactive beam facility opens the door to unrivaled precision with gains of 1-2 orders of magnitude. The method is particularly suited for short-lived nuclides such as the superallowed ß emitter 74Rb (T(1/2)=65 ms). The determination of its atomic mass and an improved Q(EC) value are presented.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adults: a qualitative study of perspectives from professional practice.

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) can cause profound and prolonged illness and disability, and poses significant problems of uncertainty for healthcare professionals in its diagnosis and management. The aim of this qualitative study was to explore the nature of professional 'best practice' in working with people with CFS/ME. METHODS: The views and experiences of health care practitioners (HCPs) were sought, who had been judged by people with CFS/ME themselves to have been particularly helpful and effective. Qualitative semi-structured interviews following a topic guide were carried out with six health care practitioners. Interviews were audio-recorded, transcribed and subject to thematic analysis. RESULTS: Five main themes were developed: 1) Diagnosis; 2) Professional perspectives on living with CFS/ME; 3) Interventions for treatment and management; 4) Professional values and support for people with CFS/ME and their families; 5) Health professional roles and working practices. Key findings related to: the diagnostic process, especially the degree of uncertainty which may be shared by primary care physicians and patients alike; the continued denial in some quarters of the existence of CFS/ME as a condition; the variability, complexity, and serious impact of the condition on life and living; the onus on the person with CFS/ME to manage their condition, supported by HCPs; the wealth of often conflicting and confusing information on the condition and options for treatment; and the vital role of extended listening and trustful relationships with patients. CONCLUSIONS: While professional frustrations were clearly expressed about the variability of services both in primary and specialist care and continuing equivocal attitudes to CFS/ME as a condition, there were also strong positive messages for people with CFS/ME where the right services are in place. Many of the findings from these practitioners seen by their patients as helping them more effectively, accord with the existing literature identifying the particular importance of listening skills, respect and trust for establishing a therapeutic relationship which recognises key features of the patient trajectory and promotes effective person-centred management of this complex condition. These findings indicate the need to build such skills and knowledge more systematically into professional training informed by the experience of specialist services and those living with the condition.

Resonant and near-threshold photoionization cross sections of Fe14+.

Photoionization (PI) of Fe14+ in the range from 450 to 1100 eV was measured at the BESSY II storage ring using an electron beam ion trap achieving high target-ion area densities of 10(10) cm(-2). Photoabsorption by this ion is observed in astrophysical spectra and plasmas, but until now cross sections and resonance energies could only be provided by calculations. We reach a resolving power E/ΔE of at least 6500, outstanding in the present energy range, which enables benchmarking and improving the most advanced theories for PI of ions in high charge states.