The Electric and Magnetic Fields Instrument Suite and Integrated Science (EMFISIS): Science, Data, and Usage Best Practices.

We provide a post-mission assessment of the science and data from the Electric and Magnetic Field Instrument Suite and Integrated Science (EMFISIS) investigation on the NASA Van Allen Probes mission. An overview of important scientific results is presented, covering all of the key wave modes and DC magnetic fields measured by EMFISIS. Discussion of the data products, which are publicly available, follows to provide users with guidance on characteristics and known issues of the measurements. We present guidance on the correct use of derived products, in particular, the wave-normal analysis (WNA) which yields fundamental wave properties such as polarization, ellipticity, and Poynting flux. We also give information about the plasma density derived from measuring the upper hybrid line in the inner magnetosphere.

The Angular Distribution of Lower Band Chorus Waves Near Plasmaspheric Plumes.

Plumes have been identified as an access region for chorus waves to enter the plasmasphere. Here, for the first time, chorus wave properties are parameterized by distance from the plume boundary. Case studies and statistical analysis indicate that the polar wave vector angle, θ k , of chorus becomes more oblique near the plume edge. Occurrence rates of θ k > 35° on the plume boundary are approximately double that observed further away from the plume. Whilst the increase in θ k is apparent on both plume edges, the distribution of θ k exhibits different behavior between the Eastward and Westward boundaries. In general, the distribution of azimuthal wave vector angles, ϕ k , is symmetric about the anti-Earthwards direction. However, near the Eastward plume boundary, an Eastwards skew of ϕ k is reported. This result provides new insight on chorus propagation in the context of the chorus-to-hiss mechanism, and has implications for quantifying wave-particle interactions in the near-plume region.

Use of a novel drape 'tent' as an infection prevention control measure for mastoid surgery.

BACKGROUND: Mastoid surgery is an aerosol-generating procedure that involves the use of a high-speed drill, which produces a mixture of water, bone, blood and tissue that may contain the viable coronavirus disease 2019 pathogen. This potentially puts the surgeon and other operating theatre personnel at risk of acquiring the severe acute respiratory syndrome coronavirus-2 from contact with droplets or aerosols. The use of an additional drape designed to limit the spread of droplets and aerosols has been described; such drapes include the 'Southampton Tent' and 'OtoTent'. OBJECTIVES: To evaluate the use of a novel drape 'tent' that has advantages over established 'tent' designs in terms of having: (1) a CE marking; (2) no requirement for modification during assembly; and (3) no obstruction to the surgical visual field. RESULTS AND CONCLUSION: During mastoid surgery, the dispersion of macroscopic droplets and other particulate matter was confined within the novel drape 'tent'. Use of this drape 'tent' had no adverse effects upon the surgeon's manual dexterity or efficiency, the view of the surgical field, or the sterility. Hence, our findings support its use during mastoid surgery in the coronavirus disease 2019 era.

Discovery of ONO-8590580: A novel, potent and selective GABAA α5 negative allosteric modulator for the treatment of cognitive disorders.

The identification and SAR development of a series of negative allosteric modulators of the GABAA α5 receptor is described. This novel series of compounds was optimised to provide analogues with high GABAA α5 binding affinity, high α5 negative allosteric modulatory activity, good functional subtype selectivity and low microsomal turnover, culminating in identification of ONO-8590580.

Longitudinal Wobbling Motion in

The rare phenomenon of nuclear wobbling motion has been investigated in the nucleus ^{187}Au. A longitudinal wobbling-bands pair has been identified and clearly distinguished from the associated signature-partner band on the basis of angular distribution measurements. Theoretical calculations in the framework of the particle rotor model are found to agree well with the experimental observations. This is the first experimental evidence for longitudinal wobbling bands where the expected signature partner band has also been identified, and establishes this exotic collective mode as a general phenomenon over the nuclear chart.

Evidence for Rigid Triaxial Deformation in

An extensive, model-independent analysis of the nature of triaxial deformation in ^{76}Ge, a candidate for neutrinoless double-beta (0νßß) decay, was carried out following multistep Coulomb excitation. Shape parameters deduced on the basis of a rotational-invariant sum-rule analysis provided considerable insight into the underlying collectivity of the ground-state and γ bands. Both sequences were determined to be characterized by the same ß and γ deformation parameter values. In addition, compelling evidence for low-spin, rigid triaxial deformation in ^{76}Ge was obtained for the first time from the analysis of the statistical fluctuations of the quadrupole asymmetry deduced from the measured E2 matrix elements. These newly determined shape parameters are important input and constraints for calculations aimed at providing, with suitable accuracy, the nuclear matrix elements relevant to 0νßß.

DNA based diagnostic for the quantification of sugarcane root DNA in the field.

Plant root systems play many key roles including nutrient and water uptake, interface with soil microorganisms and resistance to lodging. As for other crops, large and systematic studies of sugarcane root systems have always been hampered by the opaque and solid nature of the soil. In recent years, methods for efficient extraction of DNA from soil and for species-specific DNA amplification have been developed. Such tools could have potential to greatly improve root phenotyping and health diagnostic capability in sugarcane. In this paper, we present a fast, specific and efficient method for the quantification of sugarcane live root cells in soil samples. Previous studies were typically based on mass and length, so we established a calibration to convert root DNA quantity to live root mass. This diagnostic was validated on field samples and used to investigate the fate of the root system after harvest prior to regrowth of the ratoon crop. Two weeks after harvest, the sugarcane roots from the previous crop were still viable. This raises the question of the role that the root system of the harvested crop plays in the performance of the next crop and demonstrates how this test can be used to answer research questions.

Selective RET kinase inhibition for patients with RET-altered cancers.

Background: Alterations involving the RET kinase are implicated in the pathogenesis of lung, thyroid and other cancers. However, the clinical activity of multikinase inhibitors (MKIs) with anti-RET activity in RET-altered patients appears limited, calling into question the therapeutic potential of targeting RET. LOXO-292 is a selective RET inhibitor designed to inhibit diverse RET fusions, activating mutations and acquired resistance mutations. Patients and methods: Potent anti-RET activity, high selectivity, and central nervous system coverage were confirmed preclinically using a variety of in vitro and in vivo RET-dependent tumor models. Due to clinical urgency, two patients with RET-altered, MKI-resistant cancers were treated with LOXO-292, utilizing rapid dose-titration guided by real-time pharmacokinetic assessments to achieve meaningful clinical exposures safely and rapidly. Results: LOXO-292 demonstrated potent and selective anti-RET activity preclinically against human cancer cell lines harboring endogenous RET gene alterations; cells engineered to express a KIF5B-RET fusion protein -/+ the RET V804M gatekeeper resistance mutation or the common RET activating mutation M918T; and RET-altered human cancer cell line and patient-derived xenografts, including a patient-derived RET fusion-positive xenograft injected orthotopically into the brain. A patient with RET M918T-mutant medullary thyroid cancer metastatic to the liver and an acquired RET V804M gatekeeper resistance mutation, previously treated with six MKI regimens, experienced rapid reductions in tumor calcitonin, CEA and cell-free DNA, resolution of painful hepatomegaly and tumor-related diarrhea and a confirmed tumor response. A second patient with KIF5B-RET fusion-positive lung cancer, acquired resistance to alectinib and symptomatic brain metastases experienced a dramatic response in the brain, and her symptoms resolved. Conclusions: These results provide proof-of-concept of the clinical actionability of RET alterations, and identify selective RET inhibition by LOXO-292 as a promising treatment in heavily pretreated, multikinase inhibitor-experienced patients with diverse RET-altered tumors.

Masses and ß-Decay Spectroscopy of Neutron-Rich Odd-Odd

The structure of deformed neutron-rich nuclei in the rare-earth region is of significant interest for both the astrophysics and nuclear structure fields. At present, a complete explanation for the observed peak in the elemental abundances at A∼160 eludes astrophysicists, and models depend on accurate quantities, such as masses, lifetimes, and branching ratios of deformed neutron-rich nuclei in this region. Unusual nuclear structure effects are also observed, such as the unexpectedly low energies of the first 2^{+} levels in some even-even nuclei at N=98. In order to address these issues, mass and ß-decay spectroscopy measurements of the ^{160}Eu_{97} and ^{162}Eu_{99} nuclei were performed at the Californium Rare Isotope Breeder Upgrade radioactive beam facility at Argonne National Laboratory. Evidence for a gap in the single-particle neutron energies at N=98 and for large deformation (ß_{2}∼0.3) is discussed in relation to the unusual phenomena observed at this neutron number.

Isomer depletion as experimental evidence of nuclear excitation by electron capture.

The atomic nucleus and its electrons are often thought of as independent systems that are held together in the atom by their mutual attraction. Their interaction, however, leads to other important effects, such as providing an additional decay mode for excited nuclear states, whereby the nucleus releases energy by ejecting an atomic electron instead of by emitting a γ-ray. This 'internal conversion' has been known for about a hundred years and can be used to study nuclei and their interaction with their electrons. In the inverse process-nuclear excitation by electron capture (NEEC)-a free electron is captured into an atomic vacancy and can excite the nucleus to a higher-energy state, provided that the kinetic energy of the free electron plus the magnitude of its binding energy once captured matches the nuclear energy difference between the two states. NEEC was predicted in 1976 and has not hitherto been observed. Here we report evidence of NEEC in molybdenum-93 and determine the probability and cross-section for the process in a beam-based experimental scenario. Our results provide a standard for the assessment of theoretical models relevant to NEEC, which predict cross-sections that span many orders of magnitude. The greatest practical effect of the NEEC process may be on the survival of nuclei in stellar environments, in which it could excite isomers (that is, long-lived nuclear states) to shorter-lived states. Such excitations may reduce the abundance of the isotope after its production. This is an example of 'isomer depletion', which has been investigated previously through other reactions, but is used here to obtain evidence for NEEC.

Decay and Fission Hindrance of Two- and Four-Quasiparticle K Isomers in

Two isomers decaying by electromagnetic transitions with half-lives of 4.7(1.1) and 247(73) µs have been discovered in the heavy ^{254}Rf nucleus. The observation of the shorter-lived isomer was made possible by a novel application of a digital data acquisition system. The isomers were interpreted as the K^{π}=8^{-}, ν^{2}(7/2^{+}[624],9/2^{-}[734]) two-quasineutron and the K^{π}=16^{+}, 8^{-}ν^{2}(7/2^{+}[624],9/2^{-}[734])⊗8^{-}π^{2}(7/2^{-}[514],9/2^{+}[624]) four-quasiparticle configurations, respectively. Surprisingly, the lifetime of the two-quasiparticle isomer is more than 4 orders of magnitude shorter than what has been observed for analogous isomers in the lighter N=150 isotones. The four-quasiparticle isomer is longer lived than the ^{254}Rf ground state that decays exclusively by spontaneous fission with a half-life of 23.2(1.1) µs. The absence of sizable fission branches from either of the isomers implies unprecedented fission hindrance relative to the ground state.

Applying the cold plasma dispersion relation to whistler mode chorus waves: EMFISIS wave measurements from the Van Allen Probes.

Most theoretical wave models require the power in the wave magnetic field in order to determine the effect of chorus waves on radiation belt electrons. However, researchers typically use the cold plasma dispersion relation to approximate the magnetic wave power when only electric field data are available. In this study, the validity of using the cold plasma dispersion relation in this context is tested using Electric and Magnetic Field Instrument Suite and Integrated Science (EMFISIS) observations of both the electric and magnetic spectral intensities in the chorus wave band (0.1-0.9 fce). Results from this study indicate that the calculated wave intensity is least accurate during periods of enhanced wave activity. For observed wave intensities >10-3 nT2, using the cold plasma dispersion relation results in an underestimate of the wave intensity by a factor of 2 or greater 56% of the time over the full chorus wave band, 60% of the time for lower band chorus, and 59% of the time for upper band chorus. Hence, during active periods, empirical chorus wave models that are reliant on the cold plasma dispersion relation will underestimate chorus wave intensities to a significant degree, thus causing questionable calculation of wave-particle resonance effects on MeV electrons.

Transverse wobbling in

A pair of transverse wobbling bands is observed in the nucleus ^{135}Pr. The wobbling is characterized by ΔI=1, E2 transitions between the bands, and a decrease in the wobbling energy confirms its transverse nature. Additionally, a transition from transverse wobbling to a three-quasiparticle band comprised of strong magnetic dipole transitions is observed. These observations conform well to results from calculations with the tilted axis cranking model and the quasiparticle rotor model.

An overview of internet biosurveillance.

Internet biosurveillance utilizes unstructured data from diverse web-based sources to provide early warning and situational awareness of public health threats. The scope of source coverage ranges from local media in the vernacular to international media in widely read languages. Internet biosurveillance is a timely modality that is available to government and public health officials, healthcare workers, and the public and private sector, serving as a real-time complementary approach to traditional indicator-based public health disease surveillance methods. Internet biosurveillance also supports the broader activity of epidemic intelligence. This overview covers the current state of the field of Internet biosurveillance, and provides a perspective on the future of the field.

Event-based biosurveillance of respiratory disease in Mexico, 2007-2009: connection to the 2009 influenza A(H1N1) pandemic?

The emergence of the 2009 pandemic influenza A(H1N1) virus in North America and its subsequent global spread highlights the public health need for early warning of infectious disease outbreaks. Event-based biosurveillance, based on local- and regional-level Internet media reports, is one approach to early warning as well as to situational awareness. This study analyses media reports in Mexico collected by the Argus biosurveillance system between 1 October 2007 and 31 May 2009. Results from Mexico are compared with the United States and Canadian media reports obtained from the HealthMap system. A significant increase in reporting frequency of respiratory disease in Mexico during the 2008-9 influenza season relative to that of 2007-8 was observed (p<0.0001). The timing of events, based on media reports, suggests that respiratory disease was prevalent in parts of Mexico, and was reported as unusual, much earlier than the microbiological identification of the pandemic virus. Such observations suggest that abnormal respiratory disease frequency and severity was occurring in Mexico throughout the winter of 2008-2009, though its connection to the emergence of the 2009 pandemic influenza A(H1N1) virus remains unclear.

A new species of Phoma causes ascochyta blight symptoms on field peas (Pisum sativum) in South Australia.

Phoma koolunga sp. nov. is described, having been isolated from ascochyta blight lesions on field pea (Pisum sativum) in South Australia. The species is described morphologically and sequences of the internal transcribed spacer region compared with those of the accepted pathogens causing ascochyta blight of field peas. P. koolunga was distinct from Mycosphaerella pinodes (anamorph: Ascochyta pinodes), Phoma medicaginis var. pinodella and Ascochyta pisi. Under controlled conditions the symptoms on pea seedlings caused by P. koolunga were indistinguishable from those caused by M. pinodes, other than a 24 h delay in disease development. Isolates of P. koolunga differed in the severity of disease caused on pea seedlings.

Myocardial infarction and heart failure hospitalization rates in Maine, USA - variability along the urban-rural continuum.

INTRODUCTION: Cardiovascular disease, including myocardial infarction (MI) and heart failure (HF), remains the leading cause of death in wealthy countries and is of increasing concern in low- and middle-income countries as risk factors such as smoking and obesity become more common around the globe. Within each country the health burden of MI and HF generally falls more heavily on those who live in rural areas and on those who live in communities with lower average socioeconomic status (SES). Hospitalization rates are an important measure of community health because high rates may indicate a high burden of poor health, while inappropriately low rates (low hospitalization rates absent evidence of average good health) may indicate underutilization of health services. The objective of this study was to determine the predictors of MI and HF hospitalization rates at town level in the State of Maine, USA. Maine has large variations in wealth and along the urban-rural continuum at town level. Because our results shed light on variations in health and health-seeking behavior for different Maine populations (such as those living closer vs further from hospitals) they may be of interest to providers of healthcare to people who live in areas remote from healthcare, and to people who face other barriers to good cardiovascular health. METHODS: To determine predictors of HF and MI hospitalization in Maine, we constructed a geographic information system (GIS) for Maine's towns using publicly available electronic map layers, year 2000 census data, and electronic hospitalization records for all Maine hospitals. This GIS generated age-corrected MI and HF hospitalization rates for 1998-2002 as dependent variables and the following independent variables: poverty rate, unemployment rate, median income, educational attainment, rurality, physician density, and distance to the closest hospital. Univariable and multiple linear regression analysis were then performed to determine the significant predictors of MI and HF hospitalization rates. RESULTS: During the 5-year study period there were 24 452 hospitalizations of Maine residents to Maine hospitals for MI and 20 330 for HF. In multiple linear regression analysis, greater unemployment, a larger fraction of the population living in poverty, and proximity to a hospital predicted higher MI hospitalization rate (p = 0.000, r-sq = 19.1%) while greater unemployment and proximity to a hospital predicted higher HF hospitalization rate (p = 0.000, r-sq = 8.4%). CONCLUSIONS: Our finding that higher MI and HF hospitalization rates were predicted for towns that had lower SES is in agreement with many previous studies and shows the importance of these variables to health, even in a setting such as Maine with large variability in rurality. The negative relationship between the distance to a hospital and hospitalization rates likely does not represent better health in those living remotely from healthcare. Rather, it may indicate that people who live in communities distant from hospitals are less likely to seek hospitalization. This suggests that patient behavior as well as socioeconomic status may impact heart-related hospitalization in Maine. It highlights the importance of patient and provider education to ensure that people who live remotely from health care are hospitalized appropriately.

Combined electro-acoustic stimulation: a beneficial union?

BACKGROUND: The most pressing problem facing cochlear implant research is no longer making artificial hearing a reality. Instead, it is to develop devices that can more clearly reflect the capabilities of the human auditory system. Current cochlear implants rarely provide adequate pitch perception. As hearing loss commonly affects higher, more than lower frequencies, a possible solution is to preserve acoustic hearing at low frequencies by inserting a short electrode array and thus deliver combined electro-acoustic stimulation (EAS). OBJECTIVE OF REVIEW: To determine whether individuals with severe-to-profound high-frequency hearing loss have realised this predicted benefit of combined EAS, over conventional cochlear implants, with respect to pitch. TYPE OF REVIEW: A systematic review of publications pertaining to the benefits of combined EAS over conventional cochlear implantation, with specific reference to pitch perception. SEARCH STRATEGY: A systematic literature search was conducted across multiple databases and supplemented by searching the reference lists of relevant trials and identified reviews. RESULTS: The included studies suggest an overall benefit of combined EAS, over conventional cochlear implants, with respect to pitch. In addition, (i) 13% sustained a total loss of low-frequency hearing post-implantation of the short electrode array and, (ii) 24% had >20 dB hearing loss across all frequencies and/or total hearing loss. CONCLUSIONS: For patients with severe-to-profound high-frequency hearing loss combined EAS appears to offer a significant, everyday, long-term benefit. However, further clinical trials with larger numbers of candidates are necessary to confirm this finding. The risks involved cannot be ignored, but there is potential for a variety of strategies to improve the safety margin.