Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients.

PurposeMany women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain at high risk and evaluate whether they should be offered multi-gene panel testing.MethodsWe tested 300 women on a multi-gene panel who were previously enrolled in a long-term study at UCSF. As part of their long-term care, all previously tested negative for mutations in BRCA1 and BRCA2 either by limited or comprehensive sequencing. Additionally, they met one of the following criteria: (i) personal history of bilateral breast cancer, (ii) personal history of breast cancer and a first or second degree relative with ovarian cancer, and (iii) personal history of ovarian, fallopian tube, or peritoneal carcinoma.ResultsAcross the three groups, 26 women (9%) had a total of 28 pathogenic mutations associated with hereditary cancer susceptibility, and 23 women (8%) had mutations in genes other than BRCA1 and BRCA2. Ashkenazi Jewish and Hispanic women had elevated pathogenic mutation rates. In addition, two women harbored pathogenic mutations in more than one hereditary predisposition gene.ConclusionsAmong women at high risk of breast and ovarian cancer who have previously tested negative for pathogenic BRCA1 and BRCA2 mutations, we identified three groups of women who should be considered for subsequent multi-gene panel testing. The identification of women with multiple pathogenic mutations has important implications for family testing

The roles of charge exchange and dissociation in spreading Saturn's neutral clouds

Neutrals sourced directly from Enceladus's plumes are initially confined to a dense neutral torus in Enceladus's orbit around Saturn. This neutral torus is redistributed by charge exchange, impact/photodissociation, and neutral-neutral collisions to produce Saturn's neutral clouds. Here we consider the former processes in greater detail than in previous studies. In the case of dissociation, models have assumed that OH is produced with a single speed of 1 km/s, whereas laboratory measurements suggest a range of speeds between 1 and 1.6 km/s. We show that the high-speed case increases dissociation's range of influence from 9 to 15 Rs. For charge exchange, we present a new modeling approach, where the ions are followed within a neutral background, whereas neutral cloud models are conventionally constructed from the neutrals' point of view. This approach allows us to comment on the significance of the ions' gyrophase at the moment charge exchange occurs. Accounting for gyrophase: (1) has no consequence on the H2O cloud; (2) doubles the local density of OH at the orbit of Enceladus; and (3) decreases the oxygen densities at Enceladus's orbit by less than 10%. Finally, we consider velocity-dependent, as well as species-dependent cross sections and find that the oxygen cloud produced from charge exchange is spread out more than H2O, whereas the OH cloud is the most confined.Comment: Accepted to the Journal of Geophysical Research, 49 pages, 10 figure

Titan's Atomic and Molecular Nitrogen Tori

Shematovich et al. (2003) recently showed plasma induced sputtering in Titan's atmosphere is a source of neutral nitrogen in Saturn's magnetosphere comparable to the photo-dissociation source. These sources form a toroidal nitrogen cloud roughly centered at Titan's orbital radius but gravitationally bound to Saturn. Once ionized, these particles contribute to Saturn's plasma. When Titan is inside Saturn's magnetopause, newly formed ions can diffuse inward becoming inner magnetospheric energetic nitrogen where they can sputter and be implanted into icy satellite surfaces. Our 3-D simulation produces the first consistent Titan generated N and N2 neutral clouds; solar UV radiation and magnetospheric plasma subject these particles to dissociation and ionization. The cloud morphologies and associated nitrogen plasma source rates are predicted in anticipation of Cassini data. Since the amount of molecular nitrogen ejected from Titan by photo-dissociation is small, molecular nitrogen ions detection by Cassini will be an indicator of atmospheric sputtering.Comment: Accepted for Publication in Geophysical Research Letter

Plasma IMS Composition Measurements for Europa and Ganymede

NASA and ESA are planning the joint Europa Jupiter System Mission (EJSM) to the Jupiter system with specific emphasis to Europa and Ganymede, respectively. The Japanese Space Agency is also planning an orbiter mission to explore Jupiter's magnetosphere and the Galilean satellites. For NASA's Jupiter Europa Orbiter (JEO) we are developing the 3D Ion Mass Spectrometer (IMS) with two main goals which can also be applied to the other Galilean moons, 1) measure the plasma interaction between Europa and Jupiter's magnetosphere and 2) infer the 4n surface composition to trace elemental [1] and significant isotopic levels. The first goal supports the magnetometer (MAG) measurements, primarily directed at detection of Europa's sub-surface ocean, while the second gives information about transfer of material between the Galilean moons, and between the moon surfaces and subsurface layers putatively including oceans. The measurement of the interactions for all the Galilean moons can be used to trace the in situ ion measurements of pickup ions back to either Europa's or Ganymede's surface from the respectively orbiting spacecraft. The IMS instrument, being developed under NASA's Astrobiology Instrument Development Program, would maximally achieve plasma measurement requirements for JEO and EJSM while moving forward our knowledge of Jupiter system composition and source processes to far higher levels than previously envisaged

Heavy Ion Formation in Titan's Ionosphere: Magnetospheric Introduction of Free Oxygen and a Source of Titan's Aerosols?

Discovery by Cassini's plasma instrument of heavy positive and negative ions within Titan's upper atmosphere and ionosphere has advanced our understanding of ion neutral chemistry within Titan's upper atmosphere, primarily composed of molecular nitrogen, with approx.2.5% methane. The external energy flux transforms Titan's upper atmosphere and ionosphere into a medium rich in complex hydrocarbons, nitriles and haze particles extending from the surface to 1200 km altitudes. The energy sources are solar UV, solar X-rays, Saturn's magnetospheric ions and electrons, solar wind and shocked magnetosheath ions and electrons, galactic cosmic rays (CCR) and the ablation of incident meteoritic dust from Enceladus' E-ring and interplanetary medium. Here it is proposed that the heavy atmospheric ions detected in situ by Cassini for heights >950 km, are the likely seed particles for aerosols detected by the Huygens probe for altitudes <100km. These seed particles may be in the form of polycyclic aromatic hydrocarbons (PAH) containing both carbon and hydrogen atoms CnHx. There could also be hollow shells of carbon atoms, such as C60, called fullerenes which contain no hydrogen. The fullerenes may compose a significant fraction of the seed particles with PAHs contributing the rest. As shown by Cassini, the upper atmosphere is bombarded by magnetospheric plasma composed of protons, H(2+) and water group ions. The latter provide keV oxygen, hydroxyl and water ions to Titan's upper atmosphere and can become trapped within the fullerene molecules and ions. Pickup keV N(2+), N(+) and CH(4+) can also be implanted inside of fullerenes. Attachment of oxygen ions to PAH molecules is uncertain, but following thermalization O(+) can interact with abundant CH4 contributing to the CO and CO2 observed in Titan's atmosphere. If an exogenic keV O(+) ion is implanted into the haze particles, it could become free oxygen within those aerosols that eventually fall onto Titan's surface. The process of freeing oxygen within aerosols could be driven by cosmic ray interactions with aerosols at all heights. This process could drive pre-biotic chemistry within the descending aerosols. Cosmic ray interactions with grains at the surface, including water frost depositing on grains from cryovolcanism, would further add to abundance of trapped free oxygen. Pre-biotic chemistry could arise within surface microcosms of the composite organic-ice grains, in part driven by free oxygen in the presence of organics and any heat sources, thereby raising the astrobiological potential for microscopic equivalents of Darwin's "warm ponds" on Titan

Space Weathering Perspectives on Europa Amidst the Tempest of the Jupiter Magnetospheric System

Europa resides within a "perfect storm" tempest of extreme external field, plasma, and energetic particle interactions with the magnetospheric system of Jupiter. Missions to Europa must survive, functionally operate, make useful measurements, and return critical science data, while also providing full context on this ocean moon's response to the extreme environment. Related general perspectives on space weathering in the solar system are applied to mission and instrument science requirements for Europa

Earth-Affecting Solar Causes Observatory (EASCO): A Potential International Living with a Star Mission from Sun-Earth L5

This paper describes the scientific rationale for an L5 mission and a partial list of key scientific instruments the mission should carry. The L5 vantage point provides an unprecedented view of the solar disturbances and their solar sources that can greatly advance the science behind space weather. A coronagraph and a heliospheric imager at L5 will be able to view CMEs broadsided, so space speed of the Earth-directed CMEs can be measured accurately and their radial structure discerned. In addition, an inner coronal imager and a magnetograph from L5 can give advance information on active regions and coronal holes that will soon rotate on to the solar disk. Radio remote sensing at low frequencies can provide information on shock-driving CMEs, the most dangerous of all CMEs. Coordinated helioseismic measurements from the Sun Earth line and L5 provide information on the physical conditions at the base of the convection zone, where solar magnetism originates. Finally, in situ measurements at L5 can provide information on the large-scale solar wind structures (corotating interaction regions (CIRs)) heading towards Earth that potentially result in adverse space weather

Coronal Diagnostics from Narrowband Images around 30.4 nm

Images taken in the band centered at 30.4 nm are routinely used to map the radiance of the He II Ly alpha line on the solar disk. That line is one of the strongest, if not the strongest, line in the EUV observed in the solar spectrum, and one of the few lines in that wavelength range providing information on the upper chromosphere or lower transition region. However, when observing the off-limb corona the contribution from the nearby Si XI 30.3 nm line can become significant. In this work we aim at estimating the relative contribution of those two lines in the solar corona around the minimum of solar activity. We combine measurements from CDS taken in August 2008 with temperature and density profiles from semiempirical models of the corona to compute the radiances of the two lines, and of other representative coronal lines (e.g., Mg X 62.5 nm, Si XII 52.1 nm). Considering both diagnosed quantities from line ratios (temperatures and densities) and line radiances in absolute units, we obtain a good overall match between observations and models. We find that the Si XI line dominates the He II line from just above the limb up to ~2 R_Sun in streamers, while its contribution to narrowband imaging in the 30.4 nm band is expected to become smaller, even negligible in the corona beyond ~2 - 3 R_Sun, the precise value being strongly dependent on the coronal temperature profile.Comment: 26 pages, 11 figures; to be published in: Solar Physic

Identification of Saturn's magnetospheric regions and associated plasma processes: Synopsis of Cassini observations during orbit insertion

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94634/1/rog1672.pd

Lunar Hydrospheric Explorer (HYDROX)

The Lunar Hydrospheric Explorer (HYDROX) is a 6U CubeSat designed to further confirm the existence of lunar exospheric water, and to determine source processes and surface sites, through ion mass spectrometer measurements of water group (O+, OH+, H2O+) and related ions at energy charge up to 2 keV/e. and mass/charge 1-40amu/e. HYDROX would follow up on the now-concluded exospheric compositional measurements by the Neutral Mass Spectrometer on the NASA LADEE mission and on other remote sensing surface and exospheric measurements (LADEE,LRO, etc.)