Purpose: Molecular profiling may have prognostic and predictive value, and is increasingly used in the clinical setting. There are more than a dozen fibroblast growth factor receptor (FGFR) inhibitors in development. Optimal therapeutic application of FGFR inhibitors requires knowledge of the rates and types of FGFR aberrations in a variety of cancer types.Experimental Design: We analyzed frequencies of FGFR aberrations in 4,853 solid tumors that were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine) using next-generation sequencing (182 or 236 genes), and analyzed by N-of-One.Results: FGFR aberrations were found in 7.1% of cancers, with the majority being gene amplification (66% of the aberrations), followed by mutations (26%) and rearrangements (8%). FGFR1 (mostly amplification) was affected in 3.5% of 4,853 patients; FGFR2 in 1.5%; FGFR3 in 2.0%; and FGFR4 in 0.5%. Almost every type of malignancy examined showed some patients with FGFR aberrations, but the cancers most commonly affected were urothelial (32% FGFR-aberrant); breast (18%); endometrial ($13%), squamous lung cancers ($13%), and ovarian cancer ($9%). Among 35 unique FGFR mutations seen in this dataset, all but two are found in COSMIC. Seventeen of the 35 are known to be activating, and 11 are transforming.Conclusions: FGFR aberrations are common in a wide variety of cancers, with the majority being gene amplifications or activating mutations. These data suggest that FGFR inhibition could be an important therapeutic option across multiple tumor types.

Practical relevance: Feline hypertension is a common disease in older catsthat is frequently diagnosed in association with other diseases such as chronic kidney disease and hyperthyroidism (so-called secondary hypertension), although some cases of apparent primary hypertension are also reported. The clinical consequences of hypertension can be severe, related to 'target organ damage' (eye, heart and vasculature, brain and kidneys), and early diagnosis followed by appropriate therapeutic management should help reduce the morbidity associated with this condition. Clinical challenges: Despite being a common disease, routine blood pressure (BP) monitoring is generally performed infrequently, probably leading to underdiagnosis of feline hypertension in clinical practice. There is a need to: (i) ensure BP is measured as accurately as possible with a reproducible technique; (ii) identify and monitor patients at risk of developing hypertension; (iii) establish appropriate criteria for therapeutic intervention; and (iv) establish appropriate therapeutic targets. Based on current data, amlodipine besylate is the treatment of choice to manage feline hypertension and is effective in the majority of cats, but the dose needed to successfully manage hypertension varies between individuals. Some cats require long-term adjuvant therapy and, occasionally, additional therapy is necessary for emergency management of hypertensive crises. Evidence base: These Guidelines from the International Society of Feline Medicine (ISFM) are based on a comprehensive review of the currently available literature, and are aimed at providing practical recommendations to address the challenges of feline hypertension for veterinarians. There are many areas where more data is required which, in the future, will serve to confirm or modify some of the recommendations in these Guidelines.

We review the morphology and dynamics of the electrical current systems of the terrestrial magnetosphere and ionosphere. Observations from the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) over the three years 2010 to 2012 are employed to illustrate the variability of the field-aligned currents that couple the magnetosphere and ionosphere, on timescales from minutes to years, in response to the impact of solar wind disturbances on the magnetosphere and changes in the level of solar illumination of the polar ionospheres. The variability is discussed within the context of the occurrence of magnetic reconnection between the solar wind and terrestrial magnetic fields at the magnetopause, the transport of magnetic flux within the magnetosphere, and the onset of magnetic reconnection in the magnetotail. The conditions under which the currents are expected to be weak, and hence minimally contaminate measurements of the internallyproduced magnetic field of the Earth, are briefly outlined.

We reduce measurements made by the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) to give the total Birkeland (field‐aligned) current flowing in both hemispheres in monthly and hourly bins. We analyze these totals using 6 years of data (2010–2015) to examine solar zenith angle‐driven variations in the total Birkeland current flowing in both hemispheres, simultaneously, for the first time. A diurnal variation is identified in the total Birkeland current flowing, consistent with variations in the solar zenith angle. A seasonal variation is also identified, with more current flowing in the Northern (Southern) Hemisphere during Bartels rotations in northern (southern) summer. For months close to equinox, more current is found to flow in the Northern Hemisphere, contrary to our expectations. We also conduct the first test of the Milan (2013) model for estimating Birkeland current magnitudes, with modifications made to account for solar contributions to ionospheric conductance based on the observed variation of the Birkeland currents with season and time of day. The modified model, using the value of ΦD averaged by Bartels rotation (scaled by 1.7), is found to agree with the observed AMPERE currents, with a correlation of 0.87 in the Northern Hemisphere and 0.86 in the Southern Hemisphere. The improvement over the correlation with dayside reconnection rate is demonstrated to be a significant improvement to the model. The correlation of the residuals is found to be consistent with more current flowing in the Northern Hemisphere. This new observation of systematically larger current flowing in the Northern Hemisphere is discussed in the context of previous results which suggest that the Northern Hemisphere may react more strongly to dayside reconnection than the Southern Hemisphere.

Aims. We describe in detail the nature of XMM-Newton EPIC background and its various complex components, summarising the new findings of the XMM-Newton EPIC background working group, and provide XMM-Newton background blank sky event files for use in the data analysis of diffuse and extended sources. Methods. Blank sky event file data sets are produced from the stacking of data, taken from 189 observations resulting from the Second XMM-Newton Serendipitous Source Catalogue (2XMMp) reprocessing. The data underwent several filtering steps, using a revised and improved method over previous work, which we describe in detail. Results. We investigate several properties of the final blank sky data sets. The user is directed to the location of the final data sets. There is a final data set for each EPIC instrument-filter-mode combination.