Cryogenic STM in 3D vector magnetic fields realized through a rotatable insert

We acknowledge funding from EPSRC (EP/L505079/1 and EP/I031014/1).Spin-polarized scanning tunneling microscopy (SP-STM) performed in vector magnetic fields promises atomic scale imaging of magnetic structure, providing complete information on the local spin texture of a sample in three dimensions. Here, we have designed and constructed a turntable system for a low temperature STM which in combination with a 2D vector magnet provides magnetic fields of up to 5 T in any direction relative to the tip-sample geometry. This enables STM imaging and spectroscopy to be performed at the same atomic-scale location and field-of-view on the sample, and most importantly, without experiencing any change on the tip apex before and after field switching. Combined with a ferromagnetic tip, this enables us to study the magnetization of complex magnetic orders in all three spatial directions.PostprintPeer reviewe

Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly.

This work is licensed under a Creative Commons Attribution 3.0 Unported LicenseBACKGROUND: Long-acting somatostatin analogues delivered parenterally are the most widely used medical treatment in acromegaly. This patient-reported outcomes survey was designed to assess the impact of chronic injections on subjects with acromegaly. METHODS: The survey was conducted in nine pituitary centres in Germany, UK and The Netherlands. The questionnaire was developed by endocrinologists and covered aspects of acromegaly symptoms, injection-related manifestations, emotional and daily life impact, treatment satisfaction and unmet medical needs. RESULTS: In total, 195 patients participated, of which 112 (57%) were on octreotide (Sandostatin LAR) and 83 (43%) on lanreotide (Somatuline Depot). The majority (>70%) of patients reported acromegaly symptoms despite treatment. A total of 52% of patients reported that their symptoms worsen towards the end of the dosing interval. Administration site pain lasting up to a week following injection was the most frequently reported injection-related symptom (70% of patients). Other injection site reactions included nodules (38%), swelling (28%), bruising (16%), scar tissue (8%) and inflammation (7%). Injection burden was similar between octreotide and lanreotide. Only a minority of patients received injections at home (17%) and 5% were self-injecting. Over a third of patients indicated a feeling of loss of independence due to the injections, and 16% reported repeated work loss days. Despite the physical, emotional and daily life impact of injections, patients were satisfied with their treatment, yet reported that modifications that would offer major improvement over current care would be 'avoiding injections' and 'better symptom control'. CONCLUSION: Lifelong injections of long-acting somatostatin analogues have significant burden on the functioning, well-being and daily lives of patients with acromegaly.Chiasma, Inc. 60 Welles Ave, Newton, MA 02 459, USA

A prospective longitudinal study of Pasireotide in Nelson's syndrome

PURPOSE: Nelson's syndrome is a challenging condition that can develop following bilateral adrenalectomy for Cushing's disease, with high circulating ACTH levels, pigmentation and an invasive pituitary tumor. There is no established medical therapy. The aim of the study was to assess the effects of pasireotide on plasma ACTH and tumor volume in Nelson's syndrome. METHODS: Open labeled multicenter longitudinal trial in three steps: (1) a placebo-controlled acute response test; (2) 1 month pasireotide 300-600 μg s.c. twice-daily; (3) 6 months pasireotide long-acting-release (LAR) 40-60 mg monthly. RESULTS: Seven patients had s.c. treatment and 5 proceeded to LAR treatment. There was a significant reduction in morning plasma ACTH during treatment (mean ± SD; 1823 ± 1286 ng/l vs. 888.0 ± 812.8 ng/l during the s.c. phase vs. 829.0 ± 1171 ng/l during the LAR phase, p < 0.0001). Analysis of ACTH levels using a random intercept linear mixed-random effects longitudinal model showed that ACTH (before the morning dose of glucocorticoids) declined significantly by 26.1 ng/l per week during the 28-week of treatment (95% CI - 45.2 to - 7.1, p < 0.01). An acute response to a test dose predicted outcome in 4/5 patients. Overall, there was no significant change in tumor volumes (1.4 ± 0.9 vs. 1.3 ± 1.0, p = 0.86). Four patients withdrew during the study. Hyperglycemia occurred in 6 patients. CONCLUSIONS: Pasireotide lowers plasma ACTH levels in patients with Nelson's syndrome. A longer period of treatment may be needed to assess the effects of pasireotide on tumor volume. TRIAL REGISTRATION: Clinical Trials.gov ID, NCT01617733

Probing magnetic exchange interactions with helium

Funding: CT and PW acknowledge support from EPSRC (EP/R031924/1) and CMY and LSF from EP/S005005/1. C.H. acknowledges support by the Austrian Science Fund (FWF) Project No. P32144-N36 and the VSC-4 of the Vienna University of Technology. The work was partially supported by the Deutsche Forschungsgemeinschaft (DFG) through Transregional Research Collaboration TRR 80 (Augsburg, Munich, and Stuttgart).Controlling and sensing spin-polarization of electrons forms the basis of spintronics. Here, we report a study of the effect of helium on the spin-polarization of the tunneling current and magnetic contrast in spin-polarized Scanning Tunneling Microscopy. We show that the magnetic contrast in SP-STM images recorded in the presence of helium depends sensitively on the tunneling conditions. From tunneling spectra and their variation across the atomic lattice we establish that the helium can be reversibly ejected from the tunneling junction by the tunneling electrons. The energy of the tunneling electrons required to eject the helium depends on the relative spin-polarization of the tip and sample, making the microscope sensitive to the magnetic exchange interactions. We show that the time-averaged spin polarization of the tunneling current is suppressed in the presence of helium and thereby demonstrate voltage control of the spin polarization of the tunneling current across the tip-sample junction.PostprintPeer reviewe

COMPLEXO: identifying the missing heritability of breast cancer via next generation collaboration

Linkage analysis, positional cloning, candidate gene mutation scanning and genome-wide association study approaches have all contributed significantly to our understanding of the underlying genetic architecture of breast cancer. Taken together, these approaches have identified genetic variation that explains approximately 30% of the overall familial risk of breast cancer, implying that more, and likely rarer, genetic susceptibility alleles remain to be discovered.</p

Spuriously Elevated Serum IGF-1 in Adult Individuals with Delayed Puberty: A Diagnostic Pitfall

Serum insulin-like growth factor-1 (IGF-1) is a sensitive marker of growth hormone (GH) activity. The levels of IGF-1 vary widely, peaking during puberty and declining with advancing age. During adolescence, serum IGF-1 levels tend to correlate better with pubertal stage rather than chronological age. Here we discuss two cases of delayed puberty, both in their 20s, who presented with high serum IGF-1 but no clinical or biochemical evidence of hypersomatotropism as confirmed by appropriate GH response to an oral glucose challenge. Both individuals achieved full pubertal status with testosterone replacement therapy and their serum IGF-1 levels settled into normal age-specific range. We suggest that in chronologically adult individuals with delayed puberty, serum IGF-1 should not be interpreted on the basis of age-specific normal values but rather on their pubertal status. Furthermore, in the absence of another cause of elevated IGF-1, the expectation is that IGF-1 levels will decline towards age-normative ranges following androgen replacement therapy

Instrumentation and Measurement Strategy for the NOAA SENEX Aircraft Campaign as Part of the Southeast Atmosphere Study 2013

Natural emissions of ozone-and-aerosol-precursor gases such as isoprene and monoterpenes are high in the southeastern US. In addition, anthropogenic emissions are significant in the southeastern US and summertime photochemistry is rapid. The NOAA-led SENEX (Southeast Nexus) aircraft campaign was one of the major components of the Southeast Atmosphere Study (SAS) and was focused on studying the interactions between biogenic and anthropogenic emissions to form secondary pollutants. During SENEX, the NOAA WP-3D aircraft conducted 20 research flights between 27 May and 10 July 2013 based out of Smyrna, TN. Here we describe the experimental approach, the science goals and early results of the NOAA SENEX campaign. The aircraft, its capabilities and standard measurements are described. The instrument payload is summarized including detection limits, accuracy, precision and time resolutions for all gas-and-aerosol phase instruments. The inter-comparisons of compounds measured with multiple instruments on the NOAA WP-3D are presented and were all within the stated uncertainties, except two of the three NO 2 measurements. The SENEX flights included day- and nighttime flights in the southeastern US as well as flights over areas with intense shale gas extraction (Marcellus, Fayetteville and Haynesville shale). We present one example flight on 16 June 2013, which was a daytime flight over the Atlanta region, where several crosswind transects of plumes from the city and nearby point sources, such as power plants, paper mills and landfills, were flown. The area around Atlanta has large biogenic isoprene emissions, which provided an excellent case for studying the interactions between biogenic and anthropogenic emissions. In this example flight, chemistry in and outside the Atlanta plumes was observed for several hours after emission. The analysis of this flight showcases the strategies implemented to answer some of the main SENEX science questions

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes