Pulsar Results with the Fermi Large Area Telescope

The launch of the Fermi Gamma-ray Space Telescope has heralded a new era in the study of gamma-ray pulsars. The population of confirmed gamma-ray pulsars has gone from 6-7 to more than 60, and the superb sensitivity of the Large Area Telescope (LAT) on Fermi has allowed the detailed study of their spectra and light curves. Twenty-four of these pulsars were discovered in blind searches of the gamma-ray data, and twenty-one of these are, at present, radio quiet, despite deep radio follow-up observations. In addition, millisecond pulsars have been confirmed as a class of gamma-ray emitters, both individually and collectively in globular clusters. Recently, radio searches in the direction of LAT sources with no likely counterparts have been highly productive, leading to the discovery of a large number of new millisecond pulsars. Taken together, these discoveries promise a great improvement in the understanding of the gamma-ray emission properties and Galactic population of pulsars. We summarize some of the results stemming from these newly-detected pulsars and their timing and multi-wavelength follow-up observations.Comment: 21 pages, 9 figures, to appear in Proceedings of ICREA Workshop on The High-Energy Emission from Pulsars and their Systems, Sant Cugat, Spain, 2010 April 12-16 (Springer

Early Lung Function Abnormalities in Acromegaly.

BACKGROUND: Acromegaly is an insidious disorder caused by a pituitary growth hormone (GH)-secreting adenoma resulting in high circulating levels of GH and insulin-like growth factor I (IGF-I). Respiratory disorders are common complications in acromegaly, and can severely impact on quality of life, eventually affecting mortality. OBJECTIVES: The present study aimed to explore structural and functional lung alterations of acromegalic subjects. METHODS: We enrolled 10 consecutive patients (M/F: 5/5) affected by acromegaly. In all patients, magnetic resonance imaging (MRI) revealed the presence of pituitary tumor. All patients underwent clinical, lung functional, biological, and radiological assessments. Ten healthy age-matched subjects also served as controls. RESULTS: No statistically significant differences in lung function were detected between acromegalic and healthy subjects (p ≥ 0.05 for all analyses). However, the diffusing capacity for CO (TLCO) was significantly lower in the acromegalic group than in healthy subjects (TLCO% predicted: 78.1 ± 16 vs. 90 ± 6 %, respectively, p = 0.04; KCO% predicted: 77 ± 16 vs. 93 ± 5 %, p = 0.02, respectively). None of the lung function parameters correlated with duration of the disease, or with inflammatory marker of the airways. In acromegalics, biological (exhaled NO concentrations) and imaging (total lung volume, TLV, and mean lung density, MLD) evaluations were within normal values. The TLV measured by HRCT was 3540 ± 1555 ml in acromegalics, and the MLD was -711 ± 73 HU. None of the lung functional, radiological, and biological findings correlated with GH or IGF-I levels, and no correlation was found with duration of disease. CONCLUSIONS: In the current study, lung function evaluation allowed to detect early involvement of lung parenchyma, as assessed by TLCO and KCO, even in the absence of parenchymal density alterations of the lung by HRCT. These findings suggest to routinely include the carbon monoxide diffusing capacity in the lung function assessment for an early intervention in acromegaly

Binary and Millisecond Pulsars

We review the main properties, demographics and applications of binary and millisecond radio pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1700. There are now 80 binary and millisecond pulsars associated with the disk of our Galaxy, and a further 103 pulsars in 24 of the Galactic globular clusters. Recent highlights have been the discovery of the first ever double pulsar system and a recent flurry of discoveries in globular clusters, in particular Terzan 5.Comment: 77 pages, 30 figures, available on-line at http://www.livingreviews.org/lrr-2005-

Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.

Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.Funding for the project was provided by the Wellcome Trust for UK10K (WT091310) and DDD Study. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [grant number HICF-1009-003] - see www.ddduk.org/access.html for full acknowledgement. This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute and the Common Fund, NIH Office of the Director. This work was supported in part by the German Ministry of Research and Education (grant nos. 01GS08160 and 01GS08167; German Mental Retardation Network) as part of the National Genome Research Network to A.R. and D.W. and by the Deutsche Forschungsgemeinschaft (AB393/2-2) to A.R. Brain expression data was provided by the UK Human Brain Expression Consortium (UKBEC), which comprises John A. Hardy, Mina Ryten, Michael Weale, Daniah Trabzuni, Adaikalavan Ramasamy, Colin Smith and Robert Walker, affiliated with UCL Institute of Neurology (J.H., M.R., D.T.), King’s College London (M.R., M.W., A.R.) and the University of Edinburgh (C.S., R.W.)

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Anterolateral Ligament Expert Group consensus paper on the management of internal rotation and instability of the anterior cruciate ligament - deficient knee

Purpose of this paper is to provide an overview of the latest research on the anterolateral ligament (ALL) and present the consensus of the ALL Expert Group on the anatomy, radiographic landmarks, biomechanics, clinical and radiographic diagnosis, lesion classification, surgical technique and clinical outcomes. A consensus on controversial subjects surrounding the ALL and anterolateral knee instability has been established based on the opinion of experts, the latest publications on the subject and an exchange of experiences during the ALL Experts Meeting (November 2015, Lyon, France). The ALL is found deep to the iliotibial band. The femoral origin is just posterior and proximal to the lateral epicondyle; the tibial attachment is 21.6 mm posterior to Gerdy's tubercle and 4-10 mm below the tibial joint line. On a lateral radiographic view the femoral origin is located in the postero-inferior quadrant and the tibial attachment is close to the centre of the proximal tibial plateau. Favourable isometry of an ALL reconstruction is seen when the femoral position is proximal and posterior to the lateral epicondyle, with the ALL being tight upon extension and lax upon flexion. The ALL can be visualised on ultrasound, or on T2-weighted coronal MRI scans with proton density fat-suppressed evaluation. The ALL injury is associated with a Segond fracture, and often occurs in conjunction with acute anterior cruciate ligament (ACL) injury. Recognition and repair of the ALL lesions should be considered to improve the control of rotational stability provided by ACL reconstruction. For high-risk patients, a combined ACL and ALL reconstruction improves rotational control and reduces the rate of re-rupture, without increased postoperative complication rates compared to ACL-only reconstruction. In conclusion this paper provides a contemporary consensus on all studied features of the ALL. The findings warrant future research in order to further test these early observations, with the ultimate goal of improving the long-term outcomes of ACL-injured patients. Level of evidence Level V-Expert opinion

Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia

This study aimed to estimate the extent of 'overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR) = 1.45, 95% confidence intervals (CI) 1.02-2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5 to 10 years, 40-64% of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals

Strong-Field Gravity Tests with the Double Pulsar

Continued timing observations of the double pulsar PSR J0737-3039A/B, which consists of two active radio pulsars (A and B) that orbit each other with a period of 2.45 h in a mildly eccentric (e=0.088) binary system, have led to large improvements in the measurement of relativistic effects in this system. With a 16-yr data span, the results enable precision tests of theories of gravity for strongly self-gravitating bodies and also reveal new relativistic effects that have been expected but are now observed for the first time. These include effects of light propagation in strong gravitational fields which are currently not testable by any other method. In particular, we observe the effects of retardation and aberrational light bending that allow determination of the spin direction of the pulsar. In total, we detect seven post-Keplerian parameters in this system, more than for any other known binary pulsar. For some of these effects, the measurement precision is now so high that for the first time we have to take higher-order contributions into account. These include the contribution of the A pulsar's effective mass loss (due to spin-down) to the observed orbital period decay, a relativistic deformation of the orbit, and the effects of the equation of state of superdense matter on the observed post-Keplerian parameters via relativistic spin-orbit coupling. We discuss the implications of our findings, including those for the moment of inertia of neutron stars, and present the currently most precise test of general relativity's quadrupolar description of gravitational waves, validating the prediction of general relativity at a level of 1.3×10-4 with 95% confidence. We demonstrate the utility of the double pulsar for tests of alternative theories of gravity by focusing on two specific examples and also discuss some implications of the observations for studies of the interstellar medium and models for the formation of the double pulsar system. Finally, we provide context to other types of related experiments and prospects for the future