A long-period radio transient active for three decades.

Several long-period radio transients have recently been discovered, with strongly polarized coherent radio pulses appearing on timescales between tens to thousands of seconds1,2. In some cases, the radio pulses have been interpreted as coming from rotating neutron stars with extremely strong magnetic fields, known as magnetars; the origin of other, occasionally periodic and less-well-sampled radio transients is still debated3. Coherent periodic radio emission is usually explained by rotating dipolar magnetic fields and pair-production mechanisms, but such models do not easily predict radio emission from such slowly rotating neutron stars and maintain it for extended times. On the other hand, highly magnetic isolated white dwarfs would be expected to have long spin periodicities, but periodic coherent radio emission has not yet been directly detected from these sources. Here we report observations of a long-period (21 min) radio transient, which we have labelled GPM J1839-10. The pulses vary in brightness by two orders of magnitude, last between 30 and 300 s and have quasiperiodic substructure. The observations prompted a search of radio archives and we found that the source has been repeating since at least 1988. The archival data enabled constraint of the period derivative to <3.6 × 10-13 s s-1, which is at the very limit of any classical theoretical model that predicts dipolar radio emission from an isolated neutron star.

A radio transient with unusually slow periodic emission.

The high-frequency radio sky is bursting with synchrotron transients from massive stellar explosions and accretion events, but the low-frequency radio sky has, so far, been quiet beyond the Galactic pulsar population and the long-term scintillation of active galactic nuclei. The low-frequency band, however, is sensitive to exotic coherent and polarized radio-emission processes, such as electron-cyclotron maser emission from flaring M dwarfs1, stellar magnetospheric plasma interactions with exoplanets2 and a population of steep-spectrum pulsars3, making Galactic-plane searches a prospect for blind-transient discovery. Here we report an analysis of archival low-frequency radio data that reveals a periodic, low-frequency radio transient. We find that the source pulses every 18.18 min, an unusual periodicity that has, to our knowledge, not been observed previously. The emission is highly linearly polarized, bright, persists for 30-60 s on each occurrence and is visible across a broad frequency range. At times, the pulses comprise short-duration (<0.5 s) bursts; at others, a smoother profile is observed. These profiles evolve on timescales of hours. By measuring the dispersion of the radio pulses with respect to frequency, we have localized the source to within our own Galaxy and suggest that it could be an ultra-long-period magnetar.

Does weight loss reduce the severity and incidence of psoriasis or psoriatic arthritis? A Critically Appraised Topic.

CLINICAL QUESTION: Does weight loss reduce the severity and incidence of psoriasis or psoriatic arthritis (PsA) in obese individuals? BACKGROUND: Obesity presents a rising public health challenge and is more prevalent among individuals with psoriasis or PsA than in the general population. Longitudinal population-based studies suggest a causal role for obesity in psoriasis and PsA onset and that obesity drives greater disease severity. METHODS: We systematically reviewed evidence within the MEDLINE, Embase and CENTRAL databases and clinical trials registries examining lifestyle, pharmacological and surgical weight loss interventions in the treatment and prevention of psoriasis and PsA in obese individuals. Meta-analysis was conducted using random-effects models, followed by sensitivity analyses. RESULTS: Of 176 full-text articles reviewed, 14 met the inclusion criteria. Meta-analysis of six randomized control trials (RCTs) confirmed that weight loss following lifestyle interventions (diet or physical activity) improves psoriasis compared with control [mean change in Psoriasis Area and Severity Index -2·59, 95% confidence interval (CI) -4·09 to -1·09; P < 0·001]. One RCT demonstrated a greater likelihood of achieving minimal PsA activity following diet-induced weight loss (odds ratio 4·20, 95% CI 1·82-9·66; P < 0·001). Three studies of pharmacological treatments reported conflicting results, and no RCTs of bariatric surgery were identified. Two cohort studies suggested that bariatric surgery, particularly gastric bypass, reduces the risk of developing psoriasis (hazard ratio 0·52, 95% CI 0·33-0·81; P < 0·01). CONCLUSIONS: These limited data indicate that weight loss can improve pre-existing psoriasis and PsA, and prevent the onset of psoriasis in obese individuals. Together with the National Institute for Health and Care Excellence obesity guidance, this informed a local obesity screening and management pathway, providing multidisciplinary weight loss interventions alongside conventional skin-focused care for patients with psoriasis.

Increasing the accuracy of 18F-FDG PET/CT interpretation of "mildly positive" mediastinal nodes in the staging of non-small cell lung cancer.

INTRODUCTION: The aim of this study was to identify radiological factors that may reduce false-positive results and increase diagnostic accuracy when staging the mediastinum of patients with non-small cell lung carcinoma (NSCLC). METHODS: This was a retrospective, interdisciplinary, per-node analysis study. We included patients with NSCLC and mediastinal nodes with an SUV max in the range of 2.5-4.0 on PET-CT. We hypothesized that the greatest number of false positive cases would occur in this cohort of patients. RESULTS: A total of 92 mediastinal lymph nodes were analyzed in 44 patients. Mediastinal disease (N2/N3) was histologically confirmed in 15 of 44 patients and in 34 of 92 lymph nodes; positive predictive value of 37% and false positive rate of 63%. Lymph node SUV max, tumor size, ratio of node SUV max to tumor SUV max (SUVn/SUVp), and ratio of node SUV max to node size (SUV n/SADn) were significantly higher in true positive cases. Using a threshold of 0.3 for SUV node/tumor and 3 for SUV node/size yielded sensitivities of 91% and 71% and specificities of 71% and 69% respectively for the detection of mediastinal disease. Using both ratios in combination resulted in a sensitivity of 65% and a specificity of 88%. Concurrent benign lung disease was observed significantly more frequently in false-positive cases. CONCLUSION: SUVn/SUVpt and SUVn/SADn may be complimentary to conventional visual interpretation and SUV max measurement in the assessment of mediastinal disease in patients with NSCLC.

Rapid profiling of enteric coated drug delivery spheres via broadband acoustic resonance dissolution spectroscopy (BARDS).

There is an increased trend towards the use of drug and enteric coated sugar spheres for controlled oral delivery of active pharmaceutical ingredients (API). This trend is driven by increased efficacy and ease of formulation of different dosage levels. However, difficulties exist in determining the thickness of drug and enteric coatings in a time efficient manner during manufacture, quality assurance and stability testing. The thickness of the coating determines the dosage of the API and the thickness of the enteric coating determines the release rate of the drug in the gastro-intestinal tract. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) offers a rapid new approach to characterising the enteric coating thickness and the raw materials used in their manufacture. BARDS applications are based on reproducible changes in the compressibility of a solvent during dissolution which is monitored acoustically due to associated changes in the speed of sound in solution. It is demonstrated how core delivery sugar spheres have unique acoustic spectra attributable to the mean size distribution of the spheres. A steady state acoustic lag time is associated with the disintegration of the enteric coating, in basic solution. This lag time can be manipulated by varying the concentration of the base which affects the rate at which the coating dissolves. It is anticipated that the thickness/loading of the spheres can be estimated from the lag time.

Protonation-state determination in proteins using high-resolution X-ray crystallography: effects of resolution and completeness.

A bond-distance analysis has been undertaken to determine the protonation states of ionizable amino acids in trypsin, subtilisin and lysozyme. The diffraction resolutions were 1.2 Šfor trypsin (97% complete, 12% H-atom visibility at 2.5σ), 1.26 Šfor subtilisin (100% complete, 11% H-atom visibility at 2.5σ) and 0.65 Šfor lysozyme (PDB entry 2vb1; 98% complete, 30% H-atom visibility at 3σ). These studies provide a wide diffraction resolution range for assessment. The bond-length e.s.d.s obtained are as small as 0.008 Šand thus provide an exceptional opportunity for bond-length analyses. The results indicate that useful information can be obtained from diffraction data at around 1.2-1.3 Šresolution and that minor increases in resolution can have significant effects on reducing the associated bond-length standard deviations. The protonation states in histidine residues were also considered; however, owing to the smaller differences between the protonated and deprotonated forms it is much more difficult to infer the protonation states of these residues. Not even the 0.65 Šresolution lysozyme structure provided the necessary accuracy to determine the protonation states of histidine.

Effect of an α-lactalbumin-enriched infant formula with lower protein on growth.

BACKGROUND/OBJECTIVES: Protein concentration is lower in human milk (HM) than in infant formula. The objective of this study was to evaluate the effect of an α-lactalbumin-enriched formula with a lower protein concentration on infant growth, protein markers and biochemistries. SUBJECTS/METHODS: Healthy term formula-fed (FF) infants 5-14 days old were randomized in this controlled, double-blind trial to standard formula (SF: 14.1 g/l protein, 662 kcal/l) group (n=112) or experimental formula (EF: 12.8 g/l protein, 662 kcal/l) group (n=112) for 120 days; a HM reference group (n=112) was included. Primary outcome was weight gain (g/day) from D0 to D120. Secondary outcomes included serum albumin, plasma amino acids insulin and incidence of study events. Anthropometric measures were expressed as Z-scores using 2006 World Health Organization growth standards. RESULTS: A total of 321 of the 336 infants (96%) who enrolled, completed the study. Mean age was 9.6 (±2.9) days; 50% were girls. Mean weight gain (g/day) did not significantly differ between SF vs EF (P=0.67) nor between EF vs HM (P=0.11); however weight gain (g/day) was significantly greater in the SF vs HM group (P=0.04). At day 120, mean weight-for-age Z-score (WAZ) and weight-for-length Z-score (WLZ) did not significantly differ between SF vs EF nor EF vs HM; however the WAZ was significantly greater in SF vs HM (P=0.025). Secondary outcomes were within normal ranges for all groups. Incidence of study events did not differ among groups. CONCLUSIONS: α-Lactalbumin-enriched formula containing 12.8 g/l protein was safe and supported age-appropriate growth; weight gain with EF was intermediate between SF and HM groups and resulted in growth similar to HM-fed infants in terms of weight gain, WAZ and WLZ.

Current and emerging techniques in gastrointestinal imaging.

This review is devoted to current and emerging techniques in gastrointestinal (GI) imaging. It is divided into three sections focusing on areas that are both interesting and challenging: imaging of the small bowel and appendix, imaging of the colon and rectum and finally liver and pancreas in the upper abdomen. The first section covers cross-sectional imaging of the small bowel using the techniques of multidetector computed tomography (MDCT) (including CT enterography) and magnetic resonance imaging (MRI). The evaluation of mesenteric ischemia and GI tract bleeding using MDCT angiography is also reviewed. Current imaging practice in the evaluation of appendix is also reviewed and illustrated. The second section reviews CT and MR colonography and imaging of the rectum. It describes CT virtual colonoscopy (CTVC) with emphasis on the advantages and disadvantages of the technique with discussion of the role of CTVC in screening. The intriguing topic of MR colonography (MRC) is also reviewed. Imaging of the rectum with emphasis on imaging of rectal cancer is described with the roles of CT, MR, endoluminal ultrasound and positron emission tomography scanning discussed. The final section reviews current and emerging techniques in liver imaging with the role of ultrasound including contrast ultrasound, MDCT and MR (including contrast agents) discussed. The new developments and applications of imaging of pancreatic disease are discussed with emphasis on the role of MDCT and MRI with gadolinium. This review highlights the current role and advancement of imaging techniques with new diagnostic and prognostic information pertinent to gastrointestinal disease continuing to emerge.

Genitourinary imaging: current and emerging applications.

This review discusses the current and emerging techniques in urinary tract imaging. Recent technical advances and novel discoveries make this an exciting but challenging time for urinary tract imaging. The first section describes the imaging of the adrenal gland which has made great strides in the last decade, the current major adrenal imaging modalities as well as new applications are discussed with particular attention to the role of imaging in the incidentally detected adrenal lesion. In the second section the role of ultrasound, computed tomography (CT) and magnetic resonance (MR) in evaluation of the renal tract are discussed with the new technical advances leading to earlier detection and characterization of renal lesions. Complementary to this is the emerging role of CT and MR urography in assessment of the urinary tract and bladder in contrast to the demise of plain film studies/intravenous urography. The role of CT angiography in assessment of the renal vasculature is also discussed. The third section discusses the role of prostate imaging in the diagnosis, staging and management of prostate cancer. Transrectal ultrasonography, can be used to guide biopsy, CT is frequently used in staging, with bone scintigraphy and positron emission tomography having roles in advanced disease. Currently, all imaging modalities, especially MR are evolving to improve disease detection and staging. The final section discusses the recently encountered adverse reaction of nephrogenic systemic fibrosis in patients post gadolinium-enhanced MRI and how to help prevent this adverse reaction.

Crystallization and preliminary X-ray characterization of a catalytic and ATP-binding domain of a putative PhoR histidine kinase from the gamma-radioresistant bacterium Deinococcus radiodurans.

The gene product of histidine kinase DR2244 (putative phoR) encoded by Deinococcus radiodurans has been suggested to be involved in the PhoR-PhoB two-component regulatory system. This two-component signalling system is activated upon phosphate starvation in several bacteria, including D. radiodurans. Single crystals were obtained from a recombinant preparation of the catalytic/ATP-binding (CA) domain of D. radiodurans PhoR (79-224) overexpressed in Escherichia coli. The crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 46.9, b = 81.8, c = 204.6 A. The crystals contained six molecules in the asymmetric unit. Diffraction data were collected to 2.4 A resolution on beamline ID23-2 of the European Synchrotron Radiation Facility.

Structure of an N-terminally truncated Nudix hydrolase DR2204 from Deinococcus radiodurans.

Nudix pyrophosphatases are a well represented protein family in the Deinococcus radiodurans genome. These hydrolases, which are known to be enzymatically active towards nucleoside diphosphate derivatives, play a role in cleansing the cell pool of potentially deleterious damage products. Here, the structure of DR2204, the only ADP-ribose pyrophosphatase in the D. radiodurans genome that is known to be active towards flavin adenosine dinucleotide (FAD), is presented at 2.0 angstrom resolution.

Tracheo-oesophageal fistula diagnosed with multidetector computed tomography.

This case highlights important issues in investigation of patients with suspected tracheo-oesophageal fistula including the value of multidetector computed tomography, the importance of thorough imaging evaluation when high clinical suspicion of tracheo-oesophageal fistula exists and the value of close interaction between radiologists and intensive care physicians in the investigation of these patients.

Dural AVM supplied by the ophthalmic artery.

Dural arteriovenous malformations in the anterior cranial fossa are rare and are especially prone to haemorrhage. These lesions are usually treated by surgical excision. We report the embolization of an anterior cranial fossa DAVM using an endovascular approach via the ophthalmic artery.

The crystal structure of the Dps2 from Deinococcus radiodurans reveals an unusual pore profile with a non-specific metal binding site.

The crystal structure of recombinant Dps2 (DRB0092, DNA protecting protein under starved conditions) from the Gram-positive, radiation-resistant bacterium Deinococcus radiodurans has been determined in its apo and iron loaded states. Like other members of the Dps family, the bacterial DrDps2 assembles as a spherical dodecamer with an outer shell diameter of 90 A and an interior diameter of 40 A. A total of five iron sites were located in the iron loaded structure, representing the first stages of iron biomineralisation. Each subunit contains a mononuclear iron ferroxidase centre coordinated by residues highly conserved amongst the Dps family of proteins. In the structures presented, a distinct iron site is observed 6.1 A from the ferroxidase centre with a unique ligand configuration of mono coordination by the protein and no bridging ligand to the ferroxidase centre. A non-specific metallic binding site, suspected to play a regulative role in iron uptake/release from the cage, was found in a pocket located near to the external edge of the C-terminal 3-fold channel.

Automation of sample mounting for macromolecular crystallography.

A standard sample holder and vial for cryocooled macromolecular crystals has been defined for use with robotic sample changers. This SPINE standard sample holder is a modified version, with added features and specifications, of sample holders in common use. In particular, the SPINE standard meets the precision required for automatic sample exchange and includes a cap that is identified by a two-dimensional datamatrix code as well as an optional vial. At the ESRF, the sample holder standard is in use with the EMBL/ESRF/BM14 robotic sample changer (SC3) which is installed on eight beamlines. The SC3 can hold up to 50 crystals stored in five baskets. A datamatrix reader in the SC3 ensures safe management of the sample flow and facilitates fully automatic screening and characterization of samples. Tools for handling and transporting 50 samples in a dry shipping dewar have been developed. In addition to the SC3, the SPINE sample holder is currently compatible with a number of other robotic sample changers.

High-throughput sample handling and data collection at synchrotrons: embedding the ESRF into the high-throughput gene-to-structure pipeline.

An automatic data-collection system has been implemented and installed on seven insertion-device beamlines and a bending-magnet beamline at the ESRF (European Synchrotron Radiation Facility) as part of the SPINE (Structural Proteomics In Europe) development of an automated structure-determination pipeline. The system allows remote interaction with beamline-control systems and automatic sample mounting, alignment, characterization, data collection and processing. Reports of all actions taken are available for inspection via database modules and web services.