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Chronic constipation is a prevalent disorder that affects patients’ quality of life and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology & Motility journal supplement devoted to the investigation and management of constipation was published (2009;21(Suppl.2)). This included seven articles, disseminating all themes covered during a preceding two-day meeting held in London, entitled ‘Current perspectives in chronic constipation: a scientific and clinical symposium’. In October 2018, the 3rd London Masterclass, entitled ‘Contemporary management of constipation’ was held, again over two days. All faculty members were invited to author two new review articles representing a collective synthesis of talks presented and discussions held during this meeting. PURPOSEThis article represents the first of these reviews, addressing epidemiology, diagnosis, clinical associations, pathophysiology and investigation. Clearly not all aspects of the condition can be covered in adequate detail; hence, there is a focus on particular ‘hot topics’ and themes that are of contemporary interest. The second review addresses management of chronic constipation, covering behavioural, conservative, medical and surgical therapies.

Aim: Low anterior resection syndrome (LARS) is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The LARS score was designed as a simple tool for clinical evaluation of LARS. Although the LARS score has good clinical utility, it may not capture all important aspects that patients may experience. The aim of this collaboration was to develop an international consensus definition of LARS that encompasses all aspects of the condition and is informed by all stakeholders. Method: This international patient–provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting. Three expert groups participated: patients, surgeons and other health professionals from five regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in three languages (English, Spanish, and Danish). The primary outcome measured was the priorities for the definition of LARS. Results: Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96% and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to eight symptoms and eight consequences that capture essential aspects of the syndrome. Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. Conclusion: This is the first definition of LARS developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of LARS. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in LARS over time and with intervention.

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.

Kevin Nugent,1 Wallace Smart2,3 1Kinark Child and Family Services, Trent University and Sir Sanford Fleming College, Peterborough, ON, Canada; 2Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 3University of Lethbridge Health Centre, Lethbridge, AB, Canada Abstract: A PubMed review was conducted for papers reporting on attention-deficit/ hyperactivity disorder (ADHD) in postsecondary students. The review was performed in order to determine the prevalence and symptomatology of ADHD in postsecondary students, to examine its effects on academic achievement, and discuss appropriate management. The prevalence of ADHD symptoms among postsecondary students ranges from 2% to 12%. Students with ADHD have lower grade point averages and are more likely to withdraw from courses, to indulge in risky behaviors, and to have other psychiatric comorbidities than their non-ADHD peers. Ensuring that students with ADHD receive appropriate support requires documented evidence of impairment to academic and day-to-day functioning. In adults with ADHD, stimulants improve concentration and attention, although improved academic productivity remains to be demonstrated. ADHD negatively impacts academic performance in students and increases the likelihood of drug and alcohol problems. Affected students may therefore benefit from disability support services, academic accommodations, and pharmacological treatment. Keywords: adults, academic performance, stimulants, treatment

We present a case of acute hemolytic anemia, renal failure, and Clostridium perfringens bacteremia in a patient with acute myelogenous leukemia. The high fatality of C. perfringens bacteremia requires that clinicians recognize and rapidly treat patients at risk for this infection. Although other hemolytic processes are in the differential diagnosis of these events, the presence of high fever, chills, and rapidly positive blood cultures may help narrow the diagnosis. Most cases of C. perfringens bacteremia have a concomitant coinfection, which makes broad spectrum empiric therapy essential. There is a high mortality rate of C. perfringens infections associated with leukemia.

Purpose Radiochemotherapy is the standard of care for the treatment of anal carcinoma achieving good loco-regional control and sphincter preservation. This approach is however associated with acute and late toxicities including haematological, skin, bowel function and genito-urinary complications. This paper systematically reviews studies addressing the quality of life (QoL) implications of anal cancer and radiochemotherapy. The paper also evaluates how QoL is assessed in anal cancer. Methods Medline, EMBASE, CINAHL, PsycInfo, Web of Science and the Cochrane Library were searched for publications (1996–2014) reporting the effects on patients of anal cancer and radiochemotherapy. Results Of the 152 papers reporting treatment-related effects on patients, only 11 provided a formal assessment of QoL. In the absence of an anal cancer-specific measure, QoL was assessed using generic cancer instruments such as the core EORTC quality of life questionnaire (EORTC QLQ-C30) or colorectal cancer tools such as the EORTC QLQ-CR29. Bowel function, particularly diarrhoea, and sexual problems were the most commonly reported QoL concerns. The review of QoL issues of anal cancer patients treated with radiochemotherapy is limited by the QoL assessment measures used. It is argued that certain treatment-related toxicities, for example skin-induced radiation problems, are overlooked or inadequately represented in existing measures. Conclusions This review emphasises the need to develop an anal cancer-specific QoL measure and to incorporate QoL as an outcome of future trials in anal cancer. The results of this review are informative to clinicians and patients in terms of treatment decision-making.

We present a new atmospheric extinction curve for Mauna Kea spanning 3200--9700 \AA. It is the most comprehensive to date, being based on some 4285 standard star spectra obtained on 478 nights spread over a period of 7 years obtained by the Nearby SuperNova Factory using the SuperNova Integral Field Spectrograph. This mean curve and its dispersion can be used as an aid in calibrating spectroscopic or imaging data from Mauna Kea, and in estimating the calibration uncertainty associated with the use of a mean extinction curve. Our method for decomposing the extinction curve into physical components, and the ability to determine the chromatic portion of the extinction even on cloudy nights, is described and verified over the wide range of conditions sampled by our large dataset. We demonstrate good agreement with atmospheric science data obtain at nearby Mauna Loa Observatory, and with previously published measurements of the extinction above Mauna Kea., Comment: 22 pages, 24 figures, 6 tables

The introduction of electrospray ionization (ESI) in the 1980s revolutionized the analysis of biomolecules, and LC-ESI/MS (50–5000 μL/min) offers robust, high-throughput analyses for many biological applications. The introduction of nanospray (nESI) in the 1990s has made nLC-nESI/MS (10–1000 nL/min) a valuable tool for proteomics research, where high resolution and high sensitivity are maximized at the cost of sample throughput (60–240+ min per analysis) and robustness. Although protein biomarker analysis requires the high resolution and high sensitivity provided by nanoLC/MS, it also requires robustness and high throughput if it is to be useful in pharmaceutical and clinical applications. This study introduces a new axial desolvation, vacuum-assisted nano-capillary electrospray (ADVANCE) source for LC/MS, which has the robustness of LC-ESI/MS and the sensitivity of nanoLC-nanoESI/MS, but operates in the flow range from 0.2–100 μL/min. For low-abundance proteins, PTMs, and biomarker identification, an HT capLC-ADVANCE/MS system can analyze 50–150 host cell proteomic samples (digests of 1D gel slices, 2D gel spots, or MDLC fractions) in 24 h (10–30 min per analysis) at attomole to picomole sensitivities. The capLC-ADVANCE/MS system can also be used for validation of biomarker candidates, which requires comparative quantitation (ICAT, ITRAC, SILAC) of proteomic samples (5–15 min per analysis) in host cells and physiological fluids. Once protein biomarkers have been validated (very few to date), the capLC-ADVANCE/MS can be used for very high throughput (2–5 min per analysis) quantitation of biomarker signature peptides in a variety of diagnostic and therapeutic applications.

The evanescent field intensity outside a fibre can be increased several orders of magnitude by tapering it. Several tapered optical fibre based evanescent field devices have been reported in the literature. Cambridge University, UK, reported work on miniature dye lasers using a tapered fibre in a loop arrangement; but more importantly, a tapered single mode fibre bent into a small loop. This latter tapered device was used as an imunoassay for cholera antitoxin immunoglobulins and was based on fluorescence spectroscopy. The Naval Research Laboratories, USA, have reported on a MM tapered fibre which is chemically tapered to a point and can be used as a fluorescence based biosensor.

For several years the ID17 Biomedical beamline at the ESRF has developed synchrotron radiation therapy preclinical programmes to treat aggressive brain tumours. Two techniques have been developed at the ESRF: a) The Microbeam Radiation Therapy (MRT) using spatially fractionated "white beam" (energies 50-300 keV) irradiation (beam widths 25-100 μm, spacing between beams 200-400 μm ) with extremely high dose rates (up to about 20 kGy/s) and depositing very high doses (300-1000 Gy) in the targeted tissue. b) The Stereotactic Synchrotron Radiation Therapy (SSRT) using spatially homogeneous monochromatic beam with the energy closely above that of the K-edge of a contrast- or chemotherapeutical agent (iodine, gadolinium, platinum) loaded into the tumour volume for obtaining a dose-enhancement. In 2005 an International review panel of oncology experts has recommended to move to clinical trials on humans in SSRT and on large animals in MRT. The works required for this program were launched in autumn 2007 with constructing a new, dedicated experimental hutch for MRT and a major upgrade of the existing sample-positioning station to a patient-positioning station for SSRT. In parallel, safety systems are developed and progressively implemented and a patient treatment-planning system developed. © 2010 American Institute of Physics.