A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and ...management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
ABSTRACT
We report the results from a comprehensive study of 74 ultraluminous infrared
galaxies (ULIRGs) and 34 Palomar-Green (PG) quasars within
z
∼
0.3 observed with the
Spitzer
Infrared ...Spectrograph (IRS). The
contribution of nuclear activity to the bolometric luminosity in these systems
is quantified using six independent methods that span a range in wavelength and
give consistent results within ∼±10%–15% on average. This agreement suggests
that deeply buried active galactic nuclei (AGNs) invisible to
Spitzer
IRS but bright in the far-infrared are not common
in this sample. The average derived AGN contribution in ULIRGs is ∼35%–40%,
ranging from ∼15%–35% among “cool”
(
f
25
/
f
60
⩽ 0.2)
optically classified H
ii
-like and LINER ULIRGs to ∼50 and ∼75% among
warm Seyfert 2 and Seyfert 1 ULIRGs, respectively. This number exceeds ∼80% in
PG QSOs. ULIRGs fall in one of three distinct AGN classes: (1) objects with
small extinctions and large polycyclic aromatic hydrocarbon (PAH) equivalent
widths are highly starburst-dominated; (2) systems with large extinctions and
modest PAH equivalent widths have larger AGN contributions, but still tend to be
starburst-dominated; and (3) ULIRGs with both small extinctions and small PAH
equivalent widths host AGN that are at least as powerful as the starbursts. The
AGN contributions in class 2 ULIRGs are more uncertain than in the other
objects, and we cannot formally rule out the possibility that these objects
represent a physically distinct type of ULIRGs. A morphological trend is seen
along the sequence (1)–(2)–(3), in general agreement with the standard ULIRG−QSO
evolution scenario and suggestive of a broad peak in extinction during the
intermediate stages of merger evolution. However, the scatter in this sequence,
including the presence of a significant number of AGN-dominated systems prior to
coalescence and starburst-dominated but fully merged systems, implies that black
hole accretion, in addition to depending on the merger phase, also has a strong
chaotic/random component, as in local AGNs.
Coeliac disease (CD) and noncoeliac wheat or gluten sensitivity (NCWS/NCGS) are common gluten‐related disorders. Both conditions can present with gastrointestinal and extraintestinal manifestations, ...which can be a challenge for physicians to discern between. Whilst coeliac serology and histological assessment are required for the diagnosis of CD, there are no clear biomarkers for the diagnosis of NCGS. The management of both conditions is with a gluten‐free diet (GFD), although the duration, as well as strictness of adherence to a GFD in NCGS, is unclear. Adherence to a GFD in CD can also be challenging, with recent developments of noninvasive assessments, although histological assessment via duodenal biopsies remains the gold standard. The management of refractory coeliac disease remains particularly challenging, often requiring specialist input. Whilst wheat is noted to be a trigger for symptom generation in NCGS, it is unclear which components of wheat are responsible for symptom generation in this group, with further research required to elucidate the pathophysiology.
Cerebellar ataxias are the result of diverse disease processes that can be genetic or acquired. Establishing a diagnosis requires a methodical approach with expert clinical evaluation and ...investigations. We describe the causes of ataxia in 1500 patients with cerebellar ataxia.
All patients were referred to the Sheffield Ataxia Centre, UK, and underwent extensive investigations, including, where appropriate genetic testing using next-generation sequencing (NGS). Patients were followed up on a 6-monthly basis for reassessment and further investigations if indicated.
A total of 1500 patients were assessed over 20 years. Twenty per cent had a family history, the remaining having sporadic ataxia. The commonest cause of sporadic ataxia was gluten ataxia (25%). A genetic cause was identified in 156 (13%) of sporadic cases with other causes being alcohol excess (12%) and cerebellar variant of multiple system atrophy (11%). Using NGS, positive results were obtained in 32% of 146 patients tested. The commonest ataxia identified was EA2. A genetic diagnosis was achieved in 57% of all familial ataxias. The commonest genetic ataxias were Friedreich's ataxia (22%), SCA6 (14%), EA2 (13%), SPG7 (10%) and mitochondrial disease (10%). The diagnostic yield following attendance at the Sheffield Ataxia Centre was 63%.
Immune-mediated ataxias are common. Advances in genetic testing have significantly improved the diagnostic yield of patients suspected of having a genetic ataxia. Making a diagnosis of the cause of ataxia is essential due to potential therapeutic interventions for immune and some genetic ataxias.
There has been a renewed interest in the role of dietary therapies to manage irritable bowel syndrome (IBS), with diet high on the agenda for patients. Currently, interest has focussed on the use of ...traditional dietary advice (TDA), a gluten-free diet (GFD) and the low FODMAP diet (LFD). A consensus meeting was held to assess the role of these dietary therapies in IBS, in Sheffield, United Kingdom. Evidence for TDA is from case control studies and clinical experience. Randomised controlled trials (RCT) have demonstrated the benefit of soluble fibre in IBS. No studies have assessed TDA in comparison to a habitual or sham diet. There have been a number of RCTs demonstrating the efficacy of a GFD at short-term follow-up, with a lack of long-term outcomes. Whilst gluten may lead to symptom generation in IBS, other components of wheat may also play an important role, with recent interest in the role of fructans, wheat germ agglutinins, as well as alpha amylase trypsin inhibitors. There is good evidence for the use of a LFD at short-term follow-up, with emerging evidence demonstrating its efficacy at long-term follow-up. There is overlap between the LFD and GFD with IBS patients self-initiating gluten or wheat reduction as part of their LFD. Currently, there is a lack of evidence to suggest superiority of one diet over another, although TDA is more acceptable to patients. In view of this evidence, our consensus group recommends that dietary therapies for IBS should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Given the lack of dietetic services, novel approaches such as employing group clinics and online webinars may maximise capacity and accessibility for patients. Further research is also required to assess the comparative efficacy of dietary therapies to other management strategies available to manage IBS. Keywords: Irritable bowel syndrome, Low FODMAP diet, Gluten-free diet, Traditional dietary advice
Galactic superwinds occur in almost all infrared-luminous galaxies with star formation rates (SFRs) above 10 M sub( )yr super(-1), as shown by studies of the Na I D interstellar absorption line. We ...demonstrate that this result also applies to ultraluminous infrared galaxies (ULIRGs) that host an active galactic nucleus (AGN) embedded in a strong starburst (SFR 100 M sub( )yr super(-1)) by studying a sample of 26 Seyfert ULIRGs in Na I D. The infrared luminosity of these galaxies is powered jointly by the AGN and starburst. We find that there are hints of the influence of the AGN on outflows in Seyfert 2/starburst composites, but the evidence is not yet statistically conclusive. The evidence we find is lower wind detection rates (i.e., wind opening angles) in Seyfert 2 ULIRGs than in galaxies of comparable L sub(IR), higher velocities than in galaxies of comparable SFR, and correlations between the neutral gas and the ionized gas in the extended narrow-line region. Although the AGN probably contributes to the outflows in Seyfert 2 ULIRGs, its momentum and energy injection is equal to or less than that of the starburst. Similarly, the outflow mechanical luminosity (energy outflow rate) per unit radiative luminosity is the same for starburst and Seyfert 2 ULIRGs. In the nuclei of Seyfert 1 ULIRGs, we observe small-scale outflows that are powered solely by the AGN. However, in Mrk 231, we observe both a high-velocity, small-scale and low-velocity, extended outflow. The latter may be powered by a starburst or radio jet. These large-scale, lower velocity outflows certainly exist in other Seyfert 1 ULIRGs, but they are washed out by the light of the nucleus.
Recent data suggest that panchromoscopy using methylene blue can improve the detection of intraepithelial neoplastic lesions in the context of surveillance colonoscopy for patients with chronic ...ulcerative colitis. This method has also been shown to provide a more accurate diagnosis of the extent of disease and inflammatory activity. Interval cancers are known to occur in patients with chronic ulcerative colitis despite the adoption of currently accepted surveillance biopsy protocols. We hypothesised that targeted chromoscopy alone, with high-magnification imaging, may increase the total number of intraepithelial neoplastic lesions detected, compared with conventional colonoscopy and biopsy surveillance according to current protocols.
A total of 350 patients with long-standing ulcerative colitis (>or=8 years) underwent surveillance colonoscopy using high-magnification chromoscopic colonoscopy (HMCC). Quadrantic biopsies at 10-cm intervals were taken on extubation in addition to targeted biopsies of abnormal mucosal areas. Defined lesions were further evaluated using modified Kudo crypt pattern analysis. These data were compared with data from 350 disease duration- and disease extent-matched control patients who had undergone conventional colonoscopic surveillance between January 2001 and April 2005.
Significantly more intraepithelial neoplastic lesions were detected in the magnification chromoscopy group compared with controls (69 vs. 24, P<0.0001). Intraepithelial neoplasia was observed in 67 lesions, of which 53 (79%) were detected using magnification chromoscopy alone. Chromoscopy increased the number of flat lesions with intraepithelial neoplasia detected compared with controls (P<0.001). Twenty intraepithelial neoplastic lesions were detected from 12,850 non-targeted biopsies in the HMCC group (0.16%), while 49 intraepithelial neoplastic lesions were detected from the 644 targeted biopsies in the HMCC group (8%). From 12,482 non-targeted biopsies taken in the control group patients, 18 (0.14%) showed intraepithelial neoplasia. The yield of intraepithelial neoplastic lesions from targeted biopsies in the control group (i. e. without HMCC imaging), however, was only modestly improved at 1.6% (6/369). Using modified Kudo criteria, the sensitivity and specificity for differentiating neoplastic from non-neoplastic lesions using HMCC were 93% and 88% respectively. The total procedure time was significantly longer in the HMCC group compared with controls (P<0.02).
Magnification chromoscopy improves the detection of intraepithelial neoplasia in the endoscopic screening of patients with chronic ulcerative colitis. Neoplastic and non-neoplastic mucosal change can be predicted with a high overall accuracy using magnification techniques. These adjunctive endoscopic techniques have important clinical implications and may lead to changes in current practice guidelines.
Mangrove forests sequester organic carbon, nutrients and toxic metals sorbed to fine sediment, and thus restrict the mobility of pollutants through estuarine environments. However, mangrove removal ...and environmental degradation caused by industrial activity and urban growth can impact the ability of mangrove communities to provide these critical ecosystem services. Here, we use sediment profiles from an impacted tropical estuary in southwest India to provide a c. 70-year record of carbon, nutrient and trace metal burial in the context of rapid urban development and the systemic removal of mangrove communities. Our results show that carbon and nutrient accumulation rates increase sharply during the 1990's in accordance with the high rates of deforestation. Nitrogen and phosphorus accumulation rates increased fourfold and twofold, respectively, during the same period. Organic carbon accumulation was fivefold higher than the global average during this period, reflecting intense deforestation during the last three decades. The enrichment of Hg, Zn, Pb, Mo, Ni, Cu and Mn demonstrate clear anthropogenic impact starting in the 1950's and peaking in 1990. Mercury, the trace metal with the highest enrichment factor, increased sevenfold in the most recent sediments due to increased fossil fuel emissions, untreated water and incineration of medical waste and/or fertilizers used in aquaculture. Organic carbon isotope (δ13C) and C:N molar ratios indicate shifts to more terrestrial-derived source of organic matter in the most recent sediments reflecting growing deforestation of which may be prevalent in southeast Asia due to increasing development. This study emphasizes the critical role played by mangrove ecosystems in attenuating anthropogenically-derived pollutants, including carbon sequestration, and reveals the long-term consequences of mangrove deforestation in the context of rapidly developing economies.
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•Mercury enrichment has increased up to 7-fold since the 1950's.•Increasing carbon burial in a tropical estuary is related to deforestation.•Recent sediments show high rates of carbon and nutrient burial.•Tropical mangroves are important sinks for pollutants in areas of rapid development.
In the gastrointestinal tract, phasic contractions are caused by electrical activity termed slow waves. Slow waves are generated and actively propagated by interstitial cells of Cajal (ICC). The ...initiation of pacemaker activity in the ICC is caused by release of Ca2+ from inositol 1,4,5-trisphosphate (IP3) receptor-operated stores, uptake of Ca2+ into mitochondria, and the development of unitary currents. Summation of unitary currents causes depolarization and activation of a dihydropyridine-resistant Ca2+ conductance that entrains pacemaker activity in a network of ICC, resulting in the active propagation of slow waves. Slow wave frequency is regulated by a variety of physiological agonists and conditions, and shifts in pacemaker dominance can occur in response to both neural and nonneural inputs. Loss of ICC in many human motility disorders suggests exciting new hypotheses for the etiology of these disorders.
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