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Primary non-response and secondary loss of response remain a significant issue with the currently available treatment options for a significant proportion of patients with inflammatory bowel disease (IBD). There are multiple unmet needs in the IBD treatment algorithm and new treatment options are required. As our understanding of the pathogenesis of IBD evolves, new therapeutic targets are being identified. The JAK-STAT pathway has been extensively studied. Tofacitinib, a JAK1 inhibitor, is now licensed for use in the induction and maintenance of ulcerative colitis and there are a large number of molecules currently under investigation. These new small molecule drugs (SMDs) will challenge current treatment pathways at a time when clinical therapeutic outcomes are rapidly evolving and becoming more ambitious. This is a review of the current JAK1 inhibitors in IBD including the current evidence from clinical trials. [ABSTRACT FROM AUTHOR]

Adalimumab, the first fully humanised monoclonal antibody against tumour necrosis factor alpha (TNF-α), has played a leading role in the revolution brought about by the introduction of biologics, and has received the widest range of indications among TNF-α inhibitors. Post-registration, observational and registry studies of real-life use have largely supported the outcomes seen in registrational clinical trials. With the recent loss of exclusivity for the originator medicinal product in Europe, a number of biosimilar adalimumab molecules have been licensed for use in the same indications as the originator molecule across rheumatology, dermatology, gastroenterology and ophthalmology. Clinicians in these areas first gained experience with biosimilar infliximab, followed by etanercept and rituximab. However, adalimumab is likely to present unique challenges given the numbers of patients treated and the range of biosimilar adalimumab products available. The biosimilar approval pathway has an emphasis on the pre-clinical analytic data in combination with clinical studies conducted to confirm therapeutic equivalence. To date, several adalimumab biosimilars have entered the EU market following successful marketing authorisation applications and recent expiration of originator patent protection. This overview covers the extent of use of adalimumab and summarises the regulatory process involved in the development of biosimilars as well as their use in clinical practice. The authors also discuss clinical data available so far on adalimumab biosimilars and their envisaged impact in the field of immune-mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Numerous biologic drugs, including etanercept and adalimumab, are administered subcutaneously. This study reviewed the evidence on the usability and preference of self-injection devices of SB4 and SB5 compared with the reference product injectors. Methods: A systematic search was conducted in PubMed using the search string "(Imraldi OR Hadlima OR SB5 OR Benepali OR Brenzys OR SB4) AND (preference) AND (device)" covering the period from 28 January 2016 (first introduction of SB4) to 31 May 2022. Only articles and abstracts on usability or preference-rating of SB4 and SB5 autoinjectors (AI) written in English were selected. Additional papers identified via manual search supplemented the retrieved papers. Results: A total of nine articles and one conference poster were selected (seven surveys, one observational study, and two phase II studies). Overall, participants of the studies included nurses and rheumatologists, as well as patients who were from three medical specialties where these medicines are most commonly used (rheumatology, gastroenterology, and dermatology). The majority of patients and healthcare professionals rated ease of use and ease of grip as the most important device attributes. SB4/Pen and SB5/Pen were mostly preferred over their prefilled syringes (PFS), Enbrel/Pen, and Humira/Pen. Conclusion: The analyzed data on usability and device preference indicate that SB4/Pen and SB5/Pen were preferred over the other reference product autoinjectors, thanks to their button-free design, auditory and visual injection feedback, and overall ease of use. Therefore, they were preferred over the other reference product autoinjectors. Because user-friendly devices can improve treatment adherence, pharmaceutical companies should consider patient convenience when developing medical devices. [ABSTRACT FROM AUTHOR]

Background. Previous work reports an association between familial risk factors stemming from parental characteristics and offspring disruptive behavior disorders (DBDs). This association may reflect (a) the direct effects of familial environment and (b) a passive gene-environment correlation (rGE wherein the parents provide both the genes and the environment. The current study examined the contributions of direct environmental influences and passive rGEy comparing the effects of familial risk factors on child DBDs in genetically related (biological) and non-related (adoptive) families. Method. Participants were 402 adoptive and 204 biological families. Familial environment was denned as maternal and paternal maladaptive parenting and antisociality, marital conflict and divorce; offspring DBDs included attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD). Mixed-level regressions estimated the main effects of familial environment, adoption status and the familial environment by adoption status interaction term, which tested for the presence of passive rGE Results. There was a main effect of maternal and paternal maladaptive parenting and marital discord on child DBDs, indicating a direct environmental effect. There was no direct environmental effect of maternal or paternal antisociality, but maternal and paternal antisociality had stronger associations with child DBDs in biological families than adoptive families, indicating the presence of a passive rGE Conclusions. Many familial risk factors affected children equally across genetically related and non-related families, providing evidence for direct environmental effects. The relationship of parental antisociality and offspring DBDs was best explained by a passive rGEwhere a general vulnerability toward externalizing psychopathology is passed down by the parents to the children. [ABSTRACT FROM AUTHOR]

The first Crohn's disease (CD) susceptibility gene identified was CARD15, which is a member of the emerging NOD-like receptor (NLR) family. These function as intracellular cystosolic pattern recognition receptors (PRRs) and play a central role in the innate immune response. We studied other members of the NLR family using a gene-wide haplotype tagging approach in a well-characterised collection of 547 CD patients and 465 controls. Four single nucleotide polymorphisms (SNPs) in NLRP3 had P values < 0.05 and are in high linkage disequilibrium (LD) with each other ( r2 > 0.90 for all four SNPs). rs4925648 and rs10925019 were the most strongly associated with CD susceptibility ( P = 0.001, odds ratio (OR) 1.62, 95% CI 1.2–2.18; and P = 6.5 × 10−4, OR 1.65, 95% CI 1.23–2.19, respectively). rs1363758 located in NLRP11 was associated with CD susceptibility [ P = 0.002 (1.64, 1.19–2.25)], which was weakly confirmed in an independent case–cohort collection on joint analysis [ P = 0.05, (1.28, 1–1.64)]. On sub-phenotype analysis, an interesting association between NLRP1 and skin extra-intestinal manifestations and colonic, inflammatory CD was identified. None of these results was replicated in the Wellcome Trust Case Control Consortium study and therefore need replication in a further large cohort. [ABSTRACT FROM AUTHOR]

We report here the development of a three-dimensional (3D) magnetic force microscope for applying forces to and measuring responses of biological systems and materials. This instrument combines a conventional optical microscope with a free-floating or specifically bound magnetic bead used as a mechanical probe. Forces can be applied by the bead to microscopic structures of interest (specimens), while the reaction displacement of the bead is measured. This enables 3D mechanical manipulations and measurements to be performed on specimens in fluids. Force is generated by the magnetically permeable bead in reaction to fields produced by external electromagnets. The displacement is measured by interferometry using forward light scattered by the bead from a focused laser beam. The far-field interference pattern is imaged on a quadrant photodetector from which the 3D displacement can be computed over a limited range about the focal point. The bead and specimen are mounted on a 3D translation stage and feedback techniques are used to keep the bead within this limited range. We demonstrate the system with application to beads attached to cilia in human lung cell cultures. [ABSTRACT FROM AUTHOR]

: We performed an audit of methotrexate for ulcerative colitis, because efficacy is unclear.: To investigate the role of methotrexate in the management of ulcerative colitis.: Patients with ulcerative colitis treated with oral methotrexate at the inflammatory bowel disease clinics of Oxford and Wycombe General Hospital, UK, were evaluated. Efficacy was defined by remission (complete steroid withdrawal for>3 months) and response (good, partial or nil, proportionate reduction of steroids).: There were 50 patients (42 ulcerative colitis alone; eight had rheumatoid arthritis associated with ulcerative colitis and were analysed separately). Indications for methotrexate in ulcerative colitis alone were azathioprine intolerance (31 of 42) and lack of benefit from azathioprine (11 of 42). The mean dose of methotrexate in ulcerative colitis alone was 19.9 mg/week for a median of 30 weeks (range: 7–395). Remission occurred in 42%. The response was good in 54% and partial in 18%. Side-effects occurred in 23%; 10% stopped treatment because of side-effects. Of those treated with methotrexate because of treatment failure with azathioprine, three of 11 achieved remission, but four came to colectomy within 90 days of starting methotrexate. The colitis remained in remission in seven of eight of those with RA treated with methotrexate and ulcerative colitis (mean dose 15.0 mg/week).: Oral methotrexate (approximately 20 mg/week) is well-tolerated and moderately effective in steroid-dependent or steroid-refractory patients with ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background: It is unclear what impact iron deficiency has on fatigue in people with inflammatory bowel disease (IBD). This systematic review examined the evidence of whether iron deficiency, with or without anaemia, was associated with fatigue in IBD. Fatigue is a common symptom in patients with IBD that can be difficult to manage and treat. A greater understanding of the role and contribution of iron deficiency to fatigue may help improve the management of this condition. Methods: The databases searched were MEDLINE, OVID, CINAHL and Web of Science. Inclusion criteria were studies measuring iron status for iron deficiency (ID) and patient-reported outcome measures (PROMs) for fatigue in patients with IBD of any level of disease activity. Assessment of bias was conducted using the Newcastle Ottawa Scale. Studies were grouped for syntheses according to whether exposure was iron deficiency without anaemia (IDWA) or ID regardless of haemoglobin level. Results: Two hundred and eighty-five individual database results were identified and screened; 32 complete records were reviewed, from which seven studies with 1425 individuals were deemed eligible for inclusion in the results synthesis. Considerable variation in the methods and statistical analysis used to investigate the relationship between ID and fatigue prevented any quantitative synthesis. Studies varied by population disease activity levels, approaches used to define ID and PROMs used to measure fatigue. Three studies directly compared fatigue scores in IDWA to those not iron deficient, two of which showed patients with IDWA had significantly lower fatigue scores. Four studies used ID irrespective of anaemia as the exposure and reported mixed results on fatigue, with only one study reporting a higher prevalence of fatigue in the ID group. Conclusions: There was marked heterogeneity between studies in this review. Two studies found evidence of a slight increase in fatigue levels in patients with IDWA. Though this does not explain all fatigue in patients with IBD, iron replacement should be considered to improve fatigue in iron-deficient patients. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Komaki et al papers. To view these articles visit https://doi.org/10.1111/apt.13990 and https://doi.org/10.1111/apt.14060. [ABSTRACT FROM AUTHOR]

The article offers information on racial and ethnic differences in mental health (MH) service use among adolescents with depression. It states that the provision of MH services varies among various groups in U.S. including non-hispanic whites, blacks, and hispanics. The use of MH services has been reported to be lower among hispanic children.

Symptomatic ulcerative colitis (UC) can be a chronic, disabling condition. Flares in disease activity are associated with many of the negative impacts of mild-to-moderate UC. Rapid resolution of flares can provide benefits to patients and healthcare systems. i Support Therapy-Access to Rapid Treatment (iSTART) introduces patient-centered care for mild-to-moderate UC. iSTART provides patients with the ability to self-assess symptomology and self-start a short course of second-line treatment when necessary. An international panel of experts produced consensus statements and recommendations. These were informed by evidence from systematic reviews on the epidemiology, mesalazine (5-ASA) treatment, and patient use criteria for second-line therapy in UC. Optimized 5-ASA is the first-line treatment in all clinical guidelines, but may not be sufficient to induce remission in all patients. Corticosteroids should be prescribed as second-line therapy when needed, with budesonide MMX® being a preferred steroid option. Active involvement of suitable patients in management of UC flares has the potential to improve therapy, with patients able to show good accuracy for flare self-assessment using validated tools. There is a place in the UC treatment pathway for an approach such as iSTART, which has the potential to provide patient, clinical and economic benefits. [ABSTRACT FROM AUTHOR]

Summary: Background: Iron deficiency has a high prevalence in inflammatory bowel disease (IBD) patients, with negative impact on quality of life and work capacity. Aim: To propose an innovative approach based on early intervention, treating to target and tight monitoring in the management of iron deficiency in IBD patients. Methods: We conducted a literature review on PubMed and Medline using pre‐defined keywords and terms to identify relevant studies on iron deficiency in IBD. Results: Many physicians are focused on treating anaemia; however, anaemia is one of the consequences of iron deficiency. Hence, our therapeutic goal for these patients should evolve towards prevention of anaemia by screening and treating iron deficiency. Early diagnosis of iron deficiency is based on a combination of ferritin concentration and transferrin saturation. We consider that normalisation of these biomarkers reflects iron stores replenishment and should be considered as a major therapeutic goal. Treating iron deficiency regardless of the presence of anaemia seems to improve quality of life in several chronic conditions and should be considered as an innovative approach in IBD although strong evidence is still lacking. Tight monitoring is required to allow early detection of iron deficiency recurrence and to consider prompt additional iron supplementation. Conclusion: We propose to extrapolate a three‐step strategy (early detection and intervention, treating‐to‐target and tight monitoring) to the management of iron deficiency in IBD patients. Universally applied, this proactive approach is expected to result in better outcomes in IBD patients. [ABSTRACT FROM AUTHOR]

Single-occupancy isolation rooms are a finite resource in UK hospitals but are crucial in preventing transmission of infection. Patients with suspected gastroenteritis are nursed in single-occupancy rooms, but delays in laboratory testing lead to non-infectious patients remaining isolated for prolonged periods unnecessarily. Rapid molecular test panels for gastrointestinal pathogens have a run time of around 1 h but their clinical impact is unknown. We aimed to evaluate the clinical impact of syndromic molecular point-of-care testing (mPOCT) for gastrointestinal pathogens in adult patients presenting to hospital with suspected gastroenteritis on single-occupancy room use and a range of other outcome measures. In this pragmatic, open-label, randomised controlled trial, we enrolled adults hospitalised with suspected gastroenteritis in a large UK hospital. Patients were randomly allocated (1:1) to receive syndromic mPOCT of stool or rectal samples, or to routine clinical care (control) with laboratory testing. The primary outcome was the duration of time in single-occupancy rooms assessed on a modified intention-to-treat basis. Secondary outcomes included the time to results, time to de-isolation, antibiotic use, and safety outcomes. The study was registered with ISRCTN, ISRCTN88918395, and is complete. Between March 20, 2017 and March 17, 2020, from 455 patients assessed for eligibility, we enrolled 278 patients, 138 assigned to mPOCT (one withdrawal) and 140 to the control group. The duration (geometric mean) of single-occupancy room isolation was 1·8 days (95% CI 1·5–2·2) in the mPOCT group compared with 2·6 days (2·2–3·0) in the control group (exponentiated coefficient 0·70 [95% CI 0·56 to 0·87]; p=0·0017). The median (IQR) time to results was 1·7 h (1·5–2·0) for mPOCT and 44·7 h (21·2–66·1) for the control group (p<0·0001). Time to de-isolation was 0·6 days (0·3–1·8) in the mPOCT group compared with 2·2 days (1·2–3·2) in the control group, (p<0·0001). Antibiotics were given in 89 (65%) of 137 in the mPOCT group and 66 (47%) of 140 in the control group (p=0·0028). There were no differences between groups in length of hospital stay, or in safety outcomes including mortality, intensive care unit admission, or readmission to hospital. mPOCT for gastrointestinal pathogens in patients with suspected gastroenteritis returned results more rapidly than conventional testing and was associated with a reduction in single-occupancy room use. However, these benefits need to be balanced against a potential increase in antibiotic use. University Hospital Southampton NHS Foundation Trust. [ABSTRACT FROM AUTHOR]

Interleukin-13 (IL-13) is an important Type 2 T helper (Th2) cytokine, controlling biological functions in epithelium and has been linked to asthma, atopic dermatitis and ulcerative colitis (UC). Interleukin-13 signals through IL-13 receptor α-1 (IL13RA1 (gene) and IL13Rα1 (protein)), a receptor that can be regulated by microRNAs (miRs). MicroRNAs are small non-coding single-stranded RNAs with a role in several pathologies. However, their relevance in the pathophysiology of UC, a chronic inflammatory condition of the colonic mucosa, is poorly characterised. Here, we determined the expression of IL13Rα1 in UC, its potential regulation by miRs and the subsequent effect on IL-13 signalling. Inflamed mucosa of UC patients showed decreased mRNA and protein expression of IL13RA1 when compared to healthy controls. We show that miR-31 and miR-155 are upregulated in inflamed UC mucosa and that both directly target the 3' untranslated region of IL13RA1 mRNA. Transfection of miR-31 and miR-155 mimics reduced the expression of IL13RA1 mRNA and protein, and blocked IL-13-dependent phosphorylation of signal transducer and activator of transcription 6 (STAT6) in HT-29 cells, a gut epithelium cell line. Interleukin-13 activation of suppressor of cytokine signaling 1 (SOCS1) and eotaxin-3 (CCL26) expression was also diminished. MicroRNA-31/microRNA-155 mimics also downregulated IL13RA1 in ex vivo human inflamed UC biopsies. We propose that miR-31 and miR-155 have an important role in limiting IL-13 signalling in UC disease. [ABSTRACT FROM AUTHOR]

Background Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease ( CD) and ulcerative colitis ( UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors. Aim To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse. Methods This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively. Results 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4-8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC ( P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD ( P = 0.005), while an elevated white cell count was predictive at 12 months for UC ( P = 0.007). Conclusion Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis. [ABSTRACT FROM AUTHOR]

The mechanism that causes the prompt-emission episode of gamma-ray bursts (GRBs) is still widely debated despite there being thousands of prompt detections. The favoured internal shock model relates this emission to synchrotron radiation. However, it does not always explain the spectral indices of the shape of the spectrum, which is often fit with empirical functions, such as the Band function. Multi-wavelength observations are therefore required to help investigate the possible underlying mechanisms that causes the prompt emission. We present GRB 121217A, for which we were able to observe its near-infrared (NIR) emission during a secondary prompt-emission episode with the Gamma-Ray burst Optical Near-infrared Detector (GROND) in combination with the Swift and Fermi satellites, which cover an energy range of 5 orders of magnitude (10-3 keV to 100 keV). We determine a photometric redshift of z = 3:1 ± 0:1 with a line-of-sight with little or no extinction (AV ∼ 0 mag) utilising the optical/NIR SED. From the afterglow, we determine a bulk Lorentz factor of Γ0 ∼ 250 and an emission radius of R < 1018 cm. The prompt-emission broadband spectral energy distribution is well fit with a broken power law with β1 = -0:3 ± 0:1 and β2 = 0:6 ± 0:1 that has a break at E = 6:6 ± 0:9 keV, which can be interpreted as the maximum injection frequency. Self-absorption by the electron population below energies of Ea < 6 keV suggest a magnetic field strength of B ∼ 105 G. However, all the best fit models underpredict the flux observed in the NIR wavelengths, which also only rebrightens by a factor of ∼2 during the second prompt emission episode, in stark contrast to the X-ray emission, which rebrightens by a factor of ∼100. This suggests an afterglow component is dominating the emission. We present GRB 121217A, one of the few GRBs that has multi-wavelength observations of the prompt-emission period and shows that it can be understood with a synchrotron radiation model. However, due to the complexity of the GRB's emission, other mechanisms that result in Band-like spectra cannot be ruled out. [ABSTRACT FROM AUTHOR]

Long-duration gamma-ray bursts (GRBs) are an extremely rare outcome of the collapse of massive stars and are typically found in the distant universe. Because of its intrinsic luminosity (L ~ 3 x 1053 ergs per second) and its relative proximity (z = 0.34), GRB 130427A reached the highest fluence observed in the y-ray band. Here, we present a comprehensive multiwavelength view of GRB 130427A with Swift, the 2-meter Liverpool and Faulkes telescopes, and by other ground-based facilities, highlighting the evolution of the burst emission from the prompt to the afterglow phase. The properties of GRB 130427A are similar to those of the most luminous, high-redshift GRBs, suggesting that a common central engine is responsible for producing GRBs in both the contemporary and the early universe and over the full range of GRB isotropic energies. [ABSTRACT FROM AUTHOR]

Introduction Percutaneous Coronary Intervention (PCI) is widely used in the emergency and elective setting. If drug-eluting stents are deployed, dual antiplatelet therapy must continue for 12 months. Antiplatelet agents are a recognised cause of overt and occult gastrointestinal (GI) bleeding. The aim of this study was to determine the rate of GI complications following PCI in a tertiary cardiothoracic centre. Methods A cohort of 604 patients, who underwent coronary stenting in a 6-month period, was identified from cardiology records. 369 patients were tertiary referrals and so excluded from analysis as follow-up data was unavailable. The electronic notes of 235 patients were reviewed to identify GI complications in the year after PCI. These were classified as overt GI bleeding, anaemia or dyspeptic symptoms. Results The patients were aged 39-73 years (median 64 years). 78% were male and 97% were Caucasian. 80% of patients were on aspirin and clopidogrel for at least 12 months after PCI. 14% of patients were anaemic prior to PCI, defined by a local laboratory reference range of haemoglobin (Hb) <125g/L. It was not standard practice to monitor Hb in the year after PCI, but 97% of patients had Hb tested for another reason, 33% of whom had microcytosis. In the year post-PCI, 45 (19%) patients were anaemic on at least one test, with no obvious cause, such as surgery. Of these, only 16% were tested for iron deficiency anaemia (IDA). 5 of 7 patients tested had definite IDA. Prior to PCI, only 3% of the cohort were anaemic to a degree that would have prompted referral for investigation, based on Department of Health guidelines for suspected lower GI cancer (Hb <11g/dL in men, Hb <10g/dL in postmenopausal women). During treatment with aspirin and clopidogrel, this proportion rose significantly to 10% (p=0.006) Within 12 months of PCI, 10 patients had a gastroscopy, 2 patients had upper and lower GI endoscopy, and 3 had lower GI endoscopy only. The indications in these 15 patients included overt bleeding (5 patients), IDA (4 patients) and GI symptoms (4 patients). 7 of 12 patients had endoscopic signs of upper GI inflammation, with findings of oesophagitis, gastritis or duodenitis. 4 OGDs were normal and another identified Barrett's oesophagus. Significant lower GI diagnoses included rectal cancer, a sigmoid ischaemic ulcer and diverticular disease. Conclusion These results suggest dual antiplatelet therapy increases the prevalence of anaemia, which may be due to iron deficiency. Hb and iron status are not routinely monitored in the year post-PCI. Iron deficiency can cause significant symptoms of fatigue, even in the absence of anaemia and IDA may herald a more sinister underlying pathology. We suggest a review of practice post-PCI, as identification of iron deficiency may prompt timely treatment and investigation. [ABSTRACT FROM PUBLISHER]

The follow-up of inflammatory bowel disease (IBD) patients is challenging due to the relapsing remitting nature of the diseases, the wide spectrum of severity and complexity as well as the need for monitoring of long-term complications and drug treatments. Conventional outpatient follow-up lacks flexibility for patients and there are competing pressures for clinic time. Alternative follow-up pathways include telephone clinics, self-management programmes or discharging patients. The IBD virtual clinic (VC) is a further option. Patients with an established diagnosis for >2 years, who have been stable for >1 year, do not have primary sclerosing cholangitis and who give their consent, are entered into the VC system. Two months before their annual follow-up is due patients are sent blood test forms and a simple questionnaire with an information sheet. If they meet any of the criteria on the questionnaire, they are asked to contact the IBD specialist nursing team to discuss their situation. The blood test results and the patient's database entry are reviewed to ensure that they are not due surveillance investigations. The patients and their GPs then receive a letter informing them of their management plan. We currently follow-up 20% of the Southampton IBD cohort using the VC. The VC system is an innovative, efficient and patient-responsive method for following up mild to moderate IBD. It is well liked by patients but is dependent on a well-maintained database with good integration of IT systems and requires both clerical and IBD nurse specialist support. [ABSTRACT FROM AUTHOR]

Supermassive black holes have powerful gravitational fields with strong gradients that can destroy stars that get too close, producing a bright flare in ultraviolet and X-ray spectral regions from stellar debris that forms an accretion disk around the black hole. The aftermath of this process may have been seen several times over the past two decades in the form of sparsely sampled, slowly fading emission from distant galaxies, but the onset of the stellar disruption event has not hitherto been observed. Here we report observations of a bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This source increased in brightness in the X-ray band by a factor of at least 10,000 since 1990 and by a factor of at least 100 since early 2010. We conclude that we have captured the onset of relativistic jet activity from a supermassive black hole. A companion paper comes to similar conclusions on the basis of radio observations. This event is probably due to the tidal disruption of a star falling into a supermassive black hole, but the detailed behaviour differs from current theoretical models of such events. [ABSTRACT FROM AUTHOR]

Previous linkage studies have identified a region at 1p36 as the susceptibility locus (IBD7) of inflammatory bowel disease (IBD). The objective of this study was to investigate whether polymorphisms of caspase-9 ( CASP9) gene and RUNX3 are associated with IBD susceptibility and clinical phenotypes. We studied 555 Crohn's disease (CD) and 651 ulcerative colitis (UC) patients recruited from a single UK center. A total of 964 healthy Caucasian subjects were recruited as controls from general practitioner well person clinics in Oxfordshire. Fourteen single nucleotide polymorphisms (SNPs) of CASP9 and 11 SNPs of RUNX3 were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (homogenous MassEXTEND, hME, Sequenom™, Sequenom Inc., San Diego, CA). Linkage disequilibrium (LD) and haplotype association analysis were performed using and v2.0 software. No association of individual SNPs of CASP9 or RUNX3 with UC or CD was identified. The rs1052571 of CASP9 was associated with severe UC [ P = 0.0034, odds ratio (OR) = 1.957, 95% confidence interval (CI) = 1.240-3.088]. Significant haplotype associations between CASP9 and IBD were identified, while no association of RUNX3 haplotypes with either UC or CD was found. Our findings suggested that CASP9 gene might be another IBD susceptibility gene. [ABSTRACT FROM AUTHOR]

Killer immunoglobulin-like receptors (KIRs) are expressed on natural killer cells and some T-cell subsets and produce either activation or inhibitory signals upon binding with the appropriate human leucocyte antigen (HLA) ligand on target cells. Recent genetic association studies have implicated KIR genotype in the development of several inflammatory conditions. Ulcerative colitis (UC) is an inflammatory disorder of the colonic mucosa that results from an inappropriate activation of the immune system driven by host bacterial flora. We developed a polymerase chain reaction-sequence specific primer (SSP)-based assay to genotype 194 UC patients and 216 control individuals for 14 KIR genes, the HLA-Cw ligand epitopes of the KIR2D receptors and a polymorphism of the lectin-like-activating receptor NKG2D. Initial analysis found the phenotype frequency of KIR2DL2 and -2DS2 to be significantly increased in the UC cohort (P=0.030 and 0.038, respectively). Logistic regression analysis revealed a protective effect conferred by KIR2DL3 in the presence of its ligand HLA-Cw group 1 (P=0.019). These results suggest that KIR genotype and HLA ligand interaction may contribute to the genetic susceptibility of UC.Genes and Immunity (2006) 7, 576–582. doi:10.1038/sj.gene.6364333; published online 24 August 2006 [ABSTRACT FROM AUTHOR]

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z ≈ 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10″) and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from—and the localization of—the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs. [ABSTRACT FROM AUTHOR]

Although the link between long γ-ray bursts (GRBs) and supernovae has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a GRB. In particular, we do not know how the jet that defines a γ-ray burst emerges from the star's surface, nor how a GRB progenitor explodes. Here we report observations of the relatively nearby GRB 060218 (ref. 5) and its connection to supernova SN 2006aj (ref. 6). In addition to the classical non-thermal emission, GRB 060218 shows a thermal component in its X-ray spectrum, which cools and shifts into the optical/ultraviolet band as time passes. We interpret these features as arising from the break-out of a shock wave driven by a mildly relativistic shell into the dense wind surrounding the progenitor. We have caught a supernova in the act of exploding, directly observing the shock break-out, which indicates that the GRB progenitor was a Wolf–Rayet star. [ABSTRACT FROM AUTHOR]

Two short (< 2 s) γ-ray bursts (GRBs) have recently been localized and fading afterglow counterparts detected. The combination of these two results left unclear the nature of the host galaxies of the bursts, because one was a star-forming dwarf, while the other was probably an elliptical galaxy. Here we report the X-ray localization of a short burst (GRB 050724) with unusual γ-ray and X-ray properties. The X-ray afterglow lies off the centre of an elliptical galaxy at a redshift of z = 0.258 (ref. 5), coincident with the position determined by ground-based optical and radio observations. The low level of star formation typical for elliptical galaxies makes it unlikely that the burst originated in a supernova explosion. A supernova origin was also ruled out for GRB 050709 (refs 3, 31), even though that burst took place in a galaxy with current star formation. The isotropic energy for the short bursts is 2–3 orders of magnitude lower than that for the long bursts. Our results therefore suggest that an alternative source of bursts—the coalescence of binary systems of neutron stars or a neutron star-black hole pair—are the progenitors of short bursts. [ABSTRACT FROM AUTHOR]

A precise measurement of elemental abundances of galactic cosmic rays from charges Z = 20 to 34 was made by TIGER balloon experiment. Using the various path lengths in the atmosphere between 4 and 16 g/cm2 from the TIGER flight data, we derived the attenuation length of iron nuclei with the energy above 2.5 GeV/n in the atmosphere. As the result, we obtained the attenuation length of 15.5 ± 0.6 g/cm2 which is consistent with previous results of balloon measurements. [ABSTRACT FROM AUTHOR]

The prompt optical emission that arrives with the?-rays from a cosmic?-ray burst (GRB) is a signature of the engine powering the burst, the properties of the ultra-relativistic ejecta of the explosion, and the ejecta's interactions with the surroundings. Until now, only GRB 990123 had been detected at optical wavelengths during the burst phase. Its prompt optical emission was variable and uncorrelated with the prompt?-ray emission, suggesting that the optical emission was generated by a reverse shock arising from the ejecta's collision with surrounding material. Here we report prompt optical emission from GRB 041219a. It is variable and correlated with the prompt?-rays, indicating a common origin for the optical light and the?-rays. Within the context of the standard fireball model of GRBs, we attribute this new optical component to internal shocks driven into the burst ejecta by variations of the inner engine. The correlated optical emission is a direct probe of the jet isolated from the medium. The timing of the uncorrelated optical emission is strongly dependent on the nature of the medium. [ABSTRACT FROM AUTHOR]

GRB 050223 was discovered by the Swift Gamma-Ray Burst Explorer on 2005 February 23 and was the first gamma-ray burst (GRB) to be observed by both Swift and XMM–Newton. At the time of writing (2005 May), it has one of the faintest GRB afterglows ever observed. The spacecraft could not slew immediately to the burst, so the first X-ray and optical observations occurred approximately 45 min after the trigger. Although no optical emission was found by any instrument, both Swift and XMM–Newton detected the fading X-ray afterglow. Combined data from both of these observatories show the afterglow to be fading monotonically as over a time-frame between 45 min and 27 h post-burst. Spectral analysis, allowed largely by the higher throughput of XMM–Newton, implies a power law with a slope of and shows no evidence for absorption above the Galactic column of . From the X-ray decay and spectral slopes, a low electron power-law index of is derived; the slopes also imply that a jet-break has not occurred up to 27 h after the burst. The faintness of GRB 050223 may be due to a large jet opening or viewing angle or a high redshift. [ABSTRACT FROM AUTHOR]