A nearby long gamma-ray burst from a merger of compact objects.

Gamma-ray bursts (GRBs) are flashes of high-energy radiation arising from energetic cosmic explosions. Bursts of long (greater than two seconds) duration are produced by the core-collapse of massive stars1, and those of short (less than two seconds) duration by the merger of compact objects, such as two neutron stars2. A third class of events with hybrid high-energy properties was identified3, but never conclusively linked to a stellar progenitor. The lack of bright supernovae rules out typical core-collapse explosions4-6, but their distance scales prevent sensitive searches for direct signatures of a progenitor system. Only tentative evidence for a kilonova has been presented7,8. Here we report observations of the exceptionally bright GRB 211211A, which classify it as a hybrid event and constrain its distance scale to only 346 megaparsecs. Our measurements indicate that its lower-energy (from ultraviolet to near-infrared) counterpart is powered by a luminous (approximately 1042 erg per second) kilonova possibly formed in the ejecta of a compact object merger.

Clinical utility of portable electrophysiology to measure fatigue in treatment-naïve non-small cell lung cancer.

PURPOSE: Cancer-related fatigue (CRF) biology remains poorly understood. Responsible mechanisms may be central or peripheral and originate anywhere from the brain to muscle fiber. Objective measurement is complex and previously limited to specialized laboratories. Portable electroencephalography (EEG) and electromyography (EMG) may enhance objective measurement. This study evaluated the feasibility and acceptability of portable EMG-EEG in CRF assessment. METHODS: A prospective observational feasibility study compared ten outpatients with inoperable, treatment-naïve non-small cell lung cancer and CRF to ten healthy volunteers. All completed a sustained isometric hand-grip contraction at 30% maximal level until self-perceived exhaustion. 128-channel EEG and 2-channel EMG signals of forearm muscles were recorded. Device acceptability was evaluated by questionnaire. RESULTS: The task was evaluated in two stages; first and last 20 s. CRF cohort perceived exhaustion earlier than volunteers (mean 137 ± 76 s vs 208 ± 51 s). As fatigue progressed, EMG amplitude increased significantly (CRF p = 0.02; volunteers: p = 0.04) in both groups as did EMG beta band power (CRF p = 0.008; volunteers: p = 0.006). The increase was significantly less in CRF (amplitude p = 0.032; beta power: p = 0.014). EEG beta band power in the contralateral motor cortex increased significantly (CRF p = 0.03; volunteers: p = 0.019) in both cohorts but to greater extent (p = 0.024) in CRF. One hundred percent device acceptability was reported. CONCLUSIONS: A laboratory-based evaluation was successfully adapted to the outpatient setting during routine visits. High acceptability supports clinical utility. In CRF, a higher degree of cortical activation was required to drive a much lower level of muscle performance. This suggests impairment of both central and peripheral mechanisms in CRF.

The pathophysiology of cancer-related fatigue: current controversies.

Fatigue is one of the most common and debilitating cancer symptoms, and is associated with impaired quality of life. The exact pathophysiology of cancer-related fatigue (CRF) is poorly understood, but in any individual, it is likely multifactorial and involves inter-related cytokine, muscular, neurotransmitter, and neuroendocrine changes. Underlying CRF mechanisms proposed include central and peripheral hypotheses. Central mechanisms include hypotheses about cytokine dysregulation, hypothalamic-pituitary-adrenal-axis disruption, circadian rhythm disruption, serotonin, and vagal afferent nerve function while peripheral mechanisms include hypotheses about adenosine triphosphate and muscle contractile properties. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is characteristic. The purpose of this article is to provide a narrative review of the literature and present the current controversies in the pathophysiology of CRF, particularly in relation to central and peripheral hypotheses for CRF. An understanding of pathophysiology may facilitate direct and simple therapeutic interventions for those with cancer.

Subjective and objective taste and smell changes in cancer.

CONTEXT: Malnutrition is highly prevalent in cancer patients and an important predictor of morbidity, mortality, treatment response, and toxicity. Taste and smell changes (TSCs) are common and may contribute to malnutrition. Research has previously focused on patients receiving chemotherapy (CT) or head and neck radiotherapy (RT). However, TSCs may occur pre-treatment, with other treatment modalities, and in cancer survivors. This review evaluates objective and subjective assessment of taste and smell, discusses the prevalence of TSCs in cancer, and reviews the clinical sequelae of TSCs in cancer patients. OBJECTIVES: To critically evaluate objective and subjective assessment of TSCs, and the prevalence and clinical sequelae of TSCs in cancer. METHODS: A literature search was conducted using PubMed, CINAHL and Embase for English-language articles published January 2009-June 2016. Search terms included combinations of the following: chemosensory, taste, smell, cancer, chemotherapy, radiotherapy, hormone therapy, immunotherapy, survivors. Reference lists of articles retrieved were also reviewed. RESULTS: Variation in objective and subjective assessment methodologies has resulted in difficulties interpreting the literature. TSC prevalence varies depending on stage of disease and treatment regimens, from 16% to 70% and 50% to 70% during CT and RT, respectively. TSCs in patients who are treatment-naïve, receiving hormone or immunotherapy treatment, post-treatment and cancer survivors have not been adequately studied. TSCs are associated with impaired nutritional status. The relationship between cancer-associated symptoms and nutritional status is not clearly defined. CONCLUSION: There is no gold standard assessment tool for TSCs. Heterogeneity in study methods hinders conclusive identification of the most appropriate way to measure TSCs. Subjective measures may reflect the patient experience and more reliably predict changes in dietary behaviour. Evaluation of TSCs should form part of all nutritional assessments in cancer patients. The true prevalence and severity of TSCs at all stages of cancer could then be established.

Intrinsic coincident full-Stokes polarimeter using stacked organic photovoltaics.

An intrinsic coincident full-Stokes polarimeter is demonstrated by using strain-aligned polymer-based organic photovoltaics (OPVs) that can preferentially absorb certain polarized states of incident light. The photovoltaic-based polarimeter is capable of measuring four Stokes parameters by cascading four semitransparent OPVs in series along the same optical axis. This in-line polarimeter concept potentially ensures high temporal and spatial resolution with higher radiometric efficiency as compared to the existing polarimeter architecture. Two wave plates were incorporated into the system to modulate the S3 Stokes parameter so as to reduce the condition number of the measurement matrix and maximize the measured signal-to-noise ratio. Radiometric calibration was carried out to determine the measurement matrix. The polarimeter presented in this paper demonstrated an average RMS error of 0.84% for reconstructed Stokes vectors after normalized to S0. A theoretical analysis of the minimum condition number of the four-cell OPV design showed that for individually optimized OPV cells, a condition number of 2.4 is possible.

Optical modeling of fiber organic photovoltaic structures using a transmission line method.

An optical model has been developed and evaluated for the calculation of the external quantum efficiency of cylindrical fiber photovoltaic structures. The model is based on the transmission line theory and has been applied on single and bulk heterojunction fiber-photovoltaic cells. Using this model, optimum design characteristics have been proposed for both configurations, and comparison with experimental results has been assessed.

Intrinsic coincident linear polarimetry using stacked organic photovoltaics.

Polarimetry has widespread applications within atmospheric sensing, telecommunications, biomedical imaging, and target detection. Several existing methods of imaging polarimetry trade off the sensor's spatial resolution for polarimetric resolution, and often have some form of spatial registration error. To mitigate these issues, we have developed a system using oriented polymer-based organic photovoltaics (OPVs) that can preferentially absorb linearly polarized light. Additionally, the OPV cells can be made semitransparent, enabling multiple detectors to be cascaded along the same optical axis. Since each device performs a partial polarization measurement of the same incident beam, high temporal resolution is maintained with the potential for inherent spatial registration. In this paper, a Mueller matrix model of the stacked OPV design is provided. Based on this model, a calibration technique is developed and presented. This calibration technique and model are validated with experimental data, taken with a cascaded three cell OPV Stokes polarimeter, capable of measuring incident linear polarization states. Our results indicate polarization measurement error of 1.2% RMS and an average absolute radiometric accuracy of 2.2% for the demonstrated polarimeter.

Catching measles in an appropriately vaccinated group: a well-circumscribed outbreak in the South East of Ireland, September-November 2013.

A measles outbreak occurred in a school in a small town in the South East of Ireland in September-November 2013. Most (and all early) cases had one dose of the measles-mumps- rubella (MMR) vaccination. All suspected cases were followed up, in order to advise on sampling and provide public health advice to them and their contacts. MMR vaccination control measures were instituted in the town. These included early second MMR in primary schools and childcare facilities, bringing forward the planned school MMR catch-up programme, early first MMR dose for children aged 6-12 months and targeted advice to unvaccinated children. There were 20 cases (17 confirmed) of measles associated with the outbreak. Fifteen cases occurred in the index school, with four in pre-school-age children (<4 years) who had clear epidemiological links with children at the school. This was a well-circumscribed outbreak occurring, unusually, in a well-vaccinated population. The outbreak came late to the attention of Department of Public Health staff but prompt action, once notified, and institution of control measures resulted in quick termination of the outbreak and prevention of cases in a neighbouring city.

Subjective taste and smell changes in treatment-naive people with solid tumours.

PURPOSE: Taste and smell changes (TSCs) are common in head and neck (H&N) cancer and during and after chemotherapy (CT) and radiotherapy (RT). It is an area that has been under-investigated, particularly in the treatment-naive, but can negatively impact nutritional status. This study examined the prevalence, severity and characteristics of TSCs in people with non-H&N solid tumours, before CT and RT, and their relationship with co-occurring symptoms. METHODS: A prospective, observational study was conducted. Forty consecutive pre-treatment cancer patients, referred to radiation oncology outpatients over 6 weeks, were recruited. Data on TSCs, symptoms and nutritional status were obtained using the 'Taste and Smell Survey' and the 'abridged Patient-Generated Subjective Global Assessment' (abPG-SGA). BMI was measured. SPSS® was used for statistical analysis. Two-sided P values <0.05 were considered statistically significant. RESULTS: Most patients were newly diagnosed (n = 28; 70 %). Nineteen (48 %) reported TSCs; nine noted a stronger sweet and seven a stronger salt taste. Of these, four reported a stronger and four a weaker smell sensation. Those at nutritional risk reported more TSCs (n = 13/20). TSCs were significantly associated with dry mouth (P < 0.01), early satiety (P < 0.05) and fatigue (P < 0.05). CONCLUSIONS: TSCs preceded CT or RT in almost half of treatment-naive patients with solid tumours, notably stronger sweet and salt tastes. Half of the study group were at nutritional risk; the majority of these reported TSCs. TSCs were significantly associated with other symptoms. Future research and clinical guidelines, with a common terminology for assessment, diagnosis and management of cancer TSCs, are needed.

CRISPR-Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18.

Targeted knockout of genes in primary human cells using CRISPR-Cas9-mediated genome-editing represents a powerful approach to study gene function and to discern molecular mechanisms underlying complex human diseases. We used lentiviral delivery of CRISPR-Cas9 machinery and conditional reprogramming culture methods to knockout the MUC18 gene in human primary nasal airway epithelial cells (AECs). Massively parallel sequencing technology was used to confirm that the genome of essentially all cells in the edited AEC populations contained coding region insertions and deletions (indels). Correspondingly, we found mRNA expression of MUC18 was greatly reduced and protein expression was absent. Characterization of MUC18 knockout cell populations stimulated with TLR2, 3 and 4 agonists revealed that IL-8 (a proinflammatory chemokine) responses of AECs were greatly reduced in the absence of functional MUC18 protein. Our results show the feasibility of CRISPR-Cas9-mediated gene knockouts in AEC culture (both submerged and polarized), and suggest a proinflammatory role for MUC18 in airway epithelial response to bacterial and viral stimuli.

Bronchoabsorption; a novel bronchoscopic technique to improve biomarker sampling of the airway.

BACKGROUND: Current techniques used to obtain lung samples have significant limitations and do not provide reproducible biomarkers of inflammation. We have developed a novel technique that allows multiple sampling methods from the same area (or multiple areas) of the lung under direct bronchoscopic vision. It allows collection of mucosal lining fluid and bronchial brushing from the same site; biopsy samples may also be taken. The novel technique takes the same time as standard procedures and can be conducted safely. METHODS: Eight healthy smokers aged 40-65 years were included in this study. An absorptive filter paper was applied to the bronchial mucosa under direct vision using standard bronchoscopic techniques. Further samples were obtained from the same site using bronchial brushings. Bronchoalveolar lavage (BAL) was obtained using standard techniques. Chemokine (C-C Motif) Ligand 20 (CCL20), CCL4, CCL5, Chemokine (C-X-C Motif) Ligand 1 (CXCL1), CXCL8, CXCL9, CXCL10, CXCL11, Interleukin 1 beta (IL-1ß), IL-6, Vascular endothelial growth factor (VEGF), Matrix metalloproteinase 8 (MMP-8) and MMP-9 were measured in exudate and BAL. mRNA was collected from the bronchial brushings for gene expression analysis. RESULTS: A greater than 10 fold concentration of all the biomarkers was detected in lung exudate in comparison to BAL. High yield of good quality RNA with RNA integrity numbers (RIN) between 7.6 and 9.3 were extracted from the bronchial brushings. The subset of genes measured were reproducible across the samples and corresponded to the inflammatory markers measured in exudate and BAL. CONCLUSIONS: The bronchoabsorption technique as described offers the ability to sample lung fluid direct from the site of interest without the dilution effects caused by BAL. Using this method we were able to successfully measure the concentrations of biomarkers present in the lungs as well as collect high yield mRNA samples for gene expression analysis from the same site. This technique demonstrates superior sensitivity to standard BAL for the measurement of biomarkers of inflammation. It could replace BAL as the method of choice for these measurements. This method provides a systems biology approach to studying the inflammatory markers of respiratory disease progression. TRIAL REGISTRATION: NHS Health Research Authority (13/LO/0256).

A windy day in a sheep saleyard: an outbreak of Q fever in rural South Australia.

In December 2004, the Department of Human Services investigated an outbreak of Q fever in South Australia. A case-control study tested an association between attending a local saleyard and human illness. A case was defined as a person with clinical illness and evidence of seroconversion or high phase II IgM. Controls were selected from a database of community controls matched on sex, age group and postcode. Matched analysis of the first 15 cases with 45 controls indicated that contracting Q fever was associated with attending the saleyard on one particular day (adjusted odds ratio 15·3, 95% confidence interval 1·7-undefined, P = 0·014). Saleyard conditions were windy and conducive for airborne dispersal of contaminated particles. In total, 25 cases were detected. Of these, 22 cases had attended a local saleyard on the same day. This outbreak suggests cases were probably infected by a single exposure at a saleyard from infected sheep and dust. The investigation resulted in an increase in the local uptake of Q fever vaccination and extension of the Australian national vaccination programme.

A prolonged outbreak of invasive meningococcal disease in an extended Irish Traveller family across three Health Service Executive (HSE) areas in Ireland, 2010 to 2013.

Between March 2010 and November 2013 eight laboratory-confirmed cases of serogroup B, invasive meningococcal disease (IMD) were identified in an extended Irish Traveller family across three Health Service Executive (HSE) areas of Ireland. Cases were aged between 5 and 46 months, and were either a cousin or sibling of another case. All eight cases survived. Chemoprophylaxis was given to relevant nuclear family members and close contacts on each occasion, but failed to prevent further cases. Neisseria meningitidis isolates from six cases were highly related, belonging to the ST-41/44 clonal complex, and shared the porA designation 7­2,4. In November 2013, the outbreak control team recommended that directly observed ciprofloxacin chemoprophylaxis be administered simultaneously to the extended family, and that the four component meningococcal B (4CMenB) vaccine be administered to family members aged 2 months to 23 years inclusive and relevant close contacts of the eighth case. Subsequently these recommendations were implemented at three regional clinics. Additionally pharyngeal swabs (n=112) were collected to assess carriage rates of N. meningitidis in this extended family. Pharyngeal carriage of N. meningitidis was detected in 15 (13%) family members. From the epidemiological investigation and carriage study overcrowding was the most likely risk factor identified in this outbreak. To date, the combination of directly observed ciprofloxacin chemoprophylaxis and use of 4CMenB vaccine have controlled the outbreak with no further cases diagnosed.

The effects of the novel SHIP1 activator AQX-1125 on allergen-induced responses in mild-to-moderate asthma.

BACKGROUND: SH2-containing inositol-5'-phosphatase 1 (SHIP1) is an endogenous inhibitor of the phosphoinositide-3-kinase pathway that is involved in the activation and chemotaxis of inflammatory cells. AQX-1125 is a first-in-class, oral SHIP1 activator with a novel anti-inflammatory mode of action. OBJECTIVE: To evaluate the effects of AQX-1125 on airway responses to allergen challenge in mild-to-moderate asthmatic patients. METHODS: A randomized, double-blind, placebo-controlled, two-way crossover study was performed in 22 steroid-naïve mild-to-moderate asthmatics with a documented late-phase response to inhaled allergen (LAR). AQX-1125 (450 mg daily) or placebo was administered orally for 7 days. Allergen challenge was performed on day 6 (2 h postdose), followed by methacholine challenge (day 7), and induced sputum collection and fractional exhaled nitric oxide (FeNO). RESULTS: AQX-1125 significantly attenuated the late-phase response compared with placebo (FEV1 4-10 h: mean difference 150 mL, 20%; P = 0.027) and significantly increased the minimum FEV1 during LAR (mean difference 180 mL; P = 0.014). AQX-1125 had no effect on the early-phase response. AQX-1125 showed a trend in reduction of sputum eosinophils, neutrophils and macrophages although this did not achieve significance as there were only 11 paired samples for analysis. There was no effect on methacholine responsiveness or FeNO. Pharmacokinetic data showed AQX-1125 was rapidly absorbed with geometric mean Cmax and AUC0-24 h values of 1417 ng/mL and 16 727 h ng/mL, respectively. AQX-1125 was well tolerated, but mild GI side-effects (dyspepsia, nausea and abdominal pain) were described in 4/22 subjects on active treatment. These side-effects were mild self-limiting, required no further treatment and did not lead to discontinuation of therapy. CONCLUSION AND CLINICAL RELEVANCE: AQX-1125, a novel oral SHIP1 activator, significantly reduces the late response to allergen challenge, with a trend to reduce airway inflammation. AQX-1125 was safe and well tolerated and merits further investigation in inflammatory disorders.

Setipiprant, a selective CRTH2 antagonist, reduces allergen-induced airway responses in allergic asthmatics.

BACKGROUND: CRTH2 is a G-protein-coupled receptor on T helper2 cells that mediates pro-inflammatory effects of prostaglandin D2 in allergic responses. OBJECTIVE: To investigate the tolerability and pharmacokinetics of setipiprant (ACT-129968), a selective orally active CRTH2 antagonist, in allergic asthmatics and to assess the protective effects of multiple doses of this drug against allergen-induced airway responses. METHODS: In this 3-centre, double-blinded, placebo-controlled, cross-over study, 18 allergic asthmatic males were randomized to setipiprant 1000 mg or matching placebo b.i.d. for 5 consecutive days. Study periods were separated by a washout of ≥ 3 weeks. On study day 4, subjects underwent a standardized allergen challenge and airway response was recorded by FEV1 until 10 h post-allergen. Airway responsiveness to methacholine and exhaled nitric oxide (eNO) were measured pre- and post-dosing. The effects of both treatments on the allergen-induced airway responses were compared by a paired Student's t-test. RESULTS: Fifteen subjects completed the study per-protocol and were included in the analysis. Overall, setipiprant was well tolerated and no clinically relevant adverse events occurred. Trough plasma concentrations showed a high inter-subject variability. Compared with placebo, setipiprant significantly reduced the allergen-induced late asthmatic response (LAR), inhibiting the area under the response vs. time curve (AUC(3-10 h) ) by on average 25.6% (P = 0.006) and significantly protected against the allergen-induced airway hyperresponsiveness (AHR) to methacholine (P = 0.0029). There was no difference in the early asthmatic response (EAR) or in allergen-induced changes in eNO between treatments. CONCLUSION AND CLINICAL RELEVANCE: Setipiprant at multiple oral doses was well tolerated and reduced both the allergen-induced LAR and the associated AHR in allergic asthmatics. Our findings confirm that CRTH2 may be a promising target for the treatment of allergic disorders.

A role for mitogen kinase kinase 3 in pulmonary inflammation validated from a proteomic approach.

Proteomics is a powerful tool to ascertain which proteins are differentially expressed in the context of disease. We have used this approach on inflammatory cells obtained from patients with asthma to ascertain whether novel drugs targets could be illuminated and to investigate the role of any such target in a range of in vitro and in vivo models of inflammation. A proteomic study was undertaken using peripheral blood mononuclear cells from mild asthmatic subjects compared with healthy subjects. The analysis revealed an increased expression of the intracellular kinase, mitogen activated protein kinase (MKK3), and the function of this protein was investigated further in preclinical models of inflammation using MKK3 knockout mice. We describe a 3.65 fold increase in the expression of MKK3 in CD8(+) T lymphocytes obtained from subjects with asthma compared with healthy subjects using a proteomic approach which we have confirmed in CD8(+), but not in CD4(+) T lymphocytes or human bronchial epithelial cells from asthmatic patients using a Western blot technique. In wild type mice, bacterial lipopolysaccharide (LPS) caused a significant increase in MKK3 expression and significantly reduced airway neutrophilia in MKK3(-/-) mice (median, 25, 75% percentile; wild/LPS; 5.3 (0.7-9.9) × 10(5) cells/mL vs MKK3(-/-)/LPS; 0 (0-1.9) × 10(5) cells/mL, P < 0.05). In contrast, eosinophilia in sensitized wild type mice challenged with allergen (0.5 (0.16-0.65) × 10(5) cells/mL) was significantly increased in MKK3(-/-) mice (2.2 (0.9-3.5) × 10(5) cells/mL, P < 0.05). Our results suggest that asthma is associated with MKK3 over-expression in CD8(+) cells. We have also demonstrated that MKK3 may be critical for airway neutrophilia, but not eosinophilia, suggesting that this may be a target worthy of further consideration in the context of diseases associated with neutrophil activation such as severe asthma and COPD.

The 5-lipoxygenase-activating protein inhibitor, GSK2190915, attenuates the early and late responses to inhaled allergen in mild asthma.

BACKGROUND: GSK2190915, a potent 5-lipoxygenase-activating protein inhibitor, prevents the synthesis of leukotrienes and 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE). OBJECTIVE: To assess the effect of GSK2190915 on the allergen-induced asthmatic responses. METHODS: Nineteen eligible male subjects with mild asthma were enrolled in and completed this four-centre, double-blind, two-way crossover study (ClinicalTrials.gov NCT00748306). Subjects took GSK2190915 100 mg and placebo orally once daily for 5 days in randomized order. On Day 1 and 4 they had a methacholine challenge, on Day 3 they had an inhaled allergen challenge, and on Days 4 and 6 they had sputum induction. RESULTS: GSK2190915 attenuated the early (0-2 h) and late (4-10 h) asthmatic responses to inhaled allergen compared with placebo. There was a statistically significant attenuation of the early asthmatic response (EAR) by GSK2190915; treatment difference of GSK2190915 vs. placebo for the minimum FEV(1) EAR was 0.408 L (0.205, 0.611). There was a statistically significant attenuation of the late asthmatic response (LAR) by GSK2190915; the treatment difference of GSK2190915 vs. placebo for the minimum FEV(1) LAR was 0.229 L (0.041, 0.417). There was a statistically significant attenuation of allergen-induced sputum eosinophil count on Day 4 following GSK2190915: mean treatment difference (95% CI) between GSK2190915 and placebo was -9.95% (-18.15%, -1.77%). Compared with placebo, GSK2190915 100 mg reduced median sputum LTB(4) by > 90% on Days 4 and 6. There was no effect on methacholine PC(20) post allergen. GSK2190915 was generally well tolerated. CONCLUSION AND CLINICAL RELEVANCE: GSK2190915 shows potential as a treatment for patients with asthma.

Outcomes following surgery for perforating Crohn's disease.

BACKGROUND: The most common indications for surgery for patients with ileocolic Crohn's disease are fibrostenotic or perforating disease. The objective was to compare surgical outcomes of patients with perforating versus non-perforating disease following ileocolic resection. METHODS: This was a retrospective review of all patients who had their first ileocolic resection between 1990 and 2010, identified from a prospectively maintained inflammatory bowel disease database. Demographic information, preoperative medication, intraoperative findings and postoperative outcome data were collected. Outcomes in patients who had an abscess drained before surgery or were found to have a fistula or abscess at surgery or at pathology were compared with outcomes in all others. RESULTS: A total of 434 patients (56·2 per cent women) were included, 293 with perforating and 141 with non-perforating disease. Median age, tobacco use, and preoperative steroid and biological agent use were similar in the two groups. Forty patients (13·7 per cent) in the perforating group had abscesses drained before surgery and 251 patients had at least one fistula, most commonly to the sigmoid colon. Patients with perforating disease were more likely to require preoperative total parenteral nutrition, need another resection, have an ileostomy and a longer mean postoperative stay, and less likely to undergo a laparoscopic procedure. Patients in this group also developed more postoperative abscesses or leaks (4·8 versus 0 per cent; P = 0·006). The reoperation rate was similar (3·1 versus 0·7 per cent; P = 0·178). CONCLUSION: Patients with penetrating Crohn's disease are more likely to require a more complex procedure, and an ileostomy, and to a have longer postoperative stay.

The intensity of QuantiFERON TB-gold response does not differentiate active from latent tuberculosis.

We analyzed positive QuantiFERON (QFT) assays, performed between July 2009 and April 2011 in the Mercy University Hospital, Cork, Ireland, which included, 94 patients with latent tuberculosis (LTBI) and 35 patients with active tuberculosis. There was no difference in the intensity of response between patients with LTBI and active tuberculosis (p = 0.1589). In patients with LTBI, there were no correlations between age (p = 0.353), sex (p = 0.476), smoking (p = 0.323), contact (p = 0.612), Mantoux response (p = 0.055), Irish nationality (p=0.768), previous BCG vaccination (p = 0.504), WCC (p = 0.187), lymphocyte count (p = 0.786), neutrophil count (p = 0.157) and the intensity of QFT response. Similarly in patients with active TB, there were no correlations between these variables and QFT response. The intensity of QFT response does not help to differentiate active from LTBI. The intensity of QFT response is not influenced by age, sex, smoking, remoteness of contact history, Mantoux response, nationality, CXR abnormalities, BCG vaccination and peripheral lymphocyte count.