Explore the vast range of titles available.

Graham Heap, Tariq Ahmad and colleagues show that common variants in the HLA-DQA1–HLA-DRB1 region confer susceptibility to thiopurine-induced pancreatitis in individuals undergoing treatment for inflammatory bowel diseases. These findings could help identify patients at risk of developing this serious adverse reaction to thiopurine therapy. Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07–3.26, P = 2 × 10 −16 ). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the HLA region identified association with the HLA-DQA1*02:01–HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.

IntroductionDemand for colonoscopies and CT colonography (CTC) is exceeding capacity in National Health Service Trusts. In many patients colonoscopies and CTCs show no significant bowel disease (SBD). Faecal Immunochemical Testing (FIT) is being introduced to prioritise patients for colonoscopies but is insufficient to identify non-SBD patients meaning colonoscopy and CTC demand remains high. The REducing Colonoscopies in patients without significant bowEl DiseasE (RECEDE) study aims to test urine volatile organic compound (VOC) analysis alongside FIT to improve detection of SBD and to reduce the number of colonoscopies and CTCs.Methods and analysisThis is a multicentre, prospective diagnostic accuracy study evaluating whether stool FIT plus urine VOC compared with stool FIT alone improves detection of SBD in patients referred for colonoscopy or CTC due to persistent lower gastrointestinal symptoms. To ensure SBD is not missed, the dual test requires a high sensitivity, set at 97% with 95% CI width of 5%. Our assumption is that to achieve this sensitivity requires 200 participants with SBD. Further assuming 19% of all participants will have SBD and 55% of all participants will return both stool and urine samples we will recruit 1915 participants. The thresholds for FIT and VOC results diagnosing SBD have been pre-set. If either FIT or VOC exceeds the respective threshold, the participant will be classed as having suspected SBD. As an exploratory analysis we will be testing different thresholds. The reference comparator will be a complete colonoscopy or CTC. Secondary outcomes will look at optimising the FIT and VOC thresholds for SBD detection. An economic evaluation, using a denovo decision analytic model, will be carried out determine the costs, benefits and overall cost-effectiveness of FIT +VOC vs FIT followed by colonoscopy.Ethics and disseminationEthical approval was obtained by Liverpool Central Research Ethics Committee (20/NW/0346).Trial registration numberRECEDE is registered on Clinicaltrials.gov NCT04516785 & ISRCTN14982373. This protocol was written and published before results of the trial were available.

KETI BANDER, Pakistan - Villagers and rescue workers braved lashing rain and gusting winds Saturday to recover 200 bodies from the sea and rescue thousands of survivors of a powerful cyclone, officials said Saturday. The death toll from the storm that struck southern Sindh province Thursday was expected to rise, as hundreds of villagers remained unaccounted for and scores of hamlets and small islands dotting the Arabian Sea coast remained underwater. A failed rescue attempt compounded the tragedy Saturday, when a powerful ocean current swept away 11 paramilitary soldiers, said Moinuddin Haider, the governor of Sindh province.

Police wielding batons charged toward Islamic militants Tuesday to avert a mass demonstration near an air base being used to support U.S. personnel. More than 140 people were arrested, authorities and witnesses said. The party wants to expel U.S. personnel supporting the U.S.-led military campaign to root out terrorist installations in Afghanistan of Osama bin Laden, top suspect in the Sept. 11 terror attacks on the United States. President Gen. Pervez Musharraf's government says Pakistan is giving only logistical support to the United States. He has promised that no attacks on Afghanistan will be staged from Pakistani soil.

Villagers and rescue workers braved lashing rain and gusting winds Saturday to recover 200 bodies from the sea and rescue thousands of survivors of a powerful cyclone.

Villagers and rescue workers braved lashing rain and winds to recover 200 bodies from the sea yesterday and rescue thousands of survivors of a deadly cyclone that devastated hundreds of villages, officials and witnesses said. Yesterday, rescuers recovered 50 bodies from several islands off the coast and 150 bodies in neighboring Badin district, said residents of Keti Bander, also hard hit by the cyclone, which packed winds of 170 mph. In Keti Bander, some 70 miles south-east of Karachi, the water had receded, but lashing winds battered poor residents, many of whom had taken shelter in camps set up by the Pakistani navy.

Potentially toxic elements (PTEs) are a major source of pollution due to their toxicity, persistence, and bio-accumulating nature in riverine bed sediments. The sediment, as the largest storage and source of PTEs, plays an important role in transformation of mercury (Hg), lead (Pb), nickel (Ni), chromium (Cr), copper (Cu), zinc (Zn), and other toxic PTEs. Several important industrial hubs that contain a large population along the banks of different rivers, such as Kabul, Sutlej, Ravi, Jhelum, and Chenab in Pakistan, are acting as major sources of PTEs. In this study, 150 bed sediment samples (n=30 from each river) were collected from different sites. Total (acid extracted) PTE (Hg, Cu, Cr, Ni, Zn, and Pb) concentrations in bed sediments were determined using inductively coupled plasma mass spectrometry (ICP-MS). Sediment pollution indices were calculated in the major rivers of Pakistan. The results demonstrated high levels of Hg and Ni concentrations which exceeded the guideline standards of river authorities in the world. The contamination factor (CF) and contamination degree (CD) indices for Hg, Ni, and Pb showed a moderate to high (CF≥6 and CD≥24) contamination level in all the selected rivers. The values of geo-accumulation index (I geo ) were also high (I geo ≥5) for Hg and Pb and heavily polluted for Ni, while Cr, Cu, and Zn showed low to unpolluted (I geo ) values. Similarly, the enrichment factor (EF) values were moderately severe (5≤EF≤10) for Hg, Pb, and Ni in Sutlej, Ravi, and Jhelum, and severe (10≤EF≤25) in Kabul and Jhelum. Moreover, Hg and Ni showed severe to very severe enrichment in all the sampling sites. The ecological risk index (ERI) values represented considerable, moderate, and low risks, respectively, for Hg (The ERI value should not be bold. Please unbold the  ERI in the whole paper. It should be same like RI, CD and EF.  80 ≥ E R I ≥160), Pb and Ni (40≤ E R I ≤80), and Cr, Cu, and Zn ( E R I ≤40). Similarly, potential ecological risk index (PERI) values posed considerable (300≤RI≤600) risk in Ravi and moderate (150≤RI≤300) in Kabul and Jhelum, but low (RI≤150) risk in Ravi and Chenab. On the basis of the abovementioned results, it is concluded that bed sediment pollution can be dangerous for both ecological resources and human beings. Therefore, PTE contamination should be regularly monitored and a cost-effective and environmentally friendly wastewater treatment plant should be installed to ensure removal of PTEs before the discharge of effluents into the freshwater ecosystems.