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RNA helicase-regulated processing of the Synechocystis rimO-crhR operon results in differential cistron expression and accumulation of two sRNAs [Gene Regulation]

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.




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Complete characterization of the human immune cell transcriptome using accurate full-length cDNA sequencing [METHOD]

The human immune system relies on highly complex and diverse transcripts and the proteins they encode. These include transcripts encoding human leukocyte antigen (HLA) receptors as well as B cell and T cell receptors (BCR and TCR). Determining which alleles an individual possesses for each HLA gene (high-resolution HLA typing) is essential to establish donor–recipient compatibility in organ and bone marrow transplantations. In turn, the repertoires of millions of unique BCR and TCR transcripts in each individual carry a vast amount of health-relevant information. Both short-read RNA-seq-based HLA typing and BCR/TCR repertoire sequencing (AIRR-seq) currently rely on our incomplete knowledge of the genetic diversity at HLA and BCR/TCR loci. Here, we generated over 10,000,000 full-length cDNA sequences at a median accuracy of 97.9% using our nanopore sequencing-based Rolling Circle Amplification to Concatemeric Consensus (R2C2) protocol. We used this data set to (1) show that deep and accurate full-length cDNA sequencing can be used to provide isoform-level transcriptome analysis for more than 9000 loci, (2) generate accurate sequences of HLA alleles, and (3) extract detailed AIRR data for the analysis of the adaptive immune system. The HLA and AIRR analysis approaches we introduce here are untargeted and therefore do not require prior knowledge of the composition or genetic diversity of HLA and BCR/TCR loci.




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Accuracy of the Ottawa score in risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism: a systematic review and meta-analysis

In patients with cancer-associated venous thromboembolism, knowledge of the estimated rate of recurrent events is important for clinical decision-making regarding anticoagulant therapy. The Ottawa score is a clinical prediction rule designed for this purpose, stratifying patients according to their risk of recurrent venous thromboembolism during the first six months of anticoagulation. We conducted a systematic review and meta-analysis of studies validating either the Ottawa score in its original or modified versions. Two investigators independently reviewed the relevant articles published from 1st June 2012 to 15th December 2018 and indexed in MEDLINE and EMBASE. Nine eligible studies were identified; these included a total of 14,963 patients. The original score classified 49.3% of the patients as high-risk, with a sensitivity of 0.7 [95% confidence interval (CI): 0.6-0.8], a 6-month pooled rate of recurrent venous thromboembolism of 18.6% (95%CI: 13.9-23.9). In the low-risk group, the recurrence rate was 7.4% (95%CI: 3.4-12.5). The modified score classified 19.8% of the patients as low-risk, with a sensitivity of 0.9 (95%CI: 0.4-1.0) and a 6-month pooled rate of recurrent venous thromboembolism of 2.2% (95%CI: 1.6-2.9). In the high-risk group, recurrence rate was 10.2% (95%CI: 6.4-14.6). Limitations of our analysis included type and dosing of anticoagulant therapy. We conclude that new therapeutic strategies are needed in patients at high risk for recurrent cancer-associated venous thromboembolism. Low-risk patients, as per the modified score, could be good candidates for oral anticoagulation. (This systematic review was registered with the International Prospective Registry of Systematic Reviews as: PROSPERO CRD42018099506).




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How accurate are GPs at integrating evidence into prescribing decisions?




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In Situ Immune Profiling of Heart Transplant Biopsies Improves Diagnostic Accuracy and Rejection Risk Stratification

Recognizing that guideline-directed histologic grading of endomyocardial biopsy tissue samples for rejection surveillance has limited diagnostic accuracy, quantitative, in situ characterization was performed of several important immune cell types in a retrospective cohort of clinical endomyocardial tissue samples. Differences between cases were identified and were grouped by histologic grade versus clinical rejection trajectory, with significantly increased programmed death ligand 1+, forkhead box P3+, and cluster of differentiation 68+ cells suppressed in clinically evident rejections, especially cases with marked clinical-histologic discordance. Programmed death ligand 1+, forkhead box P3+, and cluster of differentiation 68+ cell proportions are also significantly higher in "never-rejection" when compared with "future-rejection." These findings suggest that in situ immune modulators regulate the severity of cardiac allograft rejection.




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How accurate is our picture of the pandemic? [News]




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Accumulation of Major Linezolid Metabolites in Patients with Renal Impairment [Pharmacology]

In patients with renal impairment (n = 22 of 39), the median serum concentrations of linezolid, PNU-142300, and PNU-142586 were 1.6-, 3.3-, 2.8-fold higher, respectively, than in patients without renal impairment. Metabolite concentrations in paired samples were poorly correlated with linezolid concentrations (r2 = 0.26 for PNU-142300 and 0.06 for PNU-142586). Linezolid and its metabolites share potential toxicophores that deserve characterization to mitigate higher myelosuppression risk in patients with renal impairment.




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Beneficial Agents for Patients With Type 2 Diabetes and Cardiovascular Disease or Obesity: Utilization in an Era of Accumulating Evidence

This study was an analysis of a national sample of U.S. medical office visits from 2014 to 2016, a period when evidence of effectiveness was emerging for a variety of beneficial type 2 diabetes agents with regard to potential reduction in diabetes comorbidities. Ideal therapy was defined as an American Diabetes Association–identified beneficial agent plus metformin. The associations between atherosclerotic cardiovascular disease or obesity and use of these agents were explored.




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Accuracy of Self-reported Colonic Polyps: Results from the Prostate, Lung, Colorectal, and Ovarian Screening Trial Study of Colonoscopy Utilization

Background:

Colonoscopy follow-up recommendations depend on the presence or absence of polyps, and if found, their number, size, and histology. Patients may be responsible for conveying results between primary and specialty care or providing medical information to family members; thus, accurate reporting is critical. This analysis assessed the accuracy of self-reported colonoscopy findings.

Methods:

3,986 participants from the Study of Colonoscopy Utilization, an ancillary study nested within the Prostate, Lung, Colorectal, and Ovarian Screening Trial, were included. Self-reports of polyp and adenoma were compared to medical records, and measures of sensitivity and specificity were calculated. Correlates of accurate self-report of polyp were assessed using logistic regression and weighted to account for study sampling.

Results:

The sensitivity and specificity of self-reported polyp findings were 88% and 85%, respectively, and for adenoma 11% and 99%, respectively. Among participants with a polyp, older age was associated with lower likelihood while polyp severity and non-white race were associated with increased likelihood of accurate recall. Among participants without a polyp, having multiple colonoscopies was associated with lower likelihood while family history of colorectal cancer was associated with increased likelihood of accurate recall. Among both groups, longer time since colonoscopy was associated with lower likelihood of accurate recall.

Conclusions:

Participants recalled with reasonable accuracy whether they had a prior polyp; however, recall of histology, specifically adenoma, was much less accurate.

Impact:

Identification of strategies to increase accurate self-report of colonic polyps are needed, particularly for patient–provider communications and patient reporting of results to family members.




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Jason Kenney calls Elizabeth May, Yves-François Blanchet 'un-Canadian,' accuses them of 'blaming the victim'

David J. Climenhaga

Now that Premier Jason Kenney has declared it "un-Canadian" to say oil is dead, I wonder if it's OK to admit Alberta's fossil fuel industry is on the ropes?

Probably. Kenney said as much himself in a remarkable rant yesterday directed at the parliamentary leader of the Bloc Québécois and the former leader of the Green Party of Canada.

But if you don't want to be accused of un-Canadian activities, you'd better make it clear none of these troubles are the fault of anything that's ever been done by any Alberta government, except perhaps the NDP's, and especially not by the United Conservative Party Kenney leads.

There is acceptable speech in Alberta, you see, and it doesn't include saying that oil is done like dinner, which is probably not true just yet, but is nevertheless a position that can be argued in respectable company almost anywhere else in the world, including a number of countries known for producing what Kenney rather sophomorically calls "dictator oil."

As has become his practice lately, Kenney took over Chief Medical Officer of Health Deena Hinshaw's daily COVID-19 briefing in Edmonton yesterday afternoon for the sustained blast of gaslighting he directed at Yves-François Blanchet and Elizabeth May.

Blanchet had dared to suggest at a news conference Wednesday that oil "is never coming back" (uttered en francais, bien sûr) and that Ottawa's bailout package should really be directed at "something which is more green." May, for her part, opined at the same event that "oil is dead."

Specifically, the MP for Saanich-Gulf Islands told the media: "My heart bleeds for people who believe the sector is going to come back. It's not. Oil is dead and for people in the sector, it's very important there be just transition funds." This may be wrong, but outside Alberta I doubt it sounds like a stab in the back or a curb-stomping.

Nevertheless, that is what sent Kenney over the edge, in a calculated sort of way, responding to a set-up question provided by Calgary Sun political columnist Rick Bell, who can be counted on to get the first question at one of Hinshaw's frequently hijacked news conferences.

"I just think it's deeply regrettable that we would see national political leaders piling on Albertans and energy workers at a time of great trial for us," Kenney said piously, opening what appeared to be a carefully rehearsed answer. "This is the opposite of leadership. Leaders should be seeking to bring us together, not to divide us."

This is a bit of an irony, of course, coming from a premier who has been ginning up an Alberta separatist threat for months while denying the oil industry had anywhere to go but up, but let's just take it as a lesson in gaslighting 101.

In his remarks, Kenney trotted out benefits he said have been conferred on Quebec by Alberta's oil industry, noted the province's equalization complaints, blamed "predatory actions" by OPEC countries that "want to dominate the world with dictator oil," reminded Quebeckers they like to drive cars and go on airplane trips, and totted up the medical equipment recently sent by Alberta to other provinces.

Having said it in English, he said it over again in French.

Tsk-tsking and shaking his head, Kenney declared, "I would say to Mr. Blanchet and Madam May: Please stop kickin' us while we're down!"

"These attacks on our natural resource industries are unwarranted, they are divisive, they're, I believe, in a way, un-Canadian at a time like this. It's like blaming the victim!" (Italics added for emphasis. And, yes, Kenney really said that.)

Premier Kenney also took particular umbrage at Blanchet's remark that Quebec receives a string of insults from Alberta -- although anyone who has paid attention to political discourse in this province for the last half century would have trouble refuting the claim.

After the news conference, backup was provided in columns filed by Bell and his Postmedia colleague Don Braid.

Bell pronounced Blanchet and May to be "the Bobbsey Twins of B.S." and the "deluded duo," and accused them of choosing "to kick Alberta when we're down" and indulging "in a little curb-stomping."

Braid, the Dinger's bookend of acceptable oilpatch opinion, charged them with "the foulest kind of cheap shot," to wit, saying "Alberta's oil and gas industry should be left prostrate in the dust with no help from the federal government."

Well, there you have it: the debased state of political discourse in Alberta in the plague year 2020. It's not reassuring.

David Climenhaga, author of the Alberta Diary blog, is a journalist, author, journalism teacher, poet and trade union communicator who has worked in senior writing and editing positions at The Globe and Mail and the Calgary Herald. This post also appears on his blog, AlbertaPolitics.ca.

Image: Screenshot of Government of Alberta video/YouTube




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Teenager Accused of Leading Ring of 'Evil Geniuses' on £19.3 Million 'Cybercrime Spree'

The hacker in question hasn't even graduated high school yet.




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Accumulation of gene mutations in chronic Graft-versus-host disease

Mutations in white blood cells can contribute to abnormal immune profile after hematopoietic stem cell transplantation.




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Sierra Leone's president accuses main opposition party of inciting violence




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In video interview, Biden's accuser says he should drop out of White House race

The woman who alleges presumptive Democratic presidential nominee Joe Biden sexually assaulted her in 1993 said in a video interview on Thursday that he should withdraw from the White House race.




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Sierra Leone's president accuses main opposition party of inciting violence

Sierra Leone's president Julius Maada Bio has accused the main opposition party of orchestrating a spate of violent incidents, deepening a political standoff that risks undermining the country's efforts to contain a coronavirus outbreak.




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Accurate 3D imaging of sperm cells moving at top speed could improve IVF treatments

Researchers have developed a safe and accurate 3D imaging method to identify sperm cells moving at a high speed. The new method has the potential to significantly improve IVF treatments.




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Abbott coronavirus test is accurate; infected mother's breast milk may protect infants

The following is a brief roundup of the latest scientific studies on the novel coronavirus and efforts to find treatments and vaccines for COVID-19, the illness caused by the virus.




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Donald Trump accuses World Health Organisation of 'horrible, tragic mistake' over early coronavirus guidance

Follow our live coronavirus updates here




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Piers Morgan tears into Oliver Dowden in heated GMB interview as he accuses Government of 'sending people out to get infected'

Piers Morgan has accused the Government of "actively sending people out to get infected" at the start of the coronavirus outbreak during a heated interview with Culture Secretary Oliver Dowden.




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Piers Morgan accuses Government of 'spectacular failure' over testing rates as he quizzes Helen Whately on GMB

Piers Morgan today hit out at the Government's "spectacular failure" for doing fewer coronavirus tests than 12 days ago.




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TV anchor accused of cheating on girlfriend after half-naked 'lover' appears on webcam during news report

Not for one Spanish TV anchor, whose video-chat blunder might have cost him his relationship.




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UK scientists create coronavirus antibody test with '99.8% accuracy and results in 35 minutes'

UK scientists have developed a new coronavirus antibody test which they say produces results in 35 minutes with 99.8 per cent accuracy.




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Antibody tests at 98% accuracy would lead to 27% of immunity diagnoses being incorrect, government advisers warn

Antibody tests at 98 per cent accuracy would put up to a quarter of population at risk of infection, government advisers have warned.




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Autumn date set for trial of policeman accused of murdering ex-Aston Villa footballer Dalian Atkinson

A police officer accused of murdering former Aston Villa star Dalian Atkinson is set to go ahead in September, despite the current uncertainty about court timetables due to coronavirus.




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Donald Trump donor to represent Joe Biden assault accuser Tara Reade

Tara Reade, the woman who has accused US Democrat presidential candidate Joe Biden of assault, will be legally represented by a donor for President Donald Trump.




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Cosham street party accused of breaching social distancing rules live on TV




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Abbott coronavirus test is accurate; infected mother's breast milk may protect infants

The following is a brief roundup of the latest scientific studies on the novel coronavirus and efforts to find treatments and vaccines for COVID-19, the illness caused by the virus. A new antibody test is highly accurate at determining whether people have been infected with the novel coronavirus, according to a study published on Friday in The Journal of Clinical Microbiology. Researchers at the University of Washington School of Medicine found the test, manufactured by Abbott Laboratories, had a specificity rate of 99.9% and a sensitivity rate of 100%, suggesting little chance of incorrectly diagnosing a healthy person as having been infected and virtually no chance of a false negative readout.





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Police drop investigation into Brexit campaigners accused of breaching spending rules

Police have dropped an investigation into two prominent Brexit campaigners accused of breaching spending rules during the referendum campaign. In 2018 the Electoral commission said that Alan Halsall, of Vote Leave, and Darren Grimes, founder of pro-Brexit youth group BeLeave, failed to declare a payment related to the campaign. The watchdog said that BeLeave "spent more than £675,000 with (Canadian data firm) Aggregate IQ under a common plan with Vote Leave". This spending took Vote Leave over its £7 million legal spending limit by almost £500,000. Vote Leave paid a £61,000 fine, but denied wrongdoing, while Mr Grimes won an appeal against his £20,000 fine in July. The Commission also referred the pair to the Metropolitan Police but on Friday it was revealed that the investigations had now been dropped. A spokesman for the Leave campaigners said: "The Metropolitan Police has written to Vote Leave board member Alan Halsall and BeLeave founder Darren Grimes to confirm that it will not be acting on allegations made against them by the Electoral Commission and various Remain campaigners. "This marks the end of a two-year ordeal for both individuals." Mr Grimes, 26, said the development called into question whether the Electoral Commission was "fit for purpose". He had insisted since the allegations were first made that he was "completely innocent" of making false declarations in relation to the £680,000 donation. In a statement, Mr Grimes, a former fashion student originally from County Durham, said: "The Metropolitan Police has found, after investigation and consultation with the Crown Prosecution Service, that there is no case to be answered. "Once again the Electoral Commission has been found to be part of the mob, a quango out of control that isn't policing elections so much as punishing Leavers who have the temerity to win them. "My ordeal at the hands of the kangaroo court that is the Electoral Commission is now over, but questions must now be asked of whether that body is fit for purpose." Mr Halsall, the responsible person for Vote Leave, said he was "delighted to have been exonerated" and thanked the police for their "professional" investigation. "I was very disappointed that my colleagues at Vote Leave and myself were never given the opportunity of making our case in person to the Electoral Commission before being fined and reported to the police," he added. "It seems a rather unusual way of conducting an inquiry into such matters that only the so-called whistleblowers who made these allegations are interviewed by the regulator." A spokesman for the Met said an investigation into the Electoral Commission's allegations against Vote Leave and BeLeave, submitted on July 17 2018, was handed over in October to the Crown Prosecution Service (CPS). "On Tuesday, March 3 preliminary advice was received from the CPS," said the force spokesman. "This advice has now been duly considered and no further action will be taken."





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Police officer accused of stealing meals from Sulhamstead centre

A THAMES Valley Police officer is accused of stealing food from his work canteen only one week into his new job.




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Anti-Semitism campaigners accuse Jeremy Corbyn allies of 'smearing' whistleblowers as internal probe finds 'no evidence'

Jeremy Corbyn's allies have been accused of using a report to "smear whistleblowers" and "discredit allegations" of anti-Semitism in the Labour Party during his tenure.




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Number 10 removes China data from daily press briefing charts amid suspicions over 'inaccurate' figures

The new group, modelled on the pro-Brexit European Research Group that scrutinised Theresa May's fated Brexit deal, will assess China's handling of the outbreak and broader security concerns.




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Keir Starmer accuses Boris Johnson of 'slow' response to coronavirus outbreak as he demands twice as many tests

Read the full interview HERE




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Tiger King: Producer accuses Joe Exotic of 'shooting animals just because he was pissed off'

TV star's also claimed to have fed a peacock he killed to his pets




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Tiger King: Former zoo manager John Reinke accuses Joe Exotic of 'blowing up' his cabin in new episode

'The man's done a lot of stupid s***'




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Quiz: Charles Ingram calls ITV drama 'terrifyingly accurate' and 'excruciatingly enjoyable'

Former 'Who Wants to Be a Millionaire?' contestant also branded original host Tarrant a 'liar'




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Ellen Pompeo: Grey's Anatomy star criticised for 'victim shaming' Harvey Weinstein's sexual assault accusers in resurfaced video

'I truly do wonder what's going on inside of her brain,' one outraged tweeter wrote




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Lord Sugar accuses Piers Morgan of 'exploiting' coronavirus pandemic: 'He's trying to become a martyr'

'Good Morning Britain' host has previously criticised Lord Sugar for his attitude towards the government's handling of the pandemic




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Ellen DeGeneres' Oscars bodyguard accuses host of being 'cold, sly and demeaning'

He claimed only approved celebrities were permitted to talk to host at awards after party




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Kirstie Allsopp defends decision to film in Devon during lockdown after accusations she put locals at risk

Presenter said she is 'proud' of craft show despite criticism




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My Secret Terrius: Netflix show predicted coronavirus outbreak with alarming accuracy in 2018

It's the most accurate one yet




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Frances Quinn: Great British Bake Off winner 'banned from Waitrose' after being accused of shoplifting

Show's 2013 winner was approached by store detectives after she appeared to not pay for her shopping




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Tommy Fury and Molly-Mae Hague accused of 'breaking lockdown rules' after travelling back to Manchester

The pair were previously spending the lockdown period at Hague's family home




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Barcelona deny 'corruption' claims from former vice president and threaten legal action after 'hand in the till' accusation

Barcelona have moved to strongly deny 'corruption' claims made by Emili Rousand and have threatened legal action against the former vice president.




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Victor Wanyama 'p***** off' over Champions League snub, accuses Tottenham of not backing him after injury

Victor Wanyama says he was "p***** off" to be dropped for Tottenham's Champions League Final defeat last season and accused the club of a lack of support following a serious knee injury in 2017.




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Ray Parlour accuses Arsenal of lacking leadership and leaving Mesut Ozil exposed over pay cut talks

Ray Parlour has blasted former club Arsenal's lack of leadership, defending Mesut Ozil as he stalls on taking a pay cut.




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Cruise companies accused of refusing to let stranded crew disembark due to cost

Death toll of crew stranded by coronavirus continues to rise as industry blames ‘impractical’ safety requirements for blocking disembarkation

Some cruise companies have refused to agree to rules that would allow tens of thousands of stranded crew back to land, citing concerns about cost and potential legal consequences, according to the US Centers for Disease Control and Prevention (CDC). The largest trade association for the cruise industry has called the CDC’s requirements for disembarkation “impractical”.

The standoff comes amid a deteriorating situation on many ships around the world and a rising death toll of crew members.

Continue reading...




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Jury hung in trial of Kulwinder Singh, who was accused of lighting his wife on fire

A Sydney jury is unable to reach a unanimous or majority verdict in the case of a Kulwinder Singh, who pleaded not guilty to setting his wife Parwinder Kaur on fire in 2013. She later died in hospital.




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Woman missing a 'chunk' of tooth, court hears in case of pair accused of posing as dentists

A court hears how a woman had a "chunk" of her tooth fall out after treatment, in a case against two people accused of posing as registered dentists.




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Geoffrey Rush accused of 'delivering lines' during Daily Telegraph defamation appeal

A $2.9 million payout is being challenged in court today after it was found Nationwide News defamed actor Geoffrey Rush in a high-profile case earlier this year.




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How the justice system turned a domestic violence victim into an accused murderer

Four years ago, Jonda Stephen found herself in a life or death situation. Her partner had hit her in the head multiple times with an iron, so she picked up a knife and stabbed him, in self-defence.



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