Scottish Parliament brings forward Bill to introduce new “group proceedings” procedure in Scotland The Civil Litigation (Expenses and Group Proceedings) (Scotland) Bill (the ‘Bill’) is currently making its way through the Sco...

Tselane Mashilo says she believes teaching should be an holistic process, that you don’t separate the body from the mind.

Court of appeal overturns High Court judgment in Lloyd v Google LLC [2019] EWCA Civ 1599 Court of Appeal judgment The Court of Appeal has given the go-ahead for a representative claim to be served on Google LLC in the U.S. for alleged data breaches,...

Finally, the wait is over. Students, now you can check your result on this page. Share with your friends also. Enter

The Italian legislation on private antitrust enforcement (Legislative Decree no. 3 of 19 January 2017 - Decree) has implemented the EU Directive no. 2014/104. The Decree sets out the rules according to which any natural or legal person who has suffe...

A pole dance instructor in Turkey has moved her studio to the internet as people across the world turn to online exercise classes amid the coronavirus pandemic.

Many anime releases have been delayed indefinitely due to the COVID-19 outbreak, but in the meantime, with their vast libraries of anime films and series, ...

Universities look at ways to deal with learning during the pandemic in a ready-to-go English lesson that includes questions and discussion topics.

Is the Leaving Cert cancelled or postponed?

PESHAWAR: The Bacha Khan Medical College in Mardan has launched online classes for its students in order to enable them to pursue their studies without any hindrance.It was the first medical college that took the initiative after the government closed all educational institutions in the country...

Currently, platform has attracted over 100 million users.

The fate of some 27,000 Hong Kong cross-border pupils living in mainland China was in limbo, as the education minister said on Friday that it could not be guaranteed whether they would be exempted from quarantine rules amid the coronavirus pandemic when classes resumed in late May.Although Hong Kong’s government last week decided to exempt these cross-border students from a 14-day mandatory quarantine period when entering the city, a similar rule had so far not been lifted by the Shenzhen…

Schools and universities are to resume classes in June, Education Minister Tarek Majzoub said Friday

Las Vegas, Nev. — HARMAN International, a wholly-owned subsidiary of Samsung Electronics Co., Ltd. focused on connected technologies for automotive, consumer and enterprise markets, is introducing the JBL L82 Classic, a modern bookshelf version of the...

Arizona State University's Thunderbird School of Global Management utilizes robots to give its students a virtual graduation ceremony. Freddie Joyner has more.

Arizona State University's Thunderbird School of Global Management utilizes robots to give its students a virtual graduation ceremony. Freddie Joyner has more.

Ditch the phone, don't stand too close and strive for optimal eye contact: the evidence-based approach to painless holiday schmoozing

Arizona State University's Thunderbird School of Global Management utilizes robots to give its students a virtual graduation ceremony. Freddie Joyner has more.

Title: New Drug Class Slashes 'Bad' Cholesterol, Review Finds
Category: Health News
Created: 4/27/2015 12:00:00 AM
Last Editorial Review: 4/28/2015 12:00:00 AM

ABSTRACT

Burkholderia pseudomallei, the founding member of the B. pseudomallei complex (Bpc), is a biothreat agent and causes melioidosis, a disease whose treatment mainly relies on ceftazidime and meropenem. The concern is that B. pseudomallei could enhance its drug resistance repertoire by the acquisition of DNA from resistant near-neighbor species. Burkholderia ubonensis, a member of the B. cepacia complex (Bcc), is commonly coisolated from environments where B. pseudomallei is present. Unlike B. pseudomallei, in which significant primary carbapenem resistance is rare, it is not uncommon in B. ubonensis, but the underlying mechanisms are unknown. We established that carbapenem resistance in B. ubonensis is due to an inducible class A PenB β-lactamase, as has been shown for other Bcc bacteria. Inducibility is not sufficient for high-level resistance but also requires other determinants, such as a PenB that is more robust than that present in susceptible isolates, as well as other resistance factors. Curiously and diagnostic for the two complexes, both Bpc and Bcc bacteria contain distinct annotated PenA class A β-lactamases. However, the protein from Bcc bacteria is missing its essential active-site serine and, therefore, is not a β-lactamase. Regulated expression of a transcriptional penB'-lacZ (β-galactosidase) fusion in the B. pseudomallei surrogate B. thailandensis confirms that although Bpc bacteria lack an inducible β-lactamase, they contain the components required for responding to aberrant peptidoglycan synthesis resulting from β-lactam challenge. Understanding the diversity of antimicrobial resistance in Burkholderia species is informative about how the challenges arising from potential resistance transfer between them can be met.

IMPORTANCE Burkholderia pseudomallei causes melioidosis, a tropical disease that is highly fatal if not properly treated. Our data show that, in contrast to B. pseudomallei, B. ubonensis β-lactam resistance is fundamentally different because intrinsic resistance is mediated by an inducible class A β-lactamase. This includes resistance to carbapenems. Our work demonstrates that studies with near-neighbor species are informative about the diversity of antimicrobial resistance in Burkholderia and can also provide clues about the potential of resistance transfer between bacteria inhabiting the same environment. Knowledge about potential adverse challenges resulting from the horizontal transfer of resistance genes between members of the two complexes enables the design of effective countermeasures.

Positive selection causes beneficial alleles to rise to high frequency, resulting in a selective sweep of the diversity surrounding the selected sites. Accordingly, the signature of a selective sweep in an ancestral population may still remain in its descendants. Identifying signatures of selection in the ancestor that are shared among its descendants is important to contextualize the timing of a sweep, but few methods exist for this purpose. We introduce the statistic SS-H12, which can identify genomic regions under shared positive selection across populations and is based on the theory of the expected haplotype homozygosity statistic H12, which detects recent hard and soft sweeps from the presence of high-frequency haplotypes. SS-H12 is distinct from comparable statistics because it requires a minimum of only two populations, and properly identifies and differentiates between independent convergent sweeps and true ancestral sweeps, with high power and robustness to a variety of demographic models. Furthermore, we can apply SS-H12 in conjunction with the ratio of statistics we term and to further classify identified shared sweeps as hard or soft. Finally, we identified both previously reported and novel shared sweep candidates from human whole-genome sequences. Previously reported candidates include the well-characterized ancestral sweeps at LCT and SLC24A5 in Indo-Europeans, as well as GPHN worldwide. Novel candidates include an ancestral sweep at RGS18 in sub-Saharan Africans involved in regulating the platelet response and implicated in sudden cardiac death, and a convergent sweep at C2CD5 between European and East Asian populations that may explain their different insulin responses.

There is increasing interest in developing diagnostics that discriminate individual mutagenic mechanisms in a range of applications that include identifying population-specific mutagenesis and resolving distinct mutation signatures in cancer samples. Analyses for these applications assume that mutagenic mechanisms have a distinct relationship with neighboring bases that allows them to be distinguished. Direct support for this assumption is limited to a small number of simple cases, e.g., CpG hypermutability. We have evaluated whether the mechanistic origin of a point mutation can be resolved using only sequence context for a more complicated case. We contrasted single nucleotide variants originating from the multitude of mutagenic processes that normally operate in the mouse germline with those induced by the potent mutagen N-ethyl-N-nitrosourea (ENU). The considerable overlap in the mutation spectra of these two samples make this a challenging problem. Employing a new, robust log-linear modeling method, we demonstrate that neighboring bases contain information regarding point mutation direction that differs between the ENU-induced and spontaneous mutation variant classes. A logistic regression classifier exhibited strong performance at discriminating between the different mutation classes. Concordance between the feature set of the best classifier and information content analyses suggest our results can be generalized to other mutation classification problems. We conclude that machine learning can be used to build a practical classification tool to identify the mutation mechanism for individual genetic variants. Software implementing our approach is freely available under an open-source license.

Brucella spp. are facultative intracellular bacteria notorious for their ability to induce a chronic, and often lifelong, infection known as brucellosis. To date, no licensed vaccine exists for prevention of human disease, and mechanisms underlying chronic illness and immune evasion remain elusive. We and others have observed that B cell-deficient mice challenged with Brucella display reduced bacterial burden following infection, but the underlying mechanism has not been clearly defined. Here, we show that at 1 month postinfection, B cell deficiency alone enhanced resistance to splenic infection ~100-fold; however, combined B and T cell deficiency did not impact bacterial burden, indicating that B cells only enhance susceptibility to infection when T cells are present. Therefore, we investigated whether B cells inhibit T cell-mediated protection against Brucella. Using B and T cell-deficient Rag1^–/– animals as recipients, we demonstrate that adoptive transfer of CD4⁺ T cells alone confers marked protection against Brucella melitensis that is abrogated by cotransfer of B cells. Interestingly, depletion of CD4⁺ T cells from B cell-deficient, but not wild-type, mice enhanced susceptibility to infection, further confirming that CD4⁺ T cell-mediated immunity against Brucella is inhibited by B cells. In addition, we found that the ability of B cells to suppress CD4⁺ T cell-mediated immunity and modulate CD4⁺ T cell effector responses during infection was major histocompatibility complex class II (MHCII)-dependent. Collectively, these findings indicate that B cells modulate CD4⁺ T cell function through an MHCII-dependent mechanism which enhances susceptibility to Brucella infection.

Limited treatment options contribute to high morbidity/mortality rates with carbapenem-resistant, Gram-negative bacterial infections. New approaches for carbapenemase-producing organism (CPO) detection may help inform clinician decision-making on patient treatment and infection control. BD Phoenix CPO detect (CPO detect) detects and classifies carbapenemases in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa during susceptibility testing. The clinical performance of CPO detect is reported here. Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa isolates were evaluated across three sites using CPO detect and a composite reference method (RM); the latter was comprised of the modified carbapenem inactivation method and a MIC screen for ertapenem, imipenem, and meropenem. Multiplex PCR testing was also utilized for Ambler class determination. Positive and negative percentages of agreement (PPA and NPA, respectively) between CPO detect and the RM were determined. The PPA and NPA for Enterobacterales were 98.5% (confidence intervals, 96.6%, 99.4%) and 97.2% (95.8%, 98.2%), respectively. The A. baumannii PPA and NPA, respectively, were 97.1% (90.2%, 99.2%) and 97.1% (89.9%, 99.2%). The P. aeruginosa PPA and NPA, respectively, were 95.9% (88.6%, 98.6%) and 92.3% (86.7%, 95.6%). The PPA values for carbapenemase class designations for all organisms combined and Enterobacterales alone, respectively, were 95.3% (90.2%, 97.8%) and 94.6% (88.8%, 97.5%) for class A, 94.0% (88.7%, 96.6%) and 96.4% (90.0%, 98.8%) for class B, and 95.0% (90.1%, 97.6%) and 99.0% (94.4%, 99.8%) for class D carbapenemases. NPA values for all organisms and Enterobacterales alone ranged from 98.5% to 100%. CPO detect provided accurate detection and classification of CPOs for the majority of isolates of Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa tested.

Extractables and leachables (E&L) are identified and quantified so that their impact on patient safety can be established and assessed. The uncertainty in the impact assessment is affected by the uncertainty in the substance's experimentally determined identity and concentration. Thus, these experimentally determined quantities must be reported not only in terms of their absolute result but also in terms of the uncertainty in the result, which is based on the amount and rigor of the information on which the result is based. In this way, the impact assessment can be tempered to account for the uncertainty in its input data. To facilitate the assignment and reporting of uncertainty, classification hierarchies are proposed and discussed for both identification and quantitation. Both hierarchies establish levels or degrees of identification and quantitation based on the uncertainty of the result and contain descriptions of the quality and quantity of information required to achieve a certain level within the hierarchy. The minimal levels that must be achieved to support impact assessment are also established.

OBJECTIVE

With rising health care costs and finite health care resources, understanding the population needs of different type 2 diabetes mellitus (T2DM) patient subgroups is important. Sparse data exist for the application of population segmentation on health care needs among Asian T2DM patients. We aimed to segment T2DM patients into distinct classes and evaluate their differential health care use, diabetes-related complications, and mortality patterns.

Cefazolin has become a prominent therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, an important concern is the cefazolin inoculum effect (CzIE), a phenomenon mediated by staphylococcal β-lactamases. Four variants of staphylococcal β-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal β-lactamases and their correlation with the CzIE. We included a large collection of 690 contemporary bloodstream MSSA isolates recovered from Latin America, a region with a high prevalence of the CzIE. We determined cefazolin MICs at standard and high inoculums by broth microdilution. Whole-genome sequencing was performed to classify the β-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for β-lactamase classification and compared it to BlaZ allotypes found in unique sequences using the genomic information. Phylogenetic analyses were performed based on the BlaZ and core-genome sequences. The overall prevalence of the CzIE was 40%. Among 641 genomes, type C was the most predominant β-lactamase (37%), followed by type A (33%). We found 29 allotypes and 43 different substitutions in BlaZ. A single allotype, designated BlaZ-2, showed a robust and statistically significant association with the CzIE. Two other allotypes (BlaZ-3 and BlaZ-5) were associated with a lack of the CzIE. Three amino acid substitutions (A9V, E112A, and G145E) showed statistically significant association with the CzIE (P = <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal β-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE.

Royal Enfield अपनी Classic 350 का न्यू जनरेशन मॉडल लॉन्च करने की तैयारी कर रही है। जानकारी के मुताबिक कंपनी इस मॉडल को इस साल के अंत तक या अगले साल के शुरुआत में ही लॉन्च कर सकती है।

This film gives us insight into a community that’s already endured plenty even before the zombies arrived.

Platform sandals meet 40-denier tights as rock’n’roll goes bourgeois at Paris fashion week

At his Celine catwalk show on Friday night, the designer Hedi Slimane distilled what looks to be the most compelling trend of this season of fashion shows. Working title: rock’n’roll bourgeois.

Slim knee-length dresses were worn with slinky chain belts; towering platform sandals with sensible 40-denier semi-sheer tights; slim bootcut velvet trousers worn with Princess-line above-the-knee coats. This was a masterclass in Parisian allure: take one part Avenue Montaigne privilege, and mix with one part backstage pass. Shaken, not stirred.

Excellent film-maker that he is, Watiti seems to fit the Marvel blueprint far more easily than he does Star Wars’ more venerable, old-school template

When entertainment reporters play Hollywood roulette, the practice of attaching directors and stars to forthcoming movies based on little more than rumour, their little white balls nearly always seem to land on Taika Waititi’s number. If you’ve been keeping a close eye on this column over the past year, you’ve probably spotted the white-hot Kiwi director being touted for a remake of Flash Gordon and the next Deadpool movie among other projects, neither of which have yet come to fruition.

Waititi’s next film, according to reports this week, will be a Star Wars episode. Will he end up making it to the first day of production on this one? The chances seem better, as Disney has officially confirmed the appointment via the space saga’s official website, with 1917 co-writer Krysty Wilson-Cairns helping deliver a script. But this is Star Wars we are talking about – Colin Trevorrow, Josh Trank, Phil Lord and Christopher Miller, David Benioff and DB Weiss are among the numerous film-makers who have cheerily signed up to try to bring back the glory days of the long-running series in recent times, only to ultimately fall foul of Lucasfilm president Kathleen Kennedy’s merciless Force choke.

You can donate at virginmoneygiving.com/fund/FoodforLondonNOW

Joe Wicks says he will be back for his PE class on Monday after undergoing hand surgery.

A man whose wife was killed in the April mass shooting in Nova Scotia is the plaintiff named in a proposed class-action lawsuit against the estate of the deceased gunman, denturist Gabriel Wortman.

On April 20, ET had reported that ICICI Bank had a $100 million exposure to Singapore based oil trading company Hin Leon Trading Pte.

Time to catch up on some of the greatest movies ever made.

Sean S. Cunningham's slasher 'Friday the 13th' is celebrating its 40th anniversary this week. Its effect on the horror genre defined the 1980s.

If Sally Rooney is the first great millennial novelist, then Marianne Sheridan is the first great millennial TV style icon

Would it make a person really shallow if their favourite thing about the TV adaptation of Normal People was Marianne’s wardrobe? Asking for a friend.

A proposed class-action lawsuit has been filed against the estate of the perpetrator of Canada’s worst mass shooting, which left 22 people dead in several Nova Scotia communities last month.

Classic casual games such as Solitaire, sudoku, crossword puzzles and pinball live on smartphones and tablets as the mobile gaming audience expands.

Nintendo plans to release remastered versions of classic titles in the Mario catalog for Nintendo Switch in 2020.

'Final Fantasy VII' is considered one of the best video games. Now, Square Enix is bringing it back with the launch of 'Final Fantasy VII Remake.'

Role-playing epic Final Fantasy VII Remake is an ambitious revisiting of one of the most beloved titles in video game history.

Whether or not the Ingrams were cheating on 'Who Wants to Be a Millionaire?', the resulting outrage was rooted in the same dynamics that have come to dominate social discourse in the years since, says Adam White

Mario Lopez, Elizabeth Berkley and Mark-Paul Gosselaar are among the show's returning cast members

Outing, written by Rod Serling, holds mirror to quarantine life