[Written by Stephen Wright] Former top Bermuda swimmers Lisa Blackburn and Julian Fletcher are among the travelling contingent of supporters cheering on the island’s athletes at the Olympic Games in Paris. Blackburn, who represented Bermuda at the Pan American Games in Toronto in 2015, met with Katura Horton-Perinchief, the island’s chef de mission, at the […]

A female driver who allegedly left the scene of a collision yesterday in Hamilton parish was “subsequently arrested at a nearby residence on suspicion of driving while impaired and causing grievous bodily harm by dangerous driving,” the police confirmed. A police spokesperson said, “Shortly after 5:30 pm on Tuesday, 24th October, 2023, police were dispatched […]

Hamilton Parish claimed a 2-1 victory over the Paget Lions in the Dudley Eve Trophy final at Wellington Oval on Sunday. Jordan Outerbridge gave Hamilton Parish the lead in the 19th minute, but Paget Lions equalized four minutes later through Diaje Hart. Macquille Walker scored the winning goal for Hamilton Parish in the 82nd minute. […]

The Department of Health and the Grow.Eat.Save Programme in collaboration with the Ministry of Public Works and the Department of Environment and Natural Resources is launching the 2024 Bermuda Parish Garden Competition, themed ‘Let’s Grow Together’ A Government spokesperson said, “This initiative encourages residents and organizations to participate in various categories, including School Garden, Community […]

Jessica Lewis will look to continue her fine form when she races at the WPA Paris Grand Prix as she builds towards the Paralympic Games in the French capital this summer. Lewis competes in the T53 100 metres tomorrow [June 13] at 7.05 am and the T53 400 on Friday at 12.06 pm. The Bermudian […]

Jessica Lewis finished second in the T53 100 metres at the WPA Paris Grand Prix in the French capital today [June 13]. Lewis clocked a time of 16.91sec to finish behind Catherine Debrunner, of Switzerland, in 15.68. Anita Scherrer, of Switzerland, came third in 19.27. Lewis, who competes in the T53 400 tomorrow, hopes to […]

[Written by Stephen Wright] Brian Wellman believes Jah-Nhai Perinchief must focus on “one jump at a time” as he prepares for the triple jump qualifiers at the Stade de France at the Olympic Games in Paris on Wednesday [August 7]. Four-time Olympian Wellman, one of the island’s greatest athletes, has travelled to the French capital […]

[Written by Stephen Wright] Para-athlete Jessica Lewis has reflected on her “unique experience” of representing Bermuda at the Paralympic Games in Paris. Lewis, the island’s most decorated para-athlete, finished fifth in the T53 100 metres and seventh in the T53 400 at the iconic Stade de France last week. The 31-year-old was joined in Paris […]

[Written by Stephen Wright] It is just 50 days until Bermuda’s athletes join more than 10,000 competitors from more than 200 nations at the Olympic Games in Paris – the largest sporting event organised in France. The opening ceremony for the 30th edition of the Summer Games promises to be an extravagant affair and the […]

[Written by Stephen Wright] A swarm of Dara Alizadeh supporters, decked out in bright pink Bermuda t-shirts and “Go Dara!” caps, descended on the Vaires-sur-Marne Nautical Stadium to cheer on the Bermuda rower. More than 30 of Alizadah’s family and friends have travelled to Paris to support the 30-year-old, who took to the water today […]

[Written by Stephen Wright] Bermuda rower Dara Alizadeh experienced his first victory in an Olympic Games race after winning his E/F semi-final at the Vaires-sur-Marne Nautical Stadium today [July 29]. Alizadeh, who competes in the men’s single sculls, claimed a comfortable win, finishing his two-kilometre race in 7min 33.38sec. The 30-year-old said he was encouraged […]

[Written by Dale Butler] The fifth Pastoral-Parishioners’ Anniversary took place on the grounds of the Christ Anglican Church, Devonshire, on Saturday, September 21, 2024 at 6.00pm with a very appetizing dinner by Kenny’s Kitchen and water donated by John Barritt & Son Limited; an exceptional night of entertainment followed. The tent, lighting, and stage backdrop […]

There has been a two vehicle road traffic collision involving a motorcar and a motorcycle in the area of Barnes Corner in Southampton Parish. A police spokesperson said, “There has been a two vehicle road traffic collision involving a motorcar and a motorcycle in the area of Barnes Corner, Southampton Parish. “Details are limited at […]

[Updated] “There has been a serious road traffic collision involving two motorcycles on Blue Hole Hill, Hamilton Parish,” the police said this evening [Nov 7]. “The roadway is currently closed, with traffic being diverted through the Grotto Bay compound. Motorists heading into or out of the east end are encouraged to delay their departure, if possible […]

I really love the card game Lost Cities, designed by Reiner Knizia. When my husband Christopher and I were first getting to know each other, we used to meet up at Starbucks sometimes and play games. Lost Cities was one of our frequent picks. It’s a head to head, two player game in which both players are trying to outscore each other by laying down ascending runs of card suits on a small board between the two of them. There’s a theme laid over the mechanism (completing expeditions in the lost world) but it’s basically pasted on and so that is the last we will speak of it. So there we were, newly in love, eyeing each other across the table, smiling and flirting, and doing our best to beat one another at Lost Cities. It was awesome. And now, with the roll & write genre having made an impressive rebound a few years ago (let’s not forget the mechanism has actually been around since the 50s with Yatzee), Knizia has ported his award winning game Lost Cities  into this format, releasing Lost Cities Roll & Write  in 2021. 

You can play the new Lost Cities  with up to 5 players, but in an ode to our romantic beginnings, Christopher and I played it exclusively with one another in successive matches.  The components are compact, lacking the pretty illustrations of the original game, and few in number – the rule book, a scorepad, three pentagonal trapezohedron dice (that’s 10 sided dice for the uninitiated), and three 6 sided custom dice with color suit symbols. Oh, and some pencils. That’s it. We could have played on an even smaller Starbucks table if we had this back in our dating days.

The cards from the original game (wager cards and numbered cards 2 to 10, in five different suits) have been translated into dice roll results. On each turn, one player rolls all the dice and chooses one of the six sided dice to represent the suit and one of the ten sided dice to represent the number. A zero on the number die can represent either zero (mimicking the wager card from the original game which serves as a multiplier for the total score in the selected suit) or ten (mimicking the highest card in each suit).

In place of the tableau built up on a central board, each player tracks the progress of wager and number cards they’ve collected for each suit in color coded columns on their individual score sheet. Wager cards have been transformed into little circular boxes to be marked off from a suit column when rolled, while the numbered cards from the original game have expanded to include the number 1 and are recorded as numbers written manually in the square boxes running up each column. Whereas in the original game, only cards higher than the last card played in a suit were permitted to be played on subsequent turns by the same player, in Lost Cities Roll & Write, numbers that are higher than or equal to the last number recorded for a suit may be written into the column after future dice rolls. Expanding beyond the concepts from the original game, Knizia has included artifact icons on select spaces in each column and when those spaces are filled by a player, they may fill in one of the jars in the artifact column. Likewise, he’s included arrow icons on select spaces and when those spaces are filled by a player, they may fill in the next box in one of their suit columns with the number from the previous box in the column – note that it does not have to be the same column in which the arrow was filled.  There’s also a column for filling in dice shapes to represent rolls where a player could not or did not want to use any of the dice results. The latter column is particularly tricky to manage effectively, as it provides a similar point progression as the rest of the columns (negative scores for the first 3 boxes filled and then positive score for the rest) up until the last box in the column. If you color in that box, your score for the dice shapes column drops from 70 to 0. The bonus points awarded in the original game (20 points for laying down at least 8 cards in a suit) have been implemented in Lost Cities Roll & Write  for each column (including the artifact and dice shape columns) as a 20 point bonus to the player who is the first to fill in 7 boxes in the column on the scorepad. The roll & write game ends when either both players have filled in the dice shapes column completely or all eight columns have passed the bonus point marker. In our experience, the completed dice shapes column is a much more common trigger.

I’ve played a ton of roll & write games over the past few years. Some are instant objects of adoration, while others are infuriating piles of poo (I’m looking at you Imperial Settlers R&W). Lost Cities Roll & Write is fantastic; a great addition to the genre. Knizia did an excellent job of translating the feel of the original game into the new mechanism. The iconography is clean and easy to read and the game can be taught and played in less than a half hour. And of course, it takes up very little table real estate, making it perfect for travel or tight spaces (when traveling as a passenger, simply roll the dice into the box cover). If you twisted my arm and forced me to choose between Lost Cities or Lost Cities Roll & Write, I’d be forced to pick the original, but only because of the lovely artwork on the cards and the sentimental value I have attached to the game after my love and I played it in our early days. But who would go around doing such arm twisting? Nobody. Therefore, with a retail price point under $15 for each of these, unless you’re down to your last $15, I recommend you pick up both. Play the card game with someone you love when you have a little more table space. Play the roll & write anywhere, with up to four additional friends. 

-------------------------------------------------

Publisher: Kosmos
Players: 2-5 (We played with 2)
Actual Playing Time (vs the guideline on the box): about 20 minutes per game
Game type: roll & write, dice rolling

Rating:

Rating scale:
OUI: I would play this game again; this game is ok. I probably would not buy this game myself but I would play it with those who own it and if someone gave it to me I would keep it.
OUI OUI: I would play this game again; this game is good. I would buy this game.
OUI OUI OUI: I LOVE THIS GAME. I MUST HAVE THIS GAME.
NON: I would not play this game again. I would return this game or give it away if it was given to me.

[BULLETIN: Quicklisp now has the latest version of FSet.]

Sycamore, primarily by Neil Dantam, is a functional collections library that is built around the same weight-balanced binary tree data structure (with leaf vectors) that FSet uses.  While the README on that page comments briefly on the differences between Sycamore and FSet, I don't feel that it does FSet justice.  Here is my analysis.

Dantam claims that his library is 30% to 50% faster than FSet on common operations.  While I haven't done comprehensive micro-benchmarking, a couple of quick tests indicates that this claim is plausible.  A look through the internals of the implementation confirms that it is clean and tight, and I must commend him.  There may be some techniques in here that I could usefully borrow.

Most of the performance difference is necessitated by two design choices that were made differently in the two libraries.  One of these Dantam mentions in his comparison: FSet's use of a single, global ordering relation implemented as a CLOS generic function, vs. Sycamore's more standard choice of requiring a comparison function to be supplied when a collection is created.  The other one he doesn't mention: the fact that FSet supports a notion of equivalent-but-unequal values, which are values that are incomparable — there's no way, or at least no obvious way, to say which is less than the other, and yet we want to treat them as unequal.  The simplest example is the integer 1 and the single-float 1.0, which have equal numerical values (and cl:= returns true on them), but which are nonetheless not eql.  (I have a previous blog post that goes into a lot more detail about equality and comparison.)  Since Sycamore expects the user-supplied comparison function to return an integer that is negative, zero, or positive to indicate the ordering of its arguments, there's no encoding for the equivalent-but-unequal case, nor is there any of the code that would be required to handle that case.

Both of these decisions were driven by my goal for the FSet project.  I didn't just want to provide a functional collections library that could be called occasionally when one had a specific need for such a data structure.  My ambition was much grander: to make functional collections into a reasonable default choice for the vast majority of programming situations.  I wanted FSet users (including, of course, myself) to be able to use functional collections freely, with very little extra effort or thought.  While Lisp by itself reaches a little bit in this direction — lists can certainly be used functionally — lists used as functional collections run into severe time complexity problems as those collections get large.  I wanted the FSet collections to be as convenient and well-supported as lists, but without the time complexity issues.

— Or rather, I wanted them to be even more convenient than lists.  Before writing FSet, I had spent years working in a little-known proprietary language called Refine, which happened to be implemented on top of Common Lisp, so it was not unusual to switch between the two languages.  And I had noticed something.  In contrast to CL, with its several different predefined equality predicates and with its functions that take :test arguments to specify which one to use, Refine has a single notiion of equality.  The value space is cleanly divided between immutable types, which are compared by value — along with numbers, these include strings, sets, maps, and seqs — and mutable objects, which are always compared by identity.  And it worked!  I found I did not miss the ability to specify an equality predicate when performing an operation such as "union".  It was just never needed.  Get equality right at the language level, and the problem goes away.

Although FSet's compare generic function isn't just for equality — it also defines an ordering that is used by the binary trees — I thought it would probably turn out to be the case that a single global ordering, implemented as a generic function and therefore extensible, would be fine the vast majority of the time.  I think experience has borne this out.  And just as you can mix types in Lisp lists — say, numbers and symbols — without further thought, so you can have any combination of types in an FSet set, effortlessly.  (A project I'm currently working on actually takes considerable advantage of this capability.)

As for supporting equivalent-but-unequal values, this desideratum flows directly from the principle of least astonishment.  While it might not be too surprising for a set or map implementation to fail distinguish the integer 1 from the float 1.0, it certainly would be very surprising, and almost certainly a source of bugs in a compiler that used it, for it to fail to distinguish two uninterned symbols with the same name.  (I saw a macro expansion recently that contained two distinct symbols that both printed as #:NEW.  It happens.)  A compiler using Sycamore for a map on symbols would have to supply a comparison function that accounted for this; it couldn't just compare the package name and symbol name.  (You'd have to do something like keep a weak hash table mapping symbols to integers, assigned in the order in which the comparison function encountered them.  It's doable, but FSet protects you from this madness.)

Along with those deep semantic design choices, I've spent a lot of time on developing a wide and featureful API for FSet (an effort that's ongoing).  FSet has many features that Sycamore lacks, including:

• seqs, a binary-tree sequence implementation that holds arbitrary Lisp objects (Sycamore ropes hold only characters, which is certainly an important special case, but why restrict ourselves?)
• default values for maps and seqs (the value to return when the key is outside the domain is associated with the collection, not supplied at the call site; this turns out to be a significant convenience)
• generic functions that operate on both lists and FSet collections, to shadow the CL builtins
  
• the powerful map-union and map-intersection operations (I'll blog about these in the future)
• more ways to iterate over the collections (the FSet tutorial has a good summary, about 3/4 of the way down)
• speaking of the tutorial, FSet has lots more documentation

Let me digress slightly to give an example of how FSet makes programming more elegant and convenient.  Joe Marshall just put up a blog post comparing Go(lang) with Common Lisp, which is worth a read on its own; I'm just going to grab a code snippet from there to show a little bit of what programming with FSet is like.  Here's Joe's code:

 (defun collate (items &key (key #'identity) (test #'eql) (merger (merge-adjoin #'eql)) (default nil))
   (let ((table (make-hash-table :test test)))
     (dolist (item items table)
       (let ((k (funcall key item)))
         (setf (gethash k table) (funcall merger (gethash k table default) item))))))

 (defun merge-adjoin (test)
   (lambda (collection item)
     (adjoin item collection :test test)))

And here's what I would write using FSet:

(Well, I would probably move result outside the dolist form to make it clearer what the return value is, but let's go with Joe's stylistic choice here.)

For those who haven't used FSet: the form (map :default (set)) creates a map whose default is the empty set, meaning that lookups on that map will return the empty set if the key is not in the map.  This saves the includef form from having to handle that possibility.

My version makes assumptions, it's true, about how you want to collect the items with a given key; it doesn't give you other choices.  It could, but what would be the point?  It's already using a general set with better time complexity than lists, and saving you from having to write anything like merge-adjoin.  The extensible global equivalence relation means you're not going to need to supply a :test either.

I think the FSet-enhanced code is cleaner, more elegant, and therefore clearer than the plain-CL version.  Don't you agree?  Maybe you wouldn't say it's a huge improvement, okay, but it's a small example; in a larger codebase, I would argue, these small improvements add up.

* * * * *

To summarize: if you just want a library you can call in a few places for specific purposes, Sycamore might work better for you (but think hard if you're writing a comparator for symbols).  FSet can certainly be used that way, but it can be much more.  If you want to see one way in which Common Lisp can be made into a better language, without giving up anything that we love about it, I urge you to give FSet a try.

FSet has changed the way I write Lisp programs.  — an FSet user

(UPDATE: the magnitude of the performance difference between FSet and Sycamore surprised me, and inspired me to do some profiling of FSet.  It turned out that I could get a 20% speedup on one micro-benchmark simply by adding some inline declarations.  Mea culpa, mea culpa, mea maxima culpa; I should have done this years ago.   With that change, the generic function overhead appears to be the only significant cause of the remaining ~20% performance difference.  I tried creating a Sycamore set using a thin wrapper around fset:compare, and the resulting performance was very similar to that of FSet with its new inlines.)

 .

It’s no secret that eCommerce is booming. In fact, a recent study by Statista shows that retail e-commerce...

The post WooCommerce Vs Shopify, a 2022 Comparison appeared first on Ignition Media.

The Paralympic Rowing Cox will compete a year after getting the all clear from cancer.

The Rugby 7s player has struggled with body image in the past, but says sport has helped

William M. Old
Oct 1, 2005; 4:1487-1502
Research

Visual Abstract

Visual Abstract

Visual Abstract

Mass spectrometry has become an indispensable tool for the characterization of glycosylation across biological systems. Our ability to generate rich fragmentation of glycopeptides has dramatically improved over the last decade yet our informatic approaches still lag behind. Although glycoproteomic informatics approaches using glycan databases have attracted considerable attention, database independent approaches have not. This has significantly limited high throughput studies of unusual or atypical glycosylation events such as those observed in bacteria. As such, computational approaches to examine bacterial glycosylation and identify chemically diverse glycans are desperately needed. Here we describe the use of wide-tolerance (up to 2000 Da) open searching as a means to rapidly examine bacterial glycoproteomes. We benchmarked this approach using N-linked glycopeptides of Campylobacter fetus subsp. fetus as well as O-linked glycopeptides of Acinetobacter baumannii and Burkholderia cenocepacia revealing glycopeptides modified with a range of glycans can be readily identified without defining the glycan masses before database searching. Using this approach, we demonstrate how wide tolerance searching can be used to compare glycan use across bacterial species by examining the glycoproteomes of eight Burkholderia species (B. pseudomallei; B. multivorans; B. dolosa; B. humptydooensis; B. ubonensis, B. anthina; B. diffusa; B. pseudomultivorans). Finally, we demonstrate how open searching enables the identification of low frequency glycoforms based on shared modified peptides sequences. Combined, these results show that open searching is a robust computational approach for the determination of glycan diversity within bacterial proteomes.

We performed an in-depth characterization and comparison of the pediatric and adult urinary glycomes using a nanoLC-MS/MS based glycomics method, which included normal healthy pediatric (1–10 years, n = 21) and adult (21–50 years, n = 22) individuals. A total of 116 N-glycan compositions were identified, and 46 of them could be reproducibly quantified. We performed quantitative comparisons of the 46 glycan compositions between different age and sex groups. The results showed significant quantitative changes between the pediatric and adult cohorts. The pediatric urinary N-glycome was found to contain a higher level of high-mannose (HM), asialylated/afucosylated glycans (excluding HM), neutral fucosylated and agalactosylated glycans, and a lower level of trisialylated glycans compared with the adult. We further analyzed gender-associated glycan changes in the pediatric and adult group, respectively. In the pediatric group, there was almost no difference of glycan levels between males and females. In adult, the majority of glycans were more abundant in males than females, except the high-mannose and tetrasialylated glycans. These findings highlight the importance to consider age-matching and adult sex-matching for urinary glycan studies. The identified normal pediatric and adult urinary glycomes can serve as a baseline reference for comparisons to other disease states affected by glycosylation.

Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. ⁶⁸Ga-labeled fibroblast activation protein inhibitor ([⁶⁸Ga]Ga-FAPI-04) PET/MRI, [¹⁸F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter’s sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [⁶⁸Ga]Ga-FAPI-04 PET/MRI and [¹⁸F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [⁶⁸Ga]Ga-FAPI-04 change in SUL_peak percentage, where SUL_peak is SUV_peak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [⁶⁸Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SUL_peak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.

U.S. Space Force has made public the prototypes of its new uniforms, which immediately drew comparisons to those worn in Star Trek and other science fiction franchises.

On the occasion of the fifth anniversary of the Paris Agreement, the event will highlight the key role of the agricultural sectors in supporting the Paris Agreement. The Paris Agreement, [...]

An increasing number of people in France espouse a clothing-free lifestyle

Paris police said Sunday that 4,000 officers and 1,600 stadium staff will be deployed for a France-Israel soccer match to ensure security a week after violence against Israeli fans in Amsterdam.

CostAware Compares Health Care Costs Based on Delaware Medical Claims NEW CASTLE (March 3, 2023) – The Delaware Department of Health and Social Services (DHSS) announced today the launch of a new version of its CostAware website, designed to help Delawareans understand how their health care dollars are spent by comparing the variation of average […]

NEW CASTLE – The Delaware Department of Health and Social Services (DHSS) announced today enhancements to the CostAware website, designed to help Delawareans understand how their health care dollars are spent by comparing the variation of average costs for different episodes of care and medical services based on actual medical and pharmacy claims in Delaware. […]

Paris Region has kept its fDi European Region of the Future title, while Dublin Region holds on to second place and North Rhine-Westphalia is in third. 

Paris — Paris police said Sunday that 4,000 officers and 1,600 stadium staff will be deployed for a France-Israel soccer match to ensure security in and around the stadium and on public transportation a week after violence against Israeli fans in Amsterdam.  France and Israel are playing in a UEFA Nations League match Thursday.  “There's a context, tensions that make that match a high-risk event for us,” Paris police chief Laurent Nuñez said on French news broadcaster BFM TV, adding authorities “won't tolerate” any violence.  Nuñez said that 2,500 police officers would be deployed around the Stade de France stadium, north of the French capital, in addition to 1,500 others in Paris and on public transportation.  “There will be an anti-terrorist security perimeter around the stadium,” Nuñez said. Security checks will be “reinforced,” he added, including with systematic pat-downs and bag searches.  Nuñez said that French organizers have been in contact with Israeli authorities and security forces to prepare for the match.  Israeli fans were assaulted last week after a soccer game in Amsterdam by hordes of   young people apparently riled up by calls on social media to target Jewish people,   according to Dutch authorities. Five people were treated at hospitals and dozens were arrested after the attacks, which were condemned as antisemitic by authorities in Amsterdam, Israel and across Europe.  On Sunday, Dutch police detained several people for taking part in a demonstration in central Amsterdam that had been outlawed following the violence targeting Israeli fans, a local broadcaster reported.  French Interior Minister Bruno Retailleau confirmed Friday that the France-Israel match would go ahead as planned.  “I think that for a symbolic reason we must not yield, we must not give up,” he said, noting that sports fans from around the world came together for the Paris Olympics this year to celebrate the “universal values” of sports. 

The Paris climate agreement's goals "are in great peril" and 2024 is on track to break new temperature records, the United Nations warned Monday as COP29 talks opened in Baku.

At the biggest summit since Copenhagen, negotiators from developed and developing countries converge in Paris to hammer out a meaningful international agreement to combat climate change.

Macron and Starmer lay wreath at Paris' Tomb of the Unknown Soldier on Armistice Day

So, the worst has happened. American voters have apparently just elected the most chaotic and kleptocratic individual in their country’s political history as their president. (We say ‘apparently’, because these days nothing can be certain about the integrity of the US political or electoral system – as is the case with far too many other […]

Ancient stone goods found across France may have been made by skilled craftspeople in what is now Paris, who traded along vast networks

BACKGROUND:Training in mechanical ventilation is a key goal in critical care fellowship education. Web-based simulators offer a cost-effective and readily available alternative to traditional on-site simulators. However, it is unclear how effective they are as teaching tools. In this study, we evaluated the test scores of fellows who underwent mechanical ventilation training by using a web-based simulator compared with fellows who used an on-site simulator during a mechanical ventilation course.METHODS:This was a nonrandomized controlled trial conducted as part of a mechanical ventilation course that involved 70 first-year critical care fellows. The course was identical except for the simulation technology used. One group of instructors used a traditional on-site simulator, the ASL 5000 Lung Solution (n = 39). The second group was instructed in using a web-based simulator, VentSim (n = 31). Each fellow completed a pre-course test and a post-course test by using a validated, case-based ventilator waveform examination that consisted of 5 questions with a total possible score of 100. The primary outcome was a comparison of the mean scores on the posttest between the 2 groups. The study was designed as a non-inferiority trial with a predetermined margin of 10 points.RESULTS:There was no significant difference in the mean ± SD pretest scores between the web-based and the on-site groups (21.1 ± 12.6 and 26.9 ± 13.6 respectively; P = .11). The mean ± SD posttest scores were 45.6 ± 25.0 for the web-based simulator and 43.4 ± 16.5 for on-site simulator (mean difference 2.2; one-sided 95% CI –7.0 to ∞; Pnon-inferiority = .02 [non-inferiority confirmed]). Changes in mean ± SD scores (posttest – pretest) were 25.9 ± 20.9 for the web-based simulator and 16.5 ± 15.9 for the on-site simulator (mean difference 9.4, one-sided 95% CI 0.9 to ∞; Pnon-inferiority < .001 [non-inferiority confirmed]).CONCLUSIONS:In the education of first-year critical care fellows on mechanical ventilation waveform analysis, a web-based mechanical ventilation simulator was non-inferior to a traditional on-site mechanical ventilation simulator.

Purpose The posterior superior alveolar (PSA) block injection is one of many techniques used to provide profound anesthesia for invasive dental procedures. This technique has a high success rate but is not without complication risks. The purpose of this study was to determine if pulpal anesthesia of the maxillary second molar could be achieved using a reduced needle depth of 10mm or 5mm compared to the traditional needle depth of 16mm.Methods Sixty participants were asked to participate in three sessions. Each session started with a pre neural response test, followed by one randomized needle depth PSA injection, and ending with a post neural response test. The neural response test consisted of two parts, a cold refrigerant and a dental probe, on the buccal and interproximal surface of the maxillary second molar. After receiving a positive neural response, each participant received a posterior superior alveolar block injection using a short (21mm), 27-gauge dental needle with a randomized needle penetration depth of 16mm, 10mm, or 5mm. A post neural response test consisting of the same two parts as the pre-test was conducted on the maxillary second molar to evaluate for profound anesthesia.Results Positive neural responses were obtained from 100% of the participants (n=167) during the pre-tests. Study results demonstrated an 85% success rate at the traditional 16mm needle depth and a 93% and 92% success rates for the reduced needle depths of 10mm and 5mm, respectively. Pulpal anesthesia of the maxillary second molar had been achieved at all three needle depths with no statistically significant difference in the rate of success. Furthermore, there were no adverse events observed.Conclusion The reduced needle depth technique showed promise in achieving desired results of pulpal anesthesia with a reduced risk for complications associated with the PSA block injection. Additional studies are recommended to achieve evidence-based support for this reduced needle depth technique.

The analysis of extractables and leachables and subsequent risk assessment is an important aspect of the determination of biocompatibility for many medical devices. Leachable chemicals have the potential to pose a toxicological risk to patients, and therefore it is required that they be adequately characterized and assessed for potential safety concerns. One important consideration in the assessment of leachables is the choice of a suitable simulating solvent intended to replicate the use condition for the device and its biological environment. This aspect of study design is especially difficult for blood-contacting medical devices due to the complexity of simulating the biological matrix. This publication reports a comparison of the extracting power of different binary solvent mixtures and saline in comparison with whole blood for a bloodline tubing set connected to a hemodialyzer. Ten different known extractables, spanning a range of physicochemical properties and molecular weights, were quantified. The results indicated that for low-molecular-weight analytes, a suitable exaggeration for whole blood can be obtained using a low-concentration ethanol/water mixture (20%), and in general, extracted quantity increases with the concentration of alcohol cosolvent. For polyvinylpyrrolidone, the opposite trend was observed, as solubility of the polymer was found to decrease with increasing alcohol concentration, resulting in lower extracted quantities at high alcohol concentrations. Analysis of ethanol/water concentrations in the extract solutions post extraction indicated no change in solvent composition.

SEquence Evaluation through k-mer Representation (SEEKR) is a method of sequence comparison that uses sequence substrings called k-mers to quantify the nonlinear similarity between nucleic acid species. We describe the development of new functions within SEEKR that enable end-users to estimate P-values that ascribe statistical significance to SEEKR-derived similarities, as well as visualize different aspects of k-mer similarity. We apply the new functions to identify chromatin-enriched lncRNAs that contain XIST-like sequence features, and we demonstrate the utility of applying SEEKR on lncRNA fragments to identify potential RNA-protein interaction domains. We also highlight ways in which SEEKR can be applied to augment studies of lncRNA conservation, and we outline the best practice of visualizing RNA-seq read density to evaluate support for lncRNA annotations before their in-depth study in cell types of interest.

The CYP3A7 enzyme accounts for ~50% of the total cytochrome P450 (P450) content in fetal and neonatal livers and is the predominant P450 involved in neonatal xenobiotic metabolism. Additionally, it is a key player in healthy birth outcomes through the oxidation of dehydroepiandrosterone (DHEA) and DHEA-sulfate. The amount of the other hepatic CYP3A isoforms, CYP3A4 and CYP3A5, expressed in neonates is low but highly variable, and therefore the activity of individual CYP3A isoforms is difficult to differentiate due to their functional similarities. Consequently, a better understanding of the contribution of CYP3A7 to drug metabolism is essential to identify the risk that drugs may pose to neonates and developing infants. To distinguish CYP3A7 activity from CYP3A4/5, we sought to further characterize the selectivity of the specific CYP3A inhibitors CYP3cide, clobetasol, and azamulin. We used three substrate probes, dibenzylfluorescein, luciferin-PPXE, and midazolam, to determine the IC₅₀ and metabolism-dependent inhibition (MDI) properties of the CYP3A inhibitors. Probe selection had a significant effect on the IC₅₀ values and P450 inactivation across all inhibitory compounds and enzymes. CYP3cide and azamulin were both identified as MDIs and were most specific for CYP3A4. Contrary to previous reports, we found that clobetasol propionate (CP) was not an MDI of CYP3A5 but was more selective for CYP3A5 over CYP3A4/7. We further investigated CYP3cide and CP’s ability to differentiate CYP3A7 activity in an equal mixture of recombinant CYP3A4, CYP3A5, and CYP3A7, and our results provide confidence of CYP3cide’s and CP’s ability to distinguish CYP3A7 activity in the presence of the other CYP3A isoforms.

The phase 3 VISION trial demonstrated that [¹⁷⁷Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]–positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor–signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [¹⁷⁷Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [¹⁷⁷Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.

The head of one of the world's largest oil companies has had it with government flip-flopping.

Chris gets cheesecake from rats. Kelley punches worms to get her Tifa back. And Josh funds a re-dub of Yakuza with Mark Hamil. Now excuse us as we go attend tonight's brawl at the local Waffle House.

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