ADB’s report on sovereign default and loss rates demonstrates the low credit risk in ADB's sovereign operations, with an average default rate of 0.54% over the last 34 years and zero new defaults from 2010 to 2021.

This study finds contract farming in Lao PDR to be effective in raising incomes of small farmers, thus reducing poverty.

to write a user manual for a website

Simple words like "force" and "particle" can mislead us as to what reality is actually like. Physicist Matt Strassler unpacks how to see things more clearly

Physicists have coaxed a cloud of atoms into having a temperature beyond absolute zero and placed them in a geometric structure that could produce an unknown form of matter

Simple words like "force" and "particle" can mislead us as to what reality is actually like. Physicist Matt Strassler unpacks how to see things more clearly

An analysis of satellite observations has identified some extreme thunderstorms over the Indian Ocean and Gulf of Mexico with lightning flashes so frequent that the sky would appear continuously lit

Title: FAQ: Steve Jobs' Pancreatic Cancer
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Introduction

Exacerbation of COPD complicated by respiratory acidaemia is the commonest indication for noninvasive ventilation (NIV). The NIV outcomes (NIVO) score offers the best estimate of survival for those ventilated. Unfortunately, two-thirds of cases of COPD are unrecognised, and patients may present without COPD having been confirmed by spirometry.

The antitumor effect of cardiotonic steroids (CTS) has stimulated the search for new methods to evaluate both kinetic and thermodynamic aspects of their binding to Na⁺/K⁺-ATPase (IUBMB Enzyme Nomenclature). We propose a real-time assay based on a chromogenic substrate for phosphatase activity (pNPPase activity), using only two concentrations with an inhibitory progression curve, to obtain the association rate (k_on), dissociation rate (k_off), and equilibrium (K_i) constants of CTS for the structure-kinetics relationship in drug screening. We show that changing conditions (from ATPase to pNPPase activity) resulted in an increase of K_i of the cardenolides digitoxigenin, essentially due to a reduction of k_on. In contrast, the K_i of the structurally related bufadienolide bufalin increased much less due to the reduction of its k_off partially compensating the decrease of its k_on. When evaluating the kinetics of 15 natural and semisynthetic CTS, we observed that both k_on and k_off correlated with K_i (Spearman test), suggesting that differences in potency depend on variations of both k_on and k_off. A rhamnose in C3 of the steroidal nucleus enhanced the inhibitory potency by a reduction of k_off rather than an increase of k_on. Raising the temperature did not alter the k_off of digitoxin, generating a H (k_off) of –10.4 ± 4.3 kJ/mol, suggesting a complex dissociation mechanism. Based on a simple and inexpensive methodology, we determined the values of k_on, k_off, and K_i of the CTS and provided original kinetics and thermodynamics differences between CTS that could help the design of new compounds.

Low-efficacy mu opioid receptor (MOR) agonists may serve as novel candidate analgesics with improved safety relative to high-efficacy opioids. This study used a recently validated assay of pain-depressed behavior in mice to evaluate a novel series of MOR-selective C9-substituted phenylmorphan opioids with graded MOR efficacies. Intraperitoneal injection of dilute lactic acid (IP acid) served as a noxious stimulus to depress locomotor activity by mice in an activity chamber composed of two compartments connected by an obstructed door. Behavioral measures included (1) crosses between compartments (vertical activity over the obstruction) and (2) movement counts quantified as photobeam breaks summed across compartments (horizontal activity). Each drug was tested alone and as a pretreatment to IP acid. A charcoal-meal test and whole-body-plethysmography assessment of breathing in 5% CO₂ were also used to assess gastrointestinal (GI) inhibition and respiratory depression, respectively. IP acid produced a concentration-dependent depression in crosses and movement that was optimally alleviated by intermediate- to low-efficacy phenylmorphans with sufficient efficacy to produce analgesia with minimal locomotor disruption. Follow-up studies with two low-efficacy phenylmorphans (JL-2-39 and DC-1-76.1) indicated that both drugs produced naltrexone-reversible antinociception with a rapid onset and a duration of ~1 h. Potency of both drugs increased when behavior was depressed by a lower IP-acid concentration, and neither drug alleviated behavioral depression by a non-pain stimulus (IP lithium chloride). Both drugs produced weaker GI inhibition and respiratory depression than fentanyl and attenuated fentanyl-induced GI inhibition and respiratory depression. Results support further consideration of selective, low-efficacy MOR agonists as candidate analgesics.

BackgroundCOVID-19 pandemic restrictions may have influenced behaviours related to weight.AimTo describe patterns of weight change among adults living in England with type 2 diabetes (T2D) and/or hypertension during the pandemic.Design and settingAn observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP.MethodClinical and sociodemographic characteristics associated with rapid weight gain (>0.5 kg/m2/year) were investigated using multivariable logistic regression.ResultsData were extracted on adults with T2D (n = 1 231 455, 43.9% female, and 76.0% White British) or hypertension (n = 3 558 405, 49.7% female, and 84.3% White British). Adults with T2D lost weight overall (median δ = −0.1 kg/m2/year [interquartile range {IQR} −0.7–0.4]). However, rapid weight gain was common (20.7%) and associated with the following: sex (male versus female: adjusted odds ratio [aOR] 0.78 [95% confidence interval {CI} = 0.77 to 0.79]); age (older age reduced odds, for example, aged 60–69 years versus 18–29 years: aOR 0.66 [95% CI = 0.61 to 0.71]); deprivation (least deprived Index of Multiple Deprivation [IMD] quintile versus most deprived IMD quintile: aOR 0.87 [95% CI = 0.85 to 0.89]); White ethnicity (Black versus White: aOR 0.95 [95% CI = 0.92 to 0.98]); mental health conditions (for example, depression: aOR 1.13 [95% CI = 1.12 to 1.15]); and diabetes treatment (non-insulin treatment versus no pharmacological treatment: aOR 0.68 [95% CI = 0.67 to 0.69]). Adults with hypertension maintained stable weight overall (median δ = 0.0 kg/m2/year [IQR −0.6–0.5]); however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D.ConclusionAmong adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common among females, younger adults, those living in more deprived areas, and those with mental health conditions.

Scottish investment giant abrdn has sold its Focus Solutions software business and is said to be eyeing other potential disposals

Kelley dishonors herself in Baldur's Gate 3 and retreats to Vampire Survivors. Chris goes on the hunt for Dr. Robotminsc. Robert hits level 50 before the third scripted battle.

The post RPG Cast – Episode 690: “Spay and Neuter Your Owlbear Cubs” appeared first on RPGamer.

I first played Taiko no Tatsujin in an arcade (in Japan, because I am very cool), where it's controlled by hitting a recreation of an actual taiko drum. It was fun enough that I wish there was a taiko drum peripheral available for PC now the series is on our platform.

Taiko no Tatsujin: Rhythm Festival is out now via Steam, where it offers over 70 songs to drum through, and a subscription service through which to unlock over 700 more. Maybe I should try to get my Donkey Konga drums working on PC, but I'll probably settle for playing it with a gamepad.

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The UK government's decision to return the Chagos Islands to Mauritius surprisingly threatens the extinction of millions of website addresses ending in ".io", and no one is quite sure what will happen next

The finale doesn’t look to provide a definitive answer to what drove Aaron’s actions, much to the show’s credit.

Krasinski scores the title of People’s Sexiest Man Alive 2024.

A Swiss-engineered robot can climb ladders, showing why it's at the cutting edge of autonomous robotic solutions for harsh industrial settings.

Former Chelsea and Arsenal defender Ashley Cole has signed a new one-year contract to remain with the LA Galaxy for a third season in Major League Soccer..

Arsenal and England midfielder Jordan Nobbs will be a columnist for 90min & BBC Sport pundit at the Women's World Cup in France this summer, as Phil Neville's Lionesses' look to secure a maiden World Cup triumph. Two wins from our first two games is obviously what we were all hoping for. The first game of a World Cup, or any other major tournament, is never going to be one where you're playing at your absolute best. But the 2-1 win over was Scotland was great given the pre-match hype, the..

Police are hunting laughing yobs who filmed themselves hurling a cat off a bridge and posted the video on Snapchat.

As many as 115 Post Office Branches and hundreds of jobs could be at risk following a strategic review held by Post Office Chairman Nigel Railton.

Narratives around addiction often reduce it to a series of poor choices, lack of values and weakness. This has real-world consequences, warns Anna Wolfe

Immigration and Customs Enforcement has arrested another illegal immigrant charged with child sex offenses, as the state's governor says police won't help the Trump administration.

Kelly Clarkson filled in for Cowell as he recuperates from back surgery.

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We spoke to Reverend Doctor Stephen Cherry, Dean of Chapel at King's College, Cambridge.

In today’s digital age, your website is more than just a virtual storefront—it’s the heart of your online presence. Whether you’re a small business, a growing startup, or an established brand, a custom-designed website can be the key to standing out in a crowded market. But what does it take to truly transform your digital […]

The post How to Transform Your Online Presence with a Custom Website appeared first on Chart Attack.

I’ve been hearing a lot about IPTV lately. There’s no denying that it’s shaken up the way we consume content. From streaming live sports events to watching your favorite shows on demand, IPTV services have become incredibly popular. But let’s be honest: with so many different subscription options out there, it can get a little […]

The post Is a Premium IPTV Subscription Worth the Extra Cost? appeared first on Chart Attack.

Broadcom acquisition was a "wake-up call" for VMware-dependent SMBs.

Bollywood star Suniel Shetty sustained a minor injury on the sets of the web series ‘Hunter 2’