BACKGROUND:Opioids are known to cause respiratory depression, aspiration, and to suppress the immune system. This study aimed to investigate the relationship between short- and long-term opioid use and the occurrence and clinical outcomes of pneumonia in South Korea.METHODS:The data for this population-based retrospective cohort analysis were obtained from the South Korean National Health Insurance Service. The opioid user group consisted of those prescribed opioids in 2016, while the non-user group, who did not receive opioid prescriptions that year, was selected using a 1:1 stratified random sampling method. The opioid users were categorized into short-term (1–89 d) and long-term (≥90 d) users. The primary end point was pneumonia incidence from January 1, 2017–December 31, 2021, with secondary end points including pneumonia-related hospitalizations and mortality rates during the study period.RESULTS:In total, 4,556,606 adults were enrolled (opioid group, 2,070,039). Opioid users had a 3% higher risk of pneumonia and an 11% higher risk of pneumonia requiring hospitalization compared to non-users. Short-term users had a 3% higher risk of pneumonia, and long-term users had a 4% higher risk compared to non-users (P < .001). Additionally, short-term users had an 8% higher risk of hospital-treated pneumonia, and long-term users had a 17% higher risk compared to non-users (P < .001).CONCLUSIONS:Both short- and long-term opioid prescriptions were associated with higher incidences of pneumonia and hospital-treated pneumonia. In addition, long-term opioid prescriptions were linked to higher mortality rates due to pneumonia.

BACKGROUND:PEEP is a cornerstone treatment for children with pediatric ARDS. Unfortunately, its titration is often performed solely by evaluating oxygen saturation, which can lead to inadequate PEEP level settings and consequent adverse effects. This study aimed to assess the impact of increasing PEEP on hemodynamics, respiratory system mechanics, and oxygenation in children with ARDS.METHODS:Children receiving mechanical ventilation and on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8 cm H2O, and again to 5 cm H2O. After 10 min at each PEEP level, hemodynamic, ventilatory, and oxygenation variables were collected.RESULTS:A total of 31 subjects were included, with median age and weight of 6 months and 6.3 kg, respectively. The main reasons for pediatric ICU admission were respiratory failure caused by acute viral bronchiolitis (45%) and community-acquired pneumonia (32%). Most subjects had mild or moderate ARDS (45% and 42%, respectively), with a median (interquartile range) oxygenation index of 8.4 (5.8–12.7). Oxygen saturation improved significantly when PEEP was increased. However, although no significant changes in blood pressure were observed, the median cardiac index at PEEP of 12 cm H2O was significantly lower than that observed at any other PEEP level (P = .001). Fourteen participants (45%) experienced a reduction in cardiac index of > 10% when PEEP was increased to 12 cm H2O. Also, the estimated oxygen delivery was significantly lower, at 12 cm H2O PEEP. Finally, respiratory system compliance significantly reduced when PEEP was increased. At a PEEP of 12 cm H2O, static compliance had a median reduction of 25% in relation to the initial assessment (PEEP of 5 cm H2O).CONCLUSIONS:Although it may improve arterial oxygen saturation, inappropriately high PEEP levels may reduce cardiac output, oxygen delivery, and respiratory system compliance in pediatric subjects with ARDS with low potential for lung recruitability.

A prefilled syringe (PFS) should be able to be adequately and consistently extruded during injection for optimal safe drug delivery and accurate dosing. To facilitate appropriate break-loose and gliding forces (BLGFs) required during injection, certain primary packaging materials (PPMs) such as the syringe barrel and plunger are usually coated with silicone oil, which acts as a lubricant. Due to its direct contact with drug, silicone oil can increase the number of particles in the syringe, which could lead to adverse interactions. Compliance with regulatory-defined silicone oil quantities in certain drug products, such as ophthalmics, presents a trade-off with the necessity for desirable low and consistent BLGF. In addition to its siliconization, the dimensional accuracy of the PPM has an important role in controlling the BLGF. The dimensions of the PPM are individualized depending on the product and its design and have certain tolerances that must be met during manufacturing. Most studies on ophthalmics focused on the adverse interactions between silicone oil and the drug. To the authors' knowledge, there have been no public studies so far that have investigated the impact of the dimensional variability of the PPM on the BLGF in ophthalmic PFSs. In this study, we applied advanced optical shaft and tactile measuring technologies to investigate this impact. The syringes investigated were first sampled during aseptic production and tested for the BLGF. Subsequently, defined dimensions of the PPM were measured individually. The results showed that the dimensional variability of the PPM can have a negative impact on the BLGF, despite their conformity to specifications, which indicates that the currently available market quality of PPMs is improvable for critical drug products such as ophthalmics. This study could serve as an approach to define product-specific requirements for primary packaging combinations and thus appropriate specifications based on data during the development stage of drug products.

Thermoregulation, responsible for maintaining a stable core temperature during wide fluctuations in external and internal thermal environments, is an iconic homeostatic process. However, we suggest that despite its fundamental physiological significance, the potential for required cool housing temperatures and thermoregulatory mechanisms to influence the interpretation of experimental data is not sufficiently appreciated. Moreover, although it is generally assumed that the major thermoregulatory pathways are well understood, here we discuss new research that suggests otherwise and reveals the emergence of a new wave of exciting ideas for this "old" field of research.

Early detection of drug-drug interactions (DDIs) can facilitate timely drug development decisions, prevent unnecessary restrictions on patient enrollment, resulting in clinical study populations that are not representative of the indicated study population, and allow for appropriate dose adjustments to ensure safety in clinical trials. All of these factors contribute to a streamlined drug approval process and enhanced patient safety. Here we describe a new approach for early prediction of the magnitude of change in exposure for cytochrome P450 (P450) CYP3A4-related DDIs of small-molecule anticancer drugs based on the model-based extrapolation of human-CYP3A4-transgenic mice pharmacokinetics to humans. Victim drugs brigatinib and lorlatinib were evaluated with the new approach in combination with the perpetrator drugs itraconazole and rifampicin. Predictions of the magnitude of change in exposure deviated at most 0.99- to 1.31-fold from clinical trial results for inhibition with itraconazole, whereas exposure predictions for the induction with rifampicin were less accurate, with deviations of 0.22- to 0.48-fold. Results for the early prediction of DDIs and their clinical impact appear promising for CYP3A4 inhibition, but validation with more victim and perpetrator drugs is essential to evaluate the performance of the new method.

ABSTRACTTraining health workers is one of the biggest challenges and cost drivers when introducing a new contraceptive method or service delivery innovation. PATH developed a digital training curriculum for family planning providers who are learning to offer subcutaneous DMPA (DMPA-SC), including through self-injection, as an option among a range of contraceptive methods. The DMPA-SC eLearning course for health workers includes 10 lessons with an emphasis on informed choice counseling and training clients to self-inject. In partnership with Ministries of Health in Senegal and Uganda, the course was rolled out in select areas in 2019–2020, including during the COVID-19 pandemic when physical distancing requirements restricted in-person training. We conducted evaluations in both countries to assess the practical application of this digital training approach for contraceptive introduction. The evaluation consisted of a post-training survey, an observational assessment conducted during post-training supportive supervision, and an estimation of training costs.In both countries, a majority (88.6% in Uganda and 64.3% in Senegal) scored above 80% on a DMPA-SC knowledge test following the training. In Senegal, where there was a comparison group of providers trained in person, those providers scored similar on the post-test to eLearners. Providers in both groups and in both countries felt more prepared to administer DMPA-SC or offer self-injection to clients after receiving a supervision visit (93%–98% of eLearners felt very prepared after supervision as compared to 45%–72% prior). The evaluation results suggest that digital approaches offer a number of benefits, can be cost-effective, and are most optimal when blended with in-person training and/or supportive supervision.

ABSTRACTIntroduction: Nigeria has the highest number of children who have not received any vaccines in Africa. The training-of-trainers (TOT) model used to train program managers (PMs) and health care workers (HCWs) is ineffective for adult learning and limits immunization programs’ success. We incorporated adult learning principles (ALPs) in designing and delivering TOT for immunization PMs and HCWs to use data to engage communities for tailored immunization strategies.Methods: Our study was implemented in 3 local government areas (LGAs) of the Federal Capital Territory, Nigeria. A training curriculum was developed, integrating ALPs and technical and operational content based on best practices in delivering immunization training and the training needs assessment findings. State PMs (n=10), LGA PMs (n=30), and HCWs (n=42) were trained on the human-centered design for tailoring immunization programs (HCD-TIP) approaches using ALPs. We used interviews and surveys with purposively and conveniently sampled PMs and HCWs, respectively, and observations to assess participants’ satisfaction, knowledge and competence, behavior changes, and results. The interviews were analyzed thematically, and surveys were statistically.Results: There was a high level of satisfaction with the training among LGA PMs (100%), state PMs (91%), and HCWs (85%), with significant knowledge and competence improvements post-training (P<.001). The trained participants conducted 2 HCD sessions with 24 undervaccinated communities and co-designed 24 prototype solutions for testing. Results showed increased coverage of the pentavalent vaccine first dose (54%) and third dose (188%) across 12 participating communities. Improved community colaboration, communication skills, and data-driven approaches were the most cited behavior changes in practice.Conclusion: The application of ALPs in training, use of HCD-TIP approaches and tools, and supportive supervision enhanced PMs’ and HCWs’ capacity for tailored interventions. Countries should consider adopting a holistic approach that focuses on using these approaches in immunization programs to strengthen the health system for equitable vaccine coverage.

The clinical impact of 16α-¹⁸F-fluoro-17β-estradiol (¹⁸F-FES) PET/CT on patient management has not been well investigated. The aim of this study was to assess the clinical impact of ¹⁸F-FES PET/CT on the management of patients with recurrent or metastatic breast cancer. Methods: Study subjects were identified retrospectively from a database of a prospective trial for postmarketing surveillance of ¹⁸F-FES between 2021 and 2023. Patients who were suspected or known to have recurrent or metastatic estrogen receptor–positive breast cancer based on a routine standard workup were included. Planned management before and actual management after ¹⁸F-FES PET/CT were assessed by 2 experienced medical oncologists via medical chart review. A 5-point questionnaire was provided to evaluate the value of ¹⁸F-FES PET/CT for management planning. The rate of intention-to-treat and interdisciplinary changes, and the impact of ¹⁸F-FES PET/CT according to PET/CT result or clinical indication, were examined. Results: Of the 344 included patients, 120 (35%) experienced a change in management after ¹⁸F-FES PET/CT. In 139 (40%) patients,¹⁸F-FES PET/CT supported the existing management decision without a change in management. Intention-to-treat and interdisciplinary changes accounted for 64% (77/120) and 68% (82/120) of all changes, respectively. A higher rate of change was observed when lesions were ¹⁸F-FES–negative (44% [36/81]) than ¹⁸F-FES–positive (30% [51/172]) or mixed ¹⁸F-FES–positive/negative (36% [33/91]). Regarding clinical indications, the highest rate of change was shown when evaluating the origins of metastasis of double primary cancers (64% [9/14]). Conclusion: ¹⁸F-FES PET/CT modified the management of recurrent or metastatic breast cancer, serving as an impactful imaging modality in clinical practice.

BACKGROUND AND PURPOSE:

Low-field 64 mT portable brain MRI has recently shown diagnostic promise for MS. This study aimed to evaluate the utility of portable MRI (pMRI) in assessing dissemination in space (DIS) in patients presenting with optic neuritis and determine whether deploying pMRI in the MS clinic can shorten the time from symptom onset to MRI.

BACKGROUND AND PURPOSE:

Intracranial vessel wall imaging is technically challenging to implement, given the simultaneous requirements of high spatial resolution, excellent blood and CSF signal suppression, and clinically acceptable gradient times. Herein, we present our preliminary findings on the evaluation of a deep learning–optimized sequence using T1-weighted imaging.

Surprisingly little attention has been given to the impact of selfing on speciation, even though selfing reduces gene flow between populations and affects other key population genetics parameters. Here we review recent theoretical work and compile empirical data from crossing experiments and genomic and phylogenetic studies to assess the effect of mating systems on the speciation process. In accordance with theoretical predictions, we find that accumulation of hybrid incompatibilities seems to be accelerated in selfers, but there is so far limited empirical support for a predicted bias toward underdominant loci. Phylogenetic evidence is scarce and contradictory, including studies suggesting that selfing either promotes or hampers speciation rate. Further studies are therefore required, which in addition to measures of reproductive barrier strength and selfing rate should routinely include estimates of demographic history and genetic divergence as a proxy for divergence time.

New research shows that bystander CPR can substantially improve a person's odds of surviving a cardiac arrest while avoiding major brain damage, especially if given immediately.

Chris is on the dice web. Kelley's cat will break her foot with a metal d20. Johnathan fights his "bad me" supervillain self.

The post RPG Cast – Episode 658: “Space Marines Were in the Bible” appeared first on RPGamer.

Stationeers and Icarus developers RocketWerkz are making a spiritual successor to beloved space sim Kerbal Space Program, which is currently titled "Kitten Space Agency" in a flagrant display of adherence to wholesome internet trends. It's based on an actual Kerbal Space Program 2 pitch the studio threw at Take-Two subsidiary Private Division back in the day. RocketWerkz CEO and original DayZ creator Dean Hall has hired several former KSP and KSP2 developers to work on the game, and is describing it on social media as a "KSP killer".

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To say that Factorio: Space Age throws out the rulebook is an understatement. It'd be more fitting to say it's somehow automated the whole process: an inserter plucked out the rulebook from my brain and deposited it in hot magma, while a new rulebook was churned out in a nearby machine and plopped into my brain from the other side - only for that to be immediately plucked out and incinerated as well. With each new planet and each new phase, Space Age reinvents itself. I'm battling hyperbole here, but ah hell, I admit defeat. Factorio: Space Age is a masterpiece, the final form of perhaps the most well-crafted building game I'll ever play.

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Could tower defence be the ultimate "it's Friday and I am here in body only" genre? I haven't really thought about it before, but Rift Riff's effusively laidback crowd control has me pondering those optimal moments in any tower defender when the incoming horde hits the flamer-MG triangle just right, and you can settle back comfortably into the role of clockwatcher.

Rift Riff encourages this behaviour by being nice to look at. Created by a trio of developers including Hidden Folks designer Adriaan de Jongh, it's a world of spacey, sun-carved mountains, forests and monoliths. The towers resemble the sacred architecture of Monument Valley, and the colour scheme and general ambience remind me of Cocoon. There's a demo, if you fancy it.

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"Where’s my Neo-Volkite pistol, Warhammer 40,000: Space Marine 2?" was my perhaps slightly ungrateful reaction upon booting the action game up after the previous patch. "I didn’t even know what a Neo-Volkite pistol was until five minutes ago, but now this whole game is trash until I get one!." As promised in the roadmap, the last big update added a whole new Operations map, complete with a gargantuan new pseudo-boss in the form of a hierophant bio-titan. It did not, however, give me my beloved pistol. It’s fine. It’s in now, along with a few, less Neo-Volkite updates to other weapons.

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To transport our planet across the universe, we would need to bring the whole solar system to sustain life on Earth – on this episode of Dead Planets Society, our hosts contemplate how to shepherd all that baggage on this scenic journey

As the International Space Station comes to the end of its life, we should recognise its biggest achievement – showing that a better world is possible

Boeing’s Starliner spacecraft had so many problems during its first crewed launch to the International Space Station that NASA officials aren’t sure whether it will be able to bring its crew back home as planned

From artificial retinas to ageing mice, here are five of the most promising results from research performed on the ISS – and what they might mean for humans on Earth and in space

On 19 and 20 August, the JUICE mission will make the first ever attempt to get a gravitational boost from both Earth and the moon on its way to Jupiter

Lightning strikes near Earth give rise to electromagnetic waves called “whistlers” that can carry energy high enough above our planet to pose a risk to satellites and astronauts

After 25 years in orbit, the Chandra X-ray Observatory is under threat. We need to protect this monument to human ingenuity, argues Chanda Prescod-Weinstein

The failure of Boeing's Starliner capsule has left two astronauts stuck in space for months – but also proved how private spaceflight can go right

The Polaris Dawn mission will include the first ever civilian spacewalk, and with a new spacesuit and no airlock, it may also be the most dangerous spacewalk ever

Ganymede, the largest moon in the solar system, has signs of an enormous ancient impact that would have redistributed its mass, changing its orientation in relation to Jupiter

A faint glow from all of the galaxies that have ever existed fills the cosmos, and NASA's New Horizons spacecraft has made the best measurement ever of just how faint it is

Four private astronauts are riding a SpaceX Crew Dragon capsule further from Earth than any human since 1972, where they will attempt the first ever civilian spacewalk

A groundbreaking civilian spacewalk saw two astronauts partially exit a SpaceX Crew Dragon capsule wearing a brand new design of spacesuit. Every previous spacewalk completed before this was performed by government-trained astronauts.

The success of the all-civilian spacewalk on SpaceX’s Polaris Dawn mission shows that private space flight is starting to catch up with government space agencies

As the space industry evolves, we need a new set of international regulations to decide who is responsible for safety, the number of satellites in space, and more

See the world's best space images from the Astronomy Photographer of the Year 2024 award

Genetic analysis shows that microbes growing inside the International Space Station have adaptations for radiation and low gravity, and may pose a threat to astronauts

The first 18 satellites of a planned Chinese mega constellation are brighter than all but 500 stars in the sky, raising fears of a huge impact on astronomy

Andrew McConnell's otherworldly photograph captures a Russian cosmonaut in front of the just-landed Soyuz MS spacecraft in Kazakhstan's remote grasslands

A detector on the International Space Station found signatures of unexpectedly abundant antimatter – which may have been created in clashes of dark matter particles

The European Space Agency's Hera spacecraft must be thoroughly tested before being sent to investigate the aftermath of the collision of NASA's DART probe with Dimorphos

SpaceX claims the fifth test flight of its Starship rocket will happen “within days”, but the Federal Aviation Administration has not yet approved the launch

Maggie Aderin-Pocock, who has worked on the JWST, catalogues the science behind its most stunning images in her new book, Webb's Universe. Here's her pick of the telescope’s best shots

SpaceX is preparing for the sixth test flight of Starship, the world's most powerful rocket. Next week's launch – if successful – will be the fastest turnaround yet

Samantha Harvey has won the UK's top fiction prize for a novel that takes place over 24 hours on the International Space Station

A new design for a nuclear battery that generates electricity from the radioactive decay of americium is unprecedentedly efficient

A quantum computing protocol makes it possible to extract energy from seemingly empty space, teleport it to a new location, then store it for later use

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

A lithium-ion battery made from three droplets of hydrogel is the smallest soft battery of its kind – and it could be used in biocompatible and biodegradable implants

Scientists have found a new building block of life deep in the cold darkness of interstellar space.

It’s the second-shortest book to be awarded the prize.