A reverse genetic screen in Drosophila using a deletion-inducing mutagen

We report the use of the cross-linking drug hexamethylphosphoramide (HMPA), which introduces small deletions, as a mutagen suitable for reverse genetics in the model organism Drosophila melanogaster. A compatible mutation-detection method based on resolution of PCR fragment-length polymorphisms on standard DNA sequencers is implemented. As the spectrum of HMPA-induced mutations is similar in a variety of organisms, it should be possible to transfer this mutagenesis and detection procedure to other model systems

Thulium Fibre Laser versus Holmium:YAG for Ureteroscopic Lithotripsy: Outcomes from a Prospective Randomised Clinical Trial

Background Holmium:yttrium-aluminium-garnet (Ho:YAG) laser is the gold standard for ureterorenoscopic (URS) lithotripsy. Thulium fibre laser (TFL) has recently been introduced as a new technology and may challenge Ho:YAG as the preferred laser owing to favourable properties as demonstrated in preclinical studies. Objective To evaluate and compare outcomes after URS lithotripsy with Ho:YAG and TFL. Design, setting, and participants In a prospective randomised trial, patients aged ≥18 yr with ureteral and/or renal stones (≥5 mm) scheduled to undergo day-case URS lithotripsy were invited to participate. In total, 120 consecutively admitted patients with signed consent were included for randomisation. Intervention URS lithotripsy with Ho:YAG or TFL. Outcome measurements and statistical analysis The primary outcome was the stone-free rate (SFR) assessed on noncontrast computed tomography at 3-mo follow-up. Secondary outcomes were the operative time and complications. Outcomes were compared between the groups using the t test and χ2 test. Results and limitations After a single session, the SFR was 67% in the Ho:YAG group and 92% in the TFL group, p = 0.001. For ureteral stones, the SFR was 100% in both groups, and for renal stones; 49% (Ho:YAG) and 86% (TFL), p = 0.001. Operative time was shorter using TFL (49 min) compared to Ho:YAG (57 min), p = 0.008. Bleeding that impaired the endoscopic view was the most frequent intraoperative adverse event and occurred in 13 patients (22%) in the Ho:YAG group and three (5%) in the TFL group, p = 0.014. Conclusions In this study, significantly more patients with renal stones achieved stone-free status and fewer experienced intraoperative complications using TFL compared to Ho:YAG. TFL is the emerging laser of choice for stone lithotripsy. Patient summary We compared outcomes after ureterorenoscopic treatment of kidney and ureteral stones using two different lasers. Our results show that the new thulium fibre laser technology is superior to the current standard laser (holmium:YAG) in clearing kidney stones and reducing operative complications.publishedVersio

Ureteroscopy for stone disease in the paediatric population: lessons learned and outcomes in a Nordic setting

Introduction: Paediatric stone disease is rare in the Nordic communities. Still, the condition can require surgical intervention in the form of ureteroscopy (URS). Here, we report outcomes achieved at a regional (tertiary) centre. Patients and methods: Retrospective analysis was performed of consecutive patients (<18 years of age) undergoing URS for stone disease between 2010 and 2021. Outcomes of interest included stone-free rate (SFR) determined using a definition of no residual fragments ⩾ 3 mm on imaging and complications classified according to Clavien–Dindo system. Results: In total, 23 patients underwent 47 URS procedures for a total of 31 stone episodes. Mean age was 9 (range 1–17) years and male-to-female ratio was 6:17. Overall, 35% had at least one medical comorbidity. Ultrasound determined preoperative stone status in 87%. Mean largest index and cumulative stone sizes were 9 (range 3–40) and 12 (range 3–40) mm, respectively. Overall, 32% had multiple stones. Lower pole was the commonest stone location (39%). No patients underwent elective pre-operative stenting. Ureteral access sheaths were not used in any cases. Access to upper urinary tract at first procedure was successful in 94%. Initial and final SFR was 61% and 90%, respectively. No intra-operative complications were recorded. Overall post-operative complication rate was 17.5%. Urinary tract infection (CD II) was the commonest adverse event (12.5%). Conclusion: Paediatric URS can be delivered in the setting of a regional centre without compromising outcomes. This includes when carried out by adult endourologists, without routine pre-stenting and omitting use of ureteric access sheath.publishedVersio

Holmium and Thulium Fiber Laser Safety in Endourological Practice: What Does the Clinician Need to Know?

Purpose of Review: To summarise the literature on laser safety during endourological practice. Recent Findings: Holmium and Thulium Fiber laser are the two main energy sources in the current clinical practice. The latter may have superior properties, but more clinical studies are needed to formally establish this. Laser injury to urothelium is more dependent on user experience rather than laser type. Smaller laser fibres allow for lower intra-renal temperature profiles. Operators should pay close attention to laser technique including maintaining the safety distance concept and only firing the laser when tip is clearly in view. When adjusting laser settings, pay close attention to resultant power given the associated heat changes. Prolonged periods of laser activation are to be avoided for the same reason. Outflow can be manipulated such as with access sheath to mitigate temperature and pressure changes. There is still limited evidence to support the mandate for compulsory use of eye protection wear during laser lithotripsy. Summary: Lasers are the gold standard energy source for stone lithotripsy. However, the safe clinical application of this technology requires an understanding of core principles as well as awareness of the safety and technical aspects that can help in protecting patient, surgeon and operating staff.publishedVersio

Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies

MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-13C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP 13C-pyruvate preparation, (2) MRI system setup and calibrations, (3) data acquisition and image reconstruction, and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the HP 13C MRI Consensus Group as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods & Equipment study groups. It further aims to provide a comprehensive reference for future consensus building as the field continues to advance human studies with this metabolic imaging modality

The Psychological Science Accelerator: Advancing Psychology Through a Distributed Collaborative Network

Source at https://doi.org/10.1177/2515245918797607.Concerns about the veracity of psychological research have been growing. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions or replicate prior research in large, diverse samples. The PSA’s mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time limited), efficient (in that structures and principles are reused for different projects), decentralized, diverse (in both subjects and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside the network). The PSA and other approaches to crowdsourced psychological science will advance understanding of mental processes and behaviors by enabling rigorous research and systematic examination of its generalizability

In COVID-19 Health Messaging, Loss Framing Increases Anxiety with Little-to-No Concomitant Benefits: Experimental Evidence from 84 Countries

The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., "If you do not practice these steps, you can endanger yourself and others") or potential gains (e.g., "If you practice these steps, you can protect yourself and others")? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions