Stress responses in surgical trainees during simulation-based training courses in laparoscopy.

BACKGROUND: Simulation-based training courses in laparoscopy have become a fundamental part of surgical training programs. Surgical skills in laparoscopy are challenging to master, and training in these skills induces stress responses in trainees. There is limited data on trainees' stress levels, the stress responses related to training on different laparoscopic simulators, and how previous experiences influence trainees' stress response during a course. This study investigates physiologic, endocrine and self-reported stress responses during simulation-based surgical skills training in a course setting. METHODS: We conducted a prospective observational study of trainees attending basic laparoscopic skills training courses at a national training centre. During the three-day course, participants trained on different laparoscopic simulators: Two box-trainers (the D-box and P.O.P. trainer) and a virtual reality simulator (LAPMentor™). Participants' stress responses were examined through heart rate variability (HRV), saliva cortisol, and the State Trait Anxiety Inventory-6 (STAI-6). The correlation between previous laparoscopic experiences and stress response measurements was explored. RESULTS: Twenty-four surgical trainees were included in the study. Compared to resting conditions, stress measures were significantly higher during simulation-training activity (the D-box (SDNN = 58.5 ± 23.4; LF/HF-ratio = 4.58 ± 2.71; STAI-6 = 12.3 ± 3.9, P < 0.05), the P.O.P trainer (SDNN = 55.7 ± 7.4; RMSSD = 32.4 ± 17.1; STAI-6 = 12.1 ± 3.9, P < 0.05), and the LAPMentor™ (SDNN = 59.1 ± 18.5; RMSSD = 34.3 ± 19.7; LF/HF-ratio = 4.71 ± 2.64; STAI-6 = 9.9 ± 3.0, P < 0.05)). A significant difference in endocrine stress response was seen for the simulation-training activity on the D-box (saliva cortisol: 3.48 ± 1.92, P < 0.05), however, no significant differences were observed between the three simulators. A moderate correlation between surgical experience, and physiologic and endocrine stress response was observed (RMSSD: r=-0.31; SDNN: r=-0.42; SD2/SD1 ratio: r = 0.29; Saliva cortisol: r = 0.46; P < 0.05), and a negative moderate correlation to self-reported stress (r=-0.42, P < 0.05). CONCLUSION: Trainees have a significant higher stress response during simulation-training compared to resting conditions, with no difference in stress response between the simulators. Significantly higher cortisol levels were observed on the D-box, indicating that simulation tasks with time pressure stress participants the most. Trainees with more surgical experience are associated with higher physiologic stress measures, but lower self-reported stress scores, demonstrating that surgical experience influences trainees' stress response during simulation-based skills training courses.

Barriers for Accessing Assistive Products in Low- and Middle-Income Countries (LMICs).

WHO implemented the Rapid Assistive Technology Assessment in 2021. This is a household survey on self-reported use, need and barriers for accessing AT in 35 countries globally. In order to obtain comparable data, all surveys followed guidelines developed by WHO, including national two-stage random sampling of households. The 2021 rATA survey included 32 of a total of 140 LMICs globally. Around 40 % of the total respondents (all countries) estimated travel distance to be <5 km, varying from less than 10 % to almost 60 % among the countries. Around 15 % had to travel more than 50 km, varying from 1.3 % to 37.5 %. More individuals living in rural as compared to urban areas had to travel more than 25 km to get their main assistive product. Gender differences were marginal. By far the most prevalent barrier to access assistive products was "Cannot afford", amounting to 39.9% and varying from 6.7 % to 79.1 % among countries. This was followed by "No support" with 14.3 %, varying from 2.3 % to 36.9 %, and "Not available" with 8.1 %, varying from 1 % to 21.5 %. More barriers were reported in rural than urban areas and women report more barriers than men. Variation between countries in both travel time and barriers is substantial and country-specific service development is needed to guide service development.

Can a Dinosaur Think? Implementation of Artificial Intelligence in Extracorporeal Shock Wave Lithotripsy.

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) of kidney stones is losing ground to more expensive and invasive endoscopic treatments. OBJECTIVE: This proof-of-concept project was initiated to develop artificial intelligence (AI)-augmented ESWL and to investigate the potential for machine learning to improve the efficacy of ESWL. DESIGN SETTING AND PARTICIPANTS: Two-dimensional ultrasound videos were captured during ESWL treatments from an inline ultrasound device with a video grabber. An observer annotated 23 212 images from 11 patients as either in or out of focus. The median hit rate was calculated on a patient level via bootstrapping. A convolutional neural network with U-Net architecture was trained on 57 ultrasound images with delineated kidney stones from the same patients annotated by a second observer. We tested U-Net on the ultrasound images annotated by the first observer. Cross-validation with a training set of nine patients, a validation set of one patient, and a test set of one patient was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Classical metrics describing classifier performance were calculated, together with an estimation of how the algorithm would affect shock wave hit rate. RESULTS AND LIMITATIONS: The median hit rate for standard ESWL was 55.2% (95% confidence interval [CI] 43.2-67.3%). The performance metrics for U-Net were accuracy 63.9%, sensitivity 56.0%, specificity 74.7%, positive predictive value 75.3%, negative predictive value 55.2%, Youden's J statistic 30.7%, no-information rate 58.0%, and Cohen's κ 0.2931. The algorithm reduced total mishits by 67.1%. The main limitation is that this is a proof-of-concept study involving only 11 patients. CONCLUSIONS: Our calculated ESWL hit rate of 55.2% (95% CI 43.2-67.3%) supports findings from earlier research. We have demonstrated that a machine learning algorithm trained on just 11 patients increases the hit rate to 75.3% and reduces mishits by 67.1%. When U-Net is trained on more and higher-quality annotations, even better results can be expected. PATIENT SUMMARY: Kidney stones can be treated by applying shockwaves to the outside of the body. Ultrasound scans of the kidney are used to guide the machine delivering the shockwaves, but the shockwaves can still miss the stone. We used artificial intelligence to improve the accuracy in hitting the stone being treated.

A new acoustic coupling fluid with ability to reduce ultrasound imaging artefacts in brain tumour surgery-a phase I study.

BACKGROUND: A novel acoustic coupling fluid (ACF), with the potential to reduce surgically induced image artefacts during intraoperative ultrasound imaging in brain tumour surgery, has been evaluated with respect to image quality and safety in a clinical phase 1 study. METHODS: Fifteen patients with glioblastoma (WHO grade IV) were included. All adverse events were registered in a 6-month study period. During acquisition of 3D ultrasound image volumes, three different concentrations of the ACF and Ringer's solution were filled into the resection cavity. The effect of ACF on the ultrasound images was rated by the operating surgeon, and by five independent neurosurgeons evaluating a pair of blinded images from all patients. Images from all patients were analysed by comparing pixel brightness in a noise-affected region and a reference region. RESULTS: The operating surgeon deemed the ACF images to have less noise than images obtained with Ringers's solution. The blinded evaluations by the independent neurosurgeons were significantly in favour of ACF (p < 0.0001). The analyses of pixel intensities showed that the ACF images had lower amount of noise than images obtained with Ringer's solution. No radiological sign of inflammation nor circulatory changes was found in the early postoperative MR images. Of the nine complications registered as serious events in the study period, none was deemed to be caused by the ACF. CONCLUSION: The ultrasound (US) images obtained using ACF have significantly less noise than US images obtained with Ringer's solution. The rate of adverse events was comparable to what has been reported for similar groups of patients.

Active galaxies. A strong magnetic field in the jet base of a supermassive black hole.

Active galactic nuclei (AGN) host some of the most energetic phenomena in the universe. AGN are thought to be powered by accretion of matter onto a rotating disk that surrounds a supermassive black hole. Jet streams can be boosted in energy near the event horizon of the black hole and then flow outward along the rotation axis of the disk. The mechanism that forms such a jet and guides it over scales from a few light-days up to millions of light-years remains uncertain, but magnetic fields are thought to play a critical role. Using the Atacama Large Millimeter/submillimeter Array (ALMA), we have detected a polarization signal (Faraday rotation) related to the strong magnetic field at the jet base of a distant AGN, PKS 1830-211. The amount of Faraday rotation (rotation measure) is proportional to the integral of the magnetic field strength along the line of sight times the density of electrons. The high rotation measures derived suggest magnetic fields of at least tens of Gauss (and possibly considerably higher) on scales of the order of light-days (0.01 parsec) from the black hole.

[The piRNAs forge an immune system for the genome]. / Les piARN forgent un système immunitaire pour le génome.

Genome integrity of germline is essential for the survival of any species. A dedicated defence mechanism based on small RNA called piRNA (PIWI-interacting RNA) has evolved to protect the germline from the deleterious effects of transposon mobility in genomes such as mutations, deletions or chromosomal rearrangements. The piRNA machinery ensures genomic integrity to germ cells by setting a response similar to the immune system. The recognition of the threat is mediated by sequence complementarity between a vast repertoire of piRNAs and the intruders, and initiates a rapid and efficient degradation of the targets. Akin to acquired immunity, the response is memorized throughout generations thanks to epigenetic modifications. Investigations are progressing to unravel the mysterious mechanisms of this exciting class of non coding RNAs. This review summarizes some of the recent advances on this exceptional immunity that protects transmission of genetic information.

Simulation model for assessing quality of ultrasound strain estimation in abdominal aortic aneurysm.

The purpose of this study was to develop a simulation model for evaluating methods for ultrasound strain estimation in abdominal aortic aneurysms. Wall geometry was obtained from a real ultrasound image and wall motion was simulated applying realistic blood pressures to a nonlinear viscoelastic wall model. The ultrasound simulation included speckle, absorption and angle dependent reflection. Gaussian white noise was added to simulate various noise levels. Despite not fully replicating real ultrasound images, the model simulated realistic circumferential variations in intensity and realistic speckle patterns and has potential for initial evaluation of strain estimation methods.

3D ultrasound reconstruction algorithms from analog and digital data.

Freehand 3D ultrasound is increasingly being introduced in the clinic for diagnostics and image-assisted interventions. Various algorithms exist for combining 2D images of regular ultrasound probes to 3D volumes, being either voxel-, pixel- or function-based. Previously, the most commonly used input to 3D ultrasound reconstruction has been digitized analog video. However, recent scanners that offer access to digital image frames exist, either as processed or unprocessed data. To our knowledge, no comparison has been performed to determine which data source gives the best reconstruction quality. In the present study we compared both reconstruction algorithms and data sources using novel comparison methods for detecting potential differences in image quality of the reconstructed volumes. The ultrasound scanner used in this study was the Sonix RP from Ultrasonix Medical Corp (Richmond, Canada), a scanner that allow third party access to unprocessed and processed digital data. The ultrasound probe used was the L14-5/38 linear probe. The assessment is based on a number of image criteria: detectability of wire targets, spatial resolution, detectability of small barely visible structures, subjective tissue image quality, and volume geometry. In addition we have also performed the more "traditional" comparison of reconstructed volumes by removing a percentage of the input data. By using these evaluation methods and data from the specific scanner, the results showed that the processed video performed better than the digital scan-line data, digital video being better than analog video. Furthermore, the results showed that the choice of video source was more important than the choice of tested reconstruction algorithms.

Degree of adhesions after repair of incisional hernia.

BACKGROUND AND OBJECTIVES: Laparoscopic treatment of incisional hernias reduces surgical traumas and postoperative pain. It requires intraperitoneal placement of a foreign body that might cause adhesions, leading to postoperative complications. The aim of this study was to improve reliability of ultrasound in quantitatively estimating adhesions to exploit the other advantages of ultrasound, such as availability and versatility. METHODS: The ultrasound examination was performed by using a hand-held 3.5 MHz curved linear probe. The image data were analyzed prior to scan conversion. Two square regions of interest were defined, one in the abdominal wall and one in the underlying bowels. A cross correlation-based algorithm tracked each region by using a time span of 3 frames. Subtracting the 2 displacement functions from each other yielded a relative displacement function, indicating the degree of bowel adhesions. This was compared with the intraoperative findings. RESULTS AND CONCLUSIONS: The method was proven to be a rapid and robust method for quantitatively estimating the degree of bowel adhesions. It is limited to evaluation of adhesions between bowel and abdominal wall. However, this ultrasound technique could assist in the safe placement of ports prior to redo laparoscopic surgery.

Deficiency of the tRNATyr:Psi 35-synthase aPus7 in Archaea of the Sulfolobales order might be rescued by the H/ACA sRNA-guided machinery.

Up to now, Psi formation in tRNAs was found to be catalysed by stand-alone enzymes. By computational analysis of archaeal genomes we detected putative H/ACA sRNAs, in four Sulfolobales species and in Aeropyrum pernix, that might guide Psi 35 formation in pre-tRNA(Tyr)(GUA). This modification is achieved by Pus7p in eukarya. The validity of the computational predictions was verified by in vitro reconstitution of H/ACA sRNPs using the identified Sulfolobus solfataricus H/ACA sRNA. Comparison of Pus7-like enzymes encoded by archaeal genomes revealed amino acid substitutions in motifs IIIa and II in Sulfolobales and A. pernix Pus7-like enzymes. These conserved RNA:Psi-synthase- motifs are essential for catalysis. As expected, the recombinant Pyrococcus abyssi aPus7 was fully active and acted at positions 35 and 13 and other positions in tRNAs, while the recombinant S. solfataricus aPus7 was only found to have a poor activity at position 13. We showed that the presence of an A residue 3' to the target U residue is required for P. abyssi aPus7 activity, and that this is not the case for the reconstituted S. solfataricus H/ACA sRNP. In agreement with the possible formation of Psi 35 in tRNA(Tyr)(GUA) by aPus7 in P. abyssi and by an H/ACA sRNP in S. solfataricus, the A36G mutation in the P. abyssi tRNA(Tyr)(GUA) abolished Psi 35 formation when using P. abyssi extract, whereas the A36G substitution in the S. solfataricus pre-tRNA(Tyr) did not affect Psi 35 formation in this RNA when using an S. solfataricus extract.

Strong limit on a variable proton-to-electron mass ratio from molecules in the distant universe.

The Standard Model of particle physics assumes that the so-called fundamental constants are universal and unchanging. Absorption lines arising in molecular clouds along quasar sightlines offer a precise test for variations in the proton-to-electron mass ratio, mu, over cosmological time and distance scales. The inversion transitions of ammonia are particularly sensitive to mu as compared to molecular rotational transitions. Comparing the available ammonia spectra observed toward the quasar B0218+357 with new, high-quality rotational spectra, we present the first detailed measurement of mu with this technique, limiting relative deviations from the laboratory value to |Deltamu/mu| < 1.8 x 10(-6) (95% confidence level) at approximately half the universe's current age-the strongest astrophysical constraint to date. Higher-quality ammonia observations will reduce both the statistical and systematic uncertainties in these observations.

Combined in silico and experimental identification of the Pyrococcus abyssi H/ACA sRNAs and their target sites in ribosomal RNAs.

How far do H/ACA sRNPs contribute to rRNA pseudouridylation in Archaea was still an open question. Hence here, by computational search in three Pyrococcus genomes, we identified seven H/ACA sRNAs and predicted their target sites in rRNAs. In parallel, we experimentally identified 17 Psi residues in P. abyssi rRNAs. By in vitro reconstitution of H/ACA sRNPs, we assigned 15 out of the 17 Psi residues to the 7 identified H/ACA sRNAs: one H/ACA motif can guide up to three distinct pseudouridylations. Interestingly, by using a 23S rRNA fragment as the substrate, one of the two remaining Psi residues could be formed in vitro by the aCBF5/aNOP10/aGAR1 complex without guide sRNA. Our results shed light on structural constraints in archaeal H/ACA sRNPs: the length of helix H2 is of 5 or 6 bps, the distance between the ANA motif and the targeted U residue is of 14 or 15 nts, and the stability of the interaction formed by the substrate rRNA and the 3'-guide sequence is more important than that formed with the 5'-guide sequence. Surprisingly, we showed that a sRNA-rRNA interaction with the targeted uridine in a single-stranded 5'-UNN-3' trinucleotide instead of the canonical 5'-UN-3' dinucleotide is functional.

Identification of determinants in the protein partners aCBF5 and aNOP10 necessary for the tRNA:Psi55-synthase and RNA-guided RNA:Psi-synthase activities.

Protein aNOP10 has an essential scaffolding function in H/ACA sRNPs and its interaction with the pseudouridine(Psi)-synthase aCBF5 is required for the RNA-guided RNA:Psi-synthase activity. Recently, aCBF5 was shown to catalyze the isomerization of U55 in tRNAs without the help of a guide sRNA. Here we show that the stable anchoring of aCBF5 to tRNAs relies on its PUA domain and the tRNA CCA sequence. Nonetheless, interaction of aNOP10 with aCBF5 can counterbalance the absence of the PUA domain or the CCA sequence and more generally helps the aCBF5 tRNA:Psi55-synthase activity. Whereas substitution of the aNOP10 residue Y14 by an alanine disturbs this activity, it only impairs mildly the RNA-guided activity. The opposite effect was observed for the aNOP10 variant H31A. Substitution K53A or R202A in aCBF5 impairs both the tRNA:Psi55-synthase and the RNA-guided RNA:Psi-synthase activities. Remarkably, the presence of aNOP10 compensates for the negative effect of these substitutions on the tRNA: Psi55-synthase activity. Substitution of the aCBF5 conserved residue H77 that is expected to extrude the targeted U residue in tRNA strongly affects the efficiency of U55 modification but has no major effect on the RNA-guided activity. This negative effect can also be compensated by the presence of aNOP10.

Identification of modified residues in RNAs by reverse transcription-based methods.

Naturally occurring modified residues derived from canonical RNA nucleotides are present in most cellular RNAs. Their detection in RNA represents a difficult task because of their great diversity and their irregular distribution within RNA molecules. Over the decades, multiple experimental techniques were developed for the identification and localization of RNA modifications. Most of them are quite laborious and require purification of individual RNA to a homogeneous state. An alternative to these techniques is the use of reverse transcription (RT)-based approaches. In these approaches, purification of RNA to homogeneity is not necessary, because the selection of the analyzed RNA species is done by specific annealing of oligonucleotide DNA primers. However, results from primer extension analysis are difficult to interpret because of the unpredictable nature of RT pauses. They depend not only on the properties of nucleotides but also on the RNA primary and secondary structure. In addition, the degradation of cellular RNA during extraction, even at a very low level, may complicate the analysis of the data. RT-based techniques for the identification of modified residues were considerably improved by the development of selected chemical reagents specifically reacting with a given modified nucleotide. The RT profile obtained after such chemical modifications generally allows unambiguous identification of the chemical nature of the modified residues and their exact location in the RNA sequence. Here, we provide experimental protocols for selective chemical modification and identification of several modified residues: pseudouridine, inosine, 5-methylcytosine, 2'-O-methylations, 7-methylguanosine, and dihydrouridine. Advice for an optimized use of these methods and for correct interpretation of the data is also given. We also provide some helpful information on the ability of other naturally occurring modified nucleotides to generate RT pauses.

A dedicated computational approach for the identification of archaeal H/ACA sRNAs.

Whereas dedicated computational approaches have been developed for the search of C/D sRNAs and snoRNAs, as yet no dedicated computational approach has been developed for the search of archaeal H/ACA sRNAs. Here we describe a computational approach allowing a fast and selective identification of H/ACA sRNAs in archaeal genomes. It is easy to use, even for biologists having no special expertise in computational biology. This approach is a stepwise knowledge-based approach, combining the search for common structural features of H/ACA motifs and the search for their putative target sequences. The first step is based on the ERPIN software. It depends on the establishment of a secondary structure-based "profile." We explain how this profile is built and how to use ERPIN to optimize the search for H/ACA motifs. Several examples of applications are given to illustrate how powerful the method is, its limits, and how the results can be evaluated. Then, the possible target rRNA sequences corresponding to the identified H/ACA motifs are searched by use of a descriptor-based method (RNAMOT). The principles and the practical aspects of this method are also explained, and several examples are given here as well to help users in the interpretation of the results.

Viscoelastic modelling of impacted morsellised bone accurately describes unloading behaviour: an experimental study of stiffness moduli and recoil properties.

Morsellised bone impaction grafting is commonly used for revision arthroplasty surgery. Several reports have described the mechanical behaviour of this bone material during impaction and loading. In this study we observed the unloading progress. The loose morsellised bone was modified by particle size, particle size distribution, water and fat content. Bone pellets were constructed using different impaction energies. After impaction, the pellets were loaded statically, after which their swelling was recorded at three unloading levels. We deduced two time-dependent recoil properties, the time resistant number (TRN) and the half total swelling time (HTST), and also one stiffness property, the unloading confined modulus of elasticity (UCME). In impacted morsellised bone, the progress of swelling is visco-elastic. Bone pellets with an even distribution of particle sizes have the most rapid recoil. Those with a high liquid content recoil more slowly, and to a significantly greater extent, than pellets with low liquid content. The recoil of pellets with low liquid content is instantaneous, i.e. unrecordable, and the displacement is significantly less than in other pellet samples.

Reconstitution of archaeal H/ACA small ribonucleoprotein complexes active in pseudouridylation.

Pseudouridine (Psi) are frequently modified residues in RNA. In Eukarya, their formation is catalyzed by enzymes or by ribonucleoprotein complexes (RNPs) containing H/ACA snoRNAs. H/ACA sRNA and putative ORFs for H/ACA sRNP proteins (L7Ae, aCBF5, aNOP10 and aGAR1) were found in Archaea. Here, by using Pyrococcus abyssi recombinant proteins and an in vitro transcribed P.abyssi H/ACA sRNA, we obtained the first complete in vitro reconstitution of an active H/ACA RNP. Both L7Ae and the aCBF5 RNA:Psi synthase bind directly the sRNA; aCBF5 also interacts directly and independently with aNOP10 and aGAR1. Presence of aCBF5, aNOP10 and a U residue at the pseudouridylation site in the target RNA are required for RNA target recruitment. In agreement, we found that the aCBF5-aNOP10 pair is the minimal set of proteins needed for the formation of a particle active for pseudouridylation. However, particles more efficient in targeted pseudouridylation can be formed with the addition of proteins L7Ae and/or aGAR1. Although necessary for optimal activity, the conserved ACA motif in the sRNA was found to be not essential.

A quantitative and qualitative analysis of bone remodelling around custom uncemented femoral stems: a five-year DEXA follow-up.

BACKGROUND: After total hip replacement bone remodelling is determinant for the implant survival. This study asked whether the immediate postoperative amount and distribution of bone can predict the changes in bone amount and distribution after five years in the case of younger patients with custom uncemented implant. METHODS: We investigated 17 hips with a mean follow-up of 5.1 years. The average patient age at follow-up was 48.5 years. We used immediate postoperative and five-year dual energy X-ray absorptiometry measurements of bone mineral content, density, and projected bone area in seven local zones forming a partition of the upper femur. A correlation was sought between the preoperative variables and the five-year variation. Qualitative bone remodelling was analysed considering each local zone in a density-area plane. Based on geometrical considerations, we introduced an index of structural remodelling, which expresses the preponderance of internal remodelling against external modelling. FINDINGS: The bone mineral content at operation correlated significantly with its relative decrease locally laterally mid-proximally and medially (P<0.01), distally, and globally for the femur (P<0.05). For the bone mineral density, the correlation was significant distally, medially and globally (P<0.05). The bone projected area shows only significant correlation laterally mid-proximally (P<0.01). The index of structural remodelling was significantly positive (P<0.01) in all local zones and was independent of the initial bone amount and structure (P>0.1). INTERPRETATION: High bone mineral content at operation correlates significantly with periprosthetic bone loss after five years in younger patients with cementless custom femoral implant. Independently of the net bone mineral content balance, external modelling is stronger than internal remodelling in all local zones.