Optimizing the Pedicled Latissimus Dorsi Myocutaneous Flap in Breast Reconstruction: Lessons Learned from 110 Consecutive Flaps.

Background: The pedicled latissimus dorsi myocutaneous flap (LDMCF) in autologous breast reconstruction has been superseded by abdominal free tissue transfer. Common complaints of the LDMCF include the asymmetric back scar, need for prosthesis, and high seroma rates. We believe that the LDMCF remains versatile, with distinct advantages over other autologous options: the flap can be harvested unilaterally or bilaterally, not 'burning any bridges' for future reconstruction in unilateral breast reconstruction; the recovery is relatively easy, without complications such as risk of long-term abdominal wall weakness; and the aesthetic results are comparable, if not superior, leading to a more "youthful" result. Methods: We performed a retrospective review over an 8-year period. Results: A total of 106 patients underwent 110 breast reconstructions. Complications included four of 106 patients (3.8%) with seroma, three of 78 (3.8%) with periprosthetic implant infection, and one case of partial flap loss. Conclusions: We learned the following: (1) Direct-to-implant can be performed in most LDMCF patients, avoiding the use of tissue expanders; (2) High BMI patients may not require an implant; (3) Back donor site aesthetics can be improved using a "bra-line-back-lift" approach; (4) Use of liposomal bupivacaine intercostal blocks and modified enhanced recovery after surgery protocol can reduce length-of-stay to overnight; (5) We achieved low seroma rates using topical fibrin glue and closed suction drains; (6) Low and high BMI patients who may not qualify for free tissue transfer are usually still surgical candidates with LDMCF; and (7) Short and long-term recovery are faster than free tissue transfer, with minimal long-term deficit.

Population genomic structure of a widespread, urban-dwelling mammal: The eastern grey squirrel (Sciurus carolinensis).

Urbanization is a persistent and widespread driver of global environmental change, potentially shaping evolutionary processes due to genetic drift and reduced gene flow in cities induced by habitat fragmentation and small population sizes. We tested this prediction for the eastern grey squirrel (Sciurus carolinensis), a common and conspicuous forest-dwelling rodent, by obtaining 44K SNPs using reduced representation sequencing (ddRAD) for 403 individuals sampled across the species' native range in eastern North America. We observed moderate levels of genetic diversity, low levels of inbreeding, and only a modest signal of isolation-by-distance. Clustering and migration analyses show that estimated levels of migration and genetic connectivity were higher than expected across cities and forested areas, specifically within the eastern portion of the species' range dominated by urbanization, and genetic connectivity was less than expected within the western range where the landscape is fragmented by agriculture. Landscape genetic methods revealed greater gene flow among individual squirrels in forested regions, which likely provide abundant food and shelter for squirrels. Although gene flow appears to be higher in areas with more tree cover, only slight discontinuities in gene flow suggest eastern grey squirrels have maintained connected populations across urban areas in all but the most heavily fragmented agricultural landscapes. Our results suggest urbanization shapes biological evolution in wildlife species depending strongly on the composition and habitability of the landscape matrix surrounding urban areas.

Butterfly foraging is remarkably synchronous in an experimental tropical macrocosm.

Diel patterns in foraging activity are dictated by a combination of abiotic, biotic and endogenous limits. Understanding these limits is important for insects because ectotherm taxa will respond more pronouncedly to ongoing climatic change, potentially affecting crucial ecosystem services. We leverage an experimental macrocosm, the Montreal Insectarium Grand Vivarium, to test the importance of endogenous mechanisms in determining temporal patterns in foraging activity of butterflies. Specifically, we assessed the degree of temporal niche partitioning among 24 butterfly species originating from the Earth's tropics within controlled environmental conditions. We found strong niche overlap, with the frequency of foraging events peaking around solar noon for 96% of the species assessed. Our models suggest that this result was not due to the extent of cloud cover, which affects radiational heating and thus limits body temperature in butterflies. Together, these findings suggest that an endogenous mechanism evolved to regulate the timing of butterfly foraging activity within suitable environmental conditions. Understanding similar mechanisms will be crucial to forecast the effects of climate change on insects, and thus on the many ecosystem services they provide.

Ts66Yah, a mouse model of Down syndrome with improved construct and face validity.

Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21). The understanding of genotype-phenotype relationships, the identification of driver genes and various proofs of concept for therapeutics have benefited from mouse models. The premier model, named Ts(1716)65Dn/J (Ts65Dn), displayed phenotypes related to human DS features. It carries an additional minichromosome with the Mir155 to Zbtb21 region of mouse chromosome 16, homologous to Hsa21, encompassing around 90 genes, fused to the centromeric part of mouse chromosome 17 from Pisd-ps2/Scaf8 to Pde10a, containing 46 genes not related to Hsa21. Here, we report the investigation of a new model, Ts66Yah, generated by CRISPR/Cas9 without the genomic region unrelated to Hsa21 on the minichromosome. As expected, Ts66Yah replicated DS cognitive features. However, certain phenotypes related to increased activity, spatial learning and molecular signatures were changed, suggesting genetic interactions between the Mir155-Zbtb21 and Scaf8-Pde10a intervals. Thus, Ts66Yah mice have stronger construct and face validity than Ts65Dn mice for mimicking consequences of DS genetic overdosage. Furthermore, this study is the first to demonstrate genetic interactions between triplicated regions homologous to Hsa21 and others unrelated to Hsa21. This article has an associated First Person interview with the first author of the paper.

Functional Performance Tests, On-Ice Testing and Game Performance in Elite Junior Ice Hockey Players.

This study aimed to explore relationships between fitness, on-ice physical abilities and game performance among elite junior male ice hockey players. Twenty-one major junior ice hockey players (18.9 ± 1.4 years old) participated in the study. Measures including five fitness tests (anthropometric measures, pull up test, bench press test, broad jump, vertical jump) and three on-ice skating tests (multi-stage aerobic skating test, 44-m sprint test, and backward skating test) were assessed during their pre-season training camp. Game performance metrics (collected during the regular season) were collected using InStat software. Results of the (on-ice and off-ice) functional performance test protocol and on-ice tests were analyzed by evaluating correlation coefficients in multiple areas of game performance: 1) physical implication (body checks), 2) offensive contribution (expected goals for, types of zone entries), and 3) defensive actions (blocked shots, expected goals against). They revealed that performance in the broad jump test was associated with skating speed. Some significant correlations were also observed between on-ice test performance indicators such as received body checks, expected goals and blocked shots. In summary, results indicate that on-ice test protocols were associated with players' performance in multiple aspects of the game. Partial correlation analyses revealed that some of these relationships were specific to the player's position. Forward skating was associated with forwards' offensive play, and backward skating was specifically related with defensemen's performance (offense and defense). The addition of on-ice physical tests appears essential for interpreting the results of ice hockey players' physical tests and integrating these results into players' physical preparation and the in-season follow-up.

The global spread of misinformation on spiders.

In the internet era, the digital architecture that keeps us connected and informed may also amplify the spread of misinformation. This problem is gaining global attention, as evidence accumulates that misinformation may interfere with democratic processes and undermine collective responses to environmental and health crises1,2. In an increasingly polluted information ecosystem, understanding the factors underlying the generation and spread of misinformation is becoming a pressing scientific and societal challenge3. Here, we studied the global spread of (mis-)information on spiders using a high-resolution global database of online newspaper articles on spider-human interactions, covering stories of spider-human encounters and biting events published from 2010-20204. We found that 47% of articles contained errors and 43% were sensationalist. Moreover, we show that the flow of spider-related news occurs within a highly interconnected global network and provide evidence that sensationalism is a key factor underlying the spread of misinformation.

An expert-curated global database of online newspaper articles on spiders and spider bites.

Mass media plays an important role in the construction and circulation of risk perception associated with animals. Widely feared groups such as spiders frequently end up in the spotlight of traditional and social media. We compiled an expert-curated global database on the online newspaper coverage of human-spider encounters over the past ten years (2010-2020). This database includes information about the location of each human-spider encounter reported in the news article and a quantitative characterisation of the content-location, presence of photographs of spiders and bites, number and type of errors, consultation of experts, and a subjective assessment of sensationalism. In total, we collected 5348 unique news articles from 81 countries in 40 languages. The database refers to 211 identified and unidentified spider species and 2644 unique human-spider encounters (1121 bites and 147 as deadly bites). To facilitate data reuse, we explain the main caveats that need to be made when analysing this database and discuss research ideas and questions that can be explored with it.

Multi-institutional review of non-hypospadiac penile urethral stricture management and outcomes.

OBJECTIVES: Penile urethral stricture disease not associated with hypospadias is rare, and there is a wide range of commonly used surgical repair techniques for this disease. We sought to compile a multi-institutional database of patients who had surgical correction of strictures in the penile urethra not limited to the meatus, and who had no history of hypospadias, for analysis using the Trauma and Urologic Reconstructive Network of Surgeons length, urethral segment and etiology classification system. METHODS: A retrospective database from 13 institutions was compiled of patients who had undergone surgical correction of Trauma and Urologic Reconstructive Network of Surgeons length, urethral segment and etiology urethral stricture segments S2b/S2c and excluding E5, with a minimum follow-up time of 4 months. Failure was defined as cystoscopically confirmed recurrence of a stricture measuring less than 16-Fr. RESULTS: We analyzed 222 patients with a median age of 57 years and a follow-up of 49 months. The overall surgical success rate was 80.2%. On multivariate analysis, the two variables identified that were predictive of surgical success were stricture length ≤2 cm as well as use of a buccal mucosa graft as compared to use of a fasciocutaneous flap, which had success rates of 83% and 52%, respectively (P = 0.0004). No statistically significant differences were found based on incisional approach or surgical technique, nor were outcomes different based on etiology or preoperative patient demographics. CONCLUSIONS: Surgical repair of penile urethral strictures of non-hypospadiac origin have a favorable overall success rate, at 80.2%. Regardless of incisional approach or surgical technique, all operations appear to have similar outcomes other than repairs using fasciocutaneous flap, which were statistically less successful than those using buccal mucosa graft.

Complications Based on Prostate Size After Plasmakinetic Enucleation of the Prostate.

Purpose: Lower urinary tract symptoms among adult men can significantly impact quality of life. We evaluated complications based on prostate size following plasmakinetic enucleation of the prostate. Materials and Methods: Patients were grouped into the small prostate group (SPG, <75 g) and large prostate group (LPG, >75 g) based on preoperative imaging. Patient data on demographics, comorbidities, preoperative international prostate symptom score (IPSS), bother index (BI), prostate-specific antigen (PSA) if indicated, postvoid residual volume (PVR), indwelling catheter or self-catheterization status, and any prior surgical intervention were evaluated. Postoperative IPSS, BI, and PVR values were assessed at 6 weeks, 4 months, and yearly. Postoperative urge urinary incontinence (UUI), stress urinary incontinence (SUI), and pad use were assessed. Results: Between September 2015 and December 2020, 296 patients who underwent bipolar enucleation with minimum follow-up of 4 months were evaluated. Postoperative IPSS, BI, PVR, and PSA values at all time points were significantly decreased compared with preoperative values (p < 0.05). There was no significant difference in the complications between groups. Univariable and multivariable analysis found that size <75 g was predictive of stricture formation and bladder neck contracture (BNC). UUI was more common at 6 weeks in the SPG, and SUI was more common at 6 weeks in the LPG, but no difference was noted at the 4-month and 1-year time points. Pad use was equal between the two groups at all time points. Conclusions: Plasmakinetic enucleation of the prostate provides an effective treatment option for prostates of all sizes; however, prostates <75 g have a higher rate of BNC and urethral strictures compared with those >75 g.

Predictors of Storage Symptom Improvement After Plasma Kinetic Enucleation of the Prostate.

OBJECTIVE: To investigate which preoperative findings portend poor improvement in storage symptoms in patients undergoing plasma kinetic enucleation of prostate (PKEP). METHODS: A single surgeon series of patients who had undergone PKEP with minimum 1 year follow up were evaluated. Patients were grouped into those with less than 33% improvement in storage symptoms (LIS) according to the international prostate symptom score (IPSS) and those with greater than 33% improvement in storage symptoms (GIS). Pre and postoperative factors were evaluated, along with IPSS, storage symptoms percentage (the total from frequency, urgency and nocturia divided by the total IPSS), bother index, and post void residual (PVR) at 6 weeks, 4 months, and yearly. RESULTS: Two hundred sixty-eight patients had a minimum 1 year of follow up and had completed the IPSS. IPSS and bother index improved significantly from preoperatively to all time points post operatively in both groups, but the difference was greater in the GIS group. Patients in the GIS group had significantly larger prostates, more prostatic ingrowth, higher preoperative PVR, and a higher overall IPSS compared to the LIS group. Those in the LIS group had a higher incidence of prior prostate surgery, and a higher BMI. However, storage symptom percentages were equal between the GIS and LIS groups at all time points. CONCLUSION: Greater prostatic ingrowth, larger prostate volume, higher preoperative PVR volume, and a higher overall IPSS was associated with greater improvement in storage symptoms. Prior prostate surgery and higher BMI portend less improvement in storage symptoms.

"What's This Bug?" Questions from the Public Provide Relevant Information on Species Distribution and Human-Insect Interactions.

In general, insects and arthropods polarizing: they either fascinate people, disgust people, or both, and they generate lots of questions. Museums are perceived as reliable sources of information and, as such, a go-to destination for the public to receive answers. Since its opening in 1990, the Montreal Insectarium has offered an entomological information service, allowing the public to send questions, photographs, and specimens for identification. All requests are answered by entomologists. Spatiotemporal variations in taxonomic, geographic, and thematic profiles of the 4163 requests received in 2010-2011 and 2017-2018 were analyzed. Requests came from 35 countries, and most of those requests came from Canada. The majority of requests were identification requests. Representing 25% of identification requests, the five most frequent species were the eastern dobsonfly Corydalus cornutus, the masked hunter Reduvius personatus, the giant water bug Lethocerus americanus, the western conifer-seed bug Leptoglossus occidentalis, and the Japanese beetle Popillia japonica. A comparison with the data from the citizen science platform iNaturalist shows that the EIS can be a valuable tool for invasive species detection. Frequent subjects included school projects, entomophagy (eating insects), and wasp and bee nests. Finally, we discuss the role of entomologists in providing scientific information but also in addressing common concerns regarding cohabitation with arthropods.

Virtue male sling outcomes and application to a contemporary nomogram.

INTRODUCTION To report outcomes of our Virtue male sling series and evaluate predictors of surgical success and failure. We also retrofit the Male Stress Incontinence Grading Scale (MSIGS) refined nomogram, including the standing cough test (SCT), to assess its application to our cohort. MATERIALS AND METHODS: A retrospective review was completed at a single institution over a 4 year period of all Virtue male slings implanted for stress urinary incontinence (SUI). Patient demographics including pad usage per day (PPD) and MSIGS were obtained on all patients after their bladders were filled cystoscopically. Failure was defined as > 1 PPD and/or conversion to another anti-incontinence procedure. Incidence, management and outcomes of complications were also evaluated. RESULTS: Forty-six men who underwent Virtue male sling at a median follow up of 15.6 months were analyzed with an objective success rate of 78% and a subjective success rate of 85%. Preoperative predictors of surgical success were ability to stop stream on physical exam, lack of total incontinence and no history of posterior urethral stricture. MSIGS alone was not predictive of sling success or failure. Penile numbness occurred in 11% of patients and reoperation with incision of the sutured together transobturator arms improved sensation in all patients. CONCLUSION: Virtue male sling has high objective and subjective success rates with a manageable side effect profile. Evidence of residual sphincteric function appears to be more predictive of sling success rather than MSIGS.

Simplified posterior urethroplasty utilizing laparoscopic instrumentation.

BACKGROUND: Posterior urethral stricture disease presents challenges for even the most skilled reconstructive urologists. Regardless of the surgical technique used, these are complex operations that occur in hard-to-access locations. We describe the use of a novel combination of laparoscopic instrumentation to simplify posterior urethral reconstruction. METHODS: We retrospectively identified patients undergoing a posterior urethral stricture repair utilizing a combination of the RD-180® suture device and the Securestrap®. These procedures were performed by a single surgeon at our institution. Patients with greater than or equal to 4 months of follow up were included in the analysis. RESULTS: From October 2016 to October 2020, 20 patients underwent posterior urethral stricture repair using these laparoscopic instruments. Median age was 70 years (28-90 years). Median follow up was 12 months (5-50 months). Mean stricture length was 3 cm (1.5-16 cm). Median operative time was 150 minutes (120-180 minutes). No peripheral neuropathies or positional injuries were noted. With failure defined as inability to pass a 16-Fr scope, success rate was 95% (19/20 patients). CONCLUSIONS: The combination of the RD-180® and the Securestrap® has become essential to our posterior urethral stricture repair armamentarium. Further data and longer follow up is needed to confirm these reliable outcomes.

Ventricular Arrhythmia in Septal and Apical Hypertrophic Cardiomyopathy: The French-Canadian Experience.

Background: Apical hypertrophic cardiomyopathy (aHCM) is thought to have a more benign clinical course compared to septal HCM (sHCM), but most data have been derived from Asian cohorts. Comparative data on clinical outcome in Caucasian aHCM cohorts are scarce, and the results are conflicting. The aim of this study was to estimate the prevalence and outcome of aHCM in French-Canadians of Caucasian descent. Methods and results: We conducted a retrospective, single-center cohort study. The primary endpoint was a composite of documented sustained ventricular arrhythmia (VA), appropriate ICD therapy, arrhythmogenic syncope, cardiac arrest, or all-cause mortality. A total of 301 HCM patients (65% males) were enrolled including 80/301 (27%) with aHCM and 221/301 (73%) with sHCM. Maximal wall thickness was similar in both groups. Left ventricular apical aneurysm was significantly more common in aHCM (10 vs. 0.5%; p < 0.001). The proportion of patients with myocardial fibrosis ≥ 15% of the left ventricular mass was similar between aHCM and sHCM (21 vs. 24%; p = 0.68). Secondary prevention ICDs were more often implanted in aHCM patients (16 vs. 7%; p = 0.02). The primary endpoint occurred in 26% of aHCM and 10.4% of sHCM patients (p = 0.001) and was driven by an increased incidence of sustained VA (10 vs. 2.3%; p = 0.01). Multivariate analysis identified apical aneurysm and a phenotype of aHCM as independent predictors of the primary endpoint and the occurrence of sustained ventricular tachycardia. Unexplained syncope and a family history of sudden cardiac death were additional predictors for sustained VA. Apical HCM was associated with an increased risk of ventricular arrhythmia even when excluding patients with apical aneurysm. Conclusions: The phenotype of apical HCM is much more common in French-Canadians (27%) of Caucasian descent compared to other Caucasian HCM populations. Apical HCM in French-Canadians is associated with an increased risk for ventricular arrhythmia.

Evaluation of Antiviral, Antibacterial and Antiproliferative Activities of the Endophytic Fungus Curvularia papendorfii, and Isolation of a New Polyhydroxyacid.

An endophytic fungus isolated from Vernonia amygdalina, a medicinal plant from Sudan, was taxonomically characterized as Curvularia papendorfii. Ethyl acetate crude extract of C. papendorfii revealed an important antiviral effect against two viral pathogens, the human coronavirus HCoV 229E and a norovirus surrogate, the feline coronavirus FCV F9. For the last one, 40% of the reduction of the virus-induced cytopathogenic effect at lower multiplicity of infection (MOI) 0.0001 was observed. Selective antibacterial activity was obtained against Staphylococcus sp. (312 µg/mL), and interesting antiproliferative activity with half maximal inhibitory concentration (IC50) value of 21.5 ± 5.9 µg/mL was observed against human breast carcinoma MCF7 cell line. Therefore, C. papendorfii crude extract was further investigated and fractionated. Twenty-two metabolites were identified by gas chromatography coupled to mass spectrometry (GC-MS), and two pure compounds, mannitol and a new polyhydroxyacid, called kheiric acid, were characterized. A combination of spectroscopic methods was used to elucidate the structure of the new aliphatic carboxylic acid: kheiric acid (3,7,11,15-tetrahydroxy-18-hydroxymethyl-14,16,20,22,24-pentamethyl-hexacosa-4E,8E,12E,16,18-pentaenoic acid). Kheiric acid showed an interesting result with a minimum inhibitory concentration (MIC) value of 62.5 µg/mL against meticillin-resistant Staphylococcus aureus (MRSA). Hence, endophytes associated with medicinal plants from Sudan merit more attention, as they could be a treasure of new bioactive compounds.

An aligned octahedral core in a nanocage: synthesis, plasmonic, and catalytic properties.

Plasmonic metal nanostructures with complex morphologies provide an important route to tunable optical responses and local electric field enhancement at the nanoscale for a variety of applications including sensing, imaging, and catalysis. Here we report a high-concentration synthesis of gold core-cage nanoparticles with a tethered and structurally aligned octahedral core and examine their plasmonic and catalytic properties. The obtained nanostructures exhibit a double band extinction in the visible-near infrared range and a large area electric field enhancement due to the unique structural features, as demonstrated using finite difference time domain (FDTD) simulations and confirmed experimentally using surface enhanced Raman scattering (SERS) tests. In addition, the obtained structures had a photoelectrochemical response useful for catalyzing the CO2 electroreduction reaction. Our work demonstrates the next generation of complex plasmonic nanostructures attainable via bottom-up synthesis and offers a variety of potential applications ranging from sensing to catalysis.

Validation of a novel single lead ambulatory ECG monitor - Cardiostat™ - Compared to a standard ECG Holter monitoring.

BACKGROUND: Cardiostat™ is a single lead ambulatory ECG monitor. Recording is made through 2 electrodes positioned in a lead 1-like configuration. We first validated its accuracy for atrial fibrillation detection compared to a 12-lead ECG. In the second phase of the study, arrhythmia detection accuracy was compared between Cardiostat™ ambulatory ECG and a standard 24 h Holter ECG monitoring. METHOD/RESULTS: Phase one of the study included patients undergoing cardioversion for atrial fibrillation (AF) or atrial flutter. Cardiostat™ tracings were compared with standard 12-lead ECG. In the second phase, patients undergoing 24 h ambulatory Holter ECG monitoring for control or suspicion of atrial fibrillation (AF) were included. Simultaneous Holter monitoring and Cardiostat™ ECG recordings were performed. Tracings were analysed and compared. Two hundred twelve monitoring were compared. AF was diagnosed in 73 patients. Agreement between Cardiostat™ ECG and standard Holter monitoring was 99% for AF detection with kappa = 0.99. Kappa correlation for atrial flutter detection was only moderate at 0.51. AF burden was similar in both recordings. Noise hindered analysis in a greater proportion with Cardiostat™ compared to Holter ambulatory ECG (8.5 vs 3.8%). CONCLUSION: Cardiostat™ ambulatory ECG device showed excellent correlation with the standard Holter ECG monitoring for AF detection. Holter monitoring was however superior to discriminate premature atrial and ventricular beats and to qualify the morphology of PVCs since it has more vectors for analysis. Added value of Cardiostat™ includes longer monitoring duration, less cumbersome installation and water resistance.

Clinical performance of different DF-4 implantable cardioverter defibrillator leads.

INTRODUCTION: Implantable cardioverter-defibrillator (ICD) DF-4 connectors have been introduced to facilitate defibrillator lead connection and to reduce the size of device header. There are limited data regarding the overall performance of those leads and no comparison between different ICD DF-4 leads. METHODS: This is a cohort study of consecutive patients implanted with ICD DF-4 lead system at one University Centre between October 2010 and February 2015. A historical control group of patients with ICD DF-1 lead implantation was used for comparison. The following ICD DF-4 leads were evaluated: St. Jude Medical Durata 7122Q (St. Jude Medical, St. Paul, MN, USA), Medtronic Sprint Quattro Secure 6935 M (Medtronic Inc., Minneapolis, MN, USA), Boston Scientific Endotak Reliance 4-Site 0293 (Boston Scientific, Marlborough, MA, USA), and Boston Scientific Reliance 4-Front 0693. This study evaluated the acute and mid-term performances of those leads as well as complications. RESULTS: A total of 812 patients (age 63 ± 12 years, 80% male, left ventricular ejection fraction 31 ± 12%) underwent implantation of an ICD DF-4 lead. Acute and follow-up R-wave sensing and threshold were excellent. Compared to implantation, intrinsic R waves were higher at follow-up for Boston Scientific and Medtronic leads, and pacing lead impedances were lower for all leads at first follow-up (P < 0.001). The number of lead dislodgement or failure was similar between all leads. The estimated lead survival rates at 3 years were 95.6% for Boston Scientific Endotak 4-Site, 97.1% for Boston Scientific 4-Front, 97.7% for Medtronic Sprint Quattro, and 97.5% for St. Jude Durata (P  =  0.553). CONCLUSION: All ICD DF-4 leads had excellent acute and mid-term electrical performances. Longer follow-up will be necessary to confirm their sustained performance.

Efficient and rapid generation of large genomic variants in rats and mice using CRISMERE.

Modelling Down syndrome (DS) in mouse has been crucial for the understanding of the disease and the evaluation of therapeutic targets. Nevertheless, the modelling so far has been limited to the mouse and, even in this model, generating duplication of genomic regions has been labour intensive and time consuming. We developed the CRISpr MEdiated REarrangement (CRISMERE) strategy, which takes advantage of the CRISPR/Cas9 system, to generate most of the desired rearrangements from a single experiment at much lower expenses and in less than 9 months. Deletions, duplications, and inversions of genomic regions as large as 24.4 Mb in rat and mouse founders were observed and germ line transmission was confirmed for fragment as large as 3.6 Mb. Interestingly we have been able to recover duplicated regions from founders in which we only detected deletions. CRISMERE is even more powerful than anticipated it allows the scientific community to manipulate the rodent and probably other genomes in a fast and efficient manner which was not possible before.