Search for magnetic monopoles produced via the Schwinger mechanism.

Electrically charged particles can be created by the decay of strong enough electric fields, a phenomenon known as the Schwinger mechanism1. By electromagnetic duality, a sufficiently strong magnetic field would similarly produce magnetic monopoles, if they exist2. Magnetic monopoles are hypothetical fundamental particles that are predicted by several theories beyond the standard model3-7 but have never been experimentally detected. Searching for the existence of magnetic monopoles via the Schwinger mechanism has not yet been attempted, but it is advantageous, owing to the possibility of calculating its rate through semi-classical techniques without perturbation theory, as well as that the production of the magnetic monopoles should be enhanced by their finite size8,9 and strong coupling to photons2,10. Here we present a search for magnetic monopole production by the Schwinger mechanism in Pb-Pb heavy ion collisions at the Large Hadron Collider, producing the strongest known magnetic fields in the current Universe11. It was conducted by the MoEDAL experiment, whose trapping detectors were exposed to 0.235 per nanobarn, or approximately 1.8 × 109, of Pb-Pb collisions with 5.02-teraelectronvolt center-of-mass energy per collision in November 2018. A superconducting quantum interference device (SQUID) magnetometer scanned the trapping detectors of MoEDAL for the presence of magnetic charge, which would induce a persistent current in the SQUID. Magnetic monopoles with integer Dirac charges of 1, 2 and 3 and masses up to 75 gigaelectronvolts per speed of light squared were excluded by the analysis at the 95% confidence level. This provides a lower mass limit for finite-size magnetic monopoles from a collider search and greatly extends previous mass bounds.

Common founder BRCA2 pathogenic variants and breast cancer characteristics in Ethiopian Jews.

PURPOSE: BRCA1/2 founder pathogenic variants (PVs) occur in various populations, but data on the mutational spectrum in Africans are limited. We examined BRCA1/2 PVs in breast cancer patients of Ethiopian Jewish (EJ) origin. METHODS: We retrospectively analyzed BRCA1/2 test results and clinical features of EJ breast cancer patients from seven medical institutions. We obtained heterozygote carrier rates in affected individuals from the laboratories of the largest Israeli HMO (Clalit). Population carrier frequency was determined in EJ controls. RESULTS: We identified three recurrent BRCA2 PVs in 11 EJ breast cancer patients (9 females, 2 males): c.7579delG, c.5159C > A, and c.9693delA. Only c.5159C > A was previously reported in Africans. In women, mean age at diagnosis was 35.7y; 8/9 were diagnosed with advanced disease. All tumors were invasive, 4/9 were triple negative. Only 3/11 carriers had relevant family history. Carrier rate in high-risk breast cancer patients was 11% (3/28; 95%CI [2.3%, 28.2%]). Combined carrier rate among controls was 1.8% (5/280; 95%CI [0.6%, 4.1%]). CONCLUSION: EJs harbor 3 recurrent BRCA2 PVs presenting with relatively severe breast cancer morbidity. Combined with the high BRCA2 carrier rate in the EJ population, these findings merit increasing awareness in this community and suggest that a culturally adapted population screening approach may be warranted.

Phenotyping OSAH patients during wakefulness.

PURPOSE: Although currently there are simplified methods to measure the pathophysiological traits that stimulate the occurrence and maintenance of obstructive sleep apnea-hypopnea (OSAH), they remain difficult to implement in routine practice. This pilot study aimed to find a simpler daytime approach to obtain a meaningful, similar pathophysiological phenotypic profile in patients with OSAH. METHODS: After obtaining diagnostic polygraphy from a group of consecutive patients with OSAH, we performed the dial-down CPAP technique during nocturnal polysomnography and used it as reference method. This allowed assessment of upper airway collapsibility, loop gain (LG), arousal threshold (AT), and upper airway muscle gain (UAG). We compared these results with a daytime protocol based on negative expiratory pressure (NEP) technique for evaluating upper airway collapsibility and UAG, on maximal voluntary apnea for LG, and on clinical predictors for AT. RESULTS: Of 15 patients studied, 13 patients with OSAH accurately completed the two procedures. There were strong (all r2 > 0.75) and significant (all p < 0.001) correlations for each phenotypic trait between the measurements obtained through the reference method and those achieved during wakefulness. CONCLUSION: It is possible to phenotype patients with OSAH from a pathophysiological point of view while they are awake. Using this approach, cutoff values corresponding to those usually adopted using the reference method can be identified to detect abnormal traits, achieving profiles similar to those obtained through the dial-down CPAP technique.

First Search for Dyons with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions.

The MoEDAL trapping detector consists of approximately 800 kg of aluminum volumes. It was exposed during run 2 of the LHC program to 6.46 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point. Evidence for dyons (particles with electric and magnetic charge) captured in the trapping detector was sought by passing the aluminum volumes comprising the detector through a superconducting quantum interference device (SQUID) magnetometer. The presence of a trapped dyon would be signaled by a persistent current induced in the SQUID magnetometer. On the basis of a Drell-Yan production model, we exclude dyons with a magnetic charge ranging up to five Dirac charges (5g_{D}) and an electric charge up to 200 times the fundamental electric charge for mass limits in the range 870-3120 GeV and also monopoles with magnetic charge up to and including 5g_{D} with mass limits in the range 870-2040 GeV.

Media matters! Alterations in the loading and release of Histoplasma capsulatum extracellular vesicles in response to different nutritional milieus.

Histoplasma capsulatum is a dimorphic fungus that most frequently causes pneumonia, but can also disseminate and proliferate in diverse tissues. Histoplasma capsulatum has a complex secretion system that mediates the release of macromolecule-degrading enzymes and virulence factors. The formation and release of extracellular vesicles (EVs) are an important mechanism for non-conventional secretion in both ascomycetes and basidiomycetes. Histoplasma capsulatum EVs contain diverse proteins associated with virulence and are immunologically active. Despite the growing knowledge of EVs from H. capsulatum and other pathogenic fungi, the extent that changes in the environment impact the sorting of organic molecules in EVs has not been investigated. In this study, we cultivated H. capsulatum with distinct culture media to investigate the potential plasticity in EV loading in response to differences in nutrition. Our findings reveal that nutrition plays an important role in EV loading and formation, which may translate into differences in biological activities of these fungi in various fluids and tissues.

The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics.

Although much is known about the migration of T cells from blood to lymph nodes, less is known about the mechanisms regulating the migration of T cells from tissues into lymph nodes through afferent lymphatics. Here we investigated T cell egress from nonlymphoid tissues into afferent lymph in vivo and developed an experimental model to recapitulate this process in vitro. Agonism of sphingosine 1-phosphate receptor 1 inhibited the entry of tissue T cells into afferent lymphatics in homeostatic and inflammatory conditions and caused the arrest, mediated at least partially by interactions of the integrin LFA-1 with its ligand ICAM-1 and of the integrin VLA-4 with its ligand VCAM-1, of polarized T cells at the basal surface of lymphatic but not blood vessel endothelium. Thus, the increased sphingosine 1-phosphate present in inflamed peripheral tissues may induce T cell retention and suppress T cell egress.

Magnetic Monopole Search with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions Interpreted in Photon-Fusion and Drell-Yan Production.

MoEDAL is designed to identify new physics in the form of stable or pseudostable highly ionizing particles produced in high-energy Large Hadron Collider (LHC) collisions. Here we update our previous search for magnetic monopoles in Run 2 using the full trapping detector with almost four times more material and almost twice more integrated luminosity. For the first time at the LHC, the data were interpreted in terms of photon-fusion monopole direct production in addition to the Drell-Yan-like mechanism. The MoEDAL trapping detector, consisting of 794 kg of aluminum samples installed in the forward and lateral regions, was exposed to 4.0 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to or above the Dirac charge are excluded in all samples. Monopole spins 0, ½, and 1 are considered and both velocity-independent and-dependent couplings are assumed. This search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.

Measuring Spatial and Temporal PM2.5 Variations in Sacramento, California, Communities Using a Network of Low-Cost Sensors.

Low-cost sensors can provide insight on the spatio-temporal variability of air pollution, provided that sufficient efforts are made to ensure data quality. Here, 19 AirBeam particulate matter (PM) sensors were deployed from December 2016 to January 2017 to determine the spatial variability of PM2.5 in Sacramento, California. Prior to, and after, the study, the 19 sensors were deployed and collocated at a regulatory air monitoring site. The sensors demonstrated a high degree of precision during all collocated measurement periods (Pearson R2 = 0.98 - 0.99 across all sensors), with little drift. A sensor-specific correction factor was developed such that each sensor reported a comparable value. Sensors had a moderate degree of correlation with regulatory monitors during the study (R2 = 0.60 - 0.68 at two sites). In a multi-linear regression model, the deviation between sensor and reference measurements of PM2.5 had the highest correlation with dew point and relative humidity. Sensor measurements were used to estimate the PM2.5 spatial variability, finding an average pairwise coefficient of divergence of 0.22 and a range of 0.14 to 0.33, indicating mostly homogeneous distributions. No significant difference in the average sensor PM concentrations between environmental justice (EJ) and non-EJ communities (p value = 0.24) was observed.

Efficient CRISPR/Cas9-based genome editing in carrot cells.

KEY MESSAGE: The first report presenting successful and efficient carrot genome editing using CRISPR/Cas9 system. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas9) is a powerful genome editing tool that has been widely adopted in model organisms recently, but has not been used in carrot-a model species for in vitro culture studies and an important health-promoting crop grown worldwide. In this study, for the first time, we report application of the CRISPR/Cas9 system for efficient targeted mutagenesis of the carrot genome. Multiplexing CRISPR/Cas9 vectors expressing two single-guide RNA (gRNAs) targeting the carrot flavanone-3-hydroxylase (F3H) gene were tested for blockage of the anthocyanin biosynthesis in a model purple-colored callus using Agrobacterium-mediated genetic transformation. This approach allowed fast and visual comparison of three codon-optimized Cas9 genes and revealed that the most efficient one in generating F3H mutants was the Arabidopsis codon-optimized AteCas9 gene with up to 90% efficiency. Knockout of F3H gene resulted in the discoloration of calli, validating the functional role of this gene in the anthocyanin biosynthesis in carrot as well as providing a visual marker for screening successfully edited events. Most resulting mutations were small Indels, but long chromosome fragment deletions of 116-119 nt were also generated with simultaneous cleavage mediated by two gRNAs. The results demonstrate successful site-directed mutagenesis in carrot with CRISPR/Cas9 and the usefulness of a model callus culture to validate genome editing systems. Given that the carrot genome has been sequenced recently, our timely study sheds light on the promising application of genome editing tools for boosting basic and translational research in this important vegetable crop.

Assessing the Utility of Low-Cost Particulate Matter Sensors over a 12-Week Period in the Cuyama Valley of California.

The use of low-cost air quality sensors has proliferated among non-profits and citizen scientists, due to their portability, affordability, and ease of use. Researchers are examining the sensors for their potential use in a wide range of applications, including the examination of the spatial and temporal variability of particulate matter (PM). However, few studies have quantified the performance (e.g., accuracy, precision, and reliability) of the sensors under real-world conditions. This study examined the performance of two models of PM sensors, the AirBeam and the Alphasense Optical Particle Counter (OPC-N2), over a 12-week period in the Cuyama Valley of California, where PM concentrations are impacted by wind-blown dust events and regional transport. The sensor measurements were compared with observations from two well-characterized instruments: the GRIMM 11-R optical particle counter, and the Met One beta attenuation monitor (BAM). Both sensor models demonstrated a high degree of collocated precision (R² = 0.8-0.99), and a moderate degree of correlation against the reference instruments (R² = 0.6-0.76). Sensor measurements were influenced by the meteorological environment and the aerosol size distribution. Quantifying the performance of sensors in real-world conditions is a requisite step to ensuring that sensors will be used in ways commensurate with their data quality.

A CRISPR/Cas9 Toolbox for Multiplexed Plant Genome Editing and Transcriptional Regulation.

The relative ease, speed, and biological scope of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated Protein9 (Cas9)-based reagents for genomic manipulations are revolutionizing virtually all areas of molecular biosciences, including functional genomics, genetics, applied biomedical research, and agricultural biotechnology. In plant systems, however, a number of hurdles currently exist that limit this technology from reaching its full potential. For example, significant plant molecular biology expertise and effort is still required to generate functional expression constructs that allow simultaneous editing, and especially transcriptional regulation, of multiple different genomic loci or multiplexing, which is a significant advantage of CRISPR/Cas9 versus other genome-editing systems. To streamline and facilitate rapid and wide-scale use of CRISPR/Cas9-based technologies for plant research, we developed and implemented a comprehensive molecular toolbox for multifaceted CRISPR/Cas9 applications in plants. This toolbox provides researchers with a protocol and reagents to quickly and efficiently assemble functional CRISPR/Cas9 transfer DNA constructs for monocots and dicots using Golden Gate and Gateway cloning methods. It comes with a full suite of capabilities, including multiplexed gene editing and transcriptional activation or repression of plant endogenous genes. We report the functionality and effectiveness of this toolbox in model plants such as tobacco (Nicotiana benthamiana), Arabidopsis (Arabidopsis thaliana), and rice (Oryza sativa), demonstrating its utility for basic and applied plant research.

Scaphoid tuberosity excursion is minimized during a dart-throwing motion: A biomechanical study.

PURPOSE: The purpose of this study was to determine whether the excursion of the scaphoid tuberosity and therefore scaphoid motion is minimized during a dart-throwing motion. METHODS: Scaphoid tuberosity excursion was studied as an indicator of scaphoid motion in 29 cadaver wrists as they were moved through wrist flexion-extension, radioulnar deviation, and a dart-throwing motion. RESULTS: Study results demonstrate that excursion was significantly less during the dart-throwing motion than during either wrist flexion-extension or radioulnar deviation. CONCLUSION: If the goal of early wrist motion after carpal ligament or distal radius injury and reconstruction is to minimize loading of the healing structures, a wrist motion in which scaphoid motion is minimal should reduce length changes in associated ligamentous structures. Therefore, during rehabilitation, if a patient uses a dart-throwing motion that minimizes his or her scaphoid tuberosity excursion, there should be minimal changes in ligament loading while still allowing wrist motion. STUDY DESIGN: Bench research, biomechanics, and cross-sectional. LEVEL OF EVIDENCE: Not applicable. The study was laboratory based.

Force variations in the distal radius and ulna: effect of ulnar variance and forearm motion.

PURPOSE: To better define normal wrist joint forces during wrist motion and forearm motion at specific wrist and forearm positions and to see if there is a relationship between these forces and the amount of ulnar variance. A secondary purpose was to determine the relationship between the thickness of the articular disk of the triangular fibrocartilage complex and the amount of force transmitted through the distal ulna. METHODS: Multi-axis load cells were attached to the distal radius and ulna of 9 fresh cadaver forearms. The axial radial and ulnar compressive forces were recorded while each wrist was moved through wrist and forearm motions using a modified wrist joint simulator. During each motion, the tendon forces required to cause each motion were recorded. The ulnar variance and triangular fibrocartilage complex articular disc thickness were measured. RESULTS: The axial force through the distal ulna and the wrist extensor forces were greatest with the forearm in pronation. No relationship was found between the amount of force through the distal ulna and the amount of ulnar variance. A strong inverse relationship was found between the triangular fibrocartilage complex thickness and the ulnar variance. CONCLUSIONS: Wrists with positive ulnar variance have generally been thought to transmit greater loads across the distal ulna, which has been felt to predispose these wrists to the development of ulnar impaction. The results of this study appear to show that all wrists have similar loading across the distal ulna regardless of ulnar variance. By comparison, pronation relatively increases loading across the distal ulna. CLINICAL RELEVANCE: Because these results suggest that within reasonable ranges of ulnar variance loading across the distal ulna is independent of ulnar variance, the clinically observed incidence of ulnar impaction is more likely the result of increased wear on a thinner and less durable triangular fibrocartilage complex than due to increased distal ulna loading in ulnar positive variant wrists.

[Mandibular third molar extractions with proximity to the inferior alveolar nerve canal: what are the alternatives?].

Throughout the evolution, modern diet became softer and led to less attrition and less mesial migration of teeth resulting in an increased incidence of teeth impaction. When a mandibular third molar extraction is indicated, damage to the inferior alveolar nerve (IAN) is one of the most important complications. The objective of this review is to provide an overview of the alternative treatment modalities to total removal for a third mandibular molar in cases of proximity to the inferior alveolar nerve. Among the discussed options are: Orthodontic intervention to slowly move the tooth apex away from the mandibular canal and thus reducing the potential for neural injury during extraction; staged approached involving removal of the mesial portion of the crown creating a space for mesial migration of the teeth; and Coronectomy which include removing of the tooth crown while leaving the root undisturbed.

Tracheotomy tubes with suction above the cuff reduce the rate of ventilator-associated pneumonia in intensive care unit patients.

OBJECTIVES: We evaluated the effect of tracheotomy tubes that enable suction immediately above the cuff on the development of ventilator-associated pneumonia (VAP). METHODS: Patients without preexisting pneumonia who required tracheotomy were randomly assigned to receive a tracheotomy tube with or without above-the-cuff suction. The suction tube provided 10 mm Hg of continuous wall suction while the tracheotomy tube cuff was inflated. Data regarding the development of VAP, time on the ventilator, and length of stay in the intensive care unit (ICU) were recorded and compared between groups. RESULTS: Eighteen patients were randomized and prospectively evaluated. Nine patients received standard tracheotomy tubes, and 9 received suction-above-the-cuff tracheotomy tubes. The prevalences of VAP were 56% in the control group and 11% in the suction tracheotomy group (p = 0.02). The mean times on the ventilator were 18 +/- 14 days in the control group and 11 +/- 11 days in the suction group (p = 0.12). The mean lengths of ICU stay were 26 +/- 15 days in the control group and 18 +/- 15 days in the suction group (p = 0.14). CONCLUSIONS: Use of suction-above-the-cuff tracheotomy tubes significantly decreases the incidence of VAP in ICU patients. There were trends toward decreased time on the ventilator and decreased length of stay in the ICU.

4-corner arthrodesis and proximal row carpectomy: a biomechanical comparison of wrist motion and tendon forces.

PURPOSE: Controversy exists as to whether a proximal row carpectomy (PRC) is a better procedure than scaphoid excision with 4-corner arthrodesis for preserving motion in the painful posttraumatic arthritic wrist. The purpose of this study was to determine how the kinematics and tendon forces of the wrist are altered after PRC and 4-corner arthrodesis. METHODS: We tested 6 fresh cadaver forearms for the extremes of wrist motion and then used a wrist simulator to move them through 4 cyclic dynamic wrist motions, during which time we continuously recorded the tendon forces. We repeated the extremes of wrist motion measurements and the dynamic motions after scaphoid excision with 4-corner arthrodesis, and then again after PRC. We analyzed extremes of wrist motion and the peak tendon forces required for each dynamic motion using a repeated measures analysis of variance. RESULTS: Wrist extremes of motion significantly decreased after both the PRC and 4-corner arthrodesis compared with the intact wrist. Wrist flexion decreased on average 13° after 4-corner arthrodesis and 12° after PRC. Extension decreased 20° after 4-corner arthrodesis and 12° after PRC. Four-corner arthrodesis significantly decreased wrist ulnar deviation from the intact wrist. Four-corner arthrodesis allowed more radial deviation but less ulnar deviation than the PRC. The average peak tendon force was significantly greater after 4-corner arthrodesis than after PRC for the extensor carpi ulnaris during wrist flexion-extension, circumduction, and dart throw motions. The peak forces were significantly greater after 4-corner arthrodesis than in the intact wrist for the extensor carpi ulnaris during the dart throw motion and for the flexor carpi ulnaris during the circumduction motion. The peak extensor carpi radialis brevis force after PRC was significantly less than in the intact wrist. CONCLUSIONS: The measured wrist extremes of motion decreased after both 4-corner arthrodesis and PRC. Larger peak tendon forces were required to achieve identical wrist motions with the 4-corner arthrodesis compared with the intact wrist. We observed smaller forces for the PRC. CLINICAL RELEVANCE: These results may help explain why PRC shows early clinical improvement, yet may lead to degenerative arthritis.

Reverse shoulder arthroplasty glenoid fixation: is there a benefit in using four instead of two screws?

BACKGROUND: To allow osseous integration to occur and thus provide long-term stability, initial glenoid baseplate fixation must be sufficiently rigid. A major contributing factor to initial rigid fixation is baseplate screw fixation. Current baseplate designs use a 4-screw fixation construct. However, recent literature suggests adequate fixation can be achieved with fewer than 4 screws. The purpose of the present study was to determine whether a 4-screw construct provides more baseplate stability than a 2-screw construct. METHODS: A flat-backed glenoid baseplate with 4 screw hole options was implanted into 6 matched pairs of cadaver scapulas using standard surgical technique. Within each pair, 2 screws or 4 screws were implanted in a randomized fashion. A glenosphere was attached allowing cyclic loading in an inferior-to-superior direction and in an anterior-to-posterior direction. Baseplate motion was measured using 4 linear voltage displacement transducers evenly spaced around the glenosphere. RESULTS: There was no statistical difference in the average peak central displacements between fixation with 2 or 4 screws (P = .338). Statistical increases in average peak central displacement with increasing load (P < .001) and with repetitive loading (P < .002) were found. CONCLUSION: This study demonstrates no statistical difference in baseplate motion between 2-screw and 4-screw constructs. Therefore, using fewer screws could potentially lead to a reduction in operative time, cost, and risk, with no significant negative effect on overall implant baseplate motion.

Scaphoid excision and midcarpal arthrodesis: the effect of triquetral excision--a biomechanical study.

PURPOSE: To evaluate the biomechanical alterations that occur after traditional scaphoid excision and midcarpal arthrodesis with and without excision of the triquetrum. The hypothesis of this study was that removal of the triquetrum increases the radiolunate contact pressure. METHODS: We cyclically moved 10 fresh cadaver wrists using a wrist joint motion simulator while measuring the contact pressures between the proximal carpal row and the distal radius and ulna using a dynamic pressure sensor. We acquired data in the intact wrist, after a midcarpal arthrodesis with the scaphoid excised, and then again with the triquetrum removed, which is also known as a capitolunate arthrodesis. RESULTS: The peak pressures in the radiolunate fossa significantly increased with either of the midcarpal arthrodeses compared with the intact wrist during each of the 3 dynamic wrist motions. In comparing the 2 midcarpal arthrodeses, the peak pressure in the ulnocarpal fossa significantly decreased after the triquetrum was removed during wrist radioulnar deviation and in the static ulnarly deviated position. After arthrodesis, we could identify no differences during any motion or static wrist position in the peak radiolunate pressures with or without the triquetrum. CONCLUSIONS: We found that scaphoid excision and 4-corner arthrodesis shifts loads to the radiolunate joint. Isolated capitolunate arthrodesis with excision of the scaphoid and triquetrum further alters carpal kinematics and loading patterns. CLINICAL RELEVANCE: These findings raise concern about routine excision of the triquetrum when performing a midcarpal arthrodesis.

Does glenoid baseplate geometry affect its fixation in reverse shoulder arthroplasty?

BACKGROUND: The effect of glenoid baseplate geometry has not been studied as it pertains to reverse shoulder arthroplasty. The purpose of this study was to compare 2 baseplate designs whose major difference is being either a flat backed design or a convex baseplate, with regard to their bone interface area, screw engagement, and bone volume removed using 3-dimensional modeling. METHODS: Three-dimensional models of 6 scapulae were used to virtually implant models of a flat backed and a convex backed glenoid baseplate. Additional reaming was performed in 1 mm increments, up to 5 mm, and the amount of baseplate screw engagement was calculated at each increment. Statistical differences between flat and convex implants were calculated. RESULTS: Insertion of the convex baseplate required statistically greater removal of bone as compared to the flat baseplate (P = .003). No statistical changes in total area were observed with reaming of the glenoid for the convex baseplate (P > .095). However, for the flat baseplate, 1 mm of reaming caused a statistical decrease in area available for fixation. The amount of total bone area in contact with a convex baseplate was statistically greater than with a flat baseplate (P = .004). The amount of screw engagement was statistically less with the convex baseplate, compared to the flat (P = .026). DISCUSSION: A convex backed glenoid baseplate can improve the contact surface area at the bone implant interface as compared to a flat backed design. However, better screw engagement and less bone volume removed during reaming favors a flat backed design, particularly when adequate bone-implant contact cannot be achieved.

A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer.

Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9-10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.