Spyglass: a framework for reproducible and shareable neuroscience research.

Scientific progress depends on reliable and reproducible results. Progress can also be accelerated when data are shared and re-analyzed to address new questions. Current approaches to storing and analyzing neural data typically involve bespoke formats and software that make replication, as well as the subsequent reuse of data, difficult if not impossible. To address these challenges, we created Spyglass, an open-source software framework that enables reproducible analyses and sharing of data and both intermediate and final results within and across labs. Spyglass uses the Neurodata Without Borders (NWB) standard and includes pipelines for several core analyses in neuroscience, including spectral filtering, spike sorting, pose tracking, and neural decoding. It can be easily extended to apply both existing and newly developed pipelines to datasets from multiple sources. We demonstrate these features in the context of a cross-laboratory replication by applying advanced state space decoding algorithms to publicly available data. New users can try out Spyglass on a Jupyter Hub hosted by HHMI and 2i2c: https://spyglass.hhmi.2i2c.cloud/.

Editorial Commentary: Dynamic Anterior Stabilization via Biceps Tenodesis to the Glenoid Is an Option for Anterior Shoulder Instability With Subcritical Glenoid Bone Loss.

A nuanced approach to treatment of anterior shoulder instability is encouraged, particularly in patients with subcritical glenoid bone loss. In patients with bone loss, recurrent instability after isolated arthroscopic Bankart repair has dampened enthusiasm for this procedure. Adjunctive treatment with remplissage or dynamic anterior stabilization via biceps tenodesis to the glenoid is an alternative to bone transfer procedures, which are effective but have higher complication rates. Dynamic anterior stabilization or tenodesis of the long head of the biceps to the 3-o'clock position on the glenoid through a subscapularis split is biomechanically superior to isolated Bankart repair for reducing anterior translation, even in the setting of minor glenoid bone loss due to a sling effect similar to that produced by the Latarjet procedure. A disadvantage is placement of a large implant into the small space of the anterior glenoid and creation of a soft-tissue defect in the capsule.

Obesity and Reverse Total Shoulder Arthroplasty.

PURPOSE OF REVIEW: Rates of obesity and reverse total shoulder arthroplasty (rTSA) in the USA have both escalated with time. Obese patients experience arthritis at higher rates than normal weight patients; therefore, these numbers go hand in hand. Obesity has been correlated with health comorbidities such as anxiety, cardiovascular disease, diabetes, and metabolic syndrome as well as poorer outcomes and higher complication rates following lower extremity arthroplasty. The current review investigates these comorbidities as they relate to obese patients undergoing rTSA. RECENT FINDINGS: Functional outcomes are similar to normal weight counterparts. Although longer operative times and a large soft tissue envelope would intuitively predispose these patients to higher risk for infection or other complications, this has not been reliably demonstrated. Technical considerations and awareness of potential risks in the obese patient demographic may aid the surgeon in preoperative planning and counseling of their patient. Obese patients undergoing rTSA have been shown to have higher risks specifically for infection, revision, and medical complications; however, this has not been consistently demonstrated in the single surgeon series where, more often, no difference in these metrics has been found. Outcomes measures and satisfaction are reliably improved, even when considering superobese patients, and majority of studies find their improvements and absolute values to be in line with their normal weight counterparts. Thus, rTSA does not seem to carry the same level of adverse risk associated with lower joint arthroplasty but potential for higher risk still bears consideration when counseling obese patients. Attention to factors that may negatively affect prosthesis positioning may optimize retention rates and limit early failure.

Patient-Reported Outcome Surveys for Femoroacetabular Impingement Syndrome Demonstrate Strong Correlations, High Minimum Clinically Important Difference Agreement and Large Ceiling Effects.

PURPOSE: To determine the correlation between different patient-reported outcome (PRO) measurements used to assess outcomes after arthroscopic treatment of femoroacetabular impingement syndrome (FAIS) in a single cohort of patients. METHODS: Patients undergoing primary hip arthroscopy for FAIS (without dysplasia, arthritis, or joint hypermobility) were retrospectively analyzed from a prospectively collected cohort. PROs collected before surgery and at 2-year follow-up included the Visual Analog Scale (VAS) for pain, modified Harris Hip Score (mHHS), Hip Disability and Osteoarthritis Outcome Scores (HOOS) with subscales for symptoms, pain, activities of daily living (ADL), sport, and quality of life (QoL), and the physical and mental components of the Short Form-12 (SF-12 PCS and SF-12 MCS). RESULTS: Three hundred patients with 2 years' follow-up (mean age 35.1 ± 11.3, BMI 24.7 ± 3.8, 52.7% female, median Tönnis grade 1) were identified. All patients underwent femoroplasty and labral repair. There was a strong correlation among nearly all the PRO surveys at 2-year follow-up, with the highest correlations identified between mHHS and HOOS-Pain (r = .86, P < .001) and mHHS and HOOS-ADL (r = .85, P < .001). Preoperative scores and the change from preoperative to postoperative scores demonstrated an overall moderate correlation between surveys. There was a consistently weak correlation between the SF-12 MCS and all other PROs. There were strong agreements (67%-77%) in the patients achieving minimal clinically important differences (MCID) for each PRO survey. All surveys except the SF-12 demonstrated a ceiling effect after surgery, with 13% to 43% of patients achieving the maximum score. CONCLUSIONS: PRO surveys used for FAIS demonstrate strong correlations, especially in the evaluation of patients during the postoperative period. MCID for VAS, mHHS, and HOOS demonstrate strong agreement, whereas large ceiling effects were seen with the mHHS and HOOS. The results support a more efficient use of PRO scores while being able to accurately capture patient outcomes. LEVEL OF EVIDENCE: IV, retrospective case series.

To Improve Pain and Function, Platelet-Rich Plasma Injections May Be an Alternative to Surgery for Treating Lateral Epicondylitis: A Systematic Review.

PURPOSE: To determine whether platelet-rich plasma (PRP) injection for lateral epicondylitis offers patients comparable outcomes to lateral epicondylar surgery. METHODS: Embase, Cochrane Library, and MEDLINE databases were searched using the terms lateral epicondylitis, lateral elbow pain, tennis elbow, lateral epicondylalgia, and elbow tendinopathy individually and combined with the terms platelet-rich plasma injections and lateral epicondylar surgery. We compared pain relief, function between the 2 treatment options, and identified whether PRP injection reduced the incidence of lateral epicondylar surgery. Studies must have compared PRP injections with lateral epicondylar surgery for the treatment of lateral epicondylitis; be of Level I, II, or III evidence; and be written in the English language. RESULTS: Three studies (1 Level II and 2 Level III) met inclusion criteria. Two of the studies suggested that PRP injections offer similar relief as surgery in the short and mid-term, one study reported that PRP injections and surgery had similar outcomes in pain improvement and return to work, whereas 1 study reported that surgery may be a better long-term solution. CONCLUSIONS: In comparison with lateral epicondylar surgery, PRP injections offer similar improvements in pain and function for patients suffering from lateral epicondylitis, especially in the short- and mid-term in 2 of the 3 included investigations. Therefore, PRP injections are an appropriate alternative for the treatment of lateral epicondylitis. LEVEL OF EVIDENCE: Level III, Systematic Review of Level III or greater evidence.

The Relationship Between Energy Drink Consumption, Caffeine Content, and Nutritional Knowledge Among College Students.

We sought to determine which demographic characteristics influence energy drink consumption habits and to examine whether caffeine content and knowledge of human nutrition affect college students' decisions to consume these beverages. We used an online survey to ask 265 college students, who did not participate in a varsity sport, to complete a survey consisting of demographic questions, the General Knowledge Questionnaire for adults, and questions about energy drink consumption habits. We found, overall, that 23.1% of our sample used energy drinks. When compared to non-consumers (76.9%), users had a significantly lower GPA, were older, and preferred drinks with a higher caffeine content. Users reported that they consumed these drinks because they wanted to feel more alert and they enjoyed the taste, even though they reported adverse effects such as trouble sleeping, shaking and tremors, and stomachaches. Knowledge of human nutrition did not affect users' choice to consume these drinks. Although the majority of college students do not consume energy drinks, room for improvement remains to curb the use of these caffeinated beverages amongst college students.

Arthroscopic Single-Portal Subscapularis Tendon Repair.

Tears of the subscapularis tendon can be challenging to diagnose and treat. Because the subscapularis plays an important role in shoulder function, careful arthroscopic evaluation and treatment are necessary to restore function. Previous surgical techniques have ranged from full open repairs to complex arthroscopic procedures needing suture passer and/or retriever devices. We describe an arthroscopic surgical technique of subscapularis repair through a single anterior portal using only penetrating graspers. This approach can be used for partial upper-border subscapularis tears, as well as complete and retracted subscapularis tendon tears.

Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease.

Sleep disturbances co-occur with and precede the onset of motor symptoms in Parkinson's disease (PD). We evaluated sleep fragmentation and thalamocortical sleep spindles in mice expressing the p.G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) gene, one of the most common genetic forms of PD. Thalamocortical sleep spindles are oscillatory events that occur during slow-wave sleep that are involved in memory consolidation. We acquired data from electrocorticography, sleep behavioral measures, and a rotarod-based motor enrichment task in 28 LRRK2-G2019S knock-in mice and 27 wild-type controls (8-10 month-old males). Sleep was more fragmented in LRRK2-G2019S mice; sleep bouts were shorter and more numerous, even though total sleep time was similar to controls. LRRK2-G2019S animals expressed more sleep spindles, and individual spindles were longer in duration than in controls. We then chronically administered the LRRK2-inhibitor MLi-2 in-diet to n = 12 LRRK2-G2019S and n = 15 wild-type mice for a within-subject analysis of the effects of kinase inhibition on sleep behavior and physiology. Treatment with MLi-2 did not impact these measures. The data indicate that the LRRK2-G2019S mutation could lead to reduced sleep quality and altered sleep spindle physiology. This suggests that sleep spindles in LRRK2-G2019S animals could serve as biomarkers for underlying alterations in sleep networks resulting from the LRRK2-G2019S mutation, and further evaluation in human LRRK2-G2019S carriers is therefore warranted.

Relationship between iHOT12 and HOS scores in hip pain patients.

To determine if scores of the International Hip Outcome Tool-12 (iHOT12) and the Hip Outcome Score (HOS) correlate with one another in hip pain patients. Patients reporting to an orthopedic clinic for their scheduled appointment for hip pain were given a paper survey consisting of the iHOT12 and the HOS. Demographic information [age, weight, height and body mass index (BMI)] was obtained by chart review. Overall, 114 patients were invited to voluntarily complete the surveys of which 23 declined. Our sample consisted of 91 (57 female and 34 male) patients (80% response rate). The HOS (iHOT12) explained 62% of the variation in iHOT12 (HOS) by using a linear model (Pearson's correlation(r) is 0.79, P < 0.001). Age, weight, BMI, gender and arthritis did not show a statistically significant predictive power explaining HOS. However, only gender had a 'statistically' significant predictive power explaining iHOT12 (P = 0.007). The relationship between the two scores are stronger for males (r = 0.81, P < 0.001) compared with females (r = 0.77, P < 0.001). The proportion of variations explained on one of the scores by the other are 0.66 for males and 0.59 for females. HOS score together with gender explained 64% of the variation in iHOT12 by using a linear model. iHOT12 together with the non-statistically significant gender term explained 62% of the variation in HOS by using a linear model. It may not be necessary to collect both the iHOT12 and HOS, since the predictive power of one on the other is high. Collecting HOS together with information on gender is preferable compared with collecting iHOT12. Level of evidence: Level III.

Do Outcomes of Arthroscopic Subscapularis Tendon Repairs Depend on Rotator Cuff Fatty Infiltration?

BACKGROUND: Rotator cuff fatty infiltration has been correlated with poorer radiographic and clinical outcomes in supraspinatus and infraspinatus tendon repairs, but this has not been well-studied in subscapularis tendon repairs. PURPOSE: To evaluate the influence of preoperative rotator cuff fatty infiltration on postoperative outcomes for patients undergoing arthroscopic subscapularis tendon repair. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients who underwent arthroscopic subscapularis repair between 2010 and 2016 were retrospectively identified, and demographic data and surgical findings were recorded. The extent of fatty infiltration was determined on preoperative magnetic resonance imaging by the Fuchs modification of the Goutallier classification. At the most recent follow-up, patients completed the Patient-Reported Outcomes Measurement Information System for Upper Extremity (PROMIS-UE) computer adaptive test and a postoperative visual analog scale for pain. The distribution of fatty infiltration was compared between patients undergoing subscapularis tendon repair versus subscapularis tendon repair combined with a posterior cuff repair. Outcomes were compared for patients using Goutallier grade 0-1 versus grade ≥2 changes in each rotator cuff muscle. Multivariate linear regression analysis was performed to evaluate the influence of muscle quality, as well as demographic factors, on PROMIS-UE scores. Significance was defined as P < .05. RESULTS: There were 140 shoulders included (mean age, 61.8 years; 42.1% female; mean follow-up, 51.7 months). The prevalence of Goutallier grade 2 changes or higher was significantly greater in patients with multitendon repair relative to isolated subscapularis tendon repair. For the overall group of all patients undergoing subscapularis tendon repair, whether in isolation or as part of a multitendon repair, PROMIS-UE scores were significantly lower for patients with infraspinatus muscle grade 2 or higher Goutallier changes relative to grade 0 or 1. After adjustment for age, body mass index, patient sex, and fatty infiltration in other rotator cuff muscles, poor infraspinatus muscle quality remained the only significant predictor for lower PROMIS-UE scores. CONCLUSION: Patients undergoing arthroscopic subscapularis tendon repair with poor infraspinatus muscle quality had worse patient-reported outcomes. This was true whether subscapularis tendon repair was isolated or was performed in conjunction with supraspinatus and infraspinatus tendon repairs.

Research Pearls: Checklists and Flowcharts to Improve Research Quality.

To instill quality in published clinical research, reporting guidelines, consisting of checklists and flowcharts, were developed to protect against reporting poorly designed research, and researchers should be aware of the available instruments and their appropriate use. With the popularity of synthetic reviews, meta-analyses, and systematic reviews, there is a greater need to assess risk of bias and study quality. This review highlights the most frequently used guidelines and checklists, risk-of-bias scales, and quality rating scales that can assist researchers with improving their research and its eventual publication.

The Quality and Accuracy of Online Resources for Total and Reverse Shoulder Replacement.

Recent literature suggests that many online patient resources are poor in quality and lack important clinical information. The purpose of this study was to investigate the value of online resources available to patients considering shoulder arthroplasty. A total of 84 websites were discovered with the terms "total shoulder replacement" (TSR) and "reverse shoulder replacement" (RSR), they were reviewed and graded for quality and accuracy. Overall quality scores were low for TSR and RSR websites, 22.8/45 (95% confidence interval (CI): 19.9-25.6) and 24.2/45 (95% CI: 21.6-26.9), respectively. The authorship of a website significantly influenced the quality for both TSR (p = 0.013) and RSR (p = 0.048). When comparing search rank to quality scores, websites that appeared earlier demonstrated significantly higher quality scores, TSR (p = 0.017) and RSR (p = 0.018). Overall, most websites were accurate but provided incomplete information. Websites authored by professional societies have higher quality scores than websites authored by medical providers or commercial entities. (Journal of Surgical Orthopaedic Advances 28(4):290-294, 2019).

Intra-articular Osteoid Osteoma of the Distal Femur Treated with Osteochondral Grafting: A Report of 2 Cases.

CASE: Intra-articular osteoid osteoma (IAOO) is a relatively rare entity and can pose a therapeutic challenge due to proximity to the cartilage surface. We present 2 cases of subchondral osteoid osteomata within the distal femur treated with excision and osteochondral grafting of the resultant defect. CONCLUSIONS: Subchondral IAOO can pose a therapeutic challenge. Our patients had an effective pain relief and return to activities with this treatment strategy.

Patient-Reported Outcomes After Isolated and Combined Arthroscopic Subscapularis Tendon Repairs.

PURPOSE: To analyze minimum 2-year postoperative patient-reported outcomes of a large group of patients after arthroscopic subscapularis (SSc) repair with respect to surgical findings and concurrent procedures. METHODS: Patients who underwent arthroscopic SSc repair from January 2010 to April 2016 completed the Patient-Reported Outcomes Measurement Information System for Upper Extremity (PROMIS-UE) test and postoperative visual analog scale pain score. Medical records were reviewed for the preoperative visual analog scale pain score and surgical findings. SSc tears were considered partial or complete. Concomitant pathology and treatment of the supraspinatus (SS), infraspinatus (IS), and biceps tendon were recorded. We compared preoperative variables and outcomes between isolated partial SSc repair, partial SSc with SS and/or IS repair, isolated complete SSc repair, and complete SSc with SS and/or IS repair. RESULTS: One hundred forty-five shoulders were included with an average age of 62.0 ± 9.8 years and average follow-up period of 52.2 ± 19.5 months. A significant reduction in the pain score occurred, from 4.8 (95% confidence interval [CI], 4.4-5.2) to 0.9 (95% CI, 0.6-1.1) (P < .001), with a mean postoperative PROMIS-UE score of 50.7 (95% CI, 49.5-52.0). Most SSc tears were partial with SS and/or IS repair (44.1%). Isolated partial SSc tears (29.9%), complete SSc tears with SS and/or IS repair (20.1%), and isolated complete SSc tears (5.9%) were less common. A significant difference in the mean postoperative PROMIS-UE score was not found between groups (P = .609). Biceps tendon pathology was significantly more common in complete SSc tears than partial SSc tears (P < .001), but there was no difference in the rate of biceps intervention (P = .110) or the PROMIS-UE score based on biceps intervention (P = .471). CONCLUSIONS: We observed significant improvements in pain and patient-reported outcomes in line with population means for a large group of patients after SSc tendon repair. Importantly, outcomes were similar despite the size of SSc tear or concurrent SS and/or IS repairs. Biceps pathology was common, and neither its presence nor its treatment influenced postoperative patient outcomes. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Partial Transphyseal Anterior Cruciate Ligament Reconstruction: Clinical, Functional, and Radiographic Outcomes.

BACKGROUND: With a steadily increasing rate of anterior cruciate ligament (ACL) injury and reconstruction in the pediatric population, disagreement remains regarding the optimal reconstruction technique for patients with ACL injury and ≥2 years of growth remaining. PURPOSE: This study aims to quantify the incidence of linear and angular growth disturbance of adolescents undergoing partial transphyseal ACL reconstruction (ACLR) while assessing graft failure rates, reoperation rates, and functional outcomes in the population. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Consecutive patients undergoing partial transphyseal ACLR by 2 surgeons were retrospectively reviewed. Radiographic outcomes, including bilateral limb length, mechanical axis deviation (MAD), mechanical lateral distal femoral angle (MLDFA), and medial proximal tibial angle (MPTA), were measured on long standing anterior-posterior view radiographs postoperatively. Growth disturbance was defined as ≥1-cm leg length discrepancy, ≥1-cm difference in MAD, or 5° difference in MLDFA or MPTA as compared with the nonoperative side and as MAD, MLDFA, or MPTA outside the established range of reference values. Clinical outcomes, including graft failure and reoperation, were recorded at each follow-up visit. Pediatric International Knee Documentation Committee (Pedi-IKDC) scores were collected electronically after last follow-up. RESULTS: Twenty-four patients (mean ± SD age, 12.3 ± 0.9 years; 79.2% male) with a mean follow-up of 31.5 ± 17.1 months met inclusion criteria for the study. Overall postoperative growth disturbance incidence was 16.7% (4 of 24), but the incidence of growth disturbance was 66.7% (2 of 3) for those patients with >5 years of growth remaining. Seven patients (29.2%) required reoperation, most frequently for hardware removal. Two patients (8.3%) had graft failure with subsequent revision ACL reconstruction. One patient underwent bilateral medial distal femur hemiepiphysiodesis for genu valgum that was present before ACLR, but no other patients required guided growth procedures. In the subset of patients who completed a Pedi-IKDC questionnaire, the mean score was 94.8 ± 5.3. CONCLUSION: Overall, partial transphyseal ACLR has good functional outcomes and graft failure and reoperation rates, comparable with those seen with transphyseal and all-epiphyseal techniques. While postoperative growth disturbance occurred in 16.7% of the cohort, the severity was mild and well tolerated without necessitating secondary procedures. There is a high rate of growth disturbance of patients with >5 years of growth remaining (66.7%). Partial transphyseal ACLR represents a valid recommendation for adolescent patients with ACL injury and ≤5 years of growth remaining.

Periportal Capsulotomy: Technique and Outcomes for a Limited Capsulotomy During Hip Arthroscopy.

PURPOSE: To present the technique and outcomes of a limited periportal capsulotomy without capsular closure for arthroscopic treatment of femoroacetabular impingement (FAI). METHODS: Retrospective review of a prospectively collected database of patients undergoing primary hip arthroscopy for symptomatic FAI was performed to analyze patients who underwent periportal capsulotomy. Periportal capsulotomy was performed through dilation of the midanterior and anterolateral portals without completion of a full interportal capsulotomy, preserving the iliofemoral ligament. Arthroscopic labral treatment and osteochondroplasty were completed as indicated without necessitating capsular closure. Patient demographics, surgical details, and complications were recorded. Pre- and postoperatively, patients completed the modified Harris Hip Score, Hip Disability and Osteoarthritis Outcome Score (HOOS), 12-item Short-Form survey, and visual analog scale. Postoperative outcome data was analyzed at 1- and 2-year follow-up. RESULTS: One hundred and forty-two patients treated with the periportal capsulotomy technique were included (mean age, 35.5 ± 11.7; body mass index, 25.4 ± 4.1; 50.7% men). There were no major postoperative complications including hip instability or reoperation. Significant improvements in mean patient-reported outcomes from preoperative scores were seen at the 1- and 2-year follow-ups (modified Harris Hip Score, 18.4 ± 19.1, 21.1 ±17.7, HOOS symptoms, 20.1 ± 21.2, 22.8 ± 23.5, HOOS pain, 23.4 ± 21.2, 27.6 ± 19.3, HOOS activities of daily life, 21.2 ± 20.8, 24.3 ± 21.6, HOOS sport, 32.5 ± 27.0, 36.5 ± 26.9, HOOS quality of life, 37.9 ± 26.7, 46.0 ± 22.8, and 12-item Short-Form survey physical component score, 16.4 ± 15.3, 20.8 ±13.2, respectively). Only the HOOS quality of life demonstrated further improvement from 1- to 2 years postoperatively (P = .043). CONCLUSIONS: Periportal capsulotomy provides safe and sufficient access to the hip joint for arthroscopic treatment of FAI without necessitating capsular closure. Using this technique, patients showed significant clinical improvement and no postoperative instability at 1 and 2 years after surgery. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Periportal Capsulotomy: A Technique for Limited Violation of the Hip Capsule During Arthroscopy for Femoroacetabular Impingement.

Hip arthroscopy has become the standard treatment for symptomatic femoroacetabular impingement as patients have shown good outcomes and high satisfaction with this intervention. However, capsular management to gain access for intra-articular procedures remains greatly debated. Capsular closure is advocated particularly in the setting of interportal or T-capsulotomy to avoid complications of instability or nonhealing capsule. We introduce a technique for capsular management through a limited periportal capsulotomy during arthroscopic treatment of femoroacetabular impingement. In using dilation of the anterolateral and mid-anterior portals without completion of a full interportal capsulotomy, the stabilizing iliofemoral ligament is preserved. We have found that periportal capsulotomy provides safe and sufficient access to the hip joint without necessitating capsular closure.

Navigating the Research in Rotator Cuff Disease: An Evidence-Based Approach to Improved Patient Outcomes.

Rotator cuff tears are prevalent injuries, yet their management and identifying patients who will benefit from surgical intervention are controversial topics. Population studies demonstrate high rates of asymptomatic tears that, with time, show a general progression of the pathologic state. However, not all tears are or will become symptomatic or require surgical intervention. Surgeons should be aware of the natural history of rotator cuff tears and be able to identify injuries at risk of progression or causing symptoms, be able to determine the cellular level of tear characteristics and healing, understand current management strategies and outcomes, and be familiar with future directions for therapies and research.

Women in Orthopaedic Surgery: Population Trends in Trainees and Practicing Surgeons.

BACKGROUND: American medical schools have gradually achieved balance in the sex of medical graduates over the past 4 decades. However, orthopaedic surgery has remained disproportionately male-dominated. Our aim was to quantify this discrepancy across surgical specialties at the residency training and academic faculty levels. We additionally sought to evaluate the prevalence of women in orthopaedic subspecialty and research societies. METHODS: Publicly available data from the Association of American Medical Colleges (AAMC) and the Accreditation Council for Graduate Medical Education (ACGME) for the 2005-2006 to 2016-2017 academic years were pooled for analysis of sex in surgical residency programs. The AAMC 2016 Faculty Roster provided data on the sex composition of academic medical faculty, including rank. Current subspecialty and research society membership demographic characteristics were obtained by directly contacting each group. RESULTS: Female orthopaedic surgery residents represented 0.92% of all female medical residents in the 2016-2017 academic year. Orthopaedic surgery remains the medical specialty with the lowest proportion of female residents at 14.0% in the 2016-2017 academic year, up from 11.0% in the 2005-2006 academic year. The percentage increase over this time period (27.3%) lags behind other male-dominated fields such as neurological surgery (56.8%) and thoracic surgery (111.2%). Women account for 17.8% of full-time orthopaedic surgery faculty at American medical schools, lower than all other medical specialties. In the 2015-2016 academic year, 1 orthopaedic surgery department chair and only 8.7% of professors of orthopaedic surgery were female. Women make up 6.5% of the American Academy of Orthopaedic Surgeons (AAOS) membership. The specialty societies with the fewest women are The Knee Society (0.5%), The Hip Society (0.6%), and the Cervical Spine Research Society (1.5%). CONCLUSIONS: Orthopaedic surgery's slow increase in the number of female residents and academic faculty lags behind that of other specialties. The lack of female orthopaedic surgeons in higher ranks within medical schools is detrimental to recruitment of female medical students to the field. Further efforts should be made toward increasing medical student exposure to orthopaedics and to female mentors in an effort to ensure that the field continues to attract the nation's top medical graduates.

A Maldiisotopic Approach to Discover Natural Products: Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens.

Genome sequencing of microorganisms has revealed a greatly increased capacity for natural products biosynthesis than was previously recognized from compound isolation efforts alone. Hence, new methods are needed for the discovery and description of this hidden secondary metabolite potential. Here we show that provision of heavy nitrogen 15N-nitrate to marine cyanobacterial cultures followed by single-filament MALDI analysis over a period of days was highly effective in identifying a new natural product with an exceptionally high nitrogen content. The compound, named cryptomaldamide, was subsequently isolated using MS to guide the purification process, and its structure determined by 2D NMR and other spectroscopic and chromatographic methods. Bioinformatic analysis of the draft genome sequence identified a 28.7 kB gene cluster that putatively encodes for cryptomaldamide biosynthesis. Notably, an amidinotransferase is proposed to initiate the biosynthetic process by transferring an amidino group from arginine to serine to produce the first residue to be incorporated by the hybrid NRPS-PKS pathway. The maldiisotopic approach presented here is thus demonstrated to provide an orthogonal method by which to discover novel chemical diversity from Nature.