Redesigning the Care of Musculoskeletal Conditions With Lifestyle Medicine.

Value-based health care has been accelerated by alternative payment models and has catalyzed the redesign of care delivery across the nation. Lifestyle medicine (LM) is one of the fastest growing medical specialties and has emerged as a high-value solution for root cause treatment of chronic disease. This review detailed a large integrated health care delivery system's value transformation efforts in the nonoperative treatment of musculoskeletal (MSK) conditions by placing patient-centric, team-based, lifestyle-focused care at the foundation. With an economic and treatment imperative to reimagine care, recognizing more intervention is not always better, a collaborative approach was designed, which placed functional improvement of the patient at the center. This article described the process of implementing LM into an MSK model of care. The change management process impacted clinical, operational, and benefit plan design to facilitate an integrated care model. A new understanding of patients' co-occurring physical impairments, medical comorbidities, and behavioral health needs was necessary for clinicians to make the shift from a pathoanatomic, transactional model of care to a biopsychosocial, longitudinal model of care. The authors explored the novel intersection of the implementation of a biopsychosocial model of care using LM principles to achieve greater value for the MSK patient population.

The effect of tuberosity healing on functional outcomes after reverse shoulder arthroplasty for proximal humerus fractures: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis compared clinical outcome measures in patients undergoing reverse shoulder arthroplasty (RSA) for proximal humerus fracture (PHF) with healed versus non-healed greater tuberosity (GT). METHODS: We performed a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines querying PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane for studies that stratified results by the GT healing status. Studies that did not attempt to repair the GT were excluded. We extracted and compared clinical outcomes including postoperative forward flexion (FF), external rotation (ER), internal rotation (IR), Constant score, and complications and revision rates. RESULTS: Of the included patients, 295 (78.5%) demonstrated GT healing while 81 did not (21.5%). The healed GT cohort exhibited increased postoperative FF (P < .001), ER (P < .001), IR (P = .006), and Constant score (P = .006) compared to the non-healed GT cohort. The overall dislocation rate was 0.8% with no study differentiating GT status of dislocation cases. CONCLUSION: Healing of the GT after RSA for PHF yields improved postoperative range of motion and strength, whereas patient-reported pain and function were largely not affected by GT healing indicating merit to RSA for PHF regardless of the likelihood of the GT healing.

Photo-induced changes in tissue stiffness alter epithelial budding morphogenesis in the embryonic lung.

Extracellular matrix (ECM) stiffness has been shown to influence the differentiation of progenitor cells in culture, but a lack of tools to perturb the mechanical properties within intact embryonic organs has made it difficult to determine how changes in tissue stiffness influence organ patterning and morphogenesis. Photocrosslinking of the ECM has been successfully used to stiffen soft tissues, such as the cornea and skin, which are optically accessible, but this technique has not yet been applied to developing embryos. Here, we use photocrosslinking with Rose Bengal (RB) to locally and ectopically stiffen the pulmonary mesenchyme of explanted embryonic lungs cultured ex vivo . This change in mechanical properties was sufficient to suppress FGF-10-mediated budding morphogenesis along the embryonic airway, without negatively impacting patterns of cell proliferation or apoptosis. A computational model of airway branching was used to determine that FGF-10-induced buds form via a growth-induced buckling mechanism and that increased mesenchymal stiffness is sufficient to inhibit epithelial buckling. Taken together, our data demonstrate that photocrosslinking can be used to create regional differences in mechanical properties within intact embryonic organs and that these differences influence epithelial morphogenesis and patterning. Further, this photocrosslinking assay can be readily adapted to other developing tissues and model systems.

Bioimaging of sense organs and the central nervous system in extant fishes and reptiles in situ: A review.

Bioimaging is changing the field of sensory biology, especially for taxa that are lesser-known, rare, and logistically difficult to source. When integrated with traditional neurobiological approaches, developing an archival, digital repository of morphological images can offer the opportunity to improve our understanding of whole neural systems without the issues of surgical intervention and negate the risk of damage and artefactual interpretation. This review focuses on current approaches to bioimaging the peripheral (sense organs) and central (brain) nervous systems in extant fishes (cartilaginous and bony) and non-avian reptiles in situ. Magnetic resonance imaging (MRI), micro-computed tomography (µCT), both super-resolution track density imaging and diffusion tensor-based imaging, and a range of other new technological advances are presented, together with novel approaches in optimizing both contrast and resolution, for developing detailed neuroanatomical atlases and enhancing comparative analyses of museum specimens. For MRI, tissue preparation, including choice of fixative, impacts tissue MR responses, where both resolving power and signal-to-noise ratio improve as field strength increases. Time in fixative, concentration of contrast agent, and duration of immersion in the contrast agent can also significantly affect relaxation times, and thus image quality. For µCT, the use of contrast-enhancing stains (iodine-, non-iodine-, or nanoparticle-based) is critical, where the type of fixative used, and the concentration of stain and duration of staining time often require species-specific optimization. Advanced reconstruction algorithms to reduce noise and artifacts and post-processing techniques, such as deconvolution and filtering, are now being used to improve image quality and resolution.

Comparative effectiveness of extended-release naltrexone and sublingual buprenorphine for treatment of opioid use disorder among Medicaid patients.

BACKGROUND AND AIMS: Extended-release naltrexone (XR-NTX) and sublingual buprenorphine (SL-BUP) are both approved for opioid use disorder (OUD) treatment in any medical setting. We aimed to compare the real-world effectiveness of XR-NTX and SL-BUP. DESIGN AND SETTING: This was an observational active comparator, new user cohort study of Medicaid claims records for patients in New Jersey and California, USA, 2016-19. PARTICIPANTS/CASES: The participants were adult Medicaid patients aged 18-64 years who initiated XR-NTX or SL-BUP for maintenance treatment of OUD and did not use medications for OUD in the 90 days before initiation. Our cohort included 1755 XR-NTX and 9886 SL-BUP patients. MEASUREMENTS: We examined two outcomes up to 180 days after medication initiation: (1) composite of medication discontinuation and death and (2) composite of overdose and death. FINDINGS: In adjusted analyses, treatment with XR-NTX was more likely to result in discontinuation or death by the end of follow-up than treatment with SL-BUP: cumulative risk 75.9% [95% confidence interval (CI) = 73.9%, 77.9%] versus 62.2% (95% CI = 61.2%, 63.2%), respectively (risk difference = 13.7 percentage points, 95% CI = 11.4, 16.0). There was minimal difference in the cumulative risk of overdose or death by the end of follow-up: XR-NTX 3.9% (95% CI = 3.0%, 4.8%) versus SL-BUP 3.3% (95% CI = 2.9%, 3.7%); risk difference = 0.5 percentage points, 95% CI = -0.4, 1.5. Results were consistent across sensitivity analyses. CONCLUSIONS: Medicaid patients in California and New Jersey, USA, receiving treatment for opioid use disorder stayed in treatment longer on sublingual buprenorphine than on extended-release naltrexone, but the risk of overdose was similar. Most patients in this study discontinued medication within 6 months, regardless of which medication was initiated.

Prescribing of extended release buprenorphine injection for Medicaid beneficiaries, 2018-2022.

BACKGROUND AND AIMS: Extended release buprenorphine injection (INJ-BUP) has been available in the United States since 2018. INJ-BUP has the potential to positively impact opioid use disorder (OUD) treatment outcomes by providing additional treatment options . As one of the largest payers of OUD treatment in the US, Medicaid coverage is important for access and uptake of INJ-BUP. Uptake of INJ-BUP among Medicaid beneficiaries has not been described since 2019 and variation in uptake by state has not previously been explored. We aimed to measure prescribing of INJ-BUP for Medicaid beneficiaries since 2018, nationwide and by state. METHODS: We analyzed State Drug Utilization Data from 2017 to 2022 and calculated the number of prescription fills for INJ-BUP and oral buprenorphine paid by Medicaid. To compare across states, we calculated the number of prescription fills per 100 Medicaid beneficiaries treated for OUD using data from Transformed Medicaid Statistical Information System Substance Use Disorder (T-MSIS SUD) Data Books. Data sources are publicly available. RESULTS: The number of prescription fills for INJ-BUP paid by Medicaid increased from 4322 (0.1% of all buprenorphine prescription fills) in 2018 to 186 861 (2.0%) in 2022. Each year the increase in fills exceeded the prior year change, indicating accelerating uptake. There was notable variability across states. CONCLUSIONS: The number of extended release buprenorphine injection prescriptions among US Medicaid beneficiaries treated for opioid use disorder increased from over 4000 prescriptions in 2018 to over 185 000 in 2022 but uptake is much less than observed in other countries over shorter time periods.

Studying Continuous, Time-varying, and/or Complex Exposures Using Longitudinal Modified Treatment Policies.

This tutorial discusses a methodology for causal inference using longitudinal modified treatment policies. This method facilitates the mathematical formalization, identification, and estimation of many novel parameters and mathematically generalizes many commonly used parameters, such as the average treatment effect. Longitudinal modified treatment policies apply to a wide variety of exposures, including binary, multivariate, and continuous, and can accommodate time-varying treatments and confounders, competing risks, loss to follow-up, as well as survival, binary, or continuous outcomes. Longitudinal modified treatment policies can be seen as an extension of static and dynamic interventions to involve the natural value of treatment and, like dynamic interventions, can be used to define alternative estimands with a positivity assumption that is more likely to be satisfied than estimands corresponding to static interventions. This tutorial aims to illustrate several practical uses of the longitudinal modified treatment policy methodology, including describing different estimation strategies and their corresponding advantages and disadvantages. We provide numerous examples of types of research questions that can be answered using longitudinal modified treatment policies. We go into more depth with one of these examples, specifically, estimating the effect of delaying intubation on critically ill COVID-19 patients' mortality. We demonstrate the use of the open-source R package lmtp to estimate the effects, and we provide code on https://github.com/kathoffman/lmtp-tutorial.

Florida's Red Flag Gun Law and Firearm and Nonfirearm Homicide and Suicide Rates.

This study estimates the association between Florida's red flag law enactment and firearm and nonfirearm homicide and suicide rates.

Development and Piloting of a Bereaved Care Partner Survey to Inform Quality Improvement in ALS Supportive Care.

OBJECTIVES: Bereaved care partner surveys typically focus on the experience with care in the final days of life. We sought to develop and pilot a novel bereaved care partner survey to understand experiences with ALS supportive care provided throughout the illness and identify opportunities for quality improvement. METHODS: We developed the survey using a multisite, interdisciplinary consensus process involving ALS and palliative care clinicians as well as patient advocates. We then piloted the survey at a single site via video interviews with care partners of patients who died from ALS between three and 15 months prior. Qualitative findings were analyzed using Rapid Qualitative Analysis. RESULTS: The survey includes 17 core questions and nine demographic items. Questions inquire about whether the patient and care partner received adequate help with physical symptoms, emotional and practical needs, education about the illness and how to provide hands-on care, preparing for what was to come, and bereavement. They also query whether care was person-centered and consistent with the patient's values and preferences. During the pilot with 18 bereaved care partners, the tool generated detailed feedback about aspects of care to preserve as well as how to improve ALS supportive care. DISCUSSION: We developed and piloted a bereaved care partner survey to understand and improve the quality of ALS supportive care, which was found to be feasible and acceptable. Next steps include testing it at additional centers in order to generate learnings that can advance ALS supportive care in ways that are meaningful to patients and care partners.

Distinct genetic origins of eumelanin levels and barring patterns in cichlid fishes.

Pigment patterns are incredibly diverse across vertebrates and are shaped by multiple selective pressures from predator avoidance to mate choice. A common pattern across fishes, but for which we know little about the underlying mechanisms, is repeated melanic vertical bars. To understand the genetic factors that modify the level or pattern of vertical barring, we generated a genetic cross of 322 F2 hybrids between two cichlid species with distinct barring patterns, Aulonocara koningsi and Metriaclima mbenjii. We identify 48 significant quantitative trait loci that underlie a series of seven phenotypes related to the relative pigmentation intensity, and four traits related to patterning of the vertical bars. We find that genomic regions that generate variation in the level of eumelanin produced are largely independent of those that control the spacing of vertical bars. Candidate genes within these intervals include novel genes and those newly-associated with vertical bars, which could affect melanophore survival, fate decisions, pigment biosynthesis, and pigment distribution. Together, this work provides insights into the regulation of pigment diversity, with direct implications for an animal's fitness and the speciation process.

Prognoses Associated With Palliative Performance Scale Scores in Modern Palliative Care Practice.

Importance: The Palliative Performance Scale (PPS) is one of the most widely used prognostic tools for patients with serious illness. However, current prognostic estimates associated with PPS scores are based on data that are over a decade old. Objective: To generate updated prognostic estimates by PPS score, care setting, and illness category, and examine how well PPS predicts short- and longer-term survival. Design, Setting, and Participants: This prognostic study was conducted at a large academic medical center with robust inpatient and outpatient palliative care practices using electronic health record data linked with data from California Vital Records. Eligible participants included patients who received a palliative care consultation between January 1, 2018, and December 31, 2020. Data analysis was conducted from November 2022 to February 2024. Exposure: Palliative care consultation with a PPS score documented. Main Outcomes and Measures: The primary outcomes were predicted 1-, 6-, and 12-month mortality and median survival of patients by PPS score in the inpatient and outpatient settings, and performance of the PPS across a range of survival times. In subgroup analyses, mortality risk by PPS score was estimated in patients with cancer vs noncancer illnesses and those seen in-person vs by video telemedicine in the outpatient setting. Results: Overall, 4779 patients (mean [SD] age, 63.5 [14.8] years; 2437 female [51.0%] and 2342 male [49.0%]) had a palliative care consultation with a PPS score documented. Of these patients, 2276 were seen in the inpatient setting and 3080 were seen in the outpatient setting. In both the inpatient and outpatient settings, 1-, 6-, and 12-month mortality were higher and median survival was shorter for patients with lower PPS scores. Prognostic estimates associated with PPS scores were substantially longer (2.3- to 11.7-fold) than previous estimates commonly used by clinicians. The PPS had good ability to discriminate between patients who lived and those who died in the inpatient setting (integrated time-dependent area under the curve [iAUC], 0.74) but its discriminative ability was lower in the outpatient setting (iAUC, 0.67). The PPS better predicted 1-month survival than longer-term survival. Mortality rates were higher for patients with cancer than other serious illnesses at most PPS levels. Conclusions and Relevance: In this prognostic study, prognostic estimates associated with PPS scores were substantially longer than previous estimates commonly used by clinicians. Based on these findings, an online calculator was updated to assist clinicians in reaching prognostic estimates that are more consistent with modern palliative care practice and specific to the patient's setting and diagnosis group.

Is nicotine vaping associated with subsequent initiation of cannabis or other substances from adolescence into young adulthood?

Prior studies estimating longitudinal associations between nicotine vaping and subsequent initiation of cannabis and other substances (e.g., cocaine, heroin) have been limited by short follow-up periods, convenience sampling, and possibly inadequate confounding control. We sought to address some of these gaps using the nationally representative Population Assessment of Tobacco and Health Study (PATH) to estimate longitudinal associations between nicotine vaping and the initiation of cannabis or other substances among adolescents transitioning to adulthood from2013 to 2019, adjusting for treatment-confounder feedback. Estimands like the longitudinal average treatment effect were not identified because of extensive practical positivity violations. Therefore, we estimated longitudinal incremental propensity score effects, which were identified. We found that reduced odds of nicotine vaping were associated with decreased risks of cannabis or other substance initiation; these associations strengthened over time. For example, by the final wave (2018-19), cannabis and other substance initiation risks were 6.2 (95%CI:4.6-7.7) and 1.8 (95%CI:0.4-3.2) percentage points lower when odds of nicotine vaping were reduced to be 90% lower in all preceding waves (2013-14 to 2016-18), as compared with observed risks. Strategies to lower nicotine vaping prevalence during this period may have resulted in fewer young people initiating cannabis and other substances.

Quantifying Spatial Patterns of Tissue Stiffness Within the Embryonic Mouse Kidney.

Biophysical factors, including changes in mechanical stiffness, have been shown to influence the morphogenesis of developing organs. There is a lack of experimental techniques, however, that can probe the mechanical properties of embryonic tissues-especially those which are not mechanically or optically accessible, such as the visceral organs of the developing mouse embryo. Here, using the embryonic kidney as a model system, we describe a method to use microindentation to quantify tissue-level regional differences in the mechanical properties of an embryonic organ. This technique is generalizable and can be used to quantify patterns of tissue stiffness within other developing organ systems. Going forward, these data will enable new experimental studies of the role of biophysical cues during organogenesis.

Pain Management Treatments and Opioid Use Disorder Risk in Medicaid Patients.

INTRODUCTION: People with chronic pain are at increased risk of opioid misuse. Less is known about the unique risk conferred by each pain management treatment, as treatments are typically implemented together, confounding their independent effects. This study estimated the extent to which pain management treatments were associated with risk of opioid use disorder (OUD) for those with chronic pain, controlling for baseline demographic and clinical confounding variables and holding other pain management treatments at their observed levels. METHODS: Data were analyzed in 2024 from 2 chronic pain subgroups within a cohort of non-pregnant Medicaid patients aged 35-64 years, 2016-2019, from 25 states: those with (1) chronic pain and physical disability (CPPD) (N=6,133) or (2) chronic pain without disability (CP) (N=67,438). Nine pain management treatments were considered: prescription opioid (1) dose and (2) duration; (3) number of opioid prescribers; opioid co-prescription with (4) benzo- diazepines, (5) muscle relaxants, and (6) gabapentinoids; (7) nonopioid pain prescription, (8) physical therapy, and (9) other pain treatment modality. The outcome was OUD risk. RESULTS: Having opioids co-prescribed with gabapentin or benzodiazepine was statistically significantly associated with a 37-45% increased OUD risk for the CP subgroup. Opioid dose and duration also were significantly associated with increased OUD risk in this subgroup. Physical therapy was significantly associated with an 18% decreased risk of OUD in the CP subgroup. DISCUSSION: Coprescription of opioids with either gabapentin or benzodiazepines may substantially increase OUD risk. More positively, physical therapy may be a relatively accessible and safe pain management strategy.

Using network science to provide insights into the structure of event knowledge.

The structure of event knowledge plays a critical role in prediction, reconstruction of memory for personal events, construction of possible future events, action, language usage, and social interactions. Despite numerous theoretical proposals such as scripts, schemas, and stories, the highly variable and rich nature of events and event knowledge have been formidable barriers to characterizing the structure of event knowledge in memory. We used network science to provide insights into the temporal structure of common events. Based on participants' production and ordering of the activities that make up events, we established empirical profiles for 80 common events to characterize the temporal structure of activities. We used the event networks to investigate multiple issues regarding the variability in the richness and complexity of people's knowledge of common events, including: the temporal structure of events; event prototypes that might emerge from learning across many experiential instances and be expressed by people; the degree to which scenes (communities) are present in various events; the degree to which people believe certain activities are central to an event; how centrality might be distributed across an event's activities; and similarities among events in terms of their content and their temporal structure. Thus, we provide novel insights into human event knowledge, and describe 18 predictions for future human studies.

An Endothelial Cell Is Not Simply an Endothelial Cell.

Endothelial cells (ECs) are a multifaceted component of the vascular system with roles in immunity, maintaining tissue fluid balance, and vascular tone. Dysregulation or dysfunction of ECs can have far-reaching implications, leading pathologies ranging from cardiovascular diseases, such as hypertension and atherosclerosis, ischemia, chronic kidney disease, blood-brain barrier integrity, dementia, and tumor metastasis. Recent advancements in regenerative medicine have highlighted the potential of stem cell-derived ECs, particularly from induced pluripotent stem cells, to treat ischemic tissues, as well as models of vascular integrity. This review summarizes what is known in the generation of ECs with an emphasis on tissue-specific ECs and EC subphenotypes important in the development of targeted cell-based therapies for patient treatment.

The role of prescription opioid and cannabis supply policies on opioid overdose deaths.

Mandatory prescription drug monitoring programs and cannabis legalization have been hypothesized to reduce overdose deaths. We examined associations between prescription monitoring programs with access mandates ("must-query PDMPs"), legalization of medical and recreational cannabis supply, and opioid overdose deaths in United States counties in 2013-2020. Using data on overdose deaths from the National Vital Statistics System, we fit Bayesian spatiotemporal models to estimate risk differences and 95% credible intervals (CrI) in county-level opioid overdose deaths associated with enactment of these state policies. Must-query PDMPs were independently associated with on average 0.8 (95% CrI: 0.5, 1.0) additional opioid-involved overdose deaths per 100,000 person-years. Legal cannabis supply was not independently associated with opioid overdose deaths in this time period. Must-query PDMPs enacted in the presence of legal (medical or recreational) cannabis supply were associated with 0.7 (95% CrI: 0.4, 0.9) more opioid-involved deaths, relative to must-query PDMPs without any legal cannabis supply. In a time when overdoses are driven mostly by non-prescribed opioids, stricter opioid prescribing policies and more expansive cannabis legalization were not associated with reduced overdose death rates.

Overcoming Data Gaps in Life Course Epidemiology by Matching Across Cohorts.

Life course epidemiology is hampered by the absence of large studies with exposures and outcomes measured at different life stages in the same individuals. We describe when the effect of an exposure ( A ) on an outcome ( Y ) in a target population is identifiable in a combined ("synthetic") cohort created by pooling an early-life cohort including measures of A with a late-life cohort including measures of Y . We enumerate causal assumptions needed for unbiased effect estimation in the synthetic cohort and illustrate by simulating target populations under four causal models. From each target population, we randomly sampled early- and late-life cohorts and created a synthetic cohort by matching individuals from the two cohorts based on mediators and confounders. We estimated the effect of A on Y in the synthetic cohort, varying matching variables, the match ratio, and the strength of association between matching variables and A . Finally, we compared bias in the synthetic cohort estimates when matching variables did not d-separate A and Y to the bias expected in the original cohort. When the set of matching variables includes all variables d-connecting exposure and outcome (i.e., variables blocking all backdoor and front-door pathways), the synthetic cohort yields unbiased effect estimates. Even when matching variables did not fully account for confounders, the synthetic cohort estimate was sometimes less biased than comparable estimates in the original cohort. Methods based on merging cohorts may hasten the evaluation of early- and mid-life determinants of late-life health but rely on available measures of both confounders and mediators.

A baseline assessment of contamination in the Sacramento deep water ship channel.

The Sacramento Deep Water Ship Channel (SDWSC) in the San Francisco Estuary, which is an active commercial port, is critical habitat for pelagic fish species including delta smelt (Hypomesus transpacificus), longfin smelt (Spirinchus thaleichthys), and Sacramento perch (Archoplites interruptus). Pelagic organism decline has been attributed to covarying factors such as manipulation of habitat, introduction of invasive species, decrease in food production, and contaminant exposure. Quantification of bioavailable toxicant loads in the SDWSC is limited despite previous surveys that have detected elevated contaminant concentrations in the sediments. Therefore, the focus of the present study was to characterize the bioavailability of the contaminants in the SDWSC from six sites along the channel. At each site, organochlorine pesticides (OCPs), pyrethroid insecticides, polyaromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) were quantified in sediment, zooplankton, and suspended solids. In addition, Tenax extraction was used to measure the bioaccessible fraction of sediment-associated contaminants freely dissolved in the water. Bioaccessible contaminants in the sediment provided an uptake route for these stressors into invertebrates and fish with bioaccessible OCPs being found at all sites, particularly 4,4'-dichlorodiphenyldichloroethylene (DDE). Bifenthrin was the only pyrethroid detected in the chosen matrices and it was found at concentrations below levels of concern. Bioaccessible PAHs were found at all sites, with highest detections for phenanthrene and pyrene. No PCBs were detected in sediments, but were detected in both suspended solids and zooplankton. Contaminant concentrations overall were significantly higher in suspended solids, followed by zooplankton and sediments. The highest sediment concentrations of DDE, fluoranthene, pyrene, and dibenzo[a,h]anthracene exceeded sediment quality benchmarks indicating potential risk to sediment-dwelling species. Finally, elevated contaminant levels were found in both suspended solids and zooplankton, suggesting additional risk to pelagic species in the SDWSC.

Maternal investment evolves with larger body size and higher diversification rate in sharks and rays.

Across vertebrates, live bearing evolved at least 150 times from ancestral egg laying into diverse forms and degrees of prepartum maternal investment.1,2 A key question is how reproductive diversity arose and whether reproductive diversification underlies species diversification.3,4,5,6,7,8,9,10,11 To test this, we evaluate the most basal jawed vertebrates: the sharks, rays, and chimaeras, which have one of the greatest ranges of reproductive and ecological diversity among vertebrates.2,12 We reconstruct the sequence of reproductive mode evolution across a phylogeny of 610 chondrichthyans.13 We reveal egg laying as ancestral, with live bearing evolving at least seven times. Matrotrophy evolved at least 15 times, with evidence of one reversal. In sharks, transitions to live bearing and matrotrophy are more prevalent in larger-bodied tropical species. Further, the evolution of live bearing is associated with a near doubling of the diversification rate, but there is only a small increase associated with the appearance of matrotrophy. Although pre-copulatory sexual selection is associated with increased rates of speciation in teleosts,3 sexual size dimorphism in chondrichthyans does not appear to be related to sexual selection,14,15 and instead we find increased rates of speciation associated with the colonization of novel habitats. This highlights a potential key difference between chondrichthyans and other fishes, specifically a slower rate of evolution of reproductive isolation following speciation, suggesting different rate-limiting mechanisms for diversification between these clades.16 The chondrichthyan diversification and radiation, particularly throughout shallow tropical shelf seas and oceanic pelagic habitats, appear to be associated with the evolution of live bearing and proliferation of a wide range of maternal investment in developing offspring.