Machine learning approach for obstructive sleep apnea screening using brain diffusion tensor imaging.

Patients with obstructive sleep apnea (OSA) show autonomic, mood, cognitive, and breathing dysfunctions that are linked to increased morbidity and mortality, which can be improved with early screening and intervention. The gold standard and other available methods for OSA diagnosis are complex, require whole-night data, and have significant wait periods that potentially delay intervention. Our aim was to examine whether using faster and less complicated machine learning models, including support vector machine (SVM) and random forest (RF), with brain diffusion tensor imaging (DTI) data can classify OSA from healthy controls. We collected two DTI series from 59 patients with OSA [age: 50.2 ± 9.9 years; body mass index (BMI): 31.5 ± 5.6 kg/m2 ; apnea-hypopnea index (AHI): 34.1 ± 21.2 events/h 23 female] and 96 controls (age: 51.8 ± 9.7 years; BMI: 26.2 ± 4.1 kg/m2 ; 51 female) using a 3.0-T magnetic resonance imaging scanner. Using DTI data, mean diffusivity maps were calculated from each series, realigned and averaged, normalised to a common space, and used to conduct cross-validation for model training and selection and to predict OSA. The RF model showed 0.73 OSA and controls classification accuracy and 0.85 area under the curve (AUC) value on the receiver-operator curve. Cross-validation showed the RF model with comparable fitting over SVM for OSA and control data (SVM; accuracy, 0.77; AUC, 0.84). The RF ML model performs similar to SVM, indicating the comparable statistical fitness to DTI data. The findings indicate that RF model has similar AUC and accuracy over SVM, and either model can be used as a faster OSA screening tool for subjects having brain DTI data.

Hierarchical Bayesian clustering design of multiple biomarker subgroups (HCOMBS).

Given the Food and Drug Administration's (FDA's) acceptance of master protocol designs in recent guidance documents, the oncology field is rapidly moving to address the paradigm shift to molecular subtype focused studies. Identifying new "marker-based" treatments requires new methodologies to address the growing demand to conduct clinical trials in smaller molecular subpopulations, identify effective treatment and marker interactions, and control for false positives. We introduce our methodology, Hierarchical Bayesian Clustering Design of Multiple Biomarker Subgroups (HCOMBS), a two-stage umbrella Phase II design with effect size clustering and information borrowing across multiple biomarker-treatment pairs. HCOMBS was designed to reduce required sample size, differentiate between varying effect sizes, and control for operating characteristics in the multi-arm setting. When compared to independently applied Simon's Optimal two-stage design, we showed through simulations that HCOMBS required less participants per treatment arm with a well-controlled family-wise error rate and desirable marginal power. Additionally, HCOMBS features a statistical approach that simultaneously conducts clustering and hypothesis testing in one step. We also applied the proposed design on the alliance brain metastases umbrella trial.

Validity of claims-based algorithms to identify neurodevelopmental disorders in children.

PURPOSE: To validate healthcare claim-based algorithms for neurodevelopmental disorders (NDD) in children using medical records as the reference. METHODS: Using a clinical data warehouse of patients receiving outpatient or inpatient care at two hospitals in Boston, we identified children (≤14 years between 2010 and 2014) with at least one of the following NDDs according to claims-based algorithms: autism spectrum disorder/pervasive developmental disorder (ASD), attention deficit disorder/other hyperkinetic syndromes of childhood (ADHD), learning disability, speech/language disorder, developmental coordination disorder (DCD), intellectual disability, and behavioral disorder. Fifty cases per outcome were randomly sampled and their medical records were independently reviewed by two physicians to adjudicate the outcome presence. Positive predictive values (PPVs) and 95% confidence intervals (CIs) were calculated. RESULTS: PPVs were 94% (95% CI, 83%-99%) for ASD, 88% (76%-95%) for ADHD, 98% (89%-100%) for learning disability, 98% (89%-100%) for speech/language disorder, 82% (69%-91%) for intellectual disability, and 92% (81%-98%) for behavioral disorder. A total of 19 of the 50 algorithm-based cases of DCD were confirmed as severe coordination disorders with functional impairment, with a PPV of 38% (25%-53%). Among the 31 false-positive cases of DCD were 7 children with coordination deficits that did not persist throughout childhood, 7 with visual-motor integration deficits, 12 with coordination issues due to an underlying medical condition and 5 with ADHD and at least one other severe NDD. CONCLUSIONS: PPVs were generally high (range: 82%-98%), suggesting that claims-based algorithms can be used to study NDDs. For DCD, additional criteria are needed to improve the classification of true cases.

Is Self-reported Return to Duty an Adequate Indicator of Return to Sport and/or Return to Function in Military Patients?

BACKGROUND: In the military, return-to-duty status has commonly been used as a functional outcome measure after orthopaedic surgery. This is sometimes regarded similarly to return to sports or as an indicator of return to full function. However, there is variability in how return-to-duty data are reported in clinical research studies, and it is unclear whether return-to-duty status alone can be used as a surrogate for return to sport or whether it is a useful marker for return to full function. QUESTIONS/PURPOSES: (1) What proportion of military patients who reported return to duty also returned to athletic participation as defined by self-reported level of physical activity? (2) What proportion of military patients who reported return to duty reported other indicators of decreased function (such as nondeployability, change in work type or level, or medical evaluation board)? METHODS: Preoperative and postoperative self-reported physical profile status (mandated physical limitation), physical activity status, work status, deployment status, military occupation specialty changes, and medical evaluation board status were retrospectively reviewed for all active-duty soldiers who underwent orthopaedic surgery at Madigan Army Medical Center, Joint Base Lewis-McChord from February 2017 to October 2018. Survey data were collected on patients preoperatively and 6, 12, and 24 months postoperatively in all subspecialty and general orthopaedic clinics. Patients were considered potentially eligible if they were on active-duty status at the time of their surgery and consented to the survey (1319 patients). A total of 89% (1175) were excluded since they did not have survey data at the 1 year mark. Of the remaining 144 patients, 9% (13) were excluded due to the same patient having undergone multiple procedures, and 2% (3) were excluded for incomplete data. This left 10% (128) of the original group available for analysis. Ninety-eight patients reported not having a physical profile at their latest postoperative visit; however, 14 of these patients also stated they were retired from the military, leaving 84 patients in the return-to-duty group. Self-reported "full-time duty with no restrictions" was originally used as the indicator for return to duty; however, the authors felt this to be too vague and instead used soldiers' self-reported profile status as a more specific indicator of return to duty. Mean length of follow-up was 13 ± 3 months. Eighty-three percent (70 of 84) of patients were men. Mean age at the preoperative visit was 35 ± 8 years. The most common surgery types were sports shoulder (n = 22) and sports knee (n = 14). The subgroups were too small to analyze by orthopaedic procedure. Based on active-duty status and requirements of the military profession, all patients were considered physically active before their injury or surgery. Return to sport was determined by asking patients how their level of physical activity compared with their level before their injury (higher, same, or lower). We identified the number of other indicators that may suggest decreased function by investigating change in work type/level, self-reported nondeployability, or medical evaluation board. This was performed with a simple survey. RESULTS: Of the 84 patients reporting return to duty at the final follow-up, 67% (56) reported an overall lower level of physical activity. Twenty-seven percent (23) reported not returning to the same work level, 32% (27) reported being nondeployable, 23% (19) reported undergoing a medical evaluation board (evaluation for medical separation from the military), and 11% (9) reported a change in military occupation specialty (change of job description). CONCLUSION: Return to duty is commonly reported in military orthopaedics to describe postoperative functional outcome. Although self-reported return to duty may have value for military study populations, based on the findings of this investigation, surgeons should not consider return to duty a marker of return to sport or return to full function. However, further investigation is required to see to what degree this general conclusion applies to the various orthopaedic subspecialties and to ascertain how self-reported return to duty compares with specific outcome measures used for particular procedures and subspecialties. LEVEL OF EVIDENCE: Level IV, therapeutic study.

A synergistic DNA logic predicts genome-wide chromatin accessibility.

Enhancers and promoters commonly occur in accessible chromatin characterized by depleted nucleosome contact; however, it is unclear how chromatin accessibility is governed. We show that log-additive cis-acting DNA sequence features can predict chromatin accessibility at high spatial resolution. We develop a new type of high-dimensional machine learning model, the Synergistic Chromatin Model (SCM), which when trained with DNase-seq data for a cell type is capable of predicting expected read counts of genome-wide chromatin accessibility at every base from DNA sequence alone, with the highest accuracy at hypersensitive sites shared across cell types. We confirm that a SCM accurately predicts chromatin accessibility for thousands of synthetic DNA sequences using a novel CRISPR-based method of highly efficient site-specific DNA library integration. SCMs are directly interpretable and reveal that a logic based on local, nonspecific synergistic effects, largely among pioneer TFs, is sufficient to predict a large fraction of cellular chromatin accessibility in a wide variety of cell types.

VA/DoD Clinical Practice Guideline: Diagnosis and Treatment of Low Back Pain.

DESCRIPTION: In September 2017, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved the joint Clinical Practice Guideline (CPG) for Diagnosis and Management of Low Back Pain. This CPG was intended to provide healthcare providers a framework by which to evaluate, treat, and manage patients with low back pain (LBP). METHODS: The VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included a multidisciplinary panel of practicing clinician stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions in collaboration with the ECRI Institute, which systematically searched and evaluated the literature through September 2016, developed an algorithm, and rated recommendations by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. A patient focus group was also convened to ensure patient values and perspectives were considered when formulating preferences and shared decision making in the guideline. RECOMMENDATIONS: The VA/DOD LBP CPG provides evidence-based recommendations for the diagnostic approach, education and self-care, non-pharmacologic and non-invasive therapy, pharmacologic therapy, dietary supplements, non-surgical invasive therapy, and team approach to treatment of low back pain.

Ability of Patient-Reported Outcomes to Characterize Patient Acceptable Symptom State (PASS) After Attending a Primary Care Physical Therapist and Medical Doctor Collaborative Service: A Cross-Sectional Study.

OBJECTIVES: To determine if the Patient-Reported Outcome Measurement Information System (PROMIS) physical function, pain interference, self-efficacy, and global rating of normal function (GRNF) scales are able to accurately characterize a patient's acceptable symptom state (PASS). DESIGN: A cross-sectional analysis, using receiver operator curves and chi-square analysis to explore criteria to determine thresholds (80% and 95% sensitivity/specificity) for PASS that are applicable to PROMIS and GRNF scales. SETTING: Phone survey after primary care. PARTICIPANTS: Patients (N=94) attending primary care for musculoskeletal problems. INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Accuracy and proportion of patients classified as PASS Yes or No. RESULTS: Receiver operator curve analysis showed significant area under the curve (AUC) values for each PROMIS scale (AUC>.72) and the GRNF rating (AUC=.74). Identified PROMIS thresholds suggested PASS was achieved when scores were at or slightly worse than the US population average. A score of ≥7 and ≤4 characterized patients that were PASS Yes and No, respectively, on the GRNF rating. A moderate (80%) specificity/sensitivity criteria yielded 72.3%-73.5% accuracy for a majority of participants (>69.9%). CONCLUSION: This analysis suggests the PROMIS and GRNF scales are able to characterize PASS status with moderate accuracy (∼70%) for a large portion of patients (∼70%). New to this study is the association of self-efficacy with PASS status. PROMIS scales at or slightly worse than the US population average characterized PASS status.

GERV: a statistical method for generative evaluation of regulatory variants for transcription factor binding.

MOTIVATION: The majority of disease-associated variants identified in genome-wide association studies reside in noncoding regions of the genome with regulatory roles. Thus being able to interpret the functional consequence of a variant is essential for identifying causal variants in the analysis of genome-wide association studies. RESULTS: We present GERV (generative evaluation of regulatory variants), a novel computational method for predicting regulatory variants that affect transcription factor binding. GERV learns a k-mer-based generative model of transcription factor binding from ChIP-seq and DNase-seq data, and scores variants by computing the change of predicted ChIP-seq reads between the reference and alternate allele. The k-mers learned by GERV capture more sequence determinants of transcription factor binding than a motif-based approach alone, including both a transcription factor's canonical motif and associated co-factor motifs. We show that GERV outperforms existing methods in predicting single-nucleotide polymorphisms associated with allele-specific binding. GERV correctly predicts a validated causal variant among linked single-nucleotide polymorphisms and prioritizes the variants previously reported to modulate the binding of FOXA1 in breast cancer cell lines. Thus, GERV provides a powerful approach for functionally annotating and prioritizing causal variants for experimental follow-up analysis. AVAILABILITY AND IMPLEMENTATION: The implementation of GERV and related data are available at http://gerv.csail.mit.edu/.

Non-Gaussian Diffusion Imaging Shows Brain Myelin and Axonal Changes in Obstructive Sleep Apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is accompanied by brain changes in areas that regulate autonomic, cognitive, and mood functions, which were initially examined by Gaussian-based diffusion tensor imaging measures, but can be better assessed with non-Gaussian measures. We aimed to evaluate axonal and myelin changes in OSA using axial (AK) and radial kurtosis (RK) measures. MATERIALS AND METHODS: We acquired diffusion kurtosis imaging data from 22 OSA and 26 controls; AK and RK maps were calculated, normalized, smoothed, and compared between groups using analysis of covariance. RESULTS: Increased AK, indicating axonal changes, emerged in the insula, hippocampus, amygdala, dorsolateral pons, and cerebellar peduncles and showed more axonal injury over previously identified damage. Higher RK, showing myelin changes, appeared in the hippocampus, amygdala, temporal and frontal lobes, insula, midline pons, and cerebellar peduncles and showed more widespread myelin damage over previously identified injury. CONCLUSIONS: Axial kurtosis and RK measures showed widespread changes over Gaussian-based techniques, suggesting a more sensitive nature of kurtoses to injury.

Lumbar computed tomography scans are not appropriate surrogates for bone mineral density scans in primary adult spinal deformity.

OBJECTIVE The authors examined the correlation between lumbar spine CT Hounsfield unit (HU) measurements and bone mineral density measurements in an adult spinal deformity (ASD) population. METHODS Patients with ASD were identified in the records of a single institution. Lumbar CT scans were reviewed, and the mean HU measurements from L1-4 were recorded. Bone mineral density (BMD) was assessed using femoral neck and lumbar spine dual-energy x-ray absorptiometry (DEXA). The number of patients who met criteria for osteoporosis was determined for each imaging modality. RESULTS Forty-eight patients underwent both preoperative DEXA and CT scanning. Forty-three patients were female and 5 were male. Forty-seven patients were Caucasian and one was African American. The mean age of the patients was 62.1 years. Femoral neck DEXA was more likely to identify osteopenia (n = 26) than lumbar spine DEXA (n = 8) or lumbar CT HU measurements (n = 6) (p < 0.001). There was a low-moderate correlation between lumbar spine CT and lumbar spine DEXA (r = 0.463, p < 0.001), and there was poor correlation between lumbar spine CT and femoral neck DEXA (r = 0.303, p = 0.036). CONCLUSIONS Despite the opportunistic utility of lumbar spine CT HU measurements in identifying osteoporosis in patients undergoing single-level fusion, these measurements were not useful in this cohort of ASD patients. The correlation between femoral neck DEXA and HU measurements was poor. DEXA assessment of BMD in ASD patients is essential to optimize the care of these complicated cases.

Associations between brain white matter integrity and disease severity in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway blockage, with continued diaphragmatic efforts to breathe during sleep. Brain structural changes in OSA appear in various regions, including white matter sites that mediate autonomic, mood, cognitive, and respiratory control. However, the relationships between brain white matter changes and disease severity in OSA are unclear. This study examines associations between an index of tissue integrity, magnetization transfer (MT) ratio values (which show MT between free and proton pools associated with tissue membranes and macromolecules), and disease severity (apnea-hypopnea index [AHI]) in OSA subjects. We collected whole-brain MT imaging data from 19 newly diagnosed, treatment-naïve OSA subjects (50.4 ± 8.6 years of age, 13 males, AHI 39.7 ± 24.3 events/hr], using a 3.0-Tesla MRI scanner. With these data, whole-brain MT ratio maps were calculated, normalized to common space, smoothed, and correlated with AHI scores by using partial correlation analyses (covariates, age and gender; P < 0.005). Multiple brain sites in OSA subjects, including superior and inferior frontal regions, ventral medial prefrontal cortex and nearby white matter, midfrontal white matter, insula, cingulate and cingulum bundle, internal and external capsules, caudate nuclei and putamen, basal forebrain, hypothalamus, corpus callosum, and temporal regions, showed principally lateralized negative correlations (P < 0.005). These regions showed significant correlations even with correction for multiple comparisons (cluster-level, family-wise error, P < 0.05), except for a few superior frontal areas. Predominantly negative correlations emerged between local MT values and OSA disease severity, indicating potential usefulness of MT imaging for examining the OSA condition. These findings indicate that OSA severity plays a significant role in white matter injury. © 2016 Wiley Periodicals, Inc.

Management of osteoporosis in spine surgery.

Osteoporosis is a burgeoning clinical problem that is characterized by decreased bone strength and density. It predisposes patients to fragility fractures and debilitating spine deformities. Several complications are associated with spine surgery in patients with osteoporosis, and there is currently no treatment algorithm to guide the spine surgeon. A multidisciplinary approach to treatment of patients with osteoporosis and spine deformity or fracture is encouraged, and preoperative planning is crucial for successful surgical outcomes. Several surgical techniques have been developed to treat osteoporosis-related deformities, including posterior instrumentation with fusion. However, achieving fixation and fusion in these patients can be difficult secondary to poor bone stock. Augmentation methods to improve pedicle screw fixation have evolved, including instrumentation at multiple levels, bioactive cement augmentation, and fenestrated or expandable pedicle screws, but their impact on clinical outcomes remains unknown. Management of osteoporosis in patients undergoing spine surgery is challenging, but with appropriate patient selection, medical optimization, and surgical techniques, these patients can experience pain relief, deformity correction, and improved function.

Pedicle screw "hubbing" in the immature thoracic spine: a biomechanical and micro-computed tomography evaluation.

BACKGROUND: A previous biomechanical study using adult thoracic vertebrae (both normal and osteoporotic bone density) demonstrated the deleterious effect of the pedicle screw hubbing technique. Pedicle screw "hubbing" involves seating and engaging the ventral aspect of the screw head onto the dorsal lamina cortex. This technique is postulated to provide a load-sharing effect by improving pullout resistance, as well as decreasing cephalocaudad toggling and implant loosening. We hypothesized the elastic properties of immature bone may mitigate, and perhaps enhance the purported benefits of the hubbing technique. We set out to evaluate pullout strength of fixed-head pedicle screws after hubbing versus standard insertion in the immature thoracic calf spine. METHODS: Twenty-two (n=22) single-level disarticulated fresh-frozen immature calf thoracic vertebra specimens (ranging from T2 to T13) were prepared. Twelve specimens were instrumented with pedicle screws in group I (nonhubbed) and group II (hubbed) in the opposite pedicle. Cyclic loading in a cephalocaudad direction was applied for 2000 cycles at a rate of 1 Hz. Pullout testing was performed in-line with the midline of the vertebra and peak pullout strength was measured in Newtons. Ten different specimens underwent micro-computed tomography evaluation to assess for trabecular architecture and incidence of iatrogenic microfractures. RESULTS: Hubbed screws resulted in significantly lower pullout strength (747±197 vs. 922±112 N, P=0.01). With the hubbing technique, the dorsal cortex demonstrated plastic deformation and conformed to the screw head in 83% of cases compared with no visible plastic deformation in the control group. Micro-computed tomography demonstrated microfractures of the dorsal cortex in 10/10 for the hubbed group compared with 1/10 for the control group. CONCLUSIONS: This is the largest study ever performed on immature thoracic vertebra to evaluate this topic. Hubbed pedicle screws have significantly decreased pullout strength and frequently cause iatrogenic microfractures of the dorsal cortex. The unique ability of immature bone to exhibit plastic deformation did not provide a protective effect on immediate fixation strength, and the increased insertional torque during the hubbing technique should not give a false sense of added fixation. This study, along with our adult study, provides critical information to the surgeon to avoid this common misunderstanding with screw insertion technique. CLINICAL RELEVANCE: In vitro fresh-frozen immature calf spine study.

The top-cited military relevant spine articles.

Introduction: Historically musculoskeletal injury has substantially affected United States (US) service members. Lumbosacral spine injuries are among the most common sites of injury for service members across all US military branches and usually presents with pain in the lower back and extremities. The aim of this study is to identify and describe the 50 most-cited articles relevant to military medicine on the subject of the spine. Methods: In April 2020 Web of Science was used to search the key words: spinal cord injury, spine, thoracic spine, lumbar spine, cervical spine, sacrum, sacral, cervical fusion, lumbar fusion, sacral fracture, combat, back pain, neck pain, and military. Articles published from 1900 to 2020 were evaluated for relevance to military spine orthopaedics and ranked based on citation number. The 50 most-cited articles were characterized based on country of origin, journal of publication, affiliated institution, topic, military branch, and conflict. Results: 1900 articles met search criteria. The 50 most-cited articles were cited 24 to 119 times and published between 1993 and 2017. 30 articles (60%) originated in the United States. Aviation, Space, and Environmental Medicine accounted for the most frequent (n = 10) destination journal followed by Spine (n = 8). 37 institutions contributed to the top 50 most-cited articles. The most common article type was clinically focused retrospective analysis 36% (n = 18), clinically focused cohort study 10% (n = 5), and clinically focused cohort questionnaire, cross-sectional analysis, and randomized study 8% each (n = 4). 90% of articles were non-surgical (n = 45). The US Army had the greatest number of associated articles. Operation Iraqi Freedom and Operation Enduring Freedom were the most-cited conflicts. Conclusion: The 50 most-cited articles relevant to military spine orthopaedics are predominantly clinically focused, arising from the US, and published in Aviation, Space, and Environmental Medicine, Spine, and The Spine Journal.

Association Between In-Training Exam Scores and Clinical Exposure During the COVID-19 Pandemic.

BACKGROUND: We sought to evaluate changes in In-Training Examination (ITE) scores and associations with clinical work during the COVID-19 pandemic. We hypothesized that residents saw a decrease in clinical encounters during the pandemic and that this would be associated with smaller gains in ITE scores. METHODS: We compared ITE score changes with data on patient notes for three classes of pediatric residents at four residency programs: one not exposed to the pandemic during their intern year who entered residency in 2018, one partially exposed to COVID-19 in March of their intern year (2019-2020), and one that was fully exposed to the pandemic, starting residency in June of 2020. RESULTS: ITE scores on average improved from the PGY1 to PGY2 year in the "no covid" and "partial COVID" cohorts. The "full COVID" cohort had little to no improvement, on average. The total number of patient encounters was not associated with a change in ITE scores from PGY1 to PGY2. There was a small but statistically significant association between change in ITE score and number of inpatient H+P notes. CONCLUSIONS: A drop in ITE scores occurred in pediatric residents who entered residency during the COVID-19 pandemic. This change was largely unrelated to clinical encounter number changes.

Diagnosis and Treatment of Low Back Pain: Synopsis of the 2021 US Department of Veterans Affairs and US Department of Defense Clinical Practice Guideline.

ABSTRACT: Low back pain is a significant issue in the US Department of Veterans Affairs and Department of Defense populations as well as the general US population at large. This type of pain can be distressing to those who experience its effects, leading patients to seek relief of their symptoms. In 2022, leadership within the US Department of Veterans Affairs and US Department of Defense approved a joint clinical practice guideline for the management of low back pain. The guideline provides evidence-based recommendations for assessing and managing low back pain. Development of the guideline included a systematic evidence review, which was guided by 12 key questions. A multidisciplinary team, which included clinical stakeholders, reviewed the evidence that was retrieved and developed 39 recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system. The scope of the clinical practice guideline is broad; however, the authors have focused on key recommendations that are important for clinicians in the evaluation and nonoperative treatment of low back pain, including pharmacologic therapies and both noninvasive and invasive nonpharmacologic treatments.

Potential environmental and human health impacts of rechargeable lithium batteries in electronic waste.

Rechargeable lithium-ion (Li-ion) and lithium-polymer (Li-poly) batteries have recently become dominant in consumer electronic products because of advantages associated with energy density and product longevity. However, the small size of these batteries, the high rate of disposal of consumer products in which they are used, and the lack of uniform regulatory policy on their disposal means that lithium batteries may contribute substantially to environmental pollution and adverse human health impacts due to potentially toxic materials. In this research, we used standardized leaching tests, life-cycle impact assessment (LCIA), and hazard assessment models to evaluate hazardous waste classification, resource depletion potential, and toxicity potentials of lithium batteries used in cellphones. Our results demonstrate that according to U.S. federal regulations, defunct Li-ion batteries are classified hazardous due to their lead (Pb) content (average 6.29 mg/L; σ = 11.1; limit 5). However, according to California regulations, all lithium batteries tested are classified hazardous due to excessive levels of cobalt (average 163,544 mg/kg; σ = 62,897; limit 8000), copper (average 98,694 mg/kg; σ = 28,734; limit 2500), and nickel (average 9525 mg/kg; σ = 11,438; limit 2000). In some of the Li-ion batteries, the leached concentrations of chromium, lead, and thallium exceeded the California regulation limits. The environmental impact associated with resource depletion and human toxicity is mainly associated with cobalt, copper, nickel, thallium, and silver, whereas the ecotoxicity potential is primarily associated with cobalt, copper, nickel, thallium, and silver. However, the relative contribution of aluminum and lithium to human toxicity and ecotoxicity could not be estimated due to insufficient toxicity data in the models. These findings support the need for stronger government policy at the local, national, and international levels to encourage recovery, recycling, and reuse of lithium battery materials.

Potential environmental impacts from the metals in incandescent, compact fluorescent lamp (CFL), and light-emitting diode (LED) bulbs.

Artificial lighting systems are transitioning from incandescent to compact fluorescent lamp (CFL) and light-emitting diode (LED) bulbs in response to the U.S. Energy Independence and Security Act and the EU Ecodesign Directive, which leads to energy savings and reduced greenhouse gas emissions. Although CFLs and LEDs are more energy-efficient than incandescent bulbs, they require more metal-containing components. There is uncertainty about the potential environmental impacts of these components and whether special provisions must be made for their disposal at the end of useful life. Therefore, the objective of this study is to analyze the resource depletion and toxicity potentials from the metals in incandescent, CFL, and LED bulbs to complement the development of sustainable energy policy. We assessed the potentials by examining whether the lighting products are to be categorized as hazardous waste under existing U.S. federal and California state regulations and by applying life cycle impact-based and hazard-based assessment methods (note that "life cycle impact-based method" does not mean a general life cycle assessment (LCA) but rather the elements in LCA used to quantify toxicity potentials). We discovered that both CFL and LED bulbs are categorized as hazardous, due to excessive levels of lead (Pb) leachability (132 and 44 mg/L, respectively; regulatory limit: 5) and the high contents of copper (111,000 and 31,600 mg/kg, respectively; limit: 2500), lead (3860 mg/kg for the CFL bulb; limit: 1000), and zinc (34,500 mg/kg for the CFL bulb; limit: 5000), while the incandescent bulb is not hazardous (note that the results for CFL bulbs excluded mercury vapor not captured during sample preparation). The CFLs and LEDs have higher resource depletion and toxicity potentials than the incandescent bulb due primarily to their high aluminum, copper, gold, lead, silver, and zinc. Comparing the bulbs on an equivalent quantity basis with respect to the expected lifetimes of the bulbs, the CFLs and LEDs have 3-26 and 2-3 times higher potential impacts than the incandescent bulb, respectively. We conclude that in addition to enhancing energy efficiency, conservation and sustainability policies should focus on the development of technologies that reduce the content of hazardous and rare metals in lighting products without compromising their performance and useful lifespan.

Outcomes following cervical disc arthroplasty in an active duty military population.

Symptomatic cervical radiculopathy is a common problem in the active duty military population and can cause significant disability leading to limited duty status and loss of operational readiness and strength. Based on their increasing experience with cervical disc arthroplasty (CDA) in this unique patient population, the authors set out to further evaluate the outcomes and complications of CDA in active duty military patients. A retrospective review of a single military tertiary medical center was performed between August 2008 and August 2012 and the clinical outcomes of patients who underwent cervical disc arthroplasty were evaluated. There were 37 active duty military patients, with a total of 41 CDA. The study found good relief of preoperative symptoms (92%) and the ability to maintain operational readiness with a high rate of return to full unrestricted duty (95%) with an average follow-up of 6 months. There was a low rate of complications related to the anterior cervical approach (5%-8%), with no device- or implant-related complications.

Biologically Aware Lighting for Newborn Intensive Care.

Objective: We designed and implemented a novel neonatal intensive care (NICU) lighting system to support current understanding of sunlight-coupled physiology. Methods: We created a system that generates wavelengths corresponding to the known blue and violet activation spectra of non-visual opsins. These are known to mediate energy management and related physiologic activity. Results: Light produced by the system spans the visible spectrum, including violet wavelengths that are blocked by modern glazing and not emitted by standard LED fixtures. System features include automated light and dark phases that mimic dawn/dusk. The system also matches length of day seasonality. Spectral composition can be varied to support translational research protocols. Implementation required a comprehensive strategy to inform bedside providers about the value and use of the lighting system. Conclusion: Full-spectrum lighting for the NICU is feasible and will inform optimization of the NICU environment of care to support optimal neonatal growth and development.