Utilization of Bone-Anchored Annular Defect Closure to Prevent Reherniation Following Lumbar Discectomy: Overcoming Barriers to Clinical Adoption and Market Access.

While achieving premarket approval from the US Food and Drug Administration represents a significant milestone in the development and commercialization of a Class III medical device, the aftermath endeavor of gaining market access can be daunting. This article provides a case study of the Barricaid annular closure device (Barricaid), a reherniation reduction device, which has been demonstrated to decrease the risk of suffering a recurrent lumbar intervertebral disc herniation. Following Food and Drug Administration approval, clinical adoption has been slow due to barriers to market access, including the perception of low-quality clinical evidence, questionable significance of the medical necessity of the procedure, and imaging evidence of increased likelihood of vertebral endplate changes. The aim of this article is to provide appropriate examination, rationale, and rebuttal of these concerns. Weighing the compendium of evidence, we offer a definition of a separate and unique current procedural terminology code to delineate this procedure. Adoption of this code will help to streamline the processing of claims and support the conduct of research, the evaluation of health care utilization, and the development of appropriate medical guidelines.

Automatic semantic segmentation of kidney cysts in MR images of patients affected by autosomal-dominant polycystic kidney disease.

PURPOSE: For patients affected by autosomal-dominant polycystic kidney disease (ADPKD), successful differentiation of cysts is useful for automatic classification of patient phenotypes, clinical decision-making, and disease progression. The objective was to develop and evaluate a fully automated semantic segmentation method to differentiate and analyze renal cysts in patients with ADPKD. METHODS: An automated deep learning approach using a convolutional neural network was trained, validated, and tested on a set of 60 MR T2-weighted images. A three-fold cross-validation approach was used to train three models on distinct training and validation sets (n = 40). An ensemble model was then built and tested on the hold out cases (n = 20), with each of the cases compared to manual segmentations performed by two readers. Segmentation agreement between readers and the automated method was assessed. RESULTS: The automated approach was found to perform at the level of interobserver variability. The automated approach had a Dice coefficient (mean ± standard deviation) of 0.86 ± 0.10 vs Reader-1 and 0.84 ± 0.11 vs. Reader-2. Interobserver Dice was 0.86 ± 0.08. In terms of total cyst volume (TCV), the automated approach had a percent difference of 3.9 ± 19.1% vs Reader-1 and 8.0 ± 24.1% vs Reader-2, whereas interobserver variability was - 2.0 ± 16.4%. CONCLUSION: This study developed and validated a fully automated approach for performing semantic segmentation of kidney cysts in MR images of patients affected by ADPKD. This approach will be useful for exploring additional imaging biomarkers of ADPKD and automatically classifying phenotypes.

Bacterial Cholangitis in Autosomal Dominant Polycystic Kidney and Liver Disease.

OBJECTIVE: To describe first episodes of bacterial cholangitis complicating autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD) and to identify risk factors for cholangitis episodes among patients with ADPKD-associated polycystic liver disease (PLD). PATIENTS AND METHODS: We searched the electronic medical records at our tertiary referral center for episodes of cholangitis in patients with ADPKD or ADPLD from January 1, 1996, through June 30, 2017. Cases were categorized as suspected or definite cholangitis by expert review. Clinical, laboratory, and radiologic data were manually abstracted. A nested case-control study was conducted to investigate risk factors for cholangitis in patients with ADPKD. RESULTS: We identified 29 cases of definite or suspected cholangitis complicating PLD (24 with ADPKD-associated PLD and 5 with ADPLD). Among patients with definite cholangitis in ADPKD-associated PLD (n=19) vs ADPLD (n=4), the mean ± SD age was 62.4±12.2 vs 55.1±8.6 years, and 9 (47.4%) vs 0 (0%), respectively, were male. The odds of gallstones (odds ratio [OR], 21.6; 95% CI, 3.17-927; P<.001), prior cholecystectomy (OR, 12.2; 95% CI, 1.59-552; P=.008), duodenal diverticulum (OR, 13.5; 95% CI, 2.44 to not estimable; P=.004), type 2 diabetes mellitus (OR, 6.41; 95% CI, 1.01 to not estimable; P=.05), prior endoscopic retrograde cholangiopancreatography (OR, 14.0; 95% CI, 1.80-631; P=.005), and prior kidney transplant (OR, 8.06; 95% CI, 1.72-76.0; P=.004) were higher in patients with ADPKD-associated PLD with definite cholangitis compared to controls. CONCLUSION: Gallstones, prior cholecystectomy, duodenal diverticulosis, type 2 diabetes mellitus, prior endoscopic retrograde cholangiopancreatography, and prior kidney transplant constituted risk factors for cholangitis among patients with ADPKD-associated PLD.

Highly Oxidized Graphene Quantum Dots from Coal as Efficient Antioxidants.

Graphene quantum dots (GQDs) have recently been employed in various fields including medicine as antioxidants, primarily because of favorable biocompatibility in comparison to common inorganic quantum dots, although the structural features that lead to the biological activities of GQDs are poorly understood. Here, we report that coal-derived GQDs and their poly(ethylene glycol)-functionalized derivatives serve as efficient antioxidants, and we evaluate their electrochemical, chemical, and in vitro biological activities.

Correction: Sex-specific alterations in preterm brain.

In the original article, the legend within Fig. 3 incorrectly read as '*p < 0.10, **p < 0.05, ***p > 0.01'. This has now been changed to '*p < 0.10, **p < 0.05, ***p < 0.01'. This has been corrected in both the PDF and HTML versions of the Article. The authors would like to apologise for this error.

Sex-specific alterations in preterm brain.

BACKGROUND: The literature on brain imaging in premature infants is mostly made up of studies that evaluate neonates, yet the most dynamic time of brain development happens from birth to 1 year of age. This study was designed to obtain quantitative brain measures from magnetic resonance imaging scans of infants born prematurely at 12 months of age. METHODS: The subject group was designed to capture a wide range of gestational age (GA) from premature to full-term infants. An age-specific atlas generated quantitative brain measures. A regression model was used to predict effects of GA and sex on brain measures. RESULTS: There was a primary effect of sex on: (1) intracranial volume, males > females; (2) proportional cerebral cortical gray matter (females > males), and (3) cerebral white matter (males > females). GA predicted cerebral volume and cerebral spinal fluid. GA also predicted cortical gray matter in a sex-specific manner with GA having a significant effect on cortical volume in the males, but not in females. CONCLUSIONS AND RELEVANCE: Sex differences in brain structure are large early in life. GA had sex-specific effects highlighting the importance evaluating sex effects in neurodevelopmental outcomes of premature infants.

Long-Term Administration of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND AND OBJECTIVES: In the 3-year Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 and 1-year Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trials, tolvaptan slowed the decline of eGFR in patients with autosomal dominant polycystic kidney disease at early and later stages of CKD, respectively. Our objective was to ascertain whether the reduction associated with the administration of tolvaptan is sustained, cumulative, and likely to delay the need for kidney replacement therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One hundred and twenty-eight patients with autosomal dominant polycystic kidney disease participated in clinical trials of tolvaptan at the Mayo Clinic. All had the opportunity to enroll into open-label extension studies. Twenty participated in short-term studies or received placebo only. The remaining 108 were analyzed for safety. Ninety seven patients treated with tolvaptan for ≥1 year (mean±SD, 4.6±2.8; range, 1.1-11.2) were analyzed for efficacy using three approaches: (1) comparison of eGFR slopes and outcome (33% reduction from baseline eGFR) to controls matched by sex, age, and baseline eGFR; (2) Stability of eGFR slopes with duration of follow-up; and (3) comparison of observed and predicted eGFRs at last follow-up. RESULTS: Patients treated with tolvaptan had lower eGFR slopes from baseline (mean±SD, -2.20±2.18 ml/min per 1.73 m2 per year) and from month 1 (mean±SD, -1.97±2.44 ml/min per 1.73 m2 per year) compared with controls (mean±SD, -3.50±2.09 ml/min per 1.73 m2 per year; P<0.001), and lower risk of a 33% reduction in eGFR (risk ratio, 0.63; 95% confidence interval, 0.38 to 0.98 from baseline; risk ratio, 0.53; 95% confidence interval, 0.31 to 0.85 from month 1). Annualized eGFR slopes of patients treated with tolvaptan did not change during follow-up and differences between observed and predicted eGFRs at last follow-up increased with duration of treatment. CONCLUSIONS: Follow-up for up to 11.2 years (average 4.6 years) showed a sustained reduction in the annual rate of eGFR decline in patients treated with tolvaptan compared with controls and an increasing separation of eGFR values over time between the two groups.

Singular wavelength dependence on the sensitization of lanthanides by graphene quantum dots.

In this manuscript, we study the sensitization of Tb3+ ions by the excited state of GQD. We found that Tb3+ cations can bind to GQDs and display photoluminescence. Excitation dependent experiments show that the Tb3+ emission is stronger at shorter excitation wavelengths, which is likely due to pseudo-isolated small aromatic moieties produced during the synthesis of the GQDs.

Physical and electrical characterization of TexasPEG: An electrically conductive neuronal scaffold.

BACKGROUND: Graphene and its derivatives have been shown to be biocompatible and electrically active materials upon which neurons readily grow. The fusogen poly(ethylene glycol) (PEG) has been shown to improve outcomes after cervical and dorsal spinal cord transection. The long and narrow PEGylated graphene nanoribbon stacks (PEG-GNRs) with their 5 µm × 200 nm × 10 nm dimensions can provide a scaffold upon which neurons can grow and fuse. We disclose here the extensive characterization data for the PEG-GNRs. METHODS: PEG-GNRs were chemically synthesized and chemically and electrically characterized. RESULTS: The average aspect ratio of the PEG-GNRs was determined to be ~85, which corresponds to a critical percolation value (the point where insulating material becomes conductive by addition of conductive particles) of 1%. However, there was not a sharp increase in AC conductivity at frequencies relevant to action potentials. CONCLUSION: A robust characterization of PEG-GNRs is discussed, though the precise origin of efficacy in improving outcomes following spinal cord transection is not known.

Microwave Heating of Functionalized Graphene Nanoribbons in Thermoset Polymers for Wellbore Reinforcement.

Here, we introduce a systematic strategy to prepare composite materials for wellbore reinforcement using graphene nanoribbons (GNRs) in a thermoset polymer irradiated by microwaves. We show that microwave absorption by GNRs functionalized with poly(propylene oxide) (PPO-GNRs) cured the composite by reaching 200 °C under 30 W of microwave power. Nanoscale PPO-GNRs diffuse deep inside porous sandstone and dramatically enhance the mechanics of the entire structure via effective reinforcement. The bulk and the local mechanical properties measured by compression and nanoindentation mechanical tests, respectively, reveal that microwave heating of PPO-GNRs and direct polymeric curing are major reasons for this significant reinforcement effect.

Getting what you want: How fit between desired and received leader sensitivity influences emotion and counterproductive work behavior.

We challenge the intuitive belief that greater leader sensitivity is always associated with desirable outcomes for employees and organizations. Specifically, we argue that followers' idiosyncratic desires for, and perceptions of, leader sensitivity behaviors play a key role in how followers react to their leader's sensitivity. Moreover, these resulting affective experiences are likely to have important consequences for organizations, specifically as they relate to employee counterproductive work behavior (CWB). Drawing from supplies-values (S-V) fit theory and the stressor-emotion model of CWB, the current study focuses on the affective and behavioral consequences of fit between subordinates' ideal leader sensitivity behavior preferences and subordinates' perceptions of their actual leader's sensitivity behaviors. Polynomial regression analyses reveal that congruence between ideal and actual leader sensitivity influences employee negative affect and, consequently, engagement in counterproductive work behavior. (PsycINFO Database Record

Chemical Mass Production of Graphene Nanoplatelets in ∼100% Yield.

Successful application of graphene is hampered by the lack of cost-effective methods for its production. Here, we demonstrate a method of mass production of graphene nanoplatelets (GNPs) by exfoliation of flake graphite in the tricomponent system made by a combination of ammonium persulfate ((NH4)2S2O8), concentrated sulfuric acid, and fuming sulfuric acid. The resulting GNPs are tens of microns in diameter and 10-35 nm in thickness. When in the liquid phase of the tricomponent media, graphite completely loses its interlayer registry. This provides a ∼100% yield of GNPs from graphite in 3-4 h at room temperature or in 10 min at 120 °C.

Bandgap engineering of coal-derived graphene quantum dots.

Bandgaps of photoluminescent graphene quantum dots (GQDs) synthesized from anthracite have been engineered by controlling the size of GQDs in two ways: either chemical oxidative treatment and separation by cross-flow ultrafiltration, or by a facile one-step chemical synthesis using successively higher temperatures to render smaller GQDs. Using these methods, GQDs were synthesized with tailored sizes and bandgaps. The GQDs emit light from blue-green (2.9 eV) to orange-red (2.05 eV), depending on size, functionalities and defects. These findings provide a deeper insight into the nature of coal-derived GQDs and demonstrate a scalable method for production of GQDs with the desired bandgaps.

Intraoperative MRI with a rotating, tiltable surgical table: a time use study and clinical results in 122 patients.

OBJECTIVE: The objective of our study was to evaluate intraoperative low-field MRI for the frequency and duration of imaging sessions needed during surgery, the direct additional procedure time attributable to imaging, and the proportion of cases in which information provided by intraoperative MRI led to a change in the procedure or otherwise was deemed valuable by operating surgeons. MATERIALS AND METHODS: One hundred twenty-two patients (65 males, 57 females; age range, 6-77 years; mean age, 43.8 years) underwent 130 neurosurgical and ENT procedures (106 craniotomies, 17 transsphenoidal pituitary resections, three biopsies, three intracranial cyst aspirations or injections, and one skull base resection) in a specially designed surgical MRI suite equipped with a 0.2-T imager and a prototype rotating, tiltable surgical table. The intraoperative MR sequences included free induction with steady-state precession (fast imaging with steady-state precession [FISP]), steady-state free precession T2-weighted, reverse fast imaging with steady-state free precession (PSIF), FLASH, spin-echo T1-weighted, turbo spin-echo (TSE) T2-weighted, and TSE FLAIR. Each case was analyzed for the number of imaging sessions, duration of each session, total imaging time during surgery, and impact of imaging information on procedure. RESULTS: Each patient underwent between one and five intraor postoperative imaging sessions. Imaging times were 1.7 seconds-8 minutes 31 seconds per sequence. The mean total imaging time was 35 minutes 17 seconds per surgical procedure. Imaging was continuous during biopsy and cyst aspiration procedures and averaged 200.67 and 54.66 minutes, respectively. Additional surgical resection based on intraoperative imaging findings was performed in 72.8% of the cases. CONCLUSION: Intraoperative low-field MRI provides valuable information for surgical decision making that is predominantly related to detection of residual tumor and the exclusion of complications. The benefits of this technology surpass the time cost associated with its implementation when using proper imaging strategies.

Cervicomedullary junction compression caused by vertebral artery dolichoectasia and requiring surgical treatment. Case report.

A case of progressive brainstem syndrome secondary to vertebral artery (VA) dolichoectasia is reported. The patient presented with partial bilateral abduction paralysis, which progressed to quadriparesis, ataxia, and areflexia. The initial diagnosis was stroke, but because of the patient's deterioration, a diagnosis of Miller-Fisher syndrome was made. Neuroimages obtained at that time revealed an ectatic left VA with minimal cervicomedullary compression. The patient continued to deteriorate despite medical management. Follow-up imaging demonstrated worsened cervicomedullary compression. An emergency posterior fossa neurovascular decompression was performed using a Gore-Tex sling and resulted in mild neurological improvement. This case emphasizes that early recognition and surgical intervention to prevent progressive neurological sequelae are crucial in symptomatic VA dolichoectasia.