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Prenatal alcohol exposure is the foremost preventable etiology of intellectual disability and leads to a collection of diagnoses known as Fetal Alcohol Spectrum Disorders (FASD). Alcohol (EtOH) impacts diverse neural cell types and activity, but the precise functional pathophysiological effects on the human fetal cerebral cortex are unclear. Here, we used human cortical organoids to study the effects of EtOH on neurogenesis and validated our findings in primary human fetal neurons. EtOH exposure produced temporally dependent cellular effects on proliferation, cell cycle, and apoptosis. In addition, we identified EtOH-induced alterations in post-translational histone modifications and chromatin accessibility, leading to impairment of cAMP and calcium signaling, glutamatergic synaptic development, and astrocytic function. Proteomic spatial profiling of cortical organoids showed region-specific, EtOH-induced alterations linked to changes in cytoskeleton, gliogenesis, and impaired synaptogenesis. Finally, multi-electrode array electrophysiology recordings confirmed the deleterious impact of EtOH on neural network formation and activity in cortical organoids, which was validated in primary human fetal tissues. Our findings demonstrate progress in defining the human molecular and cellular phenotypic signatures of prenatal alcohol exposure on functional neurodevelopment, increasing our knowledge for potential therapeutic interventions targeting FASD symptoms.

Gene expression comprises a diverse array of enzymes, proteins, non-coding transcripts, and cellular structures to guide the transfer of genetic information to its various final products. In the brain, the coordination among genes, or lack thereof, characterizes individual brain regions, mediates a variety of brain-related disorders, and brings light to fundamental differences between species. RNA processing, occurring between transcription and translation, controls an essential portion of gene expression through splicing, editing, localization, stability, and interference. The machinery to regulate transcripts must operate with precision serving as a blueprint for proteins and non-coding RNAs to derive their identity. Therefore, RNA processing has a broad scope of influence in the brain, as it modulates cell morphogenesis during development and underlies mechanisms behind certain neurological diseases. Here, we present these ideas through recent findings on RNA processing in development and post-developmental maturity to advance therapeutic discoveries and the collective knowledge of the RNA life cycle.

Early-onset epileptic encephalopathies are severe disorders often associated with specific genetic mutations. In this context, the CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by early-onset seizures, intellectual delay, and motor dysfunction. Although crucial for proper brain development, the precise targets of CDKL5 and its relation to patients’ symptoms are still unknown. Here, induced pluripotent stem cells derived from individuals deficient in CDKL5 protein were used to generate neural cells. Proteomic and phosphoproteomic approaches revealed disruption of several pathways, including microtubule-based processes and cytoskeleton organization. While CDD-derived neural progenitor cells have proliferation defects, neurons showed morphological alterations and compromised glutamatergic synaptogenesis. Moreover, the electrical activity of CDD cortical neurons revealed hyperexcitability during development, leading to an overly synchronized network. Many parameters of this hyperactive network were rescued by lead compounds selected from a human high-throughput drug screening platform. Our results enlighten cellular, molecular, and neural network mechanisms of genetic epilepsy that could ultimately promote novel therapeutic opportunities for patients.

Prenatal alcohol exposure is the foremost preventable etiology of intellectual disability and leads to a collection of diagnoses known as Fetal Alcohol Spectrum Disorders (FASD). Alcohol (EtOH) impacts diverse neural cell types and activity, but the precise functional pathophysiological effects on the human fetal cerebral cortex are unclear. Here, we used human cortical organoids to study the effects of EtOH on neurogenesis and validated our findings in primary human fetal neurons. EtOH exposure produced temporally dependent cellular effects on proliferation, cell cycle, and apoptosis. In addition, we identified EtOH-induced alterations in post-translational histone modifications and chromatin accessibility, leading to impairment of cAMP and calcium signaling, glutamatergic synaptic development, and astrocytic function. Proteomic spatial profiling of cortical organoids showed region-specific, EtOH-induced alterations linked to changes in cytoskeleton, gliogenesis, and impaired synaptogenesis. Finally, multi-electrode array electrophysiology recordings confirmed the deleterious impact of EtOH on neural network formation and activity in cortical organoids, which was validated in primary human fetal tissues. Our findings demonstrate progress in defining the human molecular and cellular phenotypic signatures of prenatal alcohol exposure on functional neurodevelopment, increasing our knowledge for potential therapeutic interventions targeting FASD symptoms.

Objective To evaluate whether preoperative computed tomography (CT) findings could predict the presence of an impacted stone. Preoperative identification of an impacted ureteral stone may influence patient preparation and operative decisions. Factors predicting ureteral stone impaction have not been clearly identified. Methods We identified all patients from June 2014 to July 2016 that underwent ureteroscopic treatment of an impacted ureteral stone. Patients that had ureteral prestenting or previous treatment for their stone were excluded. Noncontrast CT images were reviewed to calculate stone size, stone volume, degree of hydronephrosis (0-3), and Hounsfield units (HU) of the stone as well as the ureter distal and proximal to the stone. These were compared with a control group of patients that had nonimpacted stones. Results Patients with impacted stones had a greater stone size, volume, HU of the ureter under the stone, HU under/above ratio, and degree of hydronephrosis on univariate analysis. Multivariate analysis demonstrated that HU under the stone was a significant predictor of ureteral stone impaction (odds ratio 1.17; 95% confidence interval 1.11-1.25). Distal ureteral density above 27 HU demonstrated a sensitivity of 85%, specificity of 85%, positive predictive value of 89%, and negative predictive value of 81% for ureteral stone impaction. Conclusion Impacted stones are associated with ureteral density cut-off value of 27 HU or greater. Measuring this value on preoperative noncontrast CT may help predict which patients are more likely to have impacted stones.

Percutaneous nephrolithotomy (PCNL) is the preferred surgical treatment for staghorn stones. Two approaches are commonly employed to gain access into the collecting system which consists of either an upper pole (UP) approach or lower pole (LP) approach. However, opinions vary on which approach offers the best access and outcome. In this study, we aim to challenge the traditional paradigm that staghorn stones are most effectively treated through a prone UP approach. We herein report our institutional experience using a prone LP access in PCNL for patients with complete staghorn stones. Data were prospectively collected over 3 years on 473 PCNL procedures, of which 76 patients had complete staghorn calculi (five or more calyces). Operative and peri-operative outcomes were analyzed to compare a modified LP approach with the more widely accepted UP approach. A total of 59/76 (77.6%) patients had LP access. There was no difference in the ability of completing the surgery utilizing a single tract as opposed to multiple tracts (74.6% of LP patients vs. 76.5% of UP patients). Stone-free rates for LP and UP access were similar (74.5 versus 70.5%, respectively; p = 0.760. Complication rates were lower for LP access vs. UP access (3.4 vs. 23.5%, p = 0.02) with two pulmonary complications in the UP group. Overall median operative time was not significantly different between LP and UP access (112.0 vs. 126.0 min, p = 0.486). Prone LP access demonstrated similar efficacy with decreased morbidity in patients with complete staghorn calculi compared to prone UP access.

Purpose: We evaluated the outcomes of percutaneous treatment and metabolic evaluation of calyceal diverticula with associated stones.Materials and Methods: We retrospectively identified 51 patients with a calyceal diverticulum in our prospectively maintained percutaneous nephrolithotomy database. Patients with complete data were separated into 14 with stones isolated to the diverticulum and 15 with renal stones in and outside the diverticulum. A total of 571 patients with renal stones but no diverticulum were used for comparison. Statistical differences were assessed using the chi-square test and the t-test.Results: Patients with stones isolated to the diverticulum were younger (44 vs 54 years, p = 0.024), had a lower body mass index (23.2 vs 27 kg/m2, p = 0.032) and were more often female (71% vs 44%, p = 0.046) compared to patients with renal stones but no diverticulum. Calyceal diverticula were anterior in 19 of 29 cases and in the upper pole in 15. Average diverticular size was 2.5 cm with a 1.5 cm st...

To examine urine and stone bacteriology of struvite stone formers in a large cohort of patients undergoing percutaneous nephrolithotomy (PCNL).A total of 1191 patients, with stone and urine cultures, treated with PCNL for renal calculi were included in the study. Statistical differences were assessed using Mann-Whitney U and T-tests.Stone cultures were positive in 72% of patients with struvite stones. Urea-splitting organisms accounted for only half of the positive stone cultures. Enterococcus (9/50, 18%), Proteus (9/50, 18%), and Escherichia coli (6/50, 12%) were the most commonly identified organisms. Notably, two-thirds of struvite formers with negative stone culture had at least one positive culture for a urea-splitting organism on urine culture going back 1 year from the time of surgery. A majority (67%) of struvite stone cultures were found to be resistant to first- and second-generation cephalosporins.The bacteriology of struvite stones has shifted away from traditional urea-splitting organisms and antibiotic coverage must be expanded to include organisms such as Enterococcus that do not respond to cephalosporins. Causative organisms may be found by going back in time to identify the initial organism that could have induced struvite stone formation to inform preventative therapy.

Ascorbic Acid (Vitamin C) is investigated as a renewable alternative fuel for alkaline direct liquid fuel cells (DLFCs). The environmentally- and biologically-friendly compound, l -ascorbic acid (AA) has been modeled and studied experimentally under acidic fuel cell conditions. In this work, we demonstrate that ascorbic acid is a more efficient fuel in alkaline media than in acidic media. An operating direct ascorbate fuel cell is constructed with the combination of l -ascorbic acid and KOH as the anode fuel, air or oxygen as the oxidant, a polymer anion exchange membrane, metal or carbon black anode materials and metal cathode catalyst. Operation of the fuel cell at 60 °C using 1 M AA and 1 M KOH as the anode fuel and electrolyte, respectively, and oxygen gas at the cathode, produces a maximum power density of 73 mW cm-2, maximum current density of 497 mA cm−2 and an open circuit voltage of 0.90 V. This performance is significantly greater than that of an ascorbic acid fuel cell with a cation exchange membrane, and it is competitive with alkaline DLFCs fueled by alcohols.

Percutaneous nephrolithotomy (PCNL) is the gold standard procedure for large renal calculi but postoperative (PO) pain remains a concern. Modifications of the PCNL technique and intraoperative and PO strategies have been tested to reduce pain. PO pain control reducing risk of long-term pain medication and narcotic use is of considerable importance. Acupuncture is a common medical procedure shown to alleviate PO pain. Some benefits are that it is nonpharmacologic, easy to administer, and safe. The purpose of this study was to evaluate the effects of electroacupuncture (EA) on PO pain in patients undergoing PCNL.This was a randomized, double-blind, sham-controlled study. The study was Institutional Review Board approved and performed under standard ethical guidelines. Fifty-one patients undergoing PCNL by a single surgeon were randomized to one of the three groups: true EA (n = 17), sham EA (SEA, n = 17), and no acupuncture (control, n = 17). The EA and SEA were performed by a single licensed acupuncturist1 hour before operation. PCNL was performed without the use of intraoperative nerve block(s) or local anesthetic. Pain scores (visual analog scale [VAS]), narcotic use (morphine equivalents), and side effects were recorded at set intervals postoperatively.Mean VAS scores for flank and abdomen pain were lower at all time periods in the EA compared with the SEA and control groups. Mean cumulative opioid usage was lower in the EA group immediately postoperatively compared with both SEA and control groups. Two patients in the EA group did not require any PO narcotics. No differences between groups were found for PO nausea and vomiting. No adverse effects of EA or SEA were noted.EA significantly reduced PO pain and narcotic usage without any adverse effects after PCNL. This promising treatment for managing PO pain warrants further investigation.

Aims Metabolic syndrome and diabetes are associated with nephrolithiasis. Proposed mechanisms of lithogenesis include insulin resistance causing low urine pH and hyperinsulinemia leading to hypercalciuria. Herein, we sought to determine whether insulin resistance was associated with differences in stone burden and lithogenic changes on 24-hour urine samples. Materials and methods All patients that underwent comprehensive metabolic workup including 24-hour urine samples and fasting insulin levels were included. Insulin resistance was defined as a homeostasis model assessment of insulin resistance value > 5 (HOMA-IR = (glucose×insulin)/405). Patients on active metabolic therapy were excluded or the 24-hour urine sample predating treatment was utilized for analysis. Stone burden was determined by totaling the maximal diameter of all stones noted on CT. Results 18 of 30 patients (60.0%) had HOMA-IR > 5. Among patients with calculated insulin resistance, stone burden was greater (17.6 mm vs. 6.3 mm, p = 0.002) and 24-hour urine samples revealed higher urine calcium (293 mg/d vs. 159 mg/d, p = 0.02) and lower urine pH and citrate (454 mg/d vs. 639 mg/d, p = 0.04 and 5.83 vs. 6.33, p = 0.04, respectively). Conclusions Previous studies have demonstrated a correlation between metabolic syndrome, diabetes, and nephrolithiasis. This report demonstrates a quantitative increase in stone burden among patients with calculated insulin resistance. The pathway for this greater stone burden may be related to the urinary metabolic changes noted among patients with insulin resistance. In the future, targeting reduction of fasting insulin levels may represent a key element of stone disease prevention.

The association between nephrolithiasis and acromegaly has been previously described. Although the mechanism has been established, the urological literature sparsely discusses clinically suspecting that patients with recurrent nephrolithiasis could have acromegaly and subsequently referring them for accurate diagnosis and treatment. We present a case of occult acromegaly secondary to a pituitary tumor discovered 20 years after the patient's first stone episode.

Stent omission after routine ureteroscopy (rtURS) is accepted by current guidelines and may result in decreased patient morbidity and treatment costs. In a value-based healthcare model, the added morbidity and cost of routine stent placement may be scrutinized. Furthermore, data are limited on urologist cost knowledge and it is effect on ureteral stent placement. As such, we seek to describe ureteral stenting practices and urologist cost knowledge amongst US and non-US-based urologists. The ureteroscopic practice patterns and cost awareness of members of the Endourological Society were surveyed using an international email listserv. Respondents were grouped by practice location (US vs non-US). Logistic regression was used to evaluate the associations of surgeon practice location with stenting practices. 233 completed responses were received with a response rate of 13.5%. Results revealed that 55% and 71% of respondents reported ureteral stent insertion after rtURS more than 75% of the time for ureteral and renal stones, respectively. Reporting stent insertion following more than 75% of rtURS was more common among US participants for both ureteral and renal stones. Overall, reported cost knowledge was high, but lower among US participants. On multivariable analysis, US respondents were more likely to place ureteral stents after rtURS for ureteral stones more than 75% of the time when compared to those abroad (OR 3.43 p

Objectives Ritonavir and cobicistat are strong inhibitors of human cytochrome P450-3A (CYP3A) isoforms, and are used clinically as pharmacokinetic boosting agents for other antiretroviral drugs. Data reported by the manufacturer suggest that cobicistat is a more selective inhibitor of CYP3A than ritonavir. However, this claim has not been validated in clinical studies. This study evaluated the in-vitro inhibitory potency of ritonavir and cobicistat vs a series of human CYP isoforms. Method The model system utilized human liver microsomes and isoform-selective index substrates. Key findings Ritonavir and cobicistat both were strong inhibitors of CYP3A4, with IC50 values of 0.014 and 0.032 μm, respectively. A component of inhibition was time-dependent (mechanism-based). Neither drug meaningfully inhibited CYP1A2 (IC50 > 150 μm). CYP2B6, CYP2C9, CYP2C19 and CYP2D6 were inhibited by both drugs, but with IC50 values exceeding 6 μm. Conclusions Consistent with previous reports, both ritonavir and cobicistat were highly potent inhibitors of CYP3A. Both drugs were weaker inhibitors of other human CYPs, with IC50 values at least two orders of magnitude higher. There was no evidence of a meaningful difference in selectivity between the two drugs.

Immediate ureteroscopic treatment for patients presenting to the emergency room with symptomatic ureterolithiasis is more commonly being utilized. Recent reports demonstrate good efficacy for emergency ureteroscopy (URS); however, preoperative predictors of treatment success have not been described. In this study, we report our multicenter experience with emergency URS and identify predictors of successful treatment. We also describe the Emergency Ureteral Stone Treatment (EUST) score, which integrates these predictors and stratifies patients into those that are likely and unlikely to have successful treatment.Laboratory and radiographic data for all patients who underwent emergency URS for acute symptomatic ureterolithiasis from 2010 to 2015 were reviewed. Statistical difference among parameters for patients who were stone free (SF) and not SF was assessed with the Student's t-test. Cutoff values for significant predictors were determined using sensitivity and specificity analysis. The EUST score was determined based on the number of cutoffs a patient was below.Two hundred two of 247 patients (81.8%) were SF. Two complications (ureteral perforation) occurred. Stone size, duration of symptoms before presentation, and serum white blood count at presentation did not affect SF rates. 95.5% of the treatment failures were attributed to a tight ureter preventing stone access. Patients who received alpha blockers before treatment were more likely to be SF (98.0% vs 55.5%, p 0.01). Periureteral density (PUD) was lower in SF patients (2.8 HU vs 19.6 HU, p 0.01), whereas the increase in serum creatinine from baseline (ΔCr) was greater in non-SF patients (0.44 mg/dL vs 0.20 mg/dL, p 0.01). EUST score of 0, 1, and 2 correlated with SF rates of 20.6%, 81.9%, and 99.2%, respectively.Combined consideration of PUD and ΔCr with the EUST score can assist in selecting optimal candidates for immediate ureteroscopic management. Administration of alpha blockers before surgery may improve success rates by providing preoperative ureteral dilation.

Objective To assess whether horizontal vs vertical bolster orientation affects kidney position during prone percutaneous nephrolithotomy as this could impact the need for supracostal access and therefore the likelihood of pleural injury. Materials and Methods In a prospective trial, 10 subjects with 20 renal units underwent magnetic resonance imaging in prone position with standard cylindrical bolsters oriented vertically and then horizontally. Vertical bolsters were placed along the lateral aspect of the chest. Horizontal bolsters were placed at the xiphoid and symphysis pubis. The position of the kidney relative to the pleura was assessed by measuring distances from the kidney upper pole to diaphragm, to the top of the first lumbar vertebra, and inferior-most rib. Nephrostomy tract length and tract proximity to adjacent organs were also measured. Results Right and left kidney-to-diaphragm distance significantly increased with horizontal vs vertical bolsters by 3.44 cm and 1.86 cm, respectively ( P = .02, P = .01). Right kidney-to-rib distance significantly increased by 2.4 cm ( P = .025); left kidney-to-rib distance increased by 0.5 cm ( P = .123). Right kidney-to-vertebral distance significantly increased by 2.16 cm ( P = .007); left kidney-to-vertebral distance increased by 0.9 cm ( P = .059). There was no significant difference in maximum access angle, overall tract length, or colon position between horizontal and vertical bolsters. Conclusion Orienting bolsters horizontally results in caudal kidney displacement without affecting access angle, overall tract length, or colon position. In comparison with vertical orientation, this may improve safety of percutaneous nephrolithotomy by decreasing the need for supracostal access and increasing the safety of supracostal access when required.

Extreme ultraviolet (EUV) lithography is crucial to enabling technology scaling in pitch and critical dimension (CD). Currently, one of the key challenges of introducing EUV lithography to high volume manufacturing (HVM) is throughput, which requires high source power and high sensitivity chemically amplified photoresists. Important limiters of high sensitivity chemically amplified resists (CAR) are the effects of photon shot noise and resist blur on the number of photons received and of photoacids generated per feature, especially at the pitches required for 7 nm and 5 nm advanced technology nodes. These stochastic effects are reflected in via structures as hole-to-hole CD variation or local CD uniformity (LCDU). Here, we demonstrate a synergy of film stack deposition, EUV lithography, and plasma etch techniques to improve LCDU, which allows the use of high sensitivity resists required for the introduction of EUV HVM. Thus, to improve LCDU to a level required by 5 nm node and beyond, film stack deposition, EUV lithography, and plasma etch processes were combined and co-optimized to enhance LCDU reduction from synergies. Test wafers were created by depositing a pattern transfer stack on a substrate representative of a 5 nm node target layer. The pattern transfer stack consisted of an atomically smooth adhesion layer and two hardmasks and was deposited using the Lam VECTOR PECVD product family. These layers were designed to mitigate hole roughness, absorb out-of-band radiation, and provide additional outlets for etch to improve LCDU and control hole CD. These wafers were then exposed through an ASML NXE3350B EUV scanner using a variety of advanced positive tone EUV CAR. They were finally etched to the target substrate using Lam Flex dielectric etch and Kiyo conductor etch systems. Metrology methodologies to assess dimensional metrics as well as chip performance and defectivity were investigated to enable repeatable patterning process development. Illumination conditions in EUV lithography were optimized to improve normalized image log slope (NILS), which is expected to reduce shot noise related effects. It can be seen that the EUV imaging contrast improvement can further reduce post-develop LCDU from 4.1 nm to 3.9 nm and from 2.8 nm to 2.6 nm. In parallel, etch processes were developed to further reduce LCDU, to control CD, and to transfer these improvements into the final target substrate. We also demonstrate that increasing post-develop CD through dose adjustment can enhance the LCDU reduction from etch. Similar trends were also observed in different pitches down to 40 nm. The solutions demonstrated here are critical to the introduction of EUV lithography in high volume manufacturing. It can be seen that through a synergistic deposition, lithography, and etch optimization, LCDU at a 40 nm pitch can be improved to 1.6 nm (3-sigma) in a target oxide layer and to 1.4 nm (3-sigma) at the photoresist layer.

Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.

The authors examined the validity of the group interview, in which several applicants are interviewed simultaneously, vs. the traditional 1-on-1 selection interview. The authors also investigated perceptions of fairness for each interview format and whether the order in which the applicant was asked to respond in the group interview affected the quality of his or her response. Participants were 91 undergraduates who participated in 1-on-1 or group interviews for a scholarship award. The present results supported the hypothesis that interviewers in the 1-on-1 format were significantly better at predicting the applicants' academic potential. Also, in the group interviews, the order in which the applicants were asked to respond affected the quality of their responses significantly.

Over the last decade, shockwave lithotripsy (SWL) success rates have been correlated with stone density, skin-to-stone distance (SSD), and stone diameter. However, time constraints and the technical challenge of manual measurement often preclude utilization of these parameters. In this study, we describe a scoring system that accurately predicts SWL stone-free rates, is simple to calculate, and can be easily included in the radiology report.Two hundred thirty-five patients who underwent SWL from 2011 to 2014 were evaluated. One hundred thirty-three had available preoperative imaging. Stone density, SSD, ellipsoid stone volume (ESV), and stone-free rates were determined. Receiver operator characteristic (ROC) curves were generated to determine cutoff values for each parameter. The Triple D Score was calculated based upon the number of cutoff values a stone fell below.One hundred forty of the 235 patients (59.5%) who underwent SWL were stone free after single-session treatment. Seventy-six of the 133 (57.1%) patients with available preoperative imaging were stone free. ESV, SSD, and stone density were significant predictors of SWL success. Based upon the ROC curves, cutoffs of150 μL for ESV,12 cm for SSD, and600 HU for stone density were established. A Triple D Score of 0, 1, 2, and 3 correlated with SWL success rates of 21.4%, 41.3%, 78.7%, and 96.1%, respectively.Readily available predictive tools are necessary to enhance SWL cost-effectiveness. The Triple D Score is simple to calculate and can be reported by radiologists. Incorporation of the Triple D Score into preoperative planning may increase the overall SWL success rates.

and past history of ureteral stone. The association with CT parameters of stone including diameter (D), length (H), volumetric stone burden (VSB; D H 5 / 6), estimated stone location (ESL; number of axial cut images between stone and UVJ), tissue rim sign (RS; 0-3), perinephric edema (0-3), hydronephrosis (0-3), and Hounsfield unit (HU) were also analyzed. Then a logistic regression model was developed using these variables to estimate the stone-free rate after URSL. RESULTS: The stone-free rate of URSL was 85.7% (203/237). Univariate analysis found that stone diameter, length, VSB, ESL, HU and RS significantly affect the stone-free rate (p 0.000, 0.000, 0.003, 0.000, 0.005, 0.000, respectively). Multivariate analysis indicated that stone diameter (HR 1.165, p 0.005), ESL (HR 1.074, p 0.001), and RS (HR 4.635, p 0.009) significantly affect the stone-free rate. Predictive model by logistic regression analysis for stone-free rate after URSL was defined as follows: stone free rate 1/[1 exp{6.146 0.153(D) 0.071(ESL) 1.534(RS)}] with AUC 0.825 from ROC curve. Internal validation showed that stone-free rate concordance was 0.774. CONCLUSIONS: Present study demonstrated that CT-measured parameters including stone diameter, ESL and RS are independent factors affecting URSL outcome. A CT-based predictive model using these factors helps to estimate stone-free rate after URSL in individual patients and facilitates treatment planning.

Traumatic brain injury (TBI) continues to carry a significant public health burden and is anticipated to worsen worldwide over the next century. Recently the authors of several articles have suggested that exposure to beta blockers may improve mortality rates following TBI. The exact mechanism through which beta blockers mediate this effect is unknown. In this paper, the authors review the literature regarding the safety of beta blockers in patients with TBI. The findings of several recent retrospective cohort studies are examined and implications for future investigation are discussed. Future questions to be addressed include: the specific indications for the use of beta blockers in patients with TBI, the optimal type and dose of beta blocker given, the end point of beta blocker therapy, and the safety of beta blockers in cases of severe TBIs.