Resection of primary left renal vein leiomyosarcoma with renal preservation following an unusual clinical presentation.

An elderly man was referred to vascular surgery on incidental discovery of a left retroperitoneal mass ultimately found to be of left renal vein (LRV) origin. He initially presented with recurring lower back pain. CT of the abdomen/pelvis showed a 6.0×5.5 cm lobulated retroperitoneal mass anterior to the infrarenal aorta. Resection of the mass necessitated a multidisciplinary team consisting of medical oncologists, radiation oncologists, urologists and vascular surgeons. In efforts to obtain an R0 margin, en-bloc resection of the LRV from its confluence with the inferior vena cava (IVC) was necessary. A primary repair of the IVC was performed with preservation of the left kidney. The patient's back pain has since resolved after the surgery. A literature search found IVC reconstructions to be safe and effective in the removal of vascular leiomyosarcomas.

Dissociating Mechanisms That Underlie Seasonal and Developmental Programs for the Neuroendocrine Control of Physiology in Birds.

Long-term programmed rheostatic changes in physiology are essential for animal fitness. Hypothalamic nuclei and the pituitary gland govern key developmental and seasonal transitions in reproduction. The aim of this study was to identify the molecular substrates that are common and unique to developmental and seasonal timing. Adult and juvenile quail were collected from reproductively mature and immature states, and key molecular targets were examined in the mediobasal hypothalamus (MBH) and pituitary gland. qRT-PCR assays established deiodinase type 2 (DIO2) and type 3 (DIO3) expression in adults changed with photoperiod manipulations. However, DIO2 and DIO3 remain constitutively expressed in juveniles. Pituitary gland transcriptome analyses established that 340 transcripts were differentially expressed across seasonal photoperiod programs and 1,189 transcripts displayed age-dependent variation in expression. Prolactin (PRL) and follicle-stimulating hormone subunit beta (FSHß) are molecular markers of seasonal programs and are significantly upregulated in long photoperiod conditions. Growth hormone expression was significantly upregulated in juvenile quail, regardless of photoperiodic condition. These findings indicate that a level of cell autonomy in the pituitary gland governs seasonal and developmental programs in physiology. Overall, this paper yields novel insights into the molecular mechanisms that govern developmental programs and adult brain plasticity.

Cerebrovascular Disease Hospitalization Rates in End-Stage Kidney Disease Patients with Kidney Transplant and Peripheral Vascular Disease: Analysis Using the National Inpatient Sample (2005-2019).

Individuals with end-stage kidney disease (ESKD) face higher cerebrovascular risk. Yet, the impact of peripheral vascular disease (PVD) and kidney transplantation (KTx) on hospitalization rates for cerebral infarction and hemorrhage remains underexplored. Analyzing 2,713,194 ESKD hospitalizations (2005-2019) using the National Inpatient Sample, we investigated hospitalization rates for ischemic and hemorrhagic cerebrovascular diseases concerning ESKD, PVD, KTx, or their combinations. Patients hospitalized with cerebral infarction due to thrombosis/embolism/occlusion (CITO) or artery occlusion resulting in cerebral ischemia (AOSI) had higher rates of comorbid ESKD and PVD (4.17% and 7.29%, respectively) versus non-CITO or AOSI hospitalizations (2.34%, p < 0.001; 2.29%, p < 0.001). Conversely, patients hospitalized with nontraumatic intracranial hemorrhage (NIH) had significantly lower rates of ESKD and PVD (1.64%) compared to non-NIH hospitalizations (2.34%, p < 0.001). Furthermore, hospitalizations for CITO or AOSI exhibited higher rates of KTx and PVD (0.17%, 0.09%, respectively) compared to non-CITO or AOSI hospitalizations (0.05%, p = 0.033; 0.05%, p = 0.002). Patients hospitalized with NIH showed similar rates of KTx and PVD (0.04%) versus non-NIH hospitalizations (0.05%, p = 0.34). This nationwide analysis reveals that PVD in ESKD patients is associated with increased hospitalization rates with cerebral ischemic events and reduced NIH events. Among KTx recipients, PVD correlated with increased hospitalizations for ischemic events, without affecting NIH. This highlights management concerns for patients with KTx and PVD.

A Dynamic Elbow Testing Apparatus for Simulating Elbow Joint Motion in Varying Shoulder Positions.

Purpose: To develop and evaluate the capabilities of a dynamic elbow testing apparatus that simulates unconstrained elbow motion throughout the range of humerothoracic (HTA) abduction. Methods: Elbow flexion was generated by six computer-controlled electromechanical actuators that simulated muscle action, while six degree-of-freedom joint motion was measured using an optical tracking device. Repeatability of joint kinematics was assessed at four HTA angles (0°, 45°, 90°, 135°) and with two muscle force combinations (A1-biceps brachialis, brachioradialis and A2-biceps, brachioradialis). Repeatability was determined by comparing kinematics at every 10° of flexion over five flexion-extension cycles (0° to 100°). Results: Multiple muscle force combinations can be used at each HTA angle to generate elbow flexion. Trials showed that the testing apparatus produced highly repeatable joint motion at each HTA angle and with varying muscle force combinations. The intraclass correlation coefficient was greater than 0.95 for all conditions. Conclusions: Repeatable smooth cadaveric elbow motion was created that mimicked the in vivo situation. Clinical relevance: These results suggest that the dynamic elbow testing apparatus can be used to characterize elbow biomechanics in cadaver upper extremities.

The Effect of Elbow Flexion On Valgus Carrying Angle.

PURPOSE: This study aimed to examine the effect of flexion on valgus carrying angle in the human elbow using a dynamic elbow testing apparatus. METHODS: Active elbow motion was simulated in seven cadaveric upper extremities. Six electromechanical actuators simulated muscle action, while 6 degrees-of-freedom joint motion was measured with an optical tracking system to quantify the kinematics of the ulna with respect to the humerus as the elbow was flexed at the side position. Repeatability of the testing apparatus was assessed in a single elbow over five flexion-extension cycles. The varus angle change of each elbow was compared at different flexion angles with the arm at 0° of humerothoracic abduction or dependent arm position. RESULTS: The testing apparatus achieved excellent kinematic repeatability (intraclass correlation coefficient, >0.95) throughout flexion and extension. All elbows decreased their valgus carrying angle during flexion from 0° to 90° when the arm was maintained at 0° of humerothoracic abduction. Elbows underwent significant total varus angle change from full extension of 3.9° ± 3.4° (P = .007), 7.3° ± 5.2° (P = .01), and 8.9° ± 7.1° (P = .02) at 60°, 90°, and 120° of flexion, respectively. No significant varus angle change was observed between 0° and 30° of flexion (P = .66), 60° and 120° of flexion (P = .06), and 90° and 120° of flexion (P = .19). CONCLUSIONS: The dynamic elbow testing apparatus characterized a decrease of valgus carrying angle during elbow flexion and found that most varus angle changes occurred between 30° and 90° of flexion. All specimens underwent varus angle change until at least 90° of flexion. CLINICAL RELEVANCE: Our model establishes the anatomic decrease in valgus angle by flexion angle in vitro and can serve as a baseline for testing motion profiles of arthroplasty designs and ligamentous reconstruction in the dependent arm position. Future investigations should focus on characterizing motion profile change as the arm is abducted away from the body.

The arterial input function: Spatial dependence within the imaging volume and its influence on 3D quantitative dynamic contrast-enhanced MRI for head and neck cancer.

PURPOSE: To evaluate the dependence of the arterial input function (AIF) on the imaging z-axis and its effect on 3D DCE MRI pharmacokinetic parameters as mediated by the SPGR signal equation and Extended Tofts-Kermode model. THEORY: For SPGR-based 3D DCE MRI acquisition of the head and neck, inflow effects within vessels violate the assumptions underlying the SPGR signal model. Errors in the SPGR-based AIF estimate propagate through the Extended Tofts-Kermode model to affect the output pharmacokinetic parameters. MATERIALS AND METHODS: 3D DCE-MRI data were acquired for six newly diagnosed HNC patients in a prospective single arm cohort study. AIF were selected within the carotid arteries at each z-axis location. A region of interest (ROI) was placed in normal paravertebral muscle and the Extended Tofts-Kermode model solved for each pixel within the ROI for each AIF. Results were compared to those obtained with a published population average AIF. RESULTS: Due to inflow effect, the AIF showed extreme variation in their temporal shapes. Ktrans was most sensitive to the initial bolus concentration and showed more variation over the muscle ROI with AIF taken from the upstream portion of the carotid. kep was less sensitive to the peak bolus concentration and showed less variation for AIF taken from the upstream portion of the carotid. CONCLUSION: Inflow effects may introduce an unknown bias to SPGR-based 3D DCE pharmacokinetic parameters. Variation in the computed parameters depends on the selected AIF location. In the context of high flow, measurements may be limited to relative rather than absolute quantitative parameters.

Challenges in diagnosis, treatment and coordination of care of menstrual psychosis.

We present a suspected case of menstrual psychosis in an adolescent to highlight the unique attributes of this rare condition. An early adolescent female began displaying episodes of aggression, irritability, insomnia, hallucinations and disorganisation at menarche. Subsequent episodes resulted in multiple inpatient psychiatric hospital admissions coinciding with her menstrual cycle. Management from both psychiatry and gynaecology of her episodes, and abnormal hormone levels, was challenging. This report emphasises the importance of coordination between specialties, navigating diagnostic challenges and weighing the risk versus benefit of long-term neuroleptic use.

High intensity interval training exercise increases dopamine D2 levels and modulates brain dopamine signaling.

Background: Previous research has outlined the health benefits of exercise including its therapeutic potential for substance use disorders (SUD). These data have already been utilized and it is now common to find exercise as part of SUD treatment and relapse prevention programs. However, we need to better understand different exercise regimens and determine which would be the most beneficial for SUDs. Recently, high intensity interval training (HIIT) has gained attention in comparison with aerobic and resistance exercise. Little is known regarding the neurobiological mechanisms of HIIT, including its effects on dopamine signaling and receptor levels in the brain. The present study examined the effects of chronic HIIT exercise on dopamine signaling as measured by dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and tyrosine hydroxylase (TH) quantification in the brains of male and female rats as measured by [3H] SCH 23390 and [3H] spiperone autoradiography, and TH-immunoreactive optical density values. Methods: Rats were separated in two groups: sedentary and HIIT exercise. Exercise was on a treadmill for 30 min daily (10 3 min cycles) for six weeks with progressive speed increased up to 0.8 mph (21.5 m/min). Results: Results showed for D2R-like binding, a significant effect across the ventral caudate putamen (V CPU) between sexes, such that mean D2R-like binding was 14% greater for males than females. In the nucleus accumbens shell (Nac Shell), the HIIT Exercise rats showed 16% greater D2R-like binding as compared to the sedentary rats. No significant effects of HIIT exercise were found across groups for brain D1R-like binding levels or TH expression. Conclusion: These results suggest that HIIT exercise can modulate dopamine signaling by way of increased D2R. These findings support the premise that HIIT exercise plays an important role in dopamine signaling and, may provide a potential mechanism for how HIIT exercise can impact the brain and behavior.

Elevated de novo lipogenesis, slow liver triglyceride turnover, and clinical correlations in nonalcoholic steatohepatitis patients.

De novo lipogenesis (DNL) converts carbon substrates to lipids. Increased hepatic DNL could contribute to pathogenic liver triglyceride accumulation in nonalcoholic steatohepatitis (NASH) and therefore may be a potential target for pharmacological intervention. Here, we measured hepatic DNL using heavy water in 123 patients with NASH with fibrosis or cirrhosis, calculated the turnover of hepatic triglycerides to allow repeat labeling studies, and determined the associations of hepatic DNL with metabolic, fibrotic, and imaging markers. We found that hepatic DNL was higher in patients with fibrotic NASH [median (IQR), 40.7% contribution to palmitate (32.1, 47.5), n=103] than has been previously reported in healthy volunteers and remained elevated [median (IQR), 36.8% (31.0, 44.5), n=20] in patients with cirrhosis, despite lower liver fat content. We also showed that turnover of intrahepatic triglyceride pools was slow (t½ >10 days). Furthermore, DNL contribution was determined to be independent of liver stiffness by magnetic resonance imaging but was positively associated with the number of large very low density lipoprotein (VLDL) particles, the size of VLDL, the lipoprotein insulin resistance score, and levels of ApoB100, and trended toward negative associations with the fibrosis markers FIB-4, FibroSure, and APRI. Finally, we found treatment with the acetyl-CoA carboxylase inhibitor firsocostat reduced hepatic DNL at 4 and 12 weeks, using a correction model for residual label that accounts for hepatic triglyceride turnover. Taken together, these data support an important pathophysiological role for elevated hepatic DNL in NASH and demonstrate that response to pharmacological agents targeting DNL can be correlated with pretreatment DNL.

Photoperiodic regulation of avian physiology: From external coincidence to seasonal reproduction.

Seasonal cycles of environmental cues generate variation in the timing of life-history transition events across taxa. It is through the entrainment of internal, endogenous rhythms of organisms to these external, exogenous rhythms in environment, such as cycling temperature and daylight, by which organisms can regulate and time life history transitions. Here, we review the current understanding of how photoperiod both stimulates and terminates seasonal reproduction in birds. The review describes the role of external coincidence timing, the process by which photoperiod is proposed to stimulate reproductive development. Then, the molecular basis of light detection and the photoperiodic regulation of neuroendocrine timing of seasonal reproduction in birds is presented. Current data indicates that vertebrate ancient opsin is the predominant photoreceptor for light detection by the hypothalamus, compared to neuropsin and rhodopsin. The review then connects light detection to well-characterized hypothalamic and pituitary gland molecules involved in the photoperiodic regulation of reproduction. In birds, Gonadotropin-releasing hormone synthesis and release are controlled by photoperiodic cues via thyrotropin-stimulating hormone-ß (TSHß) independent and dependent pathways, respectively. The review then highlights the role of D-box and E-box binding motifs in the promoter regions of photoperiodic genes, in particular Eyes-absent 3, as the key link between circadian clock function and photoperiodic time measurement. Based on the available evidence, the review proposes that at least two molecular programs form the basis for external coincidence timing in birds: photoperiodic responsiveness by TSHß pathways and endogenous internal timing by gonadotropin synthesis.

Radiology Performed Fluoroscopy-Guided Lumbar Punctures Decrease Volume of Diagnostic Study Interpretation - Impact on Resident Training and Potential Solutions.

OBJECTIVES: Lumbar punctures performed in radiology departments have significantly increased over the last few decades and are typically performed in academic centers by radiology trainees using fluoroscopy guidance. Performing fluoroscopy-guided lumbar punctures (FGLPs) can often constitute a large portion of a trainee's workday and the impact of performing FGLPs on the trainee's clinical productivity (i.e. dictating reports on neuroradiology cross-sectional imaging) has not been studied. The purpose of the study was to evaluate the relationship between the number of FGLPs performed and cross-sectional neuroimaging studies dictated by residents during their neuroradiology rotation (NR). MATERIAL AND METHODS: The number of FGLPs and myelograms performed and neuroimaging studies dictated by radiology residents on our neuroradiology service from July 2008 to December 2017 were retrospectively reviewed. The relationship between the number of FGLPs performed and neuroimaging studies (CT and MRI) dictated per day by residents was examined. RESULTS: Radiology residents (n = 84) performed 3437 FGLPs and myelograms and interpreted 33402 cross-sectional studies. Poisson regression demonstrated an exponential decrease in number of studies dictated daily with a rising number of FGLPs performed (P = 0.0001) and the following formula was derived: Number of expected studies dictated per day assuming no FGLPs × e-0.25 x number of FGLPs = adjusted expected studies dictated for the day. CONCLUSION: We quantified the impact performing FGLPs can have on the number of neuroimaging reports residents dictate on the NR. We described solutions to potentially decrease unnecessary FGLP referrals including establishing departmental guidelines for FGLP referrals and encouraging bedside lumbar punctures attempts before referral. We also emphasized equally distributing the FGLPs among trainees to mitigate procedural burden.

Ovarian hormones induce de novo DNA methyltransferase expression in the Siberian hamster suprachiasmatic nucleus.

The present study investigated neuroanatomically localised changes in de novo DNA methyltransferase expression in the female Siberian hamster (Phodopus sungorus). The objectives were to identify the neuroendocrine substrates that exhibit rhythmic Dnmt3a and Dnmt3b expression across the oestrous cycle and also examine the role of ovarian steroids. Hypothalamic Dnmt3a expression was observed to significantly increase during the transition from pro-oestrous to oestrous. A single bolus injection of diethylstilbestrol and progesterone was sufficient to increase Dnmt3a cell numbers and Dnmt3b immunoreactive intensity in the suprachiasmatic nucleus. In vitro analyses using an embryonic rodent cell line revealed that diethylstilbestrol was sufficient to induce Dnmt3b expression. Up-regulating DNA methylation in vitro reduced the expression of vasoactive intestinal polypeptide, Vip, and the circadian clock gene, Bmal1. Together, these data indicate that ovarian steroids drive de novo DNA methyltransferase expression in the mammalian suprachiasmatic nucleus and increased methylation may regulate genes involved in the circadian timing of oestrous: Vip and Bmal1. Overall, epigenetically mediated neuroendocrine reproductive events may reflect an evolutionarily ancient process involved in the timing of female fertility.

Capnography-guided Endotracheal Intubation as an Alternative to Existing Intubation Methods in Rabbits.

Rabbits provide a unique challenge for routine endotracheal intubation in clinical practice because of various distinctive anatomic and physiologic features. Many previously proposed methods for endotracheal intubation in rabbits are limited by several factors, including the needs for expensive equipment and high levels of technical expertise. We evaluated capnography for its effectiveness in assisting endotracheal intubation in rabbits. New Zealand white rabbits were divided into 3 groups of 5 animals. In the first 2 groups, mainstream (nondiverting) or sidestream (diverting) capnography (MC and SC groups, re- spectively) was used; in the third group (LS group), a laryngoscope with a size 00 Miller blade was used to guide endotracheal tube placement. Anesthesia was induced through intramuscular administration of ketamine (10 mg/kg), medetomidine (0.1 mg/kg), and midazolam (1 mg/kg) mixed in the same syringe prior to administration. Intubation time was defined from the point of opening the jaws to the completion of the first capnogram after intubation. Intubation was accomplished successfully in all animals in both capnography groups, but 2 rabbits in the laryngoscopy group could not be intubated. Intubation time was compared among groups was compared by using one-way ANOVA, and posthoc Bonferroni testing was applied to isolate significant differences between groups. The intubation time (mean ± 1 SD) was 46.4 ± 12.6 s in the MC group, 147.2 ± 44.2 s in the SC group, and 385.0 ± 114.1 in the LS group, with intubation time significantly differing among all groups. In conclusion, both mainstream and sidestream capnography-guided endotracheal intubation techniques were more effective and efficient than conventional laryngoscope-guided endotracheal intubation in rabbits. Furthermore, mainstream capnography was preferred over sidestream capnography because mainstream capnography resulted in significantly shorter intubation times.

Effects of Beta-Blocker Withdrawal in Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study sought to evaluate the effects of beta-blocker withdrawal in acute decompensated heart failure (ADHF). BACKGROUND: Published reports showed trends for either no harm or increased risk of in-hospital mortality, short-term mortality, and rehospitalization rates in patients admitted for ADHF that discontinued beta-blockers; however, a comprehensive analysis has not been conducted. METHODS: Relevant studies from January 2000 through January 2015 were identified in the PubMed, EMBASE, and COCHRANE electronic databases. Where appropriate data were available, weighted relative risks were estimated using random-effects meta-analysis techniques. RESULTS: Five observational studies and 1 randomized clinical trial (n = 2,704 patients who continued beta-blocker therapy and n = 439 patients who discontinued beta-blocker therapy) that reported the short-term effects of beta-blocker withdrawal in ADHF were included in the analyses. In 2 studies, beta-blocker withdrawal significantly increased risk of in-hospital mortality (risk ratio: 3.72; 95% confidence interval [CI]: 1.51 to 9.14). Short-term mortality (relative risk: 1.61; 95% CI: 1.04 to 2.49; 4 studies) and combined short-term rehospitalization or death (relative risk: 1.59; 95% CI: 1.03 to 2.45; 4 studies) were also significantly increased. CONCLUSIONS: Discontinuation of beta-blockers in patients admitted with ADHF was associated with significantly increased in-hospital mortality, short-term mortality, and the combined endpoint of short-term rehospitalization or mortality. These data suggest beta-blockers should be continued in ADHF patients if their clinical picture allows.

Does Prison-Based Adult Basic Education Improve Postrelease Outcomes for Male Prisoners in Florida?

The authors use administrative data from Florida to determine the extent to which prison-based adult basic education (ABE) improves inmate's postrelease labor market outcomes, such as earnings and employment. Using two nonexperimental comparison groups, the authors find evidence that ABE participation is associated with higher postrelease earnings and employment rates, especially for minorities. The authors find that the relationship is the largest for ABE participants who had uninterrupted ABE instruction and for those who received other education services. However, the results do not find any positive effects of ABE participation on reducing recidivism.

IF YOU BUILD IT WILL THEY COME? TEACHERS' ONLINE USE OF STUDENT PERFORMANCE DATA.

Testing of students and computer systems to store, manage, analyze, and report the resulting test data have grown hand-in-hand. Extant research on teacher use of electronically stored data are largely qualitative and focused on the conditions necessary (but not sufficient) for effective teacher data use. Absent from the research is objective information on how much and in what ways teachers use computer-based student test data, even when supposed precursors of usage are in place. This paper addresses this knowledge gap by analyzing the online activities of teachers in one mid-size urban district. Utilizing Web logs collected between 2008 and 2010, I find low teacher interaction with Web-based pages that contain student test information that could potentially inform practice. I also find no evidence that teacher usage of Web-based student data are related to student achievement gains, but there is reason to believe these estimates are downwardly biased.

Validation of a scenario-based assessment of critical thinking using an externally validated tool.

With medical education transitioning from knowledge-based curricula to competency-based curricula, critical thinking skills have emerged as a major competency. While there are validated external instruments for assessing critical thinking, many educators have created their own custom assessments of critical thinking. However, the face validity of these assessments has not been challenged. The purpose of this study was to compare results from a custom assessment of critical thinking with the results from a validated external instrument of critical thinking. Students from the College of Veterinary Medicine at Western University of Health Sciences were administered a custom assessment of critical thinking (ACT) examination and the externally validated instrument, California Critical Thinking Skills Test (CCTST), in the spring of 2011. Total scores and sub-scores from each exam were analyzed for significant correlations using Pearson correlation coefficients. Significant correlations between ACT Blooms 2 and deductive reasoning and total ACT score and deductive reasoning were demonstrated with correlation coefficients of 0.24 and 0.22, respectively. No other statistically significant correlations were found. The lack of significant correlation between the two examinations illustrates the need in medical education to externally validate internal custom assessments. Ultimately, the development and validation of custom assessments of non-knowledge-based competencies will produce higher quality medical professionals.

Solubility-driven optimization of phosphodiesterase-4 inhibitors leading to a clinical candidate.

The solubility-driven optimization of a series of 1,7-napthyridine phosphodiesterase-4 inhibitors is described. Directed structural changes resulted in increased aqueous solubility, enabling superior pharmacokinetic properties with retention of PDE4 inhibition. A range of potent and orally bioavailable compounds with good in vivo efficacy in animal models of inflammation and reduced emetic potential compared to previously described drugs were synthesized. Compound 2d was taken forward as a clinical candidate for the treatment of COPD.

Finishing high school: alternative pathways and dropout recovery.

John Tyler and Magnus Lofstrom take a close look at the problems posed when students do not complete high school. The authors begin by discussing the ongoing, sometimes heated, debate over how prevalent the dropout problem is. They note that one important reason for discrepancies in reported dropout rates is whether holders of the General Educational Development (GED) credential are counted as high school graduates. The authors also consider the availability of appropriate student data. The overall national dropout rate appears to be between 22 and 25 percent, but the rate is higher among black and Hispanic students, and it has not changed much in recent decades. Tyler and Lofstrom conclude that schools are apparently doing about as well now as they were forty years ago in terms of graduating students. But the increasingly competitive pressures associated with a global economy make education ever more important in determining personal and national well-being. A student's decision to drop out of school, say the authors, is affected by a number of complex factors and is often the culmination of a long process of disengagement from school. That decision, not surprisingly, carries great cost to both the student and society. Individual costs include lower earnings, higher likelihood of unemployment, and greater likelihood of health problems. Because minority and low-income students are significantly more likely than well-to-do white students to drop out of school, the individual costs fall unevenly across groups. Societal costs include loss of tax revenue, higher spending on public assistance, and higher crime rates. Tyler and Lofstrom go on to survey research on programs designed to reduce the chances of students' dropping out. Although the research base on this question is not strong, they say, close mentoring and monitoring of students appear to be critical components of successful programs. Other dropout-prevention approaches associated with success are family outreach and attention to students' out-of-school problems, as well as curricular reforms. The authors close with a discussion of second-chance programs, including the largest such program, the GED credential.