Understanding Variation in Estimates of Diversionary Effects of Community College Entrance: A Systematic Review and Meta-analysis.

Decades of research have estimated the effect of entering a community college on bachelor's degree attainment. In this study, we examined the influence of methodological choices, including sample restrictions and identification strategies, on estimated effects from studies published between 1970 and 2017. After systematically reviewing the literature, we leveraged meta-analysis to assess average estimates and examine the role of moderators. In our preferred model, entering a community college was associated with a 23-percentage-point decrease in the probability of baccalaureate attainment, on average, compared with entering a four-year college. The size of effects appeared to grow over the past three decades, though this coincides with substantial shifts in the college-going population. Methodological choices, particularly how researchers define the treatment group, explain some variation in estimates across studies. We conclude with a discussion of the implications for future inquiry and for policy.

Accuracy and reliability of fetal heart rate monitoring using maternal abdominal surface electrodes.

OBJECTIVE: Compare the accuracy and reliability of fetal heart rate identification from maternal abdominal fetal electrocardiogram signals (ECG) and Doppler ultrasound with a fetal scalp electrode. DESIGN: Prospective open method equivalence study. SETTING: Three urban teaching hospitals in the Northeast United States. SAMPLE: 75 women with normal pregnancies in labor at >37 weeks of gestation. METHODS: Three fetal heart rate detection methods were used simultaneously in 75 parturients. The fetal scalp electrode was the standard against which abdominal fetal ECG and ultrasound were judged. MAIN OUTCOME MEASURES: The positive percent agreement with the fetal scalp electrode indicated reliability. Bland-Altman analysis determined accuracy. The confusion rate indicated how frequently the devices tracked the maternal heart rate. RESULTS: Positive percent agreement was 81.7 and 73% for the abdominal fetal ECG and ultrasound, respectively (p = 0.002). The abdominal fetal ECG had a lower root mean square error than ultrasound (5.2 vs. 10.6 bpm, p < 0.001). The confusion rate for ultrasound was 20-fold higher than for abdominal ECG (8.9 vs. 0.4%, respectively, p < 0.001). CONCLUSION: Compared with the fetal scalp electrode, fetal heart rate detection using abdominal fetal ECG was more reliable and accurate than ultrasound, and abdominal fetal ECG was less likely than ultrasound to display the maternal heart rate in place of the fetal heart rate.

Analysis of monomeric and dimeric phosphorylated forms of protein kinase R.

PKR (protein kinase R) is induced by interferon and is a key component of the innate immunity antiviral pathway. Upon binding double-stranded RNA (dsRNA) or dimerization in the absence of dsRNA, PKR undergoes autophosphorylation at multiple serines and threonines that activate the kinase. Although it has previously been demonstrated that phosphorylation enhances PKR dimerization, gel filtration analysis reveals a second monomeric phosphorylated form. These forms are termed phosphorylated dimeric PKR (pPKRd) and phosphorylated monomeric PKR (pPKRm). These two forms do not reversibly interconvert. Sedimentation equilibrium measurements reveal that pPKRm dimerizes weakly with a K(d) similar to that of unphosphorylated PKR. Isoelectric focusing and mass spectrometry demonstrate that both pPKRm and pPKRd are heterogeneous in their phosphorylation states, with an average of 9 or 10 phosphates. Equilibrium chemical denaturation analysis indicates that phosphorylation destabilizes the kinase domain by approximately 1.5 kcal/mol in the dimeric form but not in the monomeric form. Limited proteolysis also reveals that phosphorylation induces a conformational change in pPKRd that is not detected in pPKRm. pPKRm binds dsRNA with an affinity similar to that of unphosphorylated PKR, whereas binding cannot be detected with pPKRd. Despite these substantial differences in biophysical properties, both pPKRm and pPKRd are catalytically competent and are activated to phosphorylate the PKR substrate eIF2alpha in the absence of dsRNA. Thus, both monomeric and dimeric forms of phosphorylated PKR may participate in the interferon antiviral pathway.

Major Movement: Examining Meta-Major Switching at Community Colleges.

Evidence of inefficient course-taking patterns at community colleges has spurred policy conversations about how to ensure effective course sequences. Structural reforms, like guided pathways, seek to reduce major switching as a means to streamline student course taking and eliminate unnecessary credits. By placing students into broad fields of study-called meta-majors-and encouraging persistence within that general field (where coursework narrows toward a specific program over time), community colleges may help students progress toward their desired degree. But how often do students leave that meta-major, and what predicts meta-major switching? We use national data to examine meta-major switching at community colleges. Our findings suggest that almost 40 percent of students switch between meta-majors (eight broad major fields, plus undecided) between their first and third years of college. We describe the varied destinations and predictors across origin meta-majors and consider implications for colleges as they seek to assess ongoing reforms.

Crystal structure of human cyclin K, a positive regulator of cyclin-dependent kinase 9.

Cyclin K and the closely related cyclins T1, T2a, and T2b interact with cyclin-dependent kinase 9 (CDK9) forming multiple nuclear complexes, referred to collectively as positive transcription elongation factor b (P-TEFb). Through phosphorylation of the C-terminal domain of the RNA polymerase II largest subunit, distinct P-TEFb species regulate the transcriptional elongation of specific genes that play central roles in human physiology and disease development, including cardiac hypertrophy and human immunodeficiency virus-1 pathogenesis. We have determined the crystal structure of human cyclin K (residues 11-267) at 1.5 A resolution, which represents the first atomic structure of a P-TEFb subunit. The cyclin K fold comprises two typical cyclin boxes with two short helices preceding the N-terminal box. A prominent feature of cyclin K is an additional helix (H4a) in the first cyclin box that obstructs the binding pocket for the cell-cycle inhibitor p27(Kip1). Modeling of CDK9 bound to cyclin K provides insights into the structural determinants underlying the formation and regulation of this complex. A homology model of human cyclin T1 generated using the cyclin K structure as a template reveals that the two proteins have similar structures, as expected from their high level of sequence identity. Nevertheless, their CDK9-interacting surfaces display significant structural differences, which could potentially be exploited for the design of cyclin-targeted inhibitors of the CDK9-cyclin K and CDK9-cyclin T1 complexes.

Zinc finger proteins: getting a grip on RNA.

C2H2 (Cys-Cys-His-His motif) zinc finger proteins are members of a large superfamily of nucleic-acid-binding proteins in eukaryotes. On the basis of NMR and X-ray structures, we know that DNA sequence recognition involves a short alpha helix bound to the major groove. Exactly how some zinc finger proteins bind to double-stranded RNA has been a complete mystery for over two decades. This has been resolved by the long-awaited crystal structure of part of the TFIIIA-5S RNA complex. A comparison can be made with identical fingers in a TFIIIA-DNA structure. Additionally, the NMR structure of TIS11d bound to an AU-rich element reveals the molecular details of the interaction between CCCH fingers and single-stranded RNA. Together, these results contrast the different ways that zinc finger proteins bind with high specificity to their RNA targets.

Treatment Outcomes of In-Office KTP Ablation of Vocal Fold Granulomas.

OBJECTIVE: To determine the effectiveness of in-office potassium-titanyl-phosphate (KTP) treatment of vocal fold granulomas and identify any predictors of complete lesion resolution. METHODS: A retrospective review of patients who underwent in-office KTP ablation of vocal fold granulomas between 2007 and 2016 was performed. Medical records were reviewed for use of acid suppression medication, prior surgical treatment, voice therapy, laser settings, number of treatments, follow-up time, and Voice Handicap Index-10 (VHI-10) scores. RESULTS: Twenty-six patients underwent a total of 43 laser treatments. Eighty percent of patients were previously on acid suppression medication, and 42.3% had failed previous endoscopic treatments. Patients underwent a mean number of 1.65 ± 1.16 in-office treatments with decrease in size in 96.2% of cases. The VHI-10 was not significantly affected. Complete resolution occurred in 73.1% of cases with follow-up time ranging from 1 to 86 months (median = 9.5 months). No recurrences occurred in patients with complete resolution. Other than undergoing a single KTP treatment, no variable was found to be predictive of complete lesion resolution. Granuloma etiology was not predictive of lesion resolution but did correlate with symptom improvement. CONCLUSION: In-office pulsed KTP laser is an effective treatment option for vocal fold granulomas as the lesion resolves in the majority of cases.

Self-assembly of aluminium-salen coupled nanostructures from encoded modules with cleavable disulfide DNA-linkers.

DNA-directed coupling of organic modules by formation of stable aluminium-salen complexes, makes possible the subsequent reductive cleavage of disulfide linkers and release of the two oligonucleotide chains attached to each building-block.

Why can't my child see 3D television?

A child encountering difficulty in watching three-dimensional (3D) stereoscopic displays could have an underlying ocular disorder. It is therefore valuable to understand the differential diagnoses and so conduct an appropriate clinical assessment to address concerns about poor 3D vision.

Misoprostol vaginal insert and time to vaginal delivery: a randomized controlled trial.

OBJECTIVE: To compare the efficacy and safety of a 200-microgram misoprostol vaginal insert with a 10-mg dinoprostone vaginal insert for reducing the time to vaginal delivery. METHODS: In a phase III, double-blind, multicenter study, women being induced with a modified Bishop score of 4 or less were randomly assigned to receive either a 200-microgram misoprostol vaginal insert or a 10-mg dinoprostone vaginal insert. Coprimary end points were time to vaginal delivery and rate of cesarean delivery. Secondary end points included time to any delivery mode, time to onset of active labor, and oxytocin use. RESULTS: A total of 1,358 women were randomized to receive the 200-microgram misoprostol vaginal insert (n=678) or dinoprostone vaginal insert (n=680). Women receiving the misoprostol vaginal insert had a significantly shorter median time to vaginal delivery compared with patients receiving the dinoprostone vaginal insert (21.5 hours compared with 32.8 hours, P<.001). Cesarean delivery occurred in 26.0% and 27.1% of women receiving the misoprostol vaginal insert and dinoprostone vaginal insert, respectively. A significant reduction in time to any delivery (18.3 hours compared with 27.3 hours), time to onset of active labor (12.1 hours compared with 18.6 hours), and proportion of women requiring predelivery oxytocin (48.1% compared with 74.1%) was observed with the misoprostol vaginal insert compared with dinoprostone vaginal insert (P<.001 for each). Uterine tachysystole requiring intervention occurred in 13.3% and 4.0% of participants receiving the misoprostol vaginal insert and dinoprostone vaginal insert, respectively (P<.001). CONCLUSION: Use of a 200-microgram misoprostol vaginal inset significantly reduced times to vaginal delivery and active labor with reduced need for oxytocin compared with the dinoprostone vaginal insert. Cesarean delivery rates were similar with both treatments. Tachysystole was more common in women receiving the 200-microgram misoprostol vaginal insert. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01127581. LEVEL OF EVIDENCE: I.

A sequence-based survey of the complex structural organization of tumor genomes.

BACKGROUND: The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using end sequencing profiling, which relies on paired-end sequencing of cloned tumor genomes. RESULTS: In the present study brain, breast, ovary, and prostate tumors, along with three breast cancer cell lines, were surveyed using end sequencing profiling, yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization confirmed translocations and complex tumor genome structures that include co-amplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms revealed candidate somatic mutations and an elevated rate of novel single nucleotide polymorphisms in an ovarian tumor. CONCLUSION: These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than was previously appreciated and that genomic fusions, including fusion transcripts and proteins, may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.

A modular approach to DNA-programmed self-assembly of macromolecular nanostructures.

DNA-programmed organic reactions are new and powerful tools for assembling chemical compounds into predetermined complex structures and a brief review of their use is given. This approach is particular efficient for the selection and covalent coupling of multiple components. DNA-templated synthesis is used for polymerization of PNA tetramers and for copying of the connectivity information in DNA. Direct DNA-programmed multicomponent coupling of custom designed organic modules is described. The macromolecular structures obtained are highly conjugated potentially conducting nanoscaffolds. Some future developments in this area are discussed.

Structural basis for cell cycle checkpoint control by the BRCA1-CtIP complex.

The breast and ovarian tumor suppressor BRCA1 has important functions in cell cycle checkpoint control and DNA repair. Two tandem BRCA1 C-terminal (BRCT) domains are essential for the tumor suppression activity of BRCA1 and interact in a phosphorylation-dependent manner with proteins involved in DNA damage-induced checkpoint control, including the DNA helicase BACH1 and the CtBP-interacting protein (CtIP). The crystal structure of the BRCA1 BRCT repeats bound to the PTRVSpSPVFGAT phosphopeptide corresponding to residues 322-333 of human CtIP was determined at 2.5 A resolution. The peptide binds to a cleft formed by the interface of the two BRCTs in a two-pronged manner, with phospho-Ser327 and Phe330 anchoring the peptide through extensive contacts with BRCA1 residues. Several hydrogen bonds and salt bridges that stabilize the BRCA1-BACH1 complex are missing in the BRCA1-CtIP interaction, offering a structural basis for the approximately 5-fold lower affinity of BRCA1 for CtIP compared to that of BACH1, as determined by isothermal titration calorimetry. Importantly, the side chain of Arg1775 in the cancer-associated BRCA1 mutation M1775R sterically clashes with the phenyl ring of CtIP Phe330, disrupting the BRCA1-CtIP interaction. These results provide new insights into the molecular mechanisms underlying the dynamic selection of target proteins involved in DNA repair and cell cycle control by BRCA1 and reveal how certain cancer-associated mutations affect these interactions.

Modular DNA-programmed assembly of linear and branched conjugated nanostructures.

A new strategy for self-assembly and covalent coupling of encoded molecular modules into nanostructures with predetermined connectivity has been developed. The method uses DNA-functionalized oligo(phenylene ethynylene)-derived organic modules for controlling the assembly and covalent coupling of multiple modules. Rigid linear modules (LM) and tripoidal modules (TM) were functionalized with short oligonucleotides at each terminus. They can hybridize and thereby link up modules containing complementary sequences. Each terminus of the oligo(phenylene ethynylene) modules also consists of a salicylaldehyde moiety, which can form metal-salen complexes with other modules. The salicylaldehyde groups of two modules are brought in proximity when their adjoining DNA sequences are complementary, and they selectively form a manganese-salen complex in the presence of ethylenediamine and manganese acetate. The resulting structures consist of a matrix of linear and branched oligo(phenylene ethynylene)s which are linked by conjugated and rigid manganese-salen complexes. These nanostructures are potential conductors for applications in molecular electronics.