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Purpose : This article introduces the regression discontinuity design (RDD) as a valuable quasi-experimental approach for evaluating social work interventions. Methods : The RDD is outlined, providing guidance on identifying and framing research questions within its structure. Detailed explanations of analytical procedures for estimating intervention effects under both sharp (treatment assignment strictly determined by a cutoff) and fuzzy (treatment assignment is influenced but not strictly determined by a cutoff) RDD conditions are included, along with common supplemental analyses to address potential validity threats. Results : Concrete examples of social work scenarios where RDD can be effectively employed are presented, showcasing innovative approaches that can enhance the design's utility. This paper also includes code for implementing these techniques. Conclusions : By examining the applications and methodologies of RDD, this article equips social work practitioners and researchers with a versatile tool to rigorously assess the impact of interventions and advance evidence-based practice within the field. [ABSTRACT FROM AUTHOR]

The heterochronic genes of the nematode Caenorhabditis elegans control the succession of postembryonic developmental events. The 4 core heterochronic genes lin-14 , lin-28 , hbl-1 , and lin-41 act in a sequence to specify cell fates specific to each of the 4 larval stages. It was previously shown that lin-14 has 2 activities separated in time that promote L1 and L2 developmental events, respectively. Using the auxin-inducible degron system, we find that lin-28 and hbl-1 each have 2 activities that control L2 and L3 events which are also separated in time. Relative to events they control, both lin-28 and hbl-1 appear to act just prior to or concurrently with events of the L2. Relative to each other, lin-28 and hbl-1 appear to act simultaneously. By contrast, the lin-14 activity controlling L2 events precedes those of lin-28 and hbl-1 controlling the same events, suggesting that lin-14 's regulation of lin-28 is responsible for the delay. Likewise, the activities of lin-28 and hbl-1 controlling L3 fates act well in advance of those fates, suggesting a similar regulatory gap. lin-41 acts early in the L3 to affect fates of the L4, although it was not possible to determine whether it too has 2 temporally separated activities. We also uncovered a feedback phenomenon that prevents the reactivation of heterochronic gene activity late in development after it has been downregulated. This study places the heterochronic gene activities into a timeline of postembryonic development relative to one another and to the developmental events whose timing they control. [ABSTRACT FROM AUTHOR]

The heterochronic genes of Caenorhabditis elegans comprise the best-studied pathway controlling the timing of tissue and organ formation in an animal. To begin to understand the evolution of this pathway and the significance of the relationships among its components, we characterized 11 Caenorhabditis briggsae orthologs of C. elegans heterochronic genes. Using CRISPR/Cas9, we made a variety of alleles and found that several mutant phenotypes differ in significant ways from those of C. elegans. Although most mutant orthologs displayed defects in developmental timing, their phenotypes could differ in which stages were affected, the penetrance and expressivity of the phenotypes, or by having additional pleiotropies that were not obviously connected to developmental timing. However, when examining pairwise epistasis and synergistic relationships, we found those paralleled the known relationships between their C. elegans orthologs, suggesting that the arrangements of these genes in functional modules are conserved, but the modules’ relationships to each other and/or to their targets has drifted since the time of the species’ last common ancestor. Furthermore, our investigation has revealed a relationship between this pathway to other aspects of the animal’s growth and development, including gonad development, which is relevant to both species. [ABSTRACT FROM AUTHOR]

We search for merger products among the 25 most massive white dwarfs in the Montreal White Dwarf Database 100 pc sample through follow-up spectroscopy and high-cadence photometry. We find an unusually high fraction, 40 per cent, of magnetic white dwarfs among this population. In addition, we identify four outliers in transverse velocity and detect rapid rotation in five objects. Our results show that |$56^{+9}_{-10}$|  per cent of the |$M\approx 1.3\, {\rm M}_{\odot }$| ultramassive white dwarfs form through mergers. This fraction is significantly higher than expected from the default binary population synthesis calculations using the α prescription (with αλ = 2), and provides further support for efficient orbital shrinkage, such as with low values of the common-envelope efficiency. [ABSTRACT FROM AUTHOR]

To describe an optimized fiber orientation density function (fODF) rectification procedure that removes negative values and absorbs all features below a specified threshold into a constant background. The fODF for a white matter imaging voxel describes the angular density of axons. Because of signal noise and Gibbs ringing, fODFs estimated with diffusion MRI may take on unphysical negative values in some directions and contain spurious peaks. In order to suppress such artifacts, an fODF rectification procedure is proposed that both eliminates all negative values and incorporates all features below a specified threshold, η , into a constant background while at the same time minimizing the mean square deviation from the original, unrectified fODF. Calculating this fODF is straightforward, and the directions and shapes of peaks not absorbed into the background are preserved. The rectification method is illustrated for an analytic fODF model and for experimental diffusion MRI data obtained in healthy human brain, with the original fODFs being obtained from fiber ball imaging. Examples of optimal rectified fODFs are given for three choices of the background threshold referred to as minimal rectification (η = 0), average-level rectification (η ≈ 0.08), and fractional-anisotropy-axonal-based rectification (η ≈ 0.1). As η is increased, artifacts and other small features are more strongly suppressed, but the major fODF peaks are largely unaffected for the range of η values illustrated by these three alternatives. Artifactual features of fODFs estimated with diffusion MRI can be effectively suppressed by applying the proposed optimized rectification procedure. Since it minimizes fODF distortion in the mean square sense, it may be useful in the study of how fODF fine structure is affected by aging and disease. • Method for optimized rectification of fiber orientation density functions is given. • All features below a specified threshold are absorbed into a constant background. • Negative values are eliminated, and spurious peaks are suppressed. • Mean square deviation from the original function is minimized. • The method is easily implemented, and the directions of major peaks are unaltered. [ABSTRACT FROM AUTHOR]

Objective: Superiority experiments supply a critical lens to probe higher education interventions because they can dismantle the collective effect of a program and identify the relative contribution of the core components. However, such lines of inquiry are generally absent in higher education literature. We draw on experimental data to probe the dominant mechanisms of a simple but promising academic probation intervention. Methods: We used a 2 × 2 factorial experiment designed to unpack the effects of an academic probation intervention and identify the dominant mechanism. Within this framework, 500 academic probation students were assigned to one of four treatment conditions or a control condition. Treatment groups were assigned to receive notification of academic probation status by either certified or regular mail (factor A) that contained either a standard or embellished letter (factor B). Results: We found that students who received embellished warning letters significantly improved subsequent academic performance. The impact on performance was 0.35 grade points when notification sent by regular mail and amplified to 0.48 grade points when sent via certified mail. The routine notification communication message did not differ from the treatment as usual method regardless of mail delivery method. Conclusions: These findings suggest the availability of low-cost, scalable interventions are available and can be identified to positively impact at-risk students' academic achievement. [ABSTRACT FROM AUTHOR]

We investigate the evaporation process of a Kerr–de Sitter black hole with the Unruh–Hawking-like vacuum state, which is a realistic vacuum state modelling the evaporation process of a black hole originating from gravitational collapse. We also compute the greybody factors for gravitons, photons, and conformal-coupling massless scalar particles by using the analytic solutions of the Teukolsky equation in the Kerr–de Sitter background. It turns out that the cosmological constant quenches the amplification factor and it approaches to zero towards the critical point where the Nariai and extremal limits merge together. We confirm that even near the critical point, the superradiance of gravitons is more significant than that of photons and scalar particles. Angular momentum is carried out by particles several times faster than the mass energy decreases. This means that a Kerr–de Sitter black hole rapidly spins down to a nearly Schwarzschild–de Sitter black hole before it completely evaporates. We also compute the time evolution of the Bekenstein–Hawking entropy. The total entropy of the Kerr–de Sitter black hole and cosmological horizon increases with time, which is consistent with the generalized second law of thermodynamics. [ABSTRACT FROM AUTHOR]

Background: Hickman-type tunnelled catheters (Hickman), peripherally inserted central catheters (PICCs), and totally implanted ports (PORTs) are used to deliver systemic anticancer treatment (SACT) via a central vein. We aimed to compare complication rates and costs of the three devices to establish acceptability, clinical effectiveness, and cost-effectiveness of the devices for patients receiving SACT.Methods: We did an open-label, multicentre, randomised controlled trial (Cancer and Venous Access [CAVA]) of three central venous access devices: PICCs versus Hickman (non-inferiority; 10% margin); PORTs versus Hickman (superiority; 15% margin); and PORTs versus PICCs (superiority; 15% margin). Adults (aged ≥18 years) receiving SACT (≥12 weeks) for solid or haematological malignancy from 18 oncology units in the UK were included. Four randomisation options were available: Hickman versus PICCs versus PORTs (2:2:1), PICCs versus Hickman (1:1), PORTs versus Hickman (1:1), and PORTs versus PICCs (1:1). Randomisation was done using a minimisation algorithm stratifying by centre, body-mass index, type of cancer, device history, and treatment mode. The primary outcome was complication rate (composite of infection, venous thrombosis, pulmonary embolus, inability to aspirate blood, mechanical failure, and other) assessed until device removal, withdrawal from study, or 1-year follow-up. This study is registered with ISRCTN, ISRCTN44504648.Findings: Between Nov 8, 2013, and Feb 28, 2018, of 2714 individuals screened for eligibility, 1061 were enrolled and randomly assigned, contributing to the relevant comparison or comparisons (PICC vs Hickman n=424, 212 [50%] on PICC and 212 [50%] on Hickman; PORT vs Hickman n=556, 253 [46%] on PORT and 303 [54%] on Hickman; and PORT vs PICC n=346, 147 [42%] on PORT and 199 [58%] on PICC). Similar complication rates were observed for PICCs (110 [52%] of 212) and Hickman (103 [49%] of 212). Although the observed difference was less than 10%, non-inferiority of PICCs was not confirmed (odds ratio [OR] 1·15 [95% CI 0·78-1·71]) potentially due to inadequate power. PORTs were superior to Hickman with a complication rate of 29% (73 of 253) versus 43% (131 of 303; OR 0·54 [95% CI 0·37-0·77]). PORTs were superior to PICCs with a complication rate of 32% (47 of 147) versus 47% (93 of 199; OR 0·52 [0·33-0·83]).Interpretation: For most patients receiving SACT, PORTs are more effective and safer than both Hickman and PICCs. Our findings suggest that most patients receiving SACT for solid tumours should receive a PORT within the UK National Health Service.Funding: UK National Institute for Health Research Health Technology Assessment Programme. [ABSTRACT FROM AUTHOR]

We extend the concept of Hawking-Moss, or up-tunnelling, transitions in the early universe to include black hole seeds. The black hole greatly enhances the decay amplitude, however, order to have physically consistent results, we need to impose a new condition (automatically satisfied for the original Hawking-Moss instanton) that the cosmological horizon area should not increase during tunnelling. We motivate this conjecture physically in two ways. First, we look at the energetics of the process, using the formalism of extended black hole thermodynamics; secondly, we extend the stochastic inflationary formalism to include primordial black holes. Both of these methods give a physical substantiation of our conjecture. [ABSTRACT FROM AUTHOR]

We aimed to compare the findings of three research designs to bracket effect estimates of a strongly worded warning letter delivered by certified mail to students on academic probation. We embedded an experiment within a regression discontinuity design and calculated two achievement estimates, average GPA and percentage of students remaining on probation. Study participants attended a large Midwestern college. Cohen's d experimental effect size was.45. Regression discontinuity design results were validated by our experimental evidence, and outcome measures were generally statistically significant. We provided additional supportive evidence using comparative RD control group design logic. Regression point displacement design results were successfully replicated using a within-study comparison inside the experiment. In the context of probation, a diverse design, replicative approach provided considerable promise for more precise estimation of intervention effectiveness. We found no deleterious impact on reenrollment and concluded that the certified letter represents an inexpensive probation policy. [ABSTRACT FROM AUTHOR]

The inverse Funk transform of high angular resolution diffusion imaging (HARDI) data provides an estimate for the fiber orientation density function (fODF) in white matter (WM). Since the inverse Funk transform is a straightforward linear transformation, this technique, referred to as fiber ball imaging (FBI), offers a practical means of calculating the fODF that avoids the need for a response function or nonlinear numerical fitting. Nevertheless, the accuracy of FBI depends on both the choice of b -value and the number of diffusion-encoding directions used to acquire the HARDI data. To inform the design of optimal scan protocols for its implementation, FBI predictions are investigated here with in vivo data from healthy adult volunteers acquired at 3 T for b -values spanning 1000 to 10,000 s/mm2, for diffusion-encoding directions varying in number from 30 to 256 and for TE ranging from 90 to 120 ms. Our results suggest b -values above 4000 s/mm2 with at least 64 diffusion-encoding directions are adequate to achieve reasonable accuracy with FBI for calculating axon-specific diffusion measures and for performing WM fiber tractography (WMFT). • Optimization of Fiber Ball Imaging (FBI), a diffusion MRI method, is investigated. • It is recommended that b -values of 4000 s/mm2 or higher be used for FBI at 3 T. • As few as 64 encoding directions are adequate to estimate FBI diffusion parameters. • Measured FBI harmonic power is consistent with theory for b -values over 4000 s/mm2. [ABSTRACT FROM AUTHOR]

Community college students often are unaware of the stakes involved in their performance on placement exams, used to sort the students into their first math and English courses. In our randomized experiment of approximately 13,000 newly admitted community college students, we test whether informing students, via a supplemental notification letter, about the implications of placement exam scores influences their placement exam participation, preparation, and performance. We also test whether message framing (loss-framed vs. gain-framed) alters the effect of the information on study outcomes. We find that neither type of message has an effect on placement exam preparation or performance. We find limited evidence to suggest that the loss-framed message may have a small effect on the avoidance of placement exams by increasing the likelihood of students' submitting alternative evidence of academic preparation. Overall, our evidence suggests that students' prior knowledge about the ramifications of placement exams is not enough to improve performance. Colleges should consider alternative means of assessing college readiness, such as measures of high school achievement, and should provide students who still have to take placement exams with detailed information about test content and study materials before testing. [ABSTRACT FROM AUTHOR]

Abstract We study the gravitational collapse of axion dark matter in null coordinates, assuming spherical symmetry. Compared with previous studies, we use a simpler numerical scheme which can run, for relevant parameters, in a few minutes or less on a desktop computer. We use it to accurately determine the domains of parameter space in which the axion field forms a black hole, an axion star or a relativistic Bosenova. [ABSTRACT FROM AUTHOR]

Persistent oxidative stress depletes reduced glutathione (GSH), an intracellular antioxidant and an important determinant of CNS injury after hypoxia ischemia. We used standard, short echo time Stimulated Echo Acquisition Mode (STEAM) to detect GSH by magnetic resonance spectroscopy (MRS) in 24 term neonates with hypoxic-ischemic encephalopathy (HIE), on day of life 5–6, after rewarming from therapeutic hypothermia. MRS demonstrated reliable, consistent GSH of 1·64 ± 0·20 mM in the basal ganglia immediately before intravenous infusion of N-acetylcysteine. N-acetylcysteine resulted in a rapid and significant GSH increase to 1·93 ± 0.23 mM within 12–30 min after completion of infusion (n = 21, p < 0.0001, paired t-test), compared with those who did not receive N-acetylcysteine (n = 3, GSH = 1.66 ± 0.06 mM and 1.64 ± 0.09 mM). In one perinatal stroke patient, GSH in the diffusion-restricted stroke area was 1.0 mM, indicating significant compromise of intracellular redox potential, which also improved after N-acetylcysteine. For comparison, GSH in healthy term neonates has been reported at 2.5 ± 0.9 mM in the thalamus. This is the first report to show persistent oxidative stress reflected in GSH during the subacute phase in neonates with HIE and rapid response to N-acetylcysteine, using a short echo MRS sequence that is available on all clinical scanners without spectral editing. [ABSTRACT FROM AUTHOR]

We report a new method for the synthesis of novel N-aryl proline analogues. By reacting an aryne precursor with N-(2-malonyl) tetrahydropyridines in the presence of tetrabutylammonium fluoride (TBAF), a tandem aryne-capture/anion isomerisation/[2,3]-sigmatropic rearrangement is induced, leading to good yields of 3-substituted N-aryl-2-acylpyrrolidines. These products are known subunits of biological probes, sensors and drug-like fragments, and are not easily accessed directly by other methods. The reaction is also notable as the first [2,3]-rearrangement of cyclic ammonium ylides at room temperature. [ABSTRACT FROM AUTHOR]

Renal blood flow autoregulation was investigated in anesthetized C57Bl6 mice using time- and frequency-domain analyses. Autoregulation was reestablished by 15 s in two stages after a 25-mmHg step increase in renal perfusion pressure (RPP). The renal vascular resistance (RVR) response did not include a contribution from the macula densa tubuloglomerular feedback mechanism. Inhibition of nitric oxide (NO) synthase [NG-nitro-L-arginine methyl ester (L-NAME)] reduced the time for complete autoregulation to 2 s and induced 0.25-Hz oscillations in RVR. Quenching of superoxide (SOD mimetic tempol) during L-NAME normalized the speed and strength of stage 1 of the RVR increase and abolished oscillations. The slope of stage 2 was unaffected by L-NAME or tempol. These effects of L-NAME and tempol were evaluated in the frequency domain during random fluctuations in RPP. NO synthase inhibition amplified the resonance peak in admittance gain at 0.25 Hz and markedly increased the gain slope at the upper myogenic frequency range (0.06-0.25 Hz, identified as stage 1), with reversal by tempol. The slope of admittance gain in the lower half of the myogenic frequency range (equated with stage 2) was not affected by L-NAME or tempol. Our data show that the myogenic mechanism alone can achieve complete renal blood flow autoregulation in the mouse kidney following a step increase in RPP. They suggest also that the principal inhibitory action of NO is quenching of superoxide, which otherwise potentiates dynamic components of the myogenic constriction in vivo. This primarily involves the first stage of a two-stage myogenic response. [ABSTRACT FROM AUTHOR]

The peptide uroguanylin (Ugn) is expressed at significant levels only in intestine and kidney, and is stored in both tissues primarily (perhaps exclusively) as intact prouroguanylin (proUgn). Intravascular infusion of either Ugn or proUgn evokes well-characterized natriuretic responses in rodents. Furthermore, Ugn knockout mice display hypertension and salt handling deficits, indicating that the Na+ excretory mechanisms triggered when the peptides are infused into anesthetized animals are likely to operate under normal physiological conditions, and contribute to electrolyte homeostasis in conscious animals. Here, we provide strong corroborative evidence for this hypothesis, by demonstrating that UUgnV (the rate of urinary Ugn excretion) approximately doubled in conscious, unrestrained rats consuming a high-salt diet, and decreased by ~15% after salt restriction. These changes in UUgnV were not associated with altered plasma proUgn levels (shown here to be an accurate index of intestinal proUgn secretion). Furthermore, enteric Ugn mRNA levels were unaffected by salt intake, whereas renal Ugn mRNA levels increased sharply during periods of increased dietary salt consumption. Together, these data suggest that diet-evoked Ugn signals originate within the kidney, rather than the intestine, thus strengthening a growing body of evidence against a widely cited hypothesis that Ugn serves as the mediator of an entero-renal natriuretic signaling axis, while underscoring a likely intrarenal natriuretic role for the peptide. The data further suggest that intrarenal Ugn signaling is preferentially engaged when salt intake is elevated, and plays only a minor role when salt intake is restricted. [ABSTRACT FROM AUTHOR]

The discovery of the Standard Model Higgs boson opens up a range of speculative cosmological scenarios, from the formation of structure in the early universe immediately after the big bang, to relics from the electroweak phase transition one nanosecond after the big bang, on to the end of the present-day universe through vacuum decay. Higgs physics is wide ranging, and gives an impetus to go beyond the Standard Models of particle physics and cosmology to explore the physics of ultra-high energies and quantum gravity. [ABSTRACT FROM PUBLISHER]

Background: Academic probation is a nearly universal but underresearched policy practiced at most postsecondary institutions. Objectives: To evaluate the impact of probation warning letters on students’ academic performance. Research design: Employing the inferentially strong regression discontinuity design, we evaluated the impact of two versions of warning letters (U.S. mail and email), noting their impact on next semester grades. Subjects: Probation and nonprobation students at a large, Midwestern college enrolled during two, successive fall–winter semester pairs (n > 17,000, for each pair). Measures: Fall and winter grade point averages (GPAs) were identified for each individual student in the study sample. Results: Using both parametric and nonparametric analyses, we found that neither delivery method, paper or electronic, had a consistent, significant impact on subsequent GPA or odds of a GPA ≥ 2.0 during the next semester. Four of the eight measures of effect for GPA were small and positive (0.02–0.15; one significant positive outcome), and four were negative (−0.02 to −0.08; one significant negative result). A separate set of analyses that excluded students who took a single course led to further inconsistency in results. Supplementary analyses that excluded students scoring far from the cut-point yielded results consistent with a no-difference conclusion. Our findings also indicated that, after being placed on probation, only a small percentage of students were able to avoid movement to the next stage of academic sanction. Conclusions: Warning letters notifying students of probation status, lacking a staff-focused intervention, had little impact on academic performance. [ABSTRACT FROM AUTHOR]

Social rhythms, also known as daily routines (e.g. exercise, of school or work, recreation, social activities), have been identified as potential time cues to help to regulate the biological clock. Past research has shown links between regularity and healthy sleep. This study examined the regularity and frequency of daytime activities in a clinical insomnia population and a good sleeper comparison group. Participants ( N = 69) prospectively monitored their sleep and daily activities for a 2-week period. Although participants with insomnia and good sleepers had similar levels of activity, relative to good sleepers, those with insomnia were less regular in their activities. Findings from this study add to the growing number of studies that highlight the relative importance of the regularity of daytime activities on sleep. Accordingly, future research should test treatment components that focus on regulating daytime activities, which would likely improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Fatigue is a concern for both people with insomnia and with depression, yet it remains poorly understood. Participants (N= 62) included those meetingDiagnostic and Statistical Manual of Mental Disorders(4th ed., text revision) criteria for insomnia and major depressive disorder (MDD). Multiple regression examined sleep, mood, activity, and cognitive factors as predictors of mental and physical fatigue. Only the cognitive factors (i.e., unhelpful beliefs about sleep and symptom-focused rumination) were predictive of both physical and mental fatigue. Beliefs about not being able to function and needing to avoid activities after a poor night of sleep were related to both types of fatigue. Targeting these beliefs via cognitive therapy and encouraging patients to test maladaptive beliefs about sleep may enhance fatigue response in those with MDD and insomnia. [ABSTRACT FROM AUTHOR]

This study investigates how the impact of developmental education is moderated by classroom composition. Drawing on a regression discontinuity design, we used data from 3,429 community college students, nested within 223 classrooms, to explore the extent to which classroom and instructor characteristics moderated the effect of developmental English students’ performance in a successive, college-level English course. Our results suggest developmental English students’ college-level course performance benefited from developmental education but was modified by classroom and instructor characteristics. On average, the impact of participating in the developmental English program was greater when developmental students were enrolled in classrooms that contained a higher proportion of developmental students. Achievement for developmental students was also enhanced when developmental students enrolled in classrooms taught by full-time instructors. Findings suggest that after underprepared students completed developmental English, classroom composition in the first, college-level English course had significant influence on developmental students’ performance. [ABSTRACT FROM AUTHOR]

Renal blood flow (RBF) responses to arginine vasopressin (AVP) were tested in anesthetized wild-type (WT) and CD38-/- mice that lack the major calcium-mobilizing second messenger cyclic ADP ribose. AVP (3-25 ng) injected intravenously produced dose-dependent decreases in RBF, reaching a maximum of 25 ± 2% below basal RBF in WT and 27 ± 2% in CD38-/- mice with 25 ng of AVP. Renal vascular resistance (RVR) increased 75 ± 6% and 78 ± 6% in WT and CD38-/- mice. Inhibition of nitric oxide (NO) synthase with nitro-L-arginine methyl ester (L-NAME) increased the maximum RVR response to AVP to 308 ± 76% in WT and 388 ± 81% in CD38-/- (P < 0.001 for both). Cyclooxygenase inhibition with indomethacin increased the maximum RVR response to 125 ± 15% in WT and 120 ± 14% in CD38-/- mice (P < 0.001, <0.05). Superoxide suppression with tempol inhibited the maximum RVR response to AVP by 38% in both strains (P < 0.005) but was ineffective when administered after L-NAME. The rate of RBF recovery (relaxation) after AVP was slowed by L-NAME and indomethacin (P < 0.001, <0.005) but was unchanged by tempol. All vascular responses to AVP were abolished by an AVP V1a receptor antagonist. A V2 receptor agonist or antagonist had no effect on AVP-induced renal vasoconstriction. Taken together, the results indicate that renal vasoconstriction by AVP in the mouse is strongly buffered by vasodilatory actions of NO and prostanoids. The vasoconstriction depends on V1a receptor activation without involvement of CD38 or concomitant vasodilatation by V2 receptors. The role of superoxide is to enhance the contractile response to AVP, most likely by reducing the availability of NO rather than directly stimulating intracellular contraction signaling pathways. [ABSTRACT FROM AUTHOR]

Loss of functional β-cell mass is a hallmark of type 1 and type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor NK6 homeobox 1 (Nkx6.1) in rat pancreatic islets induces β-cell proliferation and enhances glucose-stimulated insulin secretion, but the pathway by which Nkx6.1 activates β-cell expansion has not been defined. Here, we demonstrate that Nkx6.1 induces expression of the nuclear receptor subfamily 4, group A, members 1 and 3 (Nr4a1 and Nr4a3) orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated β-cell proliferation. Consistent with this finding, global knockout of Nr4a1 results in a decrease in β-cell area in neonatal and young mice. Overexpression of Nkx6.1 and the Nr4a receptors results in increased expression of key cell cycle inducers E2F transcription factor 1 and cyclin E1. Furthermore, Nkx6.1 and Nr4a receptors induce components of the anaphase-promoting complex, including ubiquitin-conjugating enzyme E2C, resulting in degradation of the cell cycle inhibitor p21. These studies identify a unique bipartite pathway for activation of β-cell proliferation, suggesting several unique targets for expansion of functional β-cell mass. [ABSTRACT FROM AUTHOR]

Purpose. To determine whether prepregnancy weight was associated with children's birth weight, early physical growth, and autism diagnosis. Design. Early Childhood Longitudinal Study-Birth Cohort data. Setting. United States. Subjects. Representative sample of U.S. children followed from birth through kindergarten (n = 4800). Also, a subpopulation of the very low birth weight children was examined (n= 500). Measures. Maternal variables included age and prepregnancy body mass index. Changes in children's height, weight, and head circumference between 9 months and 2 years were used as growth metrics. Children's sex, age, birth weight, and reported autism were also considered. Analysis. Logistic and multinomial logistic models assessed the impact of prepregnancy weight on birth weight and children's subsequent rate of physical growth and autism. Results. Children born to underweight or obese mothers had increased odds of very low birth weight. Very low birth weight was related to rapid, height and weight growth and more than twice the likelihood to subsequently be diagnosed with autism. For the subgroup of very low birth weight children, rapid head growth was related to a fivefold increase in the odds of autism. After accounting for the impact birth weight and growth rates, we found prepregnancy weight indirectly impacted autism risk. Conclusion. Being underweight or obese during prepregnancy indirectly increased risk for autism from increased odds of low birth weight and accelerated postnatal growth. [ABSTRACT FROM AUTHOR]

The homeodomain transcription factor Pdx-1 has important roles in pancreatic development and β-cell function and survival. In the present study, we demonstrate that adenovirus-mediated overexpression of Pdx-1 in rat or human islets also stimulates cell replication. Moreover, cooverexpression of Pdx-1 with another homeodomain transcription factor, Nkx6.1, has an additive effect on proliferation compared to either factor alone, implying discrete activating mechanisms. Consistent with this, Nkx6.1 stimulates mainly β-cell proliferation, whereas Pdx-1 stimulates both α- and β-cell proliferation. Furthermore, cyclins D1/D2 are upregulated by Pdx-1 but not by Nkx6.1, and inhibition of cdk4 blocks Pdx-1-stimulated but not Nkx6.1-stimulated islet cell proliferation. Genes regulated by Pdx-1 but not Nkx6.1 were identified by microarray analysis. Two members of the transient receptor potential cation (TRPC) channel family, TRPC3 and TRPC6, are upregulated by Pdx-1 overexpression, and small interfering RNA (siRNA)-mediated knockdown of TRPC3/6 or TRPC6 alone inhibits Pdx-1-induced but not Nkx6.1-induced islet cell proliferation. Pdx-1 also stimulates extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, an effect partially blocked by knockdown of TRPC3/6, and blockade of ERK1/2 activation with a MEK1/2 inhibitor partially impairs Pdx-1-stimulated proliferation. These studies define a pathway by which overexpression of Pdx-1 activates islet cell proliferation that is distinct from and additive to a pathway activated by Nkx6.1. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the effectiveness of a developmental education program for five cohorts of community college students in the U.S. Demographic characteristics, course outcomes and enrollment data were obtained from the college's student information system. Each teacher had control over selection of textbooks.

Moss NG, Vogel PA, Kopple TE, Arendshorst WJ. Thromboxane- induced renal vasoconstriction is mediated by the ADPribosyl cyclase CD38 and superoxide anion. Am J Physiol Renal Physiol 305: F830 -F838, 2013. First published July 24, 2013; doi:10.1152/ajprenal.00048.2013.--The present renal hemodynamic study tested the hypothesis that CD38 and superoxide anion (O2-) participate in the vasoconstriction produced by activation of thromboxane prostanoid (TP) receptors in the mouse kidney. CD38 is the major mammalian ADP-ribosyl cyclase contributing to vasomotor tone through the generation of cADP-ribose, a second messenger that activates ryanodine receptors to release Ca2+from the sarcoplasmic reticulum in vascular smooth muscle cells. We evaluated whether the stable thromboxane mimetic U-46619 causes less pronounced renal vasoconstriction in CD38-deficient mice and the involvement of O2- in U-46619-induced renal vasoconstriction. Our results indicate that U-46619 activation of TP receptors causes renal vasoconstriction in part by activating cADP-ribose signaling in renal resistance arterioles. Based on maximal renal blood flow and renal vascular resistance responses to bolus injections of U-46619, CD38 contributes 30-40% of the TP receptor-induced vasoconstriction. We also found that the antioxidant SOD mimetic tempol attenuated the magnitude of vasoconstriction by U-46619 in both groups of mice, suggesting mediation by O2-. The degree of tempol blockage of U-46619-induced renal vasoconstriction was greater in wild-type mice, attenuating renal vasoconstriction by 40% compared with 30% in CD38-null mice. In other experiments, U-46619 rapidly stimulated O2- production (dihydroethidium fluorescence) in isolated mouse afferent arterioles, an effect abolished by tempol. These observations provide the first in vivo demonstration of CD38 and O2- involvement in the vasoconstrictor effects of TP receptor activation in the kidney and in vitro evidence for TP receptor stimulation of O2- production by the afferent arteriole. [ABSTRACT FROM AUTHOR]

To address insulin insufficiency, diabetes research has long focused on techniques for replacing insulin-producing β cells. Studies in mice have suggested that, under some conditions, α cells possess the capacity to transdifferentiate into β cells, although the mechanisms that drive this conversion are unclear. In this issue, Bramswig et al. analyzed the methylation states of purified human α, β, and acinar cells and found α cells exhibit intrinsic phenotypic plasticity associated with specific histone methylation profiles. In addition to expanding our understanding of this potential source of β cells, this compendium of carefully generated human gene expression and epigenomic data in islet cell subtypes constitutes a truly valuable resource for the field. [ABSTRACT FROM AUTHOR]

To address insulin insufficiency, diabetes research has long focused on techniques for replacing insulin-producing ß cells. Studies in mice have suggested that, under some conditions, a cells possess the capacity to transdifferentiate into ß cells, although the mechanisms that drive this conversion are unclear. In this issue, Bramswig et al. analyzed the meth-ylation states of purified human cx, ß, and acinar cells and found a cells exhibit intrinsic phenotypic plasticity associated with specific histone methylation profiles. In addition to expanding our understanding of this potential source of ß cells, this compendium of carefully generated human gene expression and epigenomic data in islet cell subtypes constitutes a truly valuable resource for the field. [ABSTRACT FROM AUTHOR]

In the context of quantum field theory, an anomaly exists when a theory has a classical symmetry which is not a symmetry of the quantum theory. This short exposition aims at introducing a new point of view, which is that the proper setting for anomaly calculations is the 'in-in', or closed-time path formulation of quantum field theory. There are also some new results for anomalies in the context of boundary value problems, and a new correction to the a5 heat-kernel coefficient. This article is part of a special issue of Journal of Physics A:Mathematical and Theoretical in honour of StuartDowker's 75th birthday devoted to 'Applications of zeta functions and other spectral functions in mathematics and physics'. [ABSTRACT FROM AUTHOR]

Sderactinian corals harbor microorganisms that form dynamic associations with the coral host and exhibit substantial genetic and ecological diversity. Microbial associates may provide defense against pathogens and serve as bioindicators of changing environmental conditions. Here we describe the bacterial assemblages associated with two of the most common and phylogeneti-cally divergent reef-building corals in the Caribbean, Montastraea faveolata and Pontes astreoides. Contrasting life history strategies and disease susceptibilities indicate potential differences in their microbiota and immune function that may in part drive changes in the composition of coral reef communities. The ribotype structure and diversity of coral-associated bacteria within the surface mucosal layer (SML) of healthy corals were assessed using denaturing gradient gel electrophoresis (DGGE) fingerprinting and 454 bar-coded pyrosequencing. Corals were sampled at disparate Caribbean locations representing various levels of anthropogenic impact. We demonstrate here that M. faveolata and P. astreoides harbor distinct, host-specific bacteria but that specificity varies by species and site. P. astreoides generally hosts a bacterial assemblage of low diversity that is largely dominated by one bacterial genus, Endozoicomonas, within the order Oceanospirillales. The bacterial assemblages associated with M. faveolata are significantly more diverse and exhibit higher specificity at the family level than P. astreoides assemblages. Both corals have more bacterial diversity and higher abundances of disease-related bacteria at sites closer to the mainland than at those furthest away. The most diverse bacterial taxa and highest relative abundance of disease-associated bacteria were seen for corals near St. Thomas, U.S. Virgin Islands (USVI) (2.5 km from shore), and the least diverse taxa and lowest relative abundance were seen for corals near our most pristine site in Belize (20 km from shore). We conclude that the two coral species studied harbor distinct bacterial assemblages within the SML, but the degree to which each species maintains specific microbial associations varies both within each site and across large spatial scales. The taxonomic scale (i.e., phylum versus genus) at which scientists examine coral-microbe associations, in addition to host-elicited factors and environmental fluctuations, must be considered carefully in future studies of the coral holobiont. [ABSTRACT FROM AUTHOR]

Abstract: Background: Delay discounting is a measure of future-oriented decision-making and impulsivity. Cigarette smoking is associated with rapid discounting of the value of delayed outcomes. In schizophrenia, however, cigarette smoking improves certain neurocognitive impairments associated with the disorder which may explain the high smoking rates in this population. This study examined the relationship between cigarette smoking and delay discounting in schizophrenia and control participants. Methods: A total of N=130 participants, including those with schizophrenia (n=68) and healthy controls (n=62) were assessed on the Kirby Delay Discounting Task and compared across smoking status (smokers; non-smokers) and smoking history (current, former; never smokers). Results: Smokers exhibited higher discounting rates (i.e., were more impulsive) than non-smokers of the same diagnostic group. Current and former smokers with schizophrenia exhibited similar and significantly higher discounting rates than never smokers, suggesting that in schizophrenia delay discounting is a trait-dependent phenomenon independent of current cigarette smoking. Consistent with previous studies, there was a trend for higher discounting rates in control current smokers compared to control former and never smokers. Conclusions: Smokers with and without schizophrenia have higher rates of delay discounting than non-smokers. However, in schizophrenia, rapid delay discounting appears to be a trait associated with having ever been a smoker (i.e., current and former smoking). [Copyright &y& Elsevier]

Purpose. To track changes in US. children's early weight status (normal, at-risk, or obese) from infancy through preschool. Design. Patterns of change in individual children's weight status are established using three time points from the Early Childhood Longitudinal Study—Birth cohort. Setting. United States. Subjects. Nationally representative sample of US. preschool children surveyed at 9 months (n = 8900), with fellow-up at 2 years (n = 7500) and preschool (n = 7000). Measures. Individual children's weight status was determined from Centers for Disease Control and Prevention growth charts at multiple time periods. Analysis. Layered, categorical data analysis of changes in weight status patterns at three time periods during infancy through preschool. Results. Young children whose early weight status was normal tend to retain a normal weight status and not to develop an unfavorable status (at-risk, obese). In contrast, children who were obese at an early age were more likely to have an at-risk or obese weight category at a later age. Overall, both favorable and unfavorable early weight statuses were highly associated with subsequent status at preschool. Conclusion. Early weight status can provide important information relevant for early entry point prevention and treatment of childhood obesity. [ABSTRACT FROM AUTHOR]

The article presents information on the application of the Strohacker Doctrine, an Arkansas rule of property, in Arkansas Courts and also reflects the amendment needed in the rule. It analyzes the Strohacker Doctrine, which is used to resolve disputes and provide faith to landowners and mineral owners. It explains the need of a rule that would improve efficiency in the leasing of mineral rights, providing benefits to mineral owners and developers of Arkansas.

Abstract: Assessing for clinical levels of anxiety is crucial, as comorbid insomnias far outnumber primary insomnias (PI). Such assessment is complex since those with Anxiety Disorders (AD) and those with PI have overlapping symptoms. Because of this overlap, we need studies that examine the assessment of anxiety in clinical insomnia groups. Participants (N = 207) were classified as having insomnia: 1) without an anxiety disorder (I-ND), or 2) with an anxiety disorder (I-AD). Mean Beck Anxiety Inventory (BAI) item responses were compared using multivariate analysis of variance (MANOVA) and follow-up ANOVAs. As a validity check, a receiver operating characteristic (ROC) curve analysis was conducted to determine if the BAI suggested clinical cutoff was valid for identifying clinical levels of anxiety in this comorbid patient group. The I-ND had lower mean BAI scores than I-AD. There were significant group differences on 12 BAI items. The ROC curve analysis revealed the suggested BAI cutoff (≥16) had 55% sensitivity and 78% specificity. Although anxiety scores were highest in those with insomnia and an anxiety disorder, those with insomnia only had scores in the mild range for anxiety. Nine items did not distinguish between those insomnia sufferers with and without an anxiety disorder. Additionally, published cutoffs for the BAI were not optimal for identifying anxiety disorders in those with insomnia. Such limitations must be considered before using this measure in insomnia patient groups. In addition, the poor specificity and high number of overlapping symptoms between insomnia and anxiety highlight the diagnostic challenges facing clinicians. [Copyright &y& Elsevier]

The peptide uroguanylin (Ugn) regulates enteric and renal electrolyte transport. Previous studies have shown that Ugn and its receptor GC-C (a ligand-activated guanylate cyclase) are abundant in the intestine. Less is known about Ugn and GC-C expression in the kidney. Here, we identify a 9.4-kDa polypeptide in rat kidney extracts that appears, based on its biochemical and immunological properties, to be authentic prouroguanylin (proUgn). This propeptide is relatively plentiful in the kidney (~16% of intestinal levels), whereas its mRNA is marginally present (<1% of intestinal levels), and free Ugn peptide levels are below detection limits (<0.4% of renal proUgn levels). The paucity of preproUgn-encoding mRNA and free Ugn peptide raises the possibility that the kidney might absorb intact proUgn from plasma, where the concentration of propeptide greatly exceeds that of Ugn. However, immunocytochemical analysis reveals that renal proUgn is found exclusively in distal tubular segments, sites previously shown not to accumulate radiolabeled proUgn after intravascular infusions. Thus proUgn appears to be synthesized within the kidney, but the factors that determine its abundance (rates of transcription, translation, processing, and secretion) must be balanced quite differently than in the gut. Surprisingly, we also find negligible expression of GC-C in the rat kidney, a result confirmed both by RT-PCR and by functional assays that measure Ugn-activated cGMP synthesis. Taken together, these data provide evidence for an intrarenal Ugn system that differs from the well-described intestinal system in its regulatory mechanisms and in the receptor targeted by the peptide. [ABSTRACT FROM AUTHOR]

Purpose. To estimate the prevalence of U.S. children's overweight risk and obesity at age 9 months and at age 2 years, to assess weight changes between the two periods, and to examine relationships between weight status (i.e., normal, at risk, or obese) changes and demographic variables. Design. Analyses of children's early weight trajectories and related demographic characteristics from the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B) are presented. Setting. United States. Subjects. The 9-month-old (n = 8900) and 2-year-old (n = 7500) ECLS-B waves were used to generate nationally representative estimates of obese and at-risk children born in 2001. Measures. Measures included child's sex, race/ethnicity, socioeconomic status, community locale, geographic region, and weight status. Analysis. Logistic and multinomial logistic regression models were used to determine the odds of children's demographic characteristics being related to weight persistence, loss, or gain. Results. Approximately one-third of U.S. children were either at risk or obese at 9 months (31.9%) and at 2 years (34.3%). Some children were at greater risk (e.g., Hispanics and low socioeconomic status children), while others had reduced risk (e.g., females and Asian/Pacific Islanders). Additional results from two trajectory models generally corroborated patterns of status change due to weight gain. Conclusions. Between age 9 months and age 2 years, U. S. children consistently moved toward less desirable weight status. Obesity risk was not uniform across demographic subgroups, suggesting that health policy might focus on those children at greatest risk. [ABSTRACT FROM AUTHOR]

The peptide uroguanylin (Ugn) is stored and released as a propeptide (proUgn) by enterochromaffin cells in the intestine, and converted to Ugn and other metabolites in the renal tubules. Both proUgn and Ugn are natriuretic, although the response to proUgn is thought to depend on its conversion to Ugn within nephrons. To assess the efficiency of intrarenal conversion of proUgn to Ugn, we measured urinary Ugn excretion in rats following intravenous infusions of proUgn or Ugn. Infusion of 2 and 10 nmol proUgn/kg body wt increased plasma proUgn concentration from 2.2 ± 0.3 to 5.6 ± 1.3 pmol/ml and to 37 ± 9.6 pmol/ml, respectively. No proUgn was detected in urine before, during, or after proUgn infusions. These two proUgn infusion doses resulted in total Ugn recovery in urine of 162 ± 64 and 206 ± 39 pmol/kg body wt (9 and 2% of the infused amount, respectively). By contrast, the same molar amounts of Ugn resulted in 1,009 ± 477 and 5,352 ± 2,133 pmol/kg body wt of Ugn in urine (recoveries of ∼50%). Unexpectedly, comparisons of natriuretic dose-response curves for each peptide showed proUgn to be about five times more potent than Ugn, despite the relatively modest amount of Ugn generated from infused proUgn. In addition, both peptides were antikaliuretic at low doses, but in this case Ugn showed greater potency than proUgn. These data do not support Ugn as the primary active principle of proUgn for regulation of renal sodium excretion. Instead, an alternative peptide fragment produced from proUgn may be responsible for natriuretic activity in the kidney, whereas Ugn itself may play an antikaliuretic role. [ABSTRACT FROM AUTHOR]

Abstract: Moduli stabilisation is explored in the context of low-energy heterotic M-theory to show that a small value of the cosmological constant can result from a balance between the negative potential energy left over from stabilising the moduli and a positive Casimir energy from the higher dimensions. Supersymmetry breaking is induced by the fermion boundary conditions on the two branes in the theory. An explicit calculation of the Casimir energy for the gravitino reveals that the energy has the correct sign, although the size of the contribution is close to the edge of the parameter range for which the calculation is valid. [Copyright &y& Elsevier]

Tobacco dependence is the leading cause of death in persons with psychiatric and substance use disorders. This has lead to interest in the development of pharmacological and behavioral treatments for tobacco dependence in this subset of smokers. However, there has been little attention paid to the development of tobacco-free environments in psychiatric institutions despite the creation of smoke-free psychiatric hospitals mandated by the Joint Commission for Accreditation of Health Organizations (JCAHO) in 1992. This review article addresses the reasons why tobacco should be excluded from psychiatric and addictions treatment settings, and strategies that can be employed to initiate and maintain tobacco-free psychiatric settings. Finally, questions for further research in this field are delineated. This Tobacco Reconceptualization in Psychiatry is long overdue, given the clear and compelling benefits of tobacco-free environments in psychiatric institutions. (Am J Addict 2010;00:1-19) [ABSTRACT FROM AUTHOR]

Abstract: Background: Patients with schizophrenia have higher rates of smoking (58–88%) than in the general population (∼22%), and are more refractory to smoking cessation. These patients also exhibit numerous neurocognitive deficits, some of which may be ameliorated by cigarette smoking. The neurocognitive benefits derived from nicotine may, in turn, contribute to elevated rates of smoking and smoking persistence in schizophrenia. The present study examined the relationship between neurocognitive function and smoking cessation in schizophrenia. Methods: Treatment-seeking smokers with schizophrenia (N =58) participated in a 10-week placebo-controlled trial of sustained-release (SR) bupropion plus transdermal nicotine patch. Neuropsychological performance was evaluated in a subset of patients (n =31), prior to pharmacological treatment, using a neurocognitive battery. Results: Subjects were compared as a function of endpoint smoking status (Quit versus Not Quit), assessed by end of trial 7-day point prevalence abstinence, confirmed by CO level (<10ppm) on demographic traits, smoking, and clinical outcomes. While there were no significant baseline differences between quitters and non-quitters, non-quitters exhibited significantly greater deficits in performance on Trail Making Test, Part B (p =0.01) and on Digit Span backwards (p =0.04) compared to quitters. No associations were found between quit status and performance on other neuropsychological measures. Conclusions: Our findings extend results of previous studies which suggest deficits in frontal executive function are associated with smoking cessation failure in schizophrenia. This may have implications for the development of tailored smoking cessation treatments in this population. [Copyright &y& Elsevier]

People with mental health and addictive (MHA) disorders smoke at high rates and require tobacco treatment as a part of their comprehensive psychiatric care. Psychiatric care providers often do not address tobacco use among people with mental illness, possibly owing to the belief that their patients will not be able to quit successfully or that even short-term abstinence will adversely influence psychiatric status. Progress in the development of treatments has been slow in part because smokers with current MHA disorders have been excluded from most smoking cessation trials. There are several smoking cessation treatment options, including psychological and pharmacological interventions, that should be offered to people with an MHA disorder who smoke. Building motivation and readiness to quit smoking is a major challenge, and therefore motivational interventions are essential. We review the treatment options for people with tobacco dependence and MHA disorders, offer recommendations on tobacco assessment and tailored treatment strategies, and provide suggestions for future research. Treatment efficacy could be enhanced through promoting smoking reduction as an initial treatment goal, extending duration of treatment, and delivering it within an integrated care model that also aims to reduce the availability of tobacco in MHA treatment settings and in the community. [ABSTRACT FROM AUTHOR]

Abstract: This Letter considers anomaly cancellation for eleven-dimensional supergravity on a manifold with boundary and theories related to heterotic M-theory. The Green–Schwartz mechanism is implemented without introducing distributions. The importance of the supersymmetry anomaly in constructing the low energy action is discussed and it is argued that a recently proposed action for low-energy heterotic M-theory gives a supersymmetric theory to all orders in the gravitational coupling κ. [Copyright &y& Elsevier]

Abstract: This paper considers eleven-dimensional supergravity on a manifold with boundary and the theories related to low energy heterotic M-theory, in which the matter is confined to the boundary. New low energy actions and boundary conditions on supergravity fields are derived. Previous problems with infinite constants in the action are overcome. The new boundary conditions are shown to be consistent with supersymmetry, and their role in the ten-dimensional reduction and gaugino condensation is briefly discussed. [Copyright &y& Elsevier]

Abstract: In brane world scenarios, inflationary vacuum energy may escape into the higher-dimensional bulk, leaving behind a dark radiation effect on the brane. This Letter analyses the damping of an inflaton by massless bulk scalar radiation and the production of dark radiation in a Randall–Sundrum type of model. [Copyright &y& Elsevier]

To evaluate the effect of uterine artery embolisation (UAE) on menstrual blood loss (MBL) and uterine volume in women with symptomatic uterine fibroids.Prospective observational study.West of Scotland gynaecology and radiology departments.Fifty women (mean age 43 years) with symptomatic fibroids undergoing UAE between January 1999 and June 2003.Women collected sanitary protection from one menses pre-embolisation and at regular intervals thereafter. This allowed objective measurement of MBL using the alkaline haematin technique. Uterine volume was calculated using magnetic resonance imaging (MRI) before and six months following embolisation. Interventional radiologists performed bilateral UAE. The Wilcoxon's signed rank test was used for statistical analysis of data.Post-embolisation MBL and uterine volume changes.Median pretreatment MBL was 162 mL (mean 234, range 9–1339). The median MBL decreased to 60 mL at 3 months (n= 34, range 0–767,P<0.001), 70 mL at 6–9 months (n= 34, range 0–1283,P<0.001), 37 mL at 12–24 months (n= 25, range 0–265,P<0.001), 18 mL at 24–36 months (n= 17, range 0–205,P<0.001) and 41 mL at 36–48 months (n= 6, range 0–66,P<0.05). The median reduction in uterine volume was 40% (n= 46, 95% CI 33.0–49.7,P<0.001).UAE causes a statistically significant reduction in objectively measured MBL. UAE is also associated with a statistically significant reduction in uterine volume at six months. There was no relationship between the changes in uterine volume and MBL. [ABSTRACT FROM AUTHOR]

We discuss the spectrum of scalar density perturbations from warm inflation when the friction coefficient Γ in the inflaton equation is dependent on the inflaton field. The spectral index of scalar fluctuations depends on a new slow-roll parameter constructed from Γ. A numerical integration of the perturbation equations is performed for a model of warm inflation and gives a good fit to the WMAP data for reasonable values of the model''s parameters. [Copyright &y& Elsevier]

A new action for eleven-dimensional supergravity on a manifold with boundary is presented. The action is a possible low energy limit of M-theory. Previous problems with infinite constants in the action are overcome and a new set of boundary conditions relating the behaviour of the supergravity fields to matter fields are obtained. One effect of these boundary conditions is that matter fields generate gravitational torsion. [Copyright &y& Elsevier]

The gene lin-28 was originally identified through a mutant of the nematode Caenorhabditis elegans displaying defects in developmental timing. It is expressed stage-specifically in tissues throughout the animal and is required for cell fates to be expressed at the appropriate stage of larval development. lin-28 encodes a cytoplasmic protein with a unique pairing of RNA-binding motifs. Diverse animals possess Lin-28 homologues and mouse Lin-28 is expressed in embryos, embryonic stem cells and embryonal carcinoma cells, but not in some differentiated cell types. To assess whether mammalian Lin-28 may function as a developmental timing regulator, we examined adult and embryonic tissues of the mouse for its expression. We observed Lin-28 protein in many diverse tissues of the embryo through the period of organogenesis and that it persists in some tissues in the adult. In addition to an overall down-regulation during embryogenesis, in at least two tissues Lin-28 expression shows temporal regulation, as opposed to cell type or tissue-specific regulation: in the developing bronchial epithelium, where it is present in the developing lung and absent in the adult, and in a subset of cells developing along the crypt–villus axis of the intestine. Interestingly, unlike epithelia, cardiac and skeletal muscle continuously express Lin-28, suggesting an ongoing need for its activity there. We also observed that Lin-28 expression is repressed during the retinoic acid-induced differentiation of mouse P19 cells into neuronal cells, suggesting that down-regulation of Lin-28 in some tissues may occur in response to hormonal signals that govern development. [Copyright &y& Elsevier]