bluuebunny/crossref_metadata_2025 huggingface dataset:
Reciprocal Regulation of MicroRNA-1 and Insulin-Like Growth Factor-1 Signal Transduction Cascade in Cardiac and Skeletal Muscle in Physiological and Pathological Conditions
Authors: Elia Leonardo , Contu Riccardo , Quintavalle Manuela , Varrone Francesca , Chimenti Cristina , Russo Matteo Antonio , Cimino Vincenzo , De Marinis Laura , Frustaci Andrea , Catalucci Daniele , Condorelli Gianluigi
Published: November 2009

Background—

MicroRNAs (miRNAs/miRs) are small conserved RNA molecules of 22 nucleotides that negatively modulate gene expression primarily through base paring to the 3′ untranslated region of target messenger RNAs. The muscle-specific miR-1 has been implicated in cardiac hypertrophy, heart development, cardiac stem cell differentiation, and arrhythmias through targeting of regulatory proteins. In this study, we investigated the molecular mechanisms through which miR-1 intervenes in regulation of muscle cell growth and differentiation.

Methods and Results—

On the basis of bioinformatics tools, biochemical assays, and in vivo models, we demonstrate that (1) insulin-like growth factor-1 (IGF-1) and IGF-1 receptor are targets of miR-1; (2) miR-1 and IGF-1 protein levels are correlated inversely in models of cardiac hypertrophy and failure as well as in the C2C12 skeletal muscle cell model of differentiation; (3) the activation state of the IGF-1 signal transduction cascade reciprocally regulates miR-1 expression through the Foxo3a transcription factor; and (4) miR-1 expression correlates inversely with cardiac mass and thickness in myocardial biopsies of acromegalic patients, in which IGF-1 is overproduced after aberrant synthesis of growth hormone.

Conclusions—

Our results reveal a critical role of miR-1 in mediating the effects of the IGF-1 pathway and demonstrate a feedback loop between miR-1 expression and the IGF-1 signal transduction cascade.
Within-Patient Reproducibility of the Aldosterone:Renin Ratio in Primary Aldosteronism
Authors: Rossi Gian Paolo , Seccia Teresa Maria , Palumbo Gaetana , Belfiore Anna , Bernini Giampaolo , Caridi Graziella , Desideri Giovambattista , Fabris Bruno , Ferri Claudio , Giacchetti Gilberta , Letizia Claudio , Maccario Mauro , Mallamaci Francesca , Mannelli Massimo , Patalano Anna , Rizzoni Damiano , Rossi Ermanno , Pessina Achille Cesare , Mantero Franco
Published: November 2009

The plasma aldosterone concentration:renin ratio (ARR) is widely used for the screening of primary aldosteronism, but its reproducibility is unknown. We, therefore, investigated the within-patient reproducibility of the ARR in a prospective multicenter study of consecutive hypertensive patients referred to specialized centers for hypertension in Italy. After the patients were carefully prepared from the pharmacological standpoint, the ARR was determined at baseline in 1136 patients and repeated after, on average, 4 weeks in the patients who had initially an ARR ≥40 and in 1 of every 4 of those with an ARR <40. The reproducibility of the ARR was assessed with Passing and Bablok and Deming regression, coefficient of reproducibility, and Bland-Altman and Mountain plots. Within-patient ARR comparison was available in 268 patients, of whom 49 had an aldosterone-producing adenoma, on the basis of the “4-corner criteria.” The ARR showed a highly significant within-patient correlation (
r
=0.69;
P
<0.0001) and reproducibility. Bland-Altman plot showed no proportional, magnitude-related, or absolute systematic error between the ARR; moreover, only 7% of the values, for example, slightly more than what could be expected by chance, fell out of the 95% CI for the between-test difference. The accuracy of each ARR for pinpointing aldosterone-producing adenoma patients was ≈80%. Thus, although it was performed under different conditions in a multicenter study, the ARR showed a good within-patient reproducibility. Hence, contrary to previously claimed poor reproducibility of the ARR, these data support its use for the screening of primary aldosteronism.
The Roles of Equatorial Trapped Waves and Internal Inertia–Gravity Waves in Driving the Quasi-Biennial Oscillation. Part I: Zonal Mean Wave Forcing
Authors: Kawatani Yoshio , Watanabe Shingo , Sato Kaoru , Dunkerton Timothy J. , Miyahara Saburo , Takahashi Masaaki
Published: November 2009

The roles of equatorial trapped waves (EQWs) and internal inertia–gravity waves in driving the quasi-biennial oscillation (QBO) are investigated using a high-resolution atmospheric general circulation model with T213L256 resolution (60-km horizontal and 300-m vertical resolution) integrated for three years. The model, which does not use a gravity wave drag parameterization, simulates a QBO. Although the simulated QBO has a shorter period than that of the real atmosphere, its amplitudes and structure in the lower stratosphere are fairly realistic. The zonal wavenumber/frequency spectra of simulated outgoing longwave radiation represent realistic signals of convectively coupled EQWs. Clear signals of EQWs are also seen in the stratospheric wind components. In the eastward wind shear of the QBO, eastward EQWs including Kelvin waves contribute up to ∼25%–50% to the driving of the QBO. The peaks of eastward wave forcing associated with EQWs and internal inertia–gravity waves occur at nearly the same time at the same altitude. On the other hand, westward EQWs contribute up to ∼10% to driving the QBO during the weak westward wind phase but make almost zero contribution during the relatively strong westward wind phase. Extratropical Rossby waves propagating into the equatorial region contribute ∼10%–25%, whereas internal inertia–gravity waves with zonal wavelength ≲1000 km are the main contributors to the westward wind shear phase of the simulated QBO.
The Roles of Equatorial Trapped Waves and Internal Inertia–Gravity Waves in Driving the Quasi-Biennial Oscillation. Part II: Three-Dimensional Distribution of Wave Forcing
Authors: Kawatani Yoshio , Watanabe Shingo , Sato Kaoru , Dunkerton Timothy J. , Miyahara Saburo , Takahashi Masaaki
Published: November 2009

Three-dimensional wave forcing of simulated quasi-biennial oscillation (QBO) is investigated using a high-resolution atmospheric general circulation model with T213L256 resolution (60-km horizontal and 300-m vertical resolution). In both the eastward and westward wind shear phases of the QBO, nearly all Eliassen–Palm flux (EP flux) divergence due to internal inertia–gravity waves (defined as fluctuations with zonal wavenumber ≥12) results from the divergence of the vertical component of the flux. On the other hand, EP flux divergence due to equatorial trapped waves (EQWs) results from both the meridional and vertical components of the flux in regions of strong vertical wind shear. Longitudinal dependence of wave forcing is also investigated by three-dimensional wave activity flux applicable to gravity waves. Near the top of the Walker circulation, strong eastward (westward) wave forcing occurs in the Eastern (Western) Hemisphere due to internal inertia–gravity waves with small horizontal phase speed. In the eastward wind shear zone associated with the QBO, the eastward wave forcing due to internal inertia–gravity waves in the Eastern Hemisphere is much larger than that in the Western Hemisphere, whereas in the westward wind shear zone, westward wave forcing does not vary much in the zonal direction. Zonal variation of wave forcing in the stratosphere results from (i) zonal variation of wave sources, (ii) the vertically sheared zonal winds associated with the Walker circulation, and (iii) the phase of the QBO.
Temporal Relations of Column Water Vapor and Tropical Precipitation
Authors: Holloway Christopher E. , Neelin J. David
Published: November 2009

Empirical studies using satellite data and radiosondes have shown that precipitation increases with column water vapor (CWV) in the tropics, and that this increase is much steeper above some critical CWV value. Here, eight years of 1-min-resolution microwave radiometer and optical gauge data at Nauru Island are analyzed to better understand the relationships among CWV, column liquid water (CLW), and precipitation at small time scales. CWV is found to have large autocorrelation times compared with CLW and precipitation. Before precipitation events, CWV increases on both a synoptic-scale time period and a subsequent shorter time period consistent with mesoscale convective activity; the latter period is associated with the highest CWV levels. Probabilities of precipitation increase greatly with CWV. Given initial high CWV, this increased probability of precipitation persists at least 10–12 h. Even in periods of high CWV, however, probabilities of initial precipitation in a 5-min period remain low enough that there tends to be a lag before the start of the next precipitation event. This is consistent with precipitation occurring stochastically within environments containing high CWV, with the latter being established by a combination of synoptic-scale and mesoscale forcing.
A General Theorem on Angular-Momentum Changes due to Potential Vorticity Mixing and on Potential-Energy Changes due to Buoyancy Mixing
Authors: Wood Richard B. , McIntyre Michael E.
Published: November 2009

An initial zonally symmetric quasigeostrophic potential vorticity (PV) distribution qi(y) is subjected to complete or partial mixing within some finite zone |y| < L, where y is latitude. The change in M, the total absolute angular momentum, between the initial and any later time is considered. For standard quasigeostrophic shallow-water beta-channel dynamics it is proved that, for any qi(y) such that dqi/dy > 0 throughout |y| < L, the change in M is always negative. This theorem holds even when “mixing” is understood in the most general possible sense. Arbitrary stirring or advective rearrangement is included, combined to an arbitrary extent with spatially inhomogeneous diffusion. The theorem holds whether or not the PV distribution is zonally symmetric at the later time. The same theorem governs Boussinesq potential-energy changes due to buoyancy mixing in the vertical. For the standard quasigeostrophic beta-channel dynamics to be valid the Rossby deformation length LD ≫ εL where ε is the Rossby number; when LD = ∞ the theorem applies not only to the beta channel but also to a single barotropic layer on the full sphere, as considered in the recent work of Dunkerton and Scott on “PV staircases.” It follows that the M-conserving PV reconfigurations studied by those authors must involve processes describable as PV unmixing, or antidiffusion, in the sense of time-reversed diffusion. Ordinary jet self-sharpening and jet-core acceleration do not, by contrast, require unmixing, as is shown here by detailed analysis. Mixing in the jet flanks suffices. The theorem extends to multiple layers and continuous stratification. A least upper bound and greatest lower bound for the change in M is obtained for cases in which qi is neither monotonic nor zonally symmetric. A corollary is a new nonlinear stability theorem for shear flows.
A Bayesian Algorithm for Reconstructing Climate Anomalies in Space and Time. Part I: Development and Applications to Paleoclimate Reconstruction Problems
Authors: Tingley Martin P. , Huybers Peter
Published: November 2009

Reconstructing the spatial pattern of a climate field through time from a dataset of overlapping instrumental and climate proxy time series is a nontrivial statistical problem. The need to transform the proxy observations into estimates of the climate field, and the fact that the observed time series are not uniformly distributed in space, further complicate the analysis. Current leading approaches to this problem are based on estimating the full covariance matrix between the proxy time series and instrumental time series over a “calibration” interval and then using this covariance matrix in the context of a linear regression to predict the missing instrumental values from the proxy observations for years prior to instrumental coverage.

A fundamentally different approach to this problem is formulated by specifying parametric forms for the spatial covariance and temporal evolution of the climate field, as well as “observation equations” describing the relationship between the data types and the corresponding true values of the climate field. A hierarchical Bayesian model is used to assimilate both proxy and instrumental datasets and to estimate the probability distribution of all model parameters and the climate field through time on a regular spatial grid. The output from this approach includes an estimate of the full covariance structure of the climate field and model parameters as well as diagnostics that estimate the utility of the different proxy time series.

This methodology is demonstrated using an instrumental surface temperature dataset after corrupting a number of the time series to mimic proxy observations. The results are compared to those achieved using the regularized expectation–maximization algorithm, and in these experiments the Bayesian algorithm produces reconstructions with greater skill. The assumptions underlying these two methodologies and the results of applying each to simple surrogate datasets are explored in greater detail in Part II.
Forcing Processes of the Summertime Circumglobal Teleconnection Pattern in a Dry AGCM
Authors: Yasui Soichiro , Watanabe Masahiro
Published: November 2009

To better understand the predictability of the wavelike circumglobal teleconnection (CGT) pattern prevailing during boreal summer, two sets of experiments are performed using a nonlinear dry atmospheric model. Each experiment consists of a 10-member ensemble of 26-yr integrations driven by the diabatic heating derived from reanalysis data: one with the monthly climatological mean heating (CLIM) and the other with the monthly heating for 1979–2004 (HIST). Both do well in reproducing the observed summer mean state, as well as the low-frequency variance distribution. The CGT pattern identified in the monthly meridional wind anomalies at 200 hPa shows zonally oriented wave packets over Eurasia. The simulated CGT has a nearly identical phase structure with the observations and indicates little difference between the CLIM and HIST results. While this indicates that the origin of CGT lies in the internal dry dynamics, the ensemble mean of the CGT in HIST is partly controlled by the slow variation in the heating field, as indicated by the high potential predictability of the simulated CGT pattern. Diagnoses using the linearized model demonstrate that the heating anomaly most responsible for the CGT-like steady response is located over the eastern Mediterranean region, where the heating may be coupled with the CGT pattern. In addition to the heating near the CGT, remote heating and cooling anomalies over North America and equatorial Africa are found to be effective at exciting stationary Rossby waves trapped on the Atlantic and Asian jets. It is thus suggested that the mechanisms generating the heating anomalies over these regions are the key to the predictability of the CGT pattern.
Nonreflecting Internal Wave Beam Propagation in the Deep Ocean
Authors: Grimshaw Roger , Pelinovsky Efim , Talipova Tatiana
Published: November 2009

Using linear internal wave theory for an ocean stratified by both density and current, several background profiles are identified for which internal wave beams can propagate without any internal reflection. These special profiles are favorably compared with available oceanic data.
Comparison of Rainfall Profiles in the West African Monsoon as Depicted by TRMM PR and the LMDZ Climate Model
Authors: Diatta Samo , Hourdin Frédéric , Gaye Amadou Thierno , Viltard Nicolas
Published: November 2009

Vertical rainfall profiles obtained with TRMM-PR 2A25 standard products are compared with rain profiles deduced from the Laboratoire de Météorologie Dynamique second generation global climate model (LMDZ, the Z stands for zoom capability) with two parameterization schemes: Emanuel’s and Tiedke’s. This paper focuses on the low layers of the atmosphere over West Africa during the monsoon [June–September (JJAS)]. The precipitation decrease above 4 km is systematically not represented in rainfall profiles generated by Emanuel’s parameterization scheme. However, Emanuel’s scheme shows a decrease similar to the observation from 4 km down to the surface, especially in the Sahel (proper depth of the layer dominated by reevaporation). As for Tiedtke’s scheme, it best describes the downward increase in the upper levels of the atmosphere, whereas the downward decrease in the lower levels begins too low when compared to the observations.

Tiedtke’s parameterization shows an overestimation of liquid water production over the ocean and over the Guinean region and a slightly too strong reevaporation in the Sahara and Sahel. The zonal distribution of vertical rain profiles is then biased with this model scheme compared to the 2A25-PR product. On the other hand, although Emanuel’s scheme detects too much reevaporation over the Sahara and underestimates liquid water production over the ocean compared to PR observation, it shows a good meridional distribution of these parameters. This is especially true in the Sahel where Emanuel’s scheme gives the best representation of reevaporation.
Observations of the Relationship between 700-mb Temperatures and Severe Weather Reports across the Contiguous United States
Authors: Bunkers Matthew J. , Wetenkamp John R. , Schild Jeffrey J. , Fischer Anthony
Published: November 2009

The relationship between 700-mb temperatures and convective severe storm reports is examined using data from 1993 to 2006 for the contiguous United States. Severe storm reports are used as a rough “proxy” for the occurrence of deep moist convection, and spatial and temporal distributions of 700-mb temperatures associated with these reports are analyzed. Secondarily, the distributions are assessed by individual severe storm report type, and convective inhibition also is evaluated. The motivation for this study is derived from the occasionally used 10°–12°C at 700 mb rule of thumb for estimating the extent and strength of the capping inversion. Whereas there is a semblance of merit for using this rule at times, its utility is shown to be strongly dependent on 1) geographic location, particularly with respect to surface elevation and the frequency of elevated mixed layers, and 2) the time of year. Calculation of convective inhibition, careful examination of the sounding, and assessment of lifting mechanisms likely are more valuable than 700-mb temperatures when forecasting the potential for deep moist convection and severe storms.
Self-Realization Options
Authors: Willig Rasmus
Published: November 2009

On a descriptive level, the article points out that Western populations have experienced an increase in possibilities for self-realization, but also that the rise in options has led to a paradoxical increase in different forms of psychic distortion. On a more normative level, it has become clear that the neo-liberal idea of freedom, which seems to state that a free market will facilitate all forms of self-realization options, is incomplete. Application of the neo-liberal idea of freedom makes it clear in two ways that the recognition—graduation semantics are twisted in such a manner that individuals cannot cognitively make sense of what can and cannot be an object of recognition, and that intersubjective recognition relations are eroding to such an extent that commonly shared pathological development tendencies are in danger of being suppressed by the lacking ability to join in a collective will-formation. It seems that the neo-liberal idea of freedom is creating a cognitive discrepancy between a promise for more and more self-realization options through deregulation and the actual stable possibilities for individual self-realization. What is becoming evident is that no secure self-realization options are offered, but rather that the individual has to have options in order to gain recognition.
Age, Size and Change in Local Voluntary Associations
Authors: Wollebæk Dag
Published: November 2009

To what extent can conventional organizational theories help us understand changes in local voluntary associations? Using unique data from all associations in a Norwegian county, the article explores hypotheses concerning how size and age affect change behaviour. The results show that high organizational age increases the probability of core change, but decreases the occurrence of peripheral change. The average age of the field in which the organization is active is negatively related to both types of change. The findings suggest that old voluntary organizations are more tenacious than for-profit actors; they choose to attempt change rather than disband if becoming obsolete or pressured by the environment. The degrees of freedom are greater in new, non-institutionalized fields than within fields with a long history. Size has a weakly positive effect on both change indicators. Stronger data and theory-building efforts are needed if we are to extend our knowledge of this under-researched, but immensely important, organization type.
Appropriation and the Body: Representation in Contemporary Black Brazilian Art
Authors: Cleveland Kimberly
Published: November 2009

In reflecting on the past and present, some contemporary Black Brazilian artists working in the secular field have identified similarities between themselves and previous generations of Africans in Brazil, based on their shared experiences of racial and sexual discrimination. Artists Eustáquio Neves and Rosana Paulino create works with historical and contemporary references that highlight past and current power imbalances in Brazilian society and seek to correct them. These artists appropriate what have traditionally been White “spaces of control” in their country and confront contemporary race-related social challenges by creating in their work alternative depictions of Africans and African descendents in Brazil. Through their representations, Neves and Paulino infuse their own and other Black bodies with meaning and respect and show that they, too, have been challenged but not broken by the struggles they have faced in their lifetimes.
Passageless Comprehension on the Nelson-Denny Reading Test: Well Above Chance for University Students
Authors: Coleman Chris , Lindstrom Jennifer , Nelson Jason , Lindstrom William , Gregg K. Noël
Published: November 2009

The comprehension section of the Nelson-Denny Reading Test (NDRT) is widely used to assess the reading comprehension skills of adolescents and adults in the United States. In this study, the authors explored the content validity of the NDRT Comprehension Test (Forms G and H) by asking university students (with and without at-risk status for learning disorders) to answer the multiple-choice comprehension questions without reading the passages. Overall accuracy rates were well above chance for both NDRT forms and both groups of students. These results raise serious questions about the validity of the NDRT and its use in the identification of reading disabilities.
The Effects of Accommodations on Adolescents’ Self-Efficacy and Test Performance
Authors: Feldman Elizabeth , Kim Jee-Seon , Elliott Stephen N.
Published: November 2009

This study examined the effects of testing accommodations on eighth-grade students’ performance on large-scale achievement tests and also on their attitudes and reactions to the tests. Findings revealed significant differences in the ways students with and without disabilities experienced testing and how testing accommodations affected students’ attitudes toward and beliefs about the tests. Results suggested that (a) students with disabilities had significantly lower test-related self-efficacy than students without disabilities, (b) self-efficacy was positively correlated with test performance for all students, and (c) accommodations improved the test performance of all students and exerted a differential boost for students with disabilities on test-related self-efficacy and motivation. These findings suggest that testing accommodations may have a positive effect on students’ test performance by improving test-related self-efficacy and motivation, especially for students with learning disabilities. The implications of these findings for future research and practice concerning psychological aspects of testing are discussed.
Moving Beyond Youth Voice
Authors: Serido Joyce , Borden Lynne M. , Perkins Daniel F.
Published: November 2009

This study combines research documenting the benefits of positive relationships between youth and caring adults on a young person’s positive development with studies on youth voice to examine the mechanisms through which participation in youth programs contributes to positive developmental outcomes. Specifically, the study explores whether youth’s perceived quality relationships with adults contribute to strengthening of youth voice and in turn how the two combine to affect youth’s perception of the benefits of program participation. The findings derived from survey data regarding 748 youth who participated in youth—adult partnership programs in 29 states suggest that young people who develop positive relationships with adults perceive they have more voice in the program and in turn perceive more benefits to program participation. Implications for research and practice are presented.
Understanding the Impact of Poverty on Critical Events in Emerging Adulthood
Authors: Berzin Stephanie Cosner , De Marco Allison C.
Published: November 2009

Current trends have allowed some youth a lengthened transition to adulthood, in part because of demographic shifts that delay the time until adolescents assume adult roles. Although these trends are well documented, less research has examined how this impacts vulnerable subgroups. Using a sample of predominantly White youth (ages 18-33) from the National Survey of Families and Households ( N = 1,517), this study traces the timing of critical events in emerging adulthood. Using survival analysis, results suggest poverty impacts youth experiences of home leaving, marriage, and parenthood. Low-income youth are at greater risk of early home leaving but less likely to leave after age 18. They are less likely to marry, though they have a greater risk of parenthood prior to age 25. Taken as whole, these outcomes can set youth up for negative trajectories throughout adulthood and may not allow poor youth the same opportunity for an extended period of emerging adulthood.
Sexual Sensation Seeking, Social Stress, and Coping Styles as Predictors of HIV/STD Risk Behaviors in Adolescents
Authors: Teva Inmaculada , Bermúdez María Paz , Buela-Casal Gualberto
Published: November 2009

The aim of this study was to assess whether coping styles, social stress, and sexual sensation seeking were predictors of HIV/STD risk behaviours in adolescents. A representative sample of 4,456 female and male Spanish high school students aged 13 to 18 years participated. A stratified random sampling procedure was used. Self-report questionnaires on coping styles, social stress, sexual sensation seeking, and sexual behavior were administered to participants at their high schools. Sexual sensation seeking predicted whether sex was with a casual partner and whether drugs were used at the last sexual intercourse in males and females. Nonproductive coping was a risk factor in the use of drugs at the last sexual intercourse in males. Problem-solving coping style was related to a lower likelihood in the use of drugs at the last sexual encounter in females and to a higher likelihood of condom use at last sexual intercourse in males. Social stress increased the likelihood of having used drugs at last sexual intercourse in females. This study highlights the need to incorporate sexual sensation seeking, social stress, and coping styles in HIV/STD prevention programs aimed at adolescents.
Population‐Based Exposure‐Efficacy Modeling of Ustekinumab in Patients With Moderate to Severe Plaque Psoriasis
Authors: Zhou Honghui , Hu Chuanpu , Zhu Yaowei , Lu Ming , Liao Sam , Yeilding Newman , Davis Hugh M.
Published: November 2009

Ustekinumab, a human immunoglobulin G1 kappa (IgG1k) monoclonal antibody that binds with high affinity to human interleukin‐12 and interleukin‐23, has demonstrated efficacy in patients with psoriasis. The objective of this study was to perform exposure‐response modeling to increase the understanding of reduction in disease severity following treatment with ustekinumab in patients with moderate to severe psoriasis who participate in two phase III studies (PHOENIX 1 and PHOENIX 2). Patients were randomly assigned to receive ustekinumab 45 mg or 90 mg (n = 1312; 11 624 Psoriasis Area and Severity Index [PASI] scores) or placebo (n = 665; 3278 PASI scores). Disease severity was assessed using PASI scores. A population mechanism‐based exposure‐response model of ustekinumab using NONMEM was developed using serum ustekinumab concentrations and PASI scores. The pharmacodynamic response effect was the reduction in PASI score. The placebo effect, although minor, was also integrated into the model. None of the covariate factors evaluated (eg, demographics, baseline disease characteristics, comorbidities) significantly contributed to the between‐subject variability in the pharmacodynamic parameters. The developed exposure‐response model can serve as a basis to support future alternative dosing regimens for ustekinumab in patients with moderate to severe plaque psoriasis. A robust exposure‐response relationship has been confirmed for ustekinumab in psoriasis.
Pharmacokinetics and Pharmacodynamics of LCZ696, a Novel Dual‐Acting Angiotensin Receptor—Neprilysin Inhibitor (ARNi)
Authors: Gu Jessie , Noe Adele , Chandra Priya , Al‐Fayoumi Suliman , Ligueros‐Saylan Monica , Sarangapani Ramesh , Maahs Suzanne , Ksander Gary , Rigel Dean F. , Jeng Arco Y. , Lin Tsu‐Han , Zheng Weiyi , Dole William P.
Published: November 2009

Angiotensin receptor blockade and neprilysin (NEP) inhibition together offer potential benefits for the treatment of hypertension and heart failure. LCZ696 is a novel single molecule comprising molecular moieties of valsartan and NEP inhibitor prodrug AHU377 (1:1 ratio). Oral administration of LCZ696 caused dose‐dependent increases in atrial natriuretic peptide immunoreactivity (due to NEP inhibition) in Sprague‐Dawley rats and provided sustained, dose‐dependent blood pressure reductions in hypertensive double‐transgenic rats. In healthy participants, a randomized, double‐blind, placebo‐controlled study (n = 80) of single‐dose (200–1200 mg) and multiple‐dose (50–900 mg once daily for 14 days) oral administration of LCZ696 showed that peak plasma concentrations were reached rapidly for valsartan (1.6–4.9 hours), AHU377 (0.5–1.1 hours), and its active moiety, LBQ657 (1.8–3.5 hours). LCZ696 treatment was associated with increases in plasma cGMP, renin concentration and activity, and angiotensin II, providing evidence for NEP inhibition and angiotensin receptor blockade. In a randomized, open‐label crossover study in healthy participants (n = 56), oral LCZ696 400 mg and valsartan 320 mg were shown to provide similar exposure to valsartan (geometric mean ratio [90% confidence interval]: AUC0‐∞ 0.90 [0.82–0.99]). LCZ696 was safe and well tolerated. These data support further clinical development of LCZ696, a novel, orally bioavailable, dual‐acting angiotensin receptor—NEP inhibitor (ARNi) for hypertension and heart failure.
Barriers to Insulin Injection Therapy
Authors: Rubin Richard R. , Peyrot Mark , Kruger Davida F. , Travis Luther B.
Published: November 2009

Objective

To compare patients’ perceptions of injection-related problems with clinicians’ estimates of those problems. Methods Data were obtained through 2 Internet surveys, one of US adults self-identified as taking insulin to treat diabe- tes and the second of health care professionals who treat people with diabetes who inject insulin, including pri- mary care physicians, endocrinologists, and diabetes educators.

Results

A substantial majority of patients would like to reduce the number of injections they take each day; almost half said that they would be more likely to take their insulin injections regularly if a product were available to ease the pain. A much smaller proportion of patients reported that (1) injections were a serious burden, (2) they were dissatisfied with the way they took insulin, (3) injections had a substantial negative impact on qual- ity of life, (4) they skipped injections they should take, or (5) injection-related problems affected the number of injections they were willing to take. Half of the patients said they mentioned injection-related problems to their provider; a similar number reported that their providers had not given them a solution to problems with injection- related pain and bruising. Although awareness of prod- ucts to ease injection pain was high among providers (especially diabetes educators), this information was not effectively transmitted to patients.

Conclusions

Patients should be encouraged to discuss their injection- related concerns, and providers should regularly ask about injection-related problems. Providers should offer patients information about tools to reduce injection- related worries, preferably by having them available to show and demonstrate
A Community-Based, Culturally Tailored Behavioral Intervention for Korean Americans With Type 2 Diabetes
Authors: Kim Miyong T. , Han Hae-Ra , Song Hee-Jung , Lee Jong-Eun , Kim Jiyun , Ryu Jai P. , Kim Kim B.
Published: November 2009

Purpose

The purpose of this study is to test the efficacy of a culturally tailored comprehensive type 2 diabetes management intervention for Korean American immigrants (KAIs) with type 2 diabetes.

Methods

A randomized controlled pilot trial with 2 parallel arms (intervention vs control) with a delayed intervention design was used. A total of 79 KAIs, recruited from the Baltimore-Washington area, completed baseline, 18-week, and 30-week follow-ups (intervention, n = 40; control, n = 39). All participants had uncontrolled type 2 diabetes (hemoglobin A1C ≥7.5%) at baseline. The authors’ comprehensive, self-help intervention program for type 2 diabetes management (SHIP-DM) consisted of a 6-week structured psychobehavioral education, home glucose monitoring with teletransmission, and bilingual nurse telephone counseling for 24 weeks. The primary outcome of the study was A1C level, and secondary outcomes included an array of psychobehavioral variables.

Results

Using analysis of covariance, the findings support that the proposed intervention was effective in significantly lowering A1C and fasting glucose and also in improving psychosocial outcomes in the sample. Specifically, the amount of reduction in A1C among intervention group participants was 1.19% at 18 weeks and 1.31% at 30 weeks, with 10% and 15.5% of the participants achieving the suggested goal of A1C <7% at 18 and 30 weeks of follow-up, respectively.

Conclusions

The results highlight the clinical efficacy of the SHIP-DM intervention composed of a 6-week education program, self-monitoring, and follow-up counseling, in terms of maintaining the improved intervention effects obtained and in terms of glucose control.
Practical Aspects of Real-Time Continuous Glucose Monitors
Authors: Ives Brett , Sikes Kristin , Urban Andrea , Stephenson Kerry , Tamborlane William V.
Published: November 2009

Real-time continuous glucose monitoring (RT-CGM) provides new dimension to diabetes management. However, there are many challenges to using RT-CGM successfully. This article aims to present how RT-CGM is integrated into diabetes clinical practice at the Yale Children’s Diabetes Program (YCDP). The authors provide factors to consider when choosing one of the commercially available RT-CGM systems and a discussion of key strategies for successful use of RT-CGM for families. Careful training and troubleshooting strategies will ensure the most positive experience possible for a family using RT-CGM.
Advice When Children Come Out: The Cultural “Tool Kits” of Parents
Authors: Martin Karin A. , Hutson David J. , Kazyak Emily , Scherrer Kristin S.
Published: November 2009

The family is one of the main areas of social life where the normalization of gay and lesbian identity is incomplete. Most research analyzes the individual and psychological aspects of how families respond to children’s disclosure of a gay or lesbian identity and ignores the social, cultural, and historical contexts. An examination of the cultural discourses, tools, and strategies that are available to parents is necessary for a full understanding of how families respond to gay and lesbian children. The authors conduct an interpretive content analysis of 29 advice books to assess this cultural field and its institutional resources. They find three broad strategies offered to parents: relying on professionals for overcoming the grief of having a gay or lesbian child, normalizing gay and lesbian identity, and using “good” parenting skills. This article discusses how these strategies demonstrate the unsettled and often contradictory cultural field of gay and lesbian identity in the family and its implications for sexual identities beyond the closet.
Technologies for Expanding the Reach of Evidence-Based Interventions: Preliminary Results for Promoting Social-Emotional Development in Early Childhood
Authors: Baggett Kathleen M. , Davis Betsy , Feil Edward G. , Sheeber Lisa L. , Landry Susan H. , Carta Judith J. , Leve Craig
Published: November 2009

In great demand are efficient mechanisms for delivery of evidence-based interventions for promoting social-emotional development and early positive behavior of all children, and especially for those with or at risk for disabilities. The rise of Internet use has created potentially new avenues for intervention delivery, which, when paired with the many recent advances in computer networking and multimedia technology, is fueling this demand. This article describes the development of an Internet-based, computer-delivered parent-training intervention, Infant Net, with infants at risk for poor social-emotional outcomes. Results of a randomized control trial of the Infant Net intervention with 40 parent-infant dyads showed significant increase, reflecting a medium to large effect size, in infant social engagement and engagement with the environment for infants in the intervention group as compared to the control group. Implications are discussed with regard to future research.
Design and Control of a Bio-inspired Human-friendly Robot
Authors: Shin Dongjun , Sardellitti Irene , Park Yong-Lae , Khatib Oussama , Cutkosky Mark
Published: November 2009

The increasing demand for physical interaction between humans and robots has led to an interest in robots that guarantee safe behavior when human contact occurs. However, attaining established levels of performance while ensuring safety creates formidable challenges in mechanical design, actuation, sensing and control. To promote safety without compromising performance, a human-friendly robotic arm has been developed using the concept of hybrid actuation. The new design employs high-power, low-impedance pneumatic artificial muscles augmented with small electrical actuators, distributed compact pressure regulators with proportional valves, and hollow plastic links. The experimental results show that significant performance improvement can be achieved with hybrid actuation over a system with pneumatic muscles alone. In this paper we evaluate the safety of the new robot arm through experiments and simulation, demonstrating that its inertia/power characteristics surpass those of previous human-friendly robots we have developed.
Patient Profiling in Cartilage Regeneration: Prognostic Factors Determining Success of Treatment for Cartilage Defects
Authors: de Windt Tommy S. , Bekkers Joris E. J. , Creemers Laura B. , Dhert Wouter J. A. , Saris Daniël B. F.
Published: November 2009

Background

Cartilage therapy for focal articular lesions has been implemented for more than a decade, and it is becoming increasingly available. What is still lacking, however, is analysis of patient characteristics to help improve outcome or select patients for specific treatment.

Purpose

To analyze the prognostic value of patient age and defect size, age, and location on clinical outcome 3 years after cartilage therapy.

Study Design

Cohort study; Level of evidence, 3.

Methods

Fifty-five patients (age, 35 ± 9 years) were randomly selected from a prospective database. Each had a traumatic knee injury, each was treated for a focal cartilage lesion, and each was assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS) 3 years after surgery. Patient characteristics (ie, patient age and defect size, age, and location) were tested for valid inclusion in the regression model. Multiple linear regression was used to determine which variables influenced clinical improvement. Binary KOOS scores were generated on the basis of age-matched healthy patients and assessed in a logistic regression analysis.

Results

Normality tests confirmed normal distribution for each variable (P < .05). Defect size did not influence clinical improvement (P > .05). Clinical outcome regarding the treatment of medial defects was better than that of the lateral defects (10.38-25.26 points for the different KOOS subscales; P < .05). The KOOS improvement from baseline was better for patients <30 years compared with patients >30 years (7.31-29.24 points for the different KOOS subscales; P <.05). Patients with defects <24 months were more likely to report the age-matched healthy reference KOOS (odds ratio, 1.8-4.0; P <.05).

Conclusion

This study illustrates the influence of patient age and defect location and age on clinical outcome 3 years after treatment of a focal cartilage lesion in patients with a traumatic knee injury.
Surgical Treatment of Osteochondral Lesions of the Talus by Open-Field Autologuous Chondrocyte Implantation
Authors: Giannini Sandro , Battaglia Milva , Buda Roberto , Cavallo Marco , Ruffilli Alberto , Vannini Francesca
Published: November 2009

Background

Ideal treatment of osteochondral lesions of the talus is still controversial. Although good clinical and histologic results have been reported for the knee, long-term results have not been reported for autologous chondrocyte implantation in the ankle. Furthermore, magnetic resonance imaging T2 mapping is becoming an increasingly used method for noninvasive assessment of repair tissue in the knee, but no experience on the ankle has been reported.

Hypothesis

The 10-year clinical results of autologous chondrocyte implantation in the treatment of osteochondral lesions of the talus has clinical efficacy comparable with the long-term efficacy of autologous chondrocyte implantation in the knee. A secondary hypothesis is that magnetic resonance imaging T2 mapping may provide noninvasive assessment of the repaired tissue quality in the ankle.

Study Design

Case series; Level of evidence, 4.

Methods

Between 1997 and 1999, 10 patients (age 25.8 6 6.4 years) with an osteochondral lesion of the talus were treated with autologous chondrocyte implantation. The mean size of the lesions was 3.1 cm2 (range, 2.2-4.3 cm2). All patients were evaluated clinically (American Orthopaedic Foot and Ankle Society score), radiographically, and by magnetic resonance imaging preoperatively and at established intervals up to a mean follow-up of 119 6 6.5 months. At the final follow-up, magnetic resonance imaging was graded with the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system and T2-mapping evaluation in 6 cases.

Results

Before surgery, the mean American Orthopaedic Foot and Ankle Society score was 37.9 6 17.8 points, while at final follow-up it was 92.7 6 9.9 (P <.0005). Magnetic resonance imaging showed well-modeled restoration of the articular surface. The regenerated cartilage showed a mean T2-mapping value of 46 microseconds (range, 34-50), with no significant difference compared with that of healthy hyaline cartilage.

Conclusion

The results of autologous chondrocyte implantation in the ankle joint are comparable with those in the knee as demonstrated by the significant clinical improvement, hyaline cartilage repair, and the durability of the results. Integration of both T2 mapping and Magnetic Resonance Observation of Cartilage Repair scoring permitted adequate evaluation of the repair site in the ankle.
Osteochondral Integration of Multiply Incised Pure Cartilage Allograft: Repair Method of Focal Chondral Defects in a Porcine Model
Authors: Bardos Tamas , Farkas Boglarka , Mezes Beata , Vancsodi Jozsef , Kvell Krisztian , Czompoly Tamas , Nemeth Peter , Bellyei Arpad , Illes Tamas
Published: November 2009

Background

A focal cartilage lesion has limited capacity to heal, and the repair modalities used at present are still unable to provide a universal solution. Pure cartilage graft implantation appears to be a simple option, but it has not been applied widely as cartilage will not reattach easily to the subchondral bone.

Hypothesis

We used a multiple-incision technique (processed chondrograft) to increase cartilage graft surface. We hypothesized that pure cartilage graft with augmented osteochondral fusion capacity may be used for cartilage repair and we compared this method with other repair techniques.

Study Design

Controlled laboratory study.

Methods

Full-thickness focal cartilage defects were created on the medial femoral condyle of 9-month-old pigs; defects were repaired using various methods including bone marrow stimulation, autologous chondrocyte implantation, and processed chon-drograft. After the repair, at weeks 6 and 24, macroscopic and histologic evaluation was carried out.

Results

Compared with other methods, processed chondrograft was found to besimilarly effective incartilage repair. Defects without repair and defects treated with bone marrow stimulation appeared slightly irregular with fibrocartilage filling. Autologous chondrocyte implantationproducedhyalinelikecartilage, althoughitscellularorganizationwasdistinguishablefromthesurroundingarticularcartilage. Processed chondrograft demonstrated good osteochondral integration, and the resulting tissue appeared to be hyaline cartilage.

Conclusion

The applied cartilage surface processing method allows acceptable osteochondral integration, and the repair tissue appears to have good macroscopic and histologic characteristics.

Clinical Relevance

If further studies confirm its efficacy, this technique could be considered for human application in the future.
Comparing the Safety Culture of Nursing Homes and Hospitals
Authors: Castle Nicholas , Wagner Laura M. , Perera Subashan , Ferguson Jamie C. , Handler Steven M.
Published: November 2009

The purpose of this study was to compare the patient safety culture between nationally representative samples of hospitals and nursing homes.This research is important in expanding our understanding of safety culture, to better understand the differences and similarities between healthcare settings, and to promote shared learning of best practices between settings. Findings from the Nursing Home Survey on Patient Safety Culture (NHSPSC) were compared with findings from the Hospital Survey on Patient Safety Culture (HSOPSC). Of the 26 highly similar items in these questionnaires, 9 of the NHSPSC scores were lower than the HSOPSC scores (indicating poorer perceptions of safety culture), 1 score was identical, and 16 of the NHSPSC scores were higher than the HSOPSC scores (indicating better perceptions of safety culture). Some learning opportunity may present itself for both nursing homes and hospitals to improve safety culture. This may have a significant impact on quality of care and quality of life for residents.