bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity of the efficacy of the 23-valent pneumococcal polysaccharide vaccine caused by various underlying conditions of chronic pulmonary disease in older patients: prospective cohort study
Authors: Inoue Satoshi , Watanuki Yuji , Kaneko Tetsuji , Sato Takashi , Miyazawa Naoki , Kaneko Takeshi , Ishigatsubo Yoshiaki , Morita Satoshi , Natsumeda Yutaka , Mizushima Shunsaku 
Published: July 2011

ObjectiveTo determine the ideal conditions for use of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in older outpatients with chronic pulmonary diseases.DesignProspective cohort study.Participants1378 outpatients with chronic pulmonary diseases ≥60 years of age.InterventionParticipants were educated about PPV23, and those who responded affirmatively were vaccinated between August and November 2002. The participants who chose no intervention served as controls. The prevaccine period was defined as August 2001 to August 2002. Participants were followed for 2 years from December 2002 or until death.Main outcome measuresEvents of interest included the first episode of bacterial (including pneumococcal) pulmonary infection (primary endpoint) and death of any cause (secondary endpoint).ResultsFrequent episodes of pulmonary infection during the prevaccine period significantly decreased event-free survival during the 2-year observation period (p<0.001). Chronic respiratory failure was associated with a decreased event-free survival only when the pulmonary infection episode did not occur in the prevaccine period (p<0.001). No significant differences in event-free survival were observed between the vaccinated and unvaccinated group during analysis of the entire cohort. In the Cox proportional hazards regression model, event-free survival decreased significantly when pulmonary infection occurred in the prevaccine period. In the subgroup analysis, the first episode of bacterial pulmonary infection (but not death of any cause) was reduced significantly by PPV23 only in patients with chronic respiratory failure who had no episodes of pulmonary infection during the prevaccine period (p=0.019).ConclusionThe efficacy of PPV23 against pulmonary infection and death of any cause might be unachievable if pulmonary infection occurs during the prevaccine period. PPV23 needs to be given to older patients with chronic pulmonary disease at an earlier time in which infectious complications in the lung have not yet occurred.
Improved communication in post-ICU care by improving writing of ICU discharge letters: a longitudinal before‐after study
Authors: Medlock Stephanie , Eslami Saeid , Askari Marjan , van Lieshout Erik Jan , Dongelmans Dave A , Abu-Hanna Ameen 
Published: July 2011

BackgroundThe discharge letter is the primary means of communication at patient discharge, yet discharge letters are often not completed on time. A multifaceted intervention was performed to improve communication in patient hand-off from the intensive care unit (ICU) to the wards by improving the timeliness of discharge letters.MethodsA management directive was operationalised by a working group of ICU staff in a longitudinal before–after study. The intervention consisted of (a) changing policy to require a letter for use as a transfer note at the time of ICU discharge, (b) changing the assignment of responsibility to an automatic process, (c) leveraging positive peer pressure by making the list of patients in need of letters visible to colleagues and (d) provision of decision support, through automatic copying of important content from the patient record to the letter and email reminders if letters were not written on time. Statistical process control charts were used to monitor the longitudinal effect of the intervention.ResultsThe intervention resulted in a 77.9% absolute improvement in the proportion of patients with a complete transfer note at the time of discharge, and an 85.2% absolute improvement in the number of discharge letters written. Statistical process control shows that the effect was sustained over time.ConclusionsA multifaceted intervention can be highly effective for improving discharge communication from the ICU.
The comparative behaviour of two combat boots under impact
Authors: Newell Nicolas , Masouros Spyros D , Pullen Andy D , Bull Anthony M J 
Published: July 2011

BackgroundImprovised explosive devices have become the characteristic weapon of conflicts in Iraq and Afghanistan. While little can be done to mitigate against the effects of blast in free-field explosions, scaled blast simulations have shown that the combat boot can attenuate the effects on the vehicle occupants of anti-vehicular mine blasts. Although the combat boot offers some protection to the lower limb, its behaviour at the energies seen in anti-vehicular mine blast has not been documented previously.MethodsThe sole of eight same-size combat boots from two brands currently used by UK troops deployed to Iraq and Afghanistan were impacted at energies of up to 518 J, using a spring-assisted drop rig.ResultsThe results showed that the Meindl Desert Fox combat boot consistently experienced a lower peak force at lower impact energies and a longer time-to-peak force at higher impact energies when compared with the Lowa Desert Fox combat boot.DiscussionThis reduction in the peak force and extended rise time, resulting in a lower energy transfer rate, is a potentially positive mitigating effect in terms of the trauma experienced by the lower limb.ConclusionCurrently, combat boots are tested under impact at the energies seen during heel strike in running. Through the identification of significantly different behaviours at high loading, this study has shown that there is rationale in adding the performance of combat boots under impact at energies above those set out in international standards to the list of criteria for the selection of a combat boot.
Mechanisms of Action of a Dual Cdc7/Cdk9 Kinase Inhibitor against Quiescent and Proliferating CLL Cells
Authors: Natoni Alessandro , Murillo Laura S. , Kliszczak Anna E. , Catherwood Mark A. , Montagnoli Alessia , Samali Afshin , O'Dwyer Michael , Santocanale Corrado 
Published: July 2011

Abstract
In chronic lymphocytic leukemia (CLL) the proliferation rate and resistance to drug-induced apoptosis are recognized as important factors in the outcome of treatment. In this study, we assess the activity and the mechanism of action of the prototype cell division cycle kinase 7 (Cdc7) inhibitor, PHA-767491, which inhibits the initiation of DNA replication but also has cyclin-dependent kinase 9 (Cdk9) inhibitory activity. We have studied the effects of this dual Cdc7/Cdk9 inhibitor in both quiescent CLL cells and CLL cells that have been induced to proliferate using a cellular coculture system that mimics the lymph node microenvironment. We find that this compound, originally developed as a DNA replication inhibitor, is particularly active in promoting mitochondrial dependent apoptosis in quiescent CLL cells purified from peripheral blood of patients regardless of recognized risk factors. In this setting, apoptosis is preceded by a decrease in the levels of Mcl-1 protein and transcript possibly due to inhibition of Cdk9. Following stimulation by CD154 and interleukin-4, CLL cells become highly chemoresistant, reenter into the cell cycle, reexpress Cdc7 kinase, a key molecular switch for the initiation of DNA replication, replicate their DNA, and undergo cell division. In this context, treatment with PHA-767491 abolished DNA synthesis by inhibiting Cdc7 but is less effective in triggering cell death, although Mcl-1 protein is no longer detectable. Thus, dual Cdc7/Cdk9 inhibition has the potential to target both the quiescent and actively proliferating CLL populations through two distinct mechanisms and may be a new therapeutic strategy in CLL. Mol Cancer Ther; 10(9); 1624–34. ©2011 AACR.
Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH)
Authors: Arnold Suzanne V. , Chan Paul S. , Jones Philip G. , Decker Carole , Buchanan Donna M. , Krumholz Harlan M. , Ho P. Michael , Spertus John A. ,   for the Cardiovascular Outcomes Research Consortium
Published: July 2011

Background—
Black patients with myocardial infarction (MI) have worse outcomes than white patients, including higher mortality rates, more angina, and worse quality of life. The Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) study was designed to examine whether racial differences in socioeconomic, clinical, genetic, metabolic, biomarker, or treatment characteristics mediate observed disparities in outcomes.

Methods and Results—
Between April 11, 2005, and December 31, 2008, 31 567 patients with MI were prospectively screened; 6152 had an eligible MI, and 4340 (71%) were enrolled from 24 US centers. Consenting patients had detailed chart abstractions of their medical history and processes of inpatient care, supplemented with a detailed baseline interview. Detailed genetic and metabolic data were obtained at hospital discharge in 2979 (69%) and 3013 patients (69%), respectively. In a subset of patients, blood and urine samples were obtained at 1 month (obtained in 27% of survivors) and blood samples at 6 months (obtained in 19% of survivors). Centralized follow-up interviews sought to quantify patients' postdischarge care and outcomes, with a focus on their health status (symptoms, function, and quality of life). At 1, 6, and 12 months, 23%, 27%, and 24%, respectively, were lost to follow-up. Vital status was available for 99% of patients at 12 months.

Conclusions—
TRIUMPH is a novel MI registry with detailed information on patients' sociodemographic, clinical, treatment, health status, metabolic, and genetic characteristics. The wealth of patient data collected in TRIUMPH will provide unique opportunities to examine factors that may mediate racial differences in mortality and health status after MI and the complex interactions between genetic and environmental determinants of post-MI outcomes.
Effect of Dietary Protein Supplementation on Blood Pressure
Authors: He Jiang , Wofford Marion R. , Reynolds Kristi , Chen Jing , Chen Chung-Shiuan , Myers Leann , Minor Deborah L. , Elmer Patricia J. , Jones Daniel W. , Whelton Paul K. 
Published: July 2011

Background—
Observational studies have reported an inverse association between dietary protein intake and blood pressure (BP). We compared the effect of soy protein, milk protein, and carbohydrate supplementation on BP among healthy adults.

Methods and Results—

We conducted a randomized, double-blind crossover trial with 3 intervention phases among 352 adults with prehypertension or stage 1 hypertension in New Orleans, LA, and Jackson, MS, from September 2003 to April 2008. The trial participants were assigned to take 40 g/d soy protein, milk protein, or carbohydrate supplementation each for 8 weeks in a random order. A 3-week washout period was implemented between the interventions. Three BPs were measured at 2 baseline and 2 termination visits during each of 3 intervention phases with a random-zero sphygmomanometer. Compared with carbohydrate controls, soy protein and milk protein supplementations were significantly associated with −2.0 mm Hg (95% confidence interval −3.2 to −0.7 mm Hg,
P
=0.002) and −2.3 mm Hg (−3.7 to −1.0 mm Hg,
P
=0.0007) net changes in systolic BP, respectively. Diastolic BP was also reduced, but this change did not reach statistical significance. There was no significant difference in the BP reductions achieved between soy or milk protein supplementation.

Conclusions—
The results from this randomized, controlled trial indicate that both soy and milk protein intake reduce systolic BP compared with a high-glycemic-index refined carbohydrate among patients with prehypertension and stage 1 hypertension. Furthermore, these findings suggest that partially replacing carbohydrate with soy or milk protein might be an important component of nutrition intervention strategies for the prevention and treatment of hypertension.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00107744.
Profibrinolytic, Antithrombotic, and Antiinflammatory Effects of an Insulin-Sensitizing Strategy in Patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial
Authors: Sobel Burton E. , Hardison Regina M. , Genuth Saul , Brooks Maria M. , McBane Robert D. , Schneider David J. , Pratley Richard E. , Huber Kurt , Wolk Robert , Krishnaswami Ashok , Frye Robert L. ,   for the BARI 2D Investigators
Published: July 2011

Background—
Effects were compared in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial of 2 mechanistically different strategies for treatment of hyperglycemia, insulin-sensitizing and insulin-providing strategies, on biomarker profiles reflecting the balance between fibrinolysis and thrombosis and the intensity of inflammation implicated in diabetic vasculopathy.

Methods and Results—

A total of 2368 patients with type 2 diabetes mellitus and clinically stable, angiographically documented coronary artery disease were randomized to treatment with 1 of the 2 strategies and followed for an average of 5 years. Plasminogen activator inhibitor type 1 antigen and activity, tissue plasminogen activator antigen, fibrinogen, D-dimer, C-reactive protein, insulin, and hemoglobin A
1c
were assayed in blood samples acquired at baseline and at 12 regular intervals throughout the follow-up interval. Higher baseline D-dimer, fibrinogen, and C-reactive protein portended a poor prognosis in patients in both groups. In contrast to the insulin-providing strategy, the insulin-sensitizing strategy led to (1) lower plasma insulin; (2) lower plasminogen activator inhibitor type 1 antigen and activity and lower tissue plasminogen activator antigen (known to track with plasminogen activator inhibitor type 1); and (3) lower C-reactive protein and fibrinogen at all intervals after baseline (
P
<0.001 for each).

Conclusions—
The insulin-sensitizing treatment strategy led to changes in biomarker profiles indicative of decreased insulin resistance, an altered balance between thrombosis and fibrinolysis favoring fibrinolysis, and diminished intensity of the systemic inflammatory state, factors that have been associated with cardiovascular risk.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00006305.
Mutation-Linked Defective Interdomain Interactions Within Ryanodine Receptor Cause Aberrant Ca
2+
Release Leading to Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Suetomi Takeshi , Yano Masafumi , Uchinoumi Hitoshi , Fukuda Masakazu , Hino Akihiro , Ono Makoto , Xu Xiaojuan , Tateishi Hiroki , Okuda Shinichi , Doi Masahiro , Kobayashi Shigeki , Ikeda Yasuhiro , Yamamoto Takeshi , Ikemoto Noriaki , Matsuzaki Masunori 
Published: July 2011

Background—
The molecular mechanism by which catecholaminergic polymorphic ventricular tachycardia is induced by single amino acid mutations within the cardiac ryanodine receptor (RyR2) remains elusive. In the present study, we investigated mutation-induced conformational defects of RyR2 using a knockin mouse model expressing the human catecholaminergic polymorphic ventricular tachycardia–associated RyR2 mutant (S2246L; serine to leucine mutation at the residue 2246).

Methods and Results—

All knockin mice we examined produced ventricular tachycardia after exercise on a treadmill. cAMP-dependent increase in the frequency of Ca
2+
sparks was more pronounced in saponin-permeabilized knockin cardiomyocytes than in wild-type cardiomyocytes. Site-directed fluorescent labeling and quartz microbalance assays of the specific binding of DP2246 (a peptide corresponding to the 2232 to 2266 region: the 2246 domain) showed that DP2246 binds with the K201-binding sequence of RyR2 (1741 to 2270). Introduction of S2246L mutation into the DP2246 increased the affinity of peptide binding. Fluorescence quench assays of interdomain interactions within RyR2 showed that tight interaction of the 2246 domain/K201-binding domain is coupled with domain unzipping of the N-terminal (1 to 600)/central (2000 to 2500) domain pair in an allosteric manner. Dantrolene corrected the mutation-caused domain unzipping of the domain switch and stopped the exercise-induced ventricular tachycardia.

Conclusions—

The catecholaminergic polymorphic ventricular tachycardia–linked mutation of RyR2, S2246L, causes an abnormally tight local subdomain-subdomain interaction within the central domain involving the mutation site, which induces defective interaction between the N-terminal and central domains. This results in an erroneous activation of Ca
2+
channel in a diastolic state reflecting on the increased Ca
2+
spark frequency, which then leads to lethal arrhythmia.
Impact of a Reduced Arctic Sea Ice Cover on Ocean and Atmospheric Properties
Authors: Sedláček Jan , Knutti Reto , Martius Olivia , Beyerle Urs 
Published: July 2011

Abstract
The Arctic sea ice cover declined over the last few decades and reached a record minimum in 2007, with a slight recovery thereafter. Inspired by this the authors investigate the response of atmospheric and oceanic properties to a 1-yr period of reduced sea ice cover. Two ensembles of equilibrium and transient simulations are produced with the Community Climate System Model. A sea ice change is induced through an albedo change of 1 yr. The sea ice area and thickness recover in both ensembles after 3 and 5 yr, respectively. The sea ice anomaly leads to changes in ocean temperature and salinity to a depth of about 200 m in the Arctic Basin. Further, the salinity and temperature changes in the surface layer trigger a “Great Salinity Anomaly” in the North Atlantic that takes roughly 8 yr to travel across the North Atlantic back to high latitudes. In the atmosphere the changes induced by the sea ice anomaly do not last as long as in the ocean. The response in the transient and equilibrium simulations, while similar overall, differs in specific regional and temporal details. The surface air temperature increases over the Arctic Basin and the anomaly extends through the whole atmospheric column, changing the geopotential height fields and thus the storm tracks. The patterns of warming and thus the position of the geopotential height changes vary in the two ensembles. While the equilibrium simulation shifts the storm tracks to the south over the eastern North Atlantic and Europe, the transient simulation shifts the storm tracks south over the western North Atlantic and North America. The authors propose that the overall reduction in sea ice cover is important for producing ocean anomalies; however, for atmospheric anomalies the regional location of the sea ice anomalies is more important.
While observed trends in Arctic sea ice are large and exceed those simulated by comprehensive climate models, there is little evidence based on this particular model that the seasonal loss of sea ice (e.g., as occurred in 2007) would constitute a threshold after which the Arctic would exhibit nonlinear, irreversible, or strongly accelerated sea ice loss. Caution should be exerted when extrapolating short-term trends to future sea ice behavior.
Precipitation Reproducibility over Tropical Oceans and Its Relationship to the Double ITCZ Problem in CMIP3 and MIROC5 Climate Models
Authors: Hirota Nagio , Takayabu Yukari N. , Watanabe Masahiro , Kimoto Masahide 
Published: July 2011

Abstract
Precipitation reproducibility over the tropical oceans in climate models is examined. Models participating in phase 3 of the Coupled Model Intercomparison Project (CMIP3) and the current (fifth) version Model for Interdisciplinary Research on Climate (MIROC5) developed by the Atmosphere and Ocean Research Institute, National Institute for Environmental Studies, and Research Institute for Global Change (AORI/NIES/RIGC) are analyzed. Scores of a pattern similarity between precipitation in the models and that in observations are evaluated. The low score models (LSMs) overestimate (underestimate) precipitation over large-scale subsidence (ascending) regions compared to the high score models (HSMs). The sensitivity of deep convection to sea surface temperature (SST) and large-scale subsidence is examined; analysis suggests that dynamical suppression of deep convection by the entrainment of environmental dry air over the subsidence region is very weak, and deep convection follows SST closely in LSMs. For example, deep convective activity is identified over the southeastern Pacific in LSMs, which corresponds to the double intertropical convergence zone (ITCZ) problem. It is suggested that the double ITCZ is associated not only with the local SST but also with the precipitation schemes that control deep convection over the entire tropical oceans. The current version, MIROC5, reproduces precipitation distributions significantly better than the older versions. Precipitation in MIROC5 has a weaker correlation with SST and a stronger correlation with environmental humidity than that in LSMs. The realistic representation of entrainment in regions with dynamical suppression is suggested to be a key factor for better reproducibility of precipitation distributions.
Precise Calculations of the Existence of Multiple AMOC Equilibria in Coupled Climate Models. Part I: Equilibrium States
Authors: Sijp Willem P. , England Matthew H. , Gregory Jonathan M. 
Published: July 2011

Abstract
This study examines criteria for the existence of two stable states of the Atlantic Meridional Overturning Circulation (AMOC) using a combination of theory and simulations from a numerical coupled atmosphere–ocean climate model. By formulating a simple collection of state parameters and their relationships, the authors reconstruct the North Atlantic Deep Water (NADW) OFF state behavior under a varying external salt-flux forcing. This part (Part I) of the paper examines the steady-state solution, which gives insight into the mechanisms that sustain the NADW OFF state in this coupled model; Part II deals with the transient behavior predicted by the evolution equation. The nonlinear behavior of the Antarctic Intermediate Water (AAIW) reverse cell is critical to the OFF state. Higher Atlantic salinity leads both to a reduced AAIW reverse cell and to a greater vertical salinity gradient in the South Atlantic. The former tends to reduce Atlantic salt export to the Southern Ocean, while the latter tends to increases it. These competing effects produce a nonlinear response of Atlantic salinity and salt export to salt forcing, and the existence of maxima in these quantities. Thus the authors obtain a natural and accurate analytical saddle-node condition for the maximal surface salt flux for which a NADW OFF state exists. By contrast, the bistability indicator proposed by De Vries and Weber does not generally work in this model. It is applicable only when the effect of the AAIW reverse cell on the Atlantic salt budget is weak.