bluuebunny/crossref_metadata_2025 huggingface dataset:
Stochastic coordination of multiple actuators reduces latency and improves chemotactic response in bacteria
Authors: Sneddon Michael W. , Pontius William , Emonet Thierry
Published: December 2011

Individual neuronal, signal transduction, and regulatory pathways often control multiple stochastic downstream actuators, which raises the question of how coordinated response to a single input can be achieved when individual actuators fluctuate independently. In
Escherichia coli
, the bacterial chemotaxis pathway controls the activity of multiple flagellar motors to generate the run-and-tumble motion of the cell. High-resolution microscopy experiments have identified the key conformational changes adopted by individual flagella during this process. By incorporating these observations into a stochastic model of the flagellar bundle, we demonstrate that the presence of multiple motors imposes a trade-off on chemotactic performance. Multiple motors reduce the latency of the response below the time scale of the stochastic switching of a single motor, which improves performance on steep gradients of attractants. However, the uncoordinated switching of multiple motors interrupts and shortens cell runs, which thereby reduces signal detection and performance on shallow gradients. Remarkably, when slow fluctuations generated by the adaptation mechanism of the chemotaxis system are incorporated in the model at levels measured in experiments, the chemotactic sensitivity and performance in shallow gradients is partially restored with marginal effects for steep gradients. The noise is beneficial because it simultaneously generates long events in the statistics of individual motors and coordinates the motors to generate a long tail in the run length distribution of the cell. Occasional long runs are known to enhance exploration of random walkers. Here we show that they have the additional benefit of enhancing the sensitivity of the bacterium to very shallow gradients.
Bacterial bioluminescence as a lure for marine zooplankton and fish
Authors: Zarubin Margarita , Belkin Shimshon , Ionescu Michael , Genin Amatzia
Published: December 2011

The benefits of bioluminescence for nonsymbiotic marine bacteria have not been elucidated fully. One of the most commonly cited explanations, proposed more than 30 y ago, is that bioluminescence augments the propagation and dispersal of bacteria by attracting fish to consume the luminous material. This hypothesis, based mostly on the prevalence of luminous bacteria in fish guts, has not been tested experimentally. Here we show that zooplankton that contacts and feeds on the luminescent bacterium
Photobacterium leiognathi
starts to glow, and demonstrate by video recordings that glowing individuals are highly vulnerable to predation by nocturnal fish. Glowing bacteria thereby are transferred to the nutritious guts of fish and zooplankton, where they survive digestion and gain effective means for growth and dispersal. Using bioluminescence as bait appears to be highly beneficial for marine bacteria, especially in food-deprived environments of the deep sea.
Immunology in the clinic review series; focus on type 1 diabetes and viruses: enterovirus, thymus and type 1 diabetes pathogenesis
Authors: Jaïdane H , Sané F , Hiar R , Goffard A , Gharbi J , Geenen V , Hober D
Published: December 2011

OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES

Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy.

Thymus dysfunction, especially immune suppression, is frequently associated with various virus infections. Whether viruses may disturb the thymus function and play a role in the pathogenesis of autoimmune diseases is an open issue. Enteroviruses, especially Coxsackievirus B4 (CV-B4), have been largely suggested as potential inducers or aggravating factors of type 1 diabetes (T1D) pathogenesis in genetically predisposed individuals. Several pathogenic mechanisms of enterovirus-induced T1D have been suggested. One of these mechanisms is the impairment of central self-tolerance due to viral infections. Coxsackievirus-B4 is able to infect murine thymus in vitro and in vivo and to infect human thymus in vitro. Thymic epithelial cells and thymocytes are targets of infection with this virus, and several abnormalities, especially disturbance of maturation/differentiation processes, were observed. Altogether, these data suggest that CV-B infection of thymus may be involved in the pathogenesis of T1D. Further investigations are needed to explore this hypothesis.
Calcium hydroxide partial pulpotomy is an alternative to formocresol pulpotomy based on a 3‐year randomized trial
Authors: TRAIRATVORAKUL CHUTIMA , KOOTHIRATRAKARN AREERAT
Published: December 2011

International Journal of Paediatric Dentistry 2012; 22: 382–389

Background.  Considering formocresol’s toxicity, Ca(OH)2 partial pulpotomy (PP) was studied as a treatment alternative.

Aim.  To compare success rates of Ca(OH)2 PP versus formocresol pulpotomy (FP) treatment of pulpally exposed lower primary molars.

Design.  A total of 84 lower primary molars, which met study criteria, from 56 child patients were randomly assigned for each treatment. After treatment, blinded clinical and radiographic evaluation with 96.9% and 90% reliability was performed at 6‐month intervals to determine treatment success/failure. Chi‐squared test was used to compare success rates between the two treatments.

Results.  The success rates from 6 to 36 months for PP ranged from 95.03% to 75%, whereas for FP, it was 92.7–74.2%. The success rates for the two treatments at each 6‐month interval were not different (P ≥ 0.05). The most frequent failure was internal resorption, affecting five FP teeth and three PP teeth. The resorption was arrested in five of the teeth and was replaced by a radiopaque calcified tissue in one case.

Conclusion.  Considering the favourable clinical and radiographic success rate of PP and the potentially toxic effects of formocresol leads us to recommend the use of PP instead of FP in primary teeth with deep carious lesions.
Assessing quality of life of older people with dementia: a comparison of quantitative self‐report and proxy accounts
Authors: Moyle Wendy , Murfield Jenny E. , Griffiths Susan G. , Venturato Lorraine
Published: December 2011

moyle w., murfield j.e., griffiths s.g. & venturato l. (2012) Assessing quality of life of older people with dementia: a comparison of quantitative self‐report and proxy accounts. Journal of Advanced Nursing68(10), 2237–2246.

Aims.  This article reports on a study of quality of life of older people with dementia, as assessed by the person with dementia, family carer and care staff.

Background.  People with dementia can give meaningful assessments of their quality of life, but these often differ from proxy ratings. In understanding this discrepancy, the influence of age, extent of cognitive impairment and activity limitation has been investigated. A lack of conclusive associations between quality of life ratings and these variables indicates a need for further research.

Methods.  Fifty‐eight triads comprising the person with dementia, family carer and member of care staff from four long‐term care facilities were surveyed on the Quality of Life‐Alzheimer’s Disease questionnaire between August and December 2007.

Results.  There was an important difference in the Quality of Life‐Alzheimer’s Disease questionnaire total mean scores between groups, with the person with dementia providing the highest ratings. Level of impairment in Activities of Daily Living had an important effect on quality of life ratings, with proxies, particularly care staff, providing lower ratings when there was greater activity limitation. This was not replicated for assessments made by the person with dementia. Age or level of cognitive impairment did not influence any ratings.

Conclusion.  People with dementia can give assessments of their quality of life. However, discrepancy in ratings, with greater activity limitation affecting proxy ratings but not those made by the person with dementia, indicates the importance of including both self‐report and proxy measures in research and care planning.
The nurses’ role in the prevention of Solanum infection: dealing with a zombie epidemic
Authors: Stanley David
Published: December 2011

Aims.  To outline the background and nursing interventions for Solanum infection in the event of a zombie epidemic.

Background.  Literature and feature film evidence supports the theoretical probability for an outbreak of a Solanum infection which could result in a zombie epidemic. This paper discusses the causative agent, history of zombiism, signs and symptoms, diagnosis and nursing interventions.

Design.  Review.

Methods.  Academic and general literature and web sites were searched up to February 2011 for the key words, ‘zombie’, ‘zombie nurses’, ‘zombie epidemic’ and ‘zombie nursing interventions’. Limited academic literature was sourced pointing to a serious knowledge deficit in this area.

Results.  If nurses are to respond successfully to a potential Solanum epidemic they need to be prepared and able to recognise Solanum infection, prevent its spread and care appropriately for sufferers and victims of a zombie attack. Advice is offered on prevention, initial nursing management and secondary nursing interventions including dealing with reanimation, palliative care and psychological support.

Conclusion.  History offers numerous examples of the sudden appearance of a serious disease that has impacted on man kind’s survival. While difficult to conceive, a zombie epidemic is theoretically possible and nurses have a responsibility to be as prepared as possible to support and care for victims.

Relevance to clinical practice.  Nurses are likely to be the front line staff faced with initiating most primary and secondary care interventions, including isolation and infection control, wound care, pain relief, documentation observations, support for activities of daily living, nutrition and fluid support, medication administration and other interventions.
Chlamydia pneumoniae induces a pro‐inflammatory phenotype in murine vascular smooth muscle cells independently of elevating reactive oxygen species
Authors: Rivera Jennifer , Walduck Anna K , Strugnell Richard A , Sobey Christopher G , Drummond Grant R
Published: December 2011

NADPH oxidases (Nox) are reactive oxygen species (ROS)‐generating enzymes that play important physiological roles in host defence and redox signalling. However, Nox activity is upregulated in the vascular wall during atherosclerosis and contributes to plaque formation by promoting oxidative stress and inflammation.

  The bacterium Chlamydia pneumoniae has been detected in vascular smooth muscle cells (VSMC) of human atheroma. We hypothesized that C. pneumoniae infection of VSMC causes Nox activation, which initially limits infection but ultimately causes oxidative stress, activation of pro‐inflammatory pathways and an atherogenic phenotype.

  Chlamydia pneumoniae infection of mouse cultured VSMC significantly increased ROS production by twofold but did not upregulate mRNA expression of Nox1 or Nox4. Chlamydia pneumoniae did increase Nox2 mRNA levels significantly by threefold, but this did not translate to elevated Nox2 protein expression.

  The Nox inhibitor gp91ds‐tat had no effect on C. pneumoniae‐induced ROS production. In contrast, apocynin significantly reduced ROS levels by 75% in C. pneumoniae‐infected VSMC, an effect most likely attributable to its direct anti‐oxidant action.

  Although apocynin had no effect on C. pneumoniae‐induced expression of inflammatory markers, bacteria recovered from apocynin‐treated VSMC displayed a higher degree of infectivity in HEp‐2 cells.

  In conclusion, C. pneumoniae infection increases ROS production in VSMC independently of Nox activity. Although elevated ROS production appears to serve a protective role by limiting the spread of infection, we speculate that this response will be detrimental over the long term by causing oxidative stress and a smouldering inflammatory response by maintaining C. pneumoniae persistence within the cell.
Going It Together: Persistence of Older Adults’ Accompaniment to Physician Visits by a Family Companion
Authors: Wolff Jennifer L. , Boyd Cynthia M. , Gitlin Laura N. , Bruce Martha L. , Roter Debra L.
Published: December 2011

Objectives

Although older adults are often accompanied to routine physician visits and commonly receive disability‐related task assistance, the overlap and persistence of this help is not well understood. This study investigates whether older adults who are accompanied to routine physician visits (1) also receive task assistance and (2) continue to be accompanied at 12‐months by the same family companion.

Design

Observational study.

Setting

Nationally representative survey.

Participants

Community‐dwelling adults aged 65 and older who responded to the Medicare Current Beneficiary Survey (MCBS) in 2006 (n = 11,582) and a subset (n = 7,510) who responded in 2005 and 2006.

Measurements

Accompaniment to physician visits by a family companion and receipt of task assistance with activities of daily living (ADLs) or instrumental activities of daily living (IADLs). Persistent accompaniment and consistent family companion involvement was ascertained from 2005 and 2006 survey responses.

Results

Among community‐dwelling older adults, 18.6% were accompanied to physician visits only, and 12.7% were accompanied to physician visits and received task assistance. Accompanied older adults who received task assistance were older, less educated, and had worse self‐rated health than their counterparts who were accompanied only. Family companions who provided task assistance (vs those who did not) were more actively engaged in physician visit processes and more often identified as always present. Three‐fourths (74.5%) of accompanied older adults were persistently accompanied to physician visits at 12 months, nearly always (87.9%) by the same family companion. Receipt of task assistance was strongly associated with persistent accompaniment (aOR = 2.52; 95% CI: 1.93–3.29).

Conclusions

Older adults’ accompaniment to physician visits typically persists, most often by consistently involved family companions. Findings have implications for the patient–physician partnership and the patient‐centered medical home.
A Probabilistic Transmission and Population Dynamic Model to Assess Tuberculosis Infection Risk
Authors: Liao Chung‐Min , Cheng Yi‐Hsien , Lin Yi‐Jun , Hsieh Nan‐Hung , Huang Tang‐Luen , Chio Chia‐Pin , Chen Szu‐Chieh , Ling Min‐Pei
Published: December 2011

The purpose of this study was to examine tuberculosis (TB) population dynamics and to assess potential infection risk in Taiwan. A well‐established mathematical model of TB transmission built on previous models was adopted to study the potential impact of TB transmission. A probabilistic risk model was also developed to estimate site‐specific risks of developing disease soon after recent primary infection, exogenous reinfection, or through endogenous reactivation (latently infected TB) among Taiwan regions. Here, we showed that the proportion of endogenous reactivation (53–67%) was larger than that of exogenous reinfection (32–47%). Our simulations showed that as epidemic reaches a steady state, age distribution of cases would finally shift toward older age groups dominated by latently infected TB cases as a result of endogenous reactivation. A comparison of age‐weighted TB incidence data with our model simulation output with 95% credible intervals revealed that the predictions were in an apparent agreement with observed data. The median value of overall basic reproduction number (R0) in eastern Taiwan ranged from 1.65 to 1.72, whereas northern Taiwan had the lowest R0 estimate of 1.50. We found that total TB incidences in eastern Taiwan had 25–27% probabilities of total proportion of infected population exceeding 90%, whereas there were 36–66% probabilities having exceeded 20% of total proportion of infected population attributed to latently infected TB. We suggested that our Taiwan‐based analysis can be extended to the context of developing countries, where TB remains a substantial cause of elderly morbidity and mortality.
Investigations into the Hypothesis of Transgenic Cannabis*
Authors: Cascini Fidelia
Published: December 2011

Abstract:  The unusual concentration of cannabinoids recently found in marijuana samples submitted to the forensic laboratory for chemical analysis prompted an investigation into whether genetic modifications have been made to the DNA of Cannabis sativa L. to increase its potency. Traditional methods for the detection of genetically modified organisms (GMO) were used to analyze herbal cannabis preparations. Our analyses support the hypothesis that marijuana samples submitted to forensic laboratories and characterized by an abnormal level of Δ9‐THC are the product of breeding selection rather than of transgenic modifications. Further, this research has shown a risk of false positive results associated with the poor quality of the seized samples and probably due to the contamination by other transgenic vegetable products. On the other hand, based on these data, a conclusive distinction between the hypothesis of GMO plant contamination and the other of genetic modification of cannabis cannot be made requiring further studies on comparative chemical and genetic analyses to find out an explanation for the recently detected increased potency of cannabis.
Natural Vibration of Functionally Graded Cylindrical Shells With Infinite and Finite Lengths
Authors: Cao Zhiyuan , Tang Shougao
Published: December 2011

Upon the basic theory of functionally graded material cylindrical shell, the original 3-D foundational equations with variable coefficients are transformed into anisotropic and membrane-bending coupling 2-D equations with constant coefficients. The separation-of-variables mode shape functions in axial and circumferential directions for cylindrical shells with infinite and finite lengths are proposed for analytic solutions, which satisfy the basic differential equations, of natural vibration. The general approach presented in the paper for the solutions of natural frequency and mode shape of functionally graded cylindrical shells can be applied to cylindrical shells with any kind of functionally graded material, different length, and boundary conditions.
The Reactivity of 2-Ethoxy-4-Chloroquinazoline and Its Use in Synthesis of Novel Quinazoline Derivatives
Authors: El-Hashash M. A. , Darwish K. M. , Rizk S. A. , El-Bassiouny F. A.
Published: December 2011

The behavior of 2-ethoxy-4-chloroquinazoline 2 towards various nitrogen nucleophiles, namely: thiosemicarbazide, sodium azide, glucosamine, ethanol, and hydrazine hydrate has been discussed. Also, the behavior of 4-(2-ethoxyquinazolin-4-yl)thiosemicarbazide towards one-carbon, for example, ethyl chloroformate, and two-carbon donors, for example, ethyl chloroacetate and diethyl oxalate has been investigated. On the other hand, new 5-ethoxy-2-substituted[1,2,4]-triazolo-[1,5-c]quinazoline derivatives have been obtained by ring closure accompanied with Dimroth rearrangement through the interaction of compound 2 with hydrazides of acetic, benzoic, crotonic, cinnamic, 2-furoic, and phthalimidoacetic acids. Structures of the novel products were confirmed by elemental, IR, MS, and 1H-NMR spectral analyses.
DNA Methyltransferase Inhibitor, Zebularine, Delays Tumor Growth and Induces Apoptosis in a Genetically Engineered Mouse Model of Breast Cancer
Authors: Chen Min , Shabashvili Daniel , Nawab Akbar , Yang Sherry X. , Dyer Lisa M. , Brown Kevin D. , Hollingshead Melinda , Hunter Kent W. , Kaye Frederic J. , Hochwald Steven N. , Marquez Victor E. , Steeg Patricia , Zajac-Kaye Maria
Published: December 2011

Zebularine is a novel potent inhibitor of both cytidine deaminase and DNA methylation. We examined the effect of zebularine on mammary tumor growth in genetically engineered MMTV-PyMT transgenic mice that develop mammary tumors at 60 days of age with 100% penetrance. The MMTV-PyMT transgenic mice were randomized at 46 days of age into control (n = 25) and zebularine (n = 25) treatment groups and monitored for parameters of tumor growth. Zebularine was administered at 5 mg/mL in drinking water. We observed a significant delay in the growth of mammary tumors in zebularine-treated mice with a statistically significant reduction (P = 0.0135) in total tumor burden at 94 days of age when the mice were sacrificed. After 48 days of zebularine treatment, the tumors were predominantly necrotic compared with untreated animals. In addition, a high apoptotic index by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay was observed as early as 13 days following treatment. Immunoblot analysis showed depletion of DNMT1 and partial depletion of DNMT3b after zebularine treatment. Microarray analyses of global gene expression identified upregulation of twelve methylation-regulated genes as well as a set of candidate cancer genes that participate in cell growth and apoptosis. In summary, zebularine inhibits the growth of spontaneous mammary tumors and causes early onset of tumor cell necrosis and apoptosis in a genetically engineered mouse model of breast cancer. Defining the parameters of zebularine-mediated tumor inhibition may advance the future development of DNA methyltransferase inhibitors as an effective cancer treatment. Mol Cancer Ther; 11(2); 370–82. ©2011 AACR.
Dual Combination Therapy Targeting DR5 and EMMPRIN in Pancreatic Adenocarcinoma
Authors: Kim Hyunki , Zhai Guihua , Samuel Sharon L. , Rigell Christopher J. , Umphrey Heidi R. , Rana Samir , Stockard Cecil R. , Fineberg Naomi S. , Zinn Kurt R.
Published: December 2011

The goal of the study was to assess the efficacy of combined extracellular matrix metalloprotease inducer (EMMPRIN)- and death receptor 5 (DR5)-targeted therapy for pancreatic adenocarcinoma in orthotopic mouse models with multimodal imaging. Cytotoxicity of anti-EMMPRIN antibody and anti-DR5 antibody (TRA-8) in MIA PaCa-2 and PANC-1 cell lines was measured by ATPlite assay in vitro. The distributions of Cy5.5-labeled TRA-8 and Cy3-labeled anti-EMMPRIN antibody in the 2 cell lines were analyzed by fluorescence imaging in vitro. Groups 1 to 12 of severe combined immunodeficient mice bearing orthotopic MIA PaCa-2 (groups 1–8) or PANC-1 (groups 9–12) tumors were used for in vivo studies. Dynamic contrast-enhanced–MRI was applied in group 1 (untreated) or group 2 (anti-EMMPRIN antibody). The tumor uptake of Tc-99m-labeled TRA-8 was measured in group 3 (untreated) and group 4 (anti-EMMPRIN antibody). Positron emission tomography/computed tomography imaging with 18F-FDG was applied in groups 5 to 12. Groups 5 to 8 (or groups 9 to 12) were untreated or treated with anti-EMMPRIN antibody, TRA-8, and combination, respectively. TRA-8 showed high killing efficacy for both MIA PaCa-2 and PANC-1 cells in vitro, but additional anti-EMMPRIN treatment did not improve the cytotoxicity. Cy5.5–TRA-8 formed cellular caps in both the cell lines, whereas the maximum signal intensity was correlated with TRA-8 cytotoxicity. Anti-EMMPRIN therapy significantly enhanced the tumor delivery of the MR contrast agent, but not Tc-99m–TRA-8. Tumor growth was significantly suppressed by the combination therapy, and the additive effect of the combination was shown in both MIA PaCa-2 and PANC-1 tumor models. Mol Cancer Ther; 11(2); 405–15. ©2011 AACR.
They Think They're Normal: Enduring Questions and New Research on North Korea—A Review Essay
Authors: Kang David C.
Published: December 2011

A wave of recent scholarship, built on rich empirical research, provides new perspectives on enduring questions about North Korea. Three books, in particular—Patrick McEachern's Inside the Red Box, Stephan Haggard and Marcus Noland's Famine in North Korea, and Suk-Young Kim's Illusive Utopia—present a comprehensive and panoramic vision of North Korea today. This essay reviews these books and makes two overarching arguments. First, North Korea is more “normal” than is often thought, and its domestic politics, economy, and society function in ways familiar to other countries around the world. When viewed from the inside out, North Korea's institutions, economic life, and its people act in ways that are not only similar to those of others around the world, but that differ only in their level of intensity. Second, North Korea's continuing nuclear and military challenge is only one aspect of its overall relations with the world, and policies designed to minimize its threatening military behavior may work at cross-purposes with policies designed to improve its economy and the lives of its people. The complexities that arise in dealing with North Korea create a number of contradictory policy choices, and making progress on one issue has often meant overlooking another, or even allowing it to become worse.
Predictors of Tonsillectomy after Previous Adenoidectomy for Upper Airway Obstruction
Authors: Gov‐Ari Eliav , Mills Jonathan C. , Basler Keith J.
Published: December 2011

Objective

(1) Characterize risk factors for subsequent tonsillectomy in pediatric patients undergoing primary adenoidectomy for upper airway obstruction. (2) Compare rates of subsequent tonsillectomy between adenoidectomy patients with and without upper airway obstruction.

Study Design

Historical cohort study with a nested case‐control study. Cohort data were analyzed using Kaplan‐Meier plots and a multiple regression model. Case‐control data were analyzed using logistic regression.

Subjects and Methods

Patients undergoing adenoidectomy without tonsillectomy at the University of Missouri between 1995 and 2010 were identified using billing records and selected chart review. A nested case‐control study with detailed chart review was conducted to determine predictors of subsequent tonsillectomy in patients with upper airway obstruction.

Results

Of 1291 patients identified in the historical cohort, 7.8% later underwent tonsillectomy. Age younger than 3 years (P =. 027), female sex (P <. 0001), and upper airway obstruction (P =. 001) were found to be significant predictors of subsequent tonsillectomy. In the nested case‐control study, potential predictors investigated included adenoidectomy indications, symptoms, smoke exposure, weight, comorbidities, and tonsil size at the time of adenoidectomy. Of these, only tonsil size was significant, with an increased odds of future tonsillectomy of 2.5 (P =. 01) for each unit increase in tonsil size.

Conclusion

Patients undergoing adenoidectomy for upper airway obstruction are likely to be at an increased risk of subsequent tonsillectomy when compared with those with other indications. Within this subgroup of patients with upper airway obstruction, young age, female sex, and large tonsil size may further increase the risk of subsequent tonsillectomy.
Comparison of 70/30 Biphasic Insulin With Glargine/Lispro Regimen in Non–Critically Ill Diabetic Patients on Continuous Enteral Nutrition Therapy
Authors: Hsia Elisa , Seggelke Stacey A. , Gibbs Joanna , Rasouli Neda , Draznin Boris
Published: December 2011

Despite significant advances in inpatient diabetes management, it is still a challenge to choose the safest and most efficacious subcutaneous insulin regimen for diabetic patients on continuous enteral nutrition (EN) therapy. The authors conducted a retrospective analysis of glycemic control in 22 non–critically ill diabetic patients, receiving at least 3 days of continuous EN. Patients received different insulin regimens while on continuous EN, including a basal/bolus glargine/lispro regimen (group 1, n = 8), 70/30 biphasic insulin twice daily (group 2, n = 8), and 70/30 biphasic insulin 3 times a day (group 3, n = 6). The glucose data from 72 hours from the initiation of EN were analyzed (12 point‐of‐contact glucose measurements per patient). Overall, the degree of control was comparable in all groups, with target range maintained more consistently in group 3 (70/30 insulin administered 3 times daily). In this group, 69% of values were in the target range (140–180 mg/dL) as compared with 24% in glargine/lispro group and 22% in the 70/30 insulin bid group. Eight hypoglycemic episodes occurred among the 3 groups: 5 episodes in group 1 (5.4%), 2 episodes in group 2 (2.1%), and 1 episode in group 3 (1.4%) (P = .05, groups 2 and 3 vs group 1). Administration of 70/30 biphasic insulin 3 times daily is a safe therapeutic regimen in diabetic patients on continuous EN as it maintains glycemia in the target range and might produce fewer episodes of hypoglycemia.
Monitoring Parenteral Nutrition in Hospitalized Patients
Authors: Fairholm Lydia , Saqui Olivia , Baun Mary , Yeung Millie , Fernandes Gail , Allard Johane P.
Published: December 2011

Background: Monitoring hospitalized patients receiving parenteral nutrition requires regular bloodwork. However, blood specimens, if not drawn appropriately, may be contaminated by parenteral nutrition, leading to spurious results and unnecessary medical interventions. The objective was to determine, in a large academic center, the frequency of spurious bloodwork, unnecessary medical interventions, and contributing factors. Methods: This was a 1‐year prospective cohort study monitoring hospitalized patients receiving parenteral nutrition and their bloodwork. Sudden unexplained changes in serum levels of glucose, potassium, and sodium were identified. Subsequent medical interventions were tracked. Factors affecting blood collection, such as technique, shifts, nursing units, nursing, and patient demography, were assessed and compared with those of a control group. Results: Out of 201 patients, 34 had 63 incidents of spurious bloodwork. This led to 23 medical interventions. The most frequent problem was the failure to clamp the parenteral nutrition infusion prior to blood collection or too short a time between clamping and drawing. There was an increased occurrence of spurious bloodwork drawn by nurses with < 10 years of experience due to failure in following blood collection policy. Cost of spurious bloodwork and subsequent interventions for 63 incidents was approximately $3480 (CAD) per year. This excluded physician time. Conclusions: Spurious bloodwork was due to parenteral nutrition contamination by incorrect blood draw techniques. This led to a policy amendment to incorporate a “wait time” between stopping the parenteral nutrition infusion and drawing blood and to an institution‐wide nursing reeducation.
Novel features of ARS selection in budding yeast Lachancea kluyveri
Authors: Liachko Ivan , Tanaka Emi , Cox Katherine , Chung Shau Chee Claire , Yang Lu , Seher Arael , Hallas Lindsay , Cha Eugene , Kang Gina , Pace Heather , Barrow Jasmine , Inada Maki , Tye Bik-Kwoon , Keich Uri
Published: December 2011

Background

The characterization of DNA replication origins in yeast has shed much light on the mechanisms of initiation of DNA replication. However, very little is known about the evolution of origins or the evolution of mechanisms through which origins are recognized by the initiation machinery. This lack of understanding is largely due to the vast evolutionary distances between model organisms in which origins have been examined.

Results

In this study we have isolated and characterized autonomously replicating sequences (ARSs) in Lachancea kluyveri - a pre-whole genome duplication (WGD) budding yeast. Through a combination of experimental work and rigorous computational analysis, we show that L. kluyveri ARSs require a sequence that is similar but much longer than the ARS Consensus Sequence well defined in Saccharomyces cerevisiae. Moreover, compared with S. cerevisiae and K. lactis, the replication licensing machinery in L. kluyveri seems more tolerant to variations in the ARS sequence composition. It is able to initiate replication from almost all S. cerevisiae ARSs tested and most Kluyveromyces lactis ARSs. In contrast, only about half of the L. kluyveri ARSs function in S. cerevisiae and less than 10% function in K. lactis.

Conclusions

Our findings demonstrate a replication initiation system with novel features and underscore the functional diversity within the budding yeasts. Furthermore, we have developed new approaches for analyzing biologically functional DNA sequences with ill-defined motifs.
The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts
Authors: Wehby George L , Castilla Eduardo E , Goco Norman , Rittler Monica , Cosentino Viviana , Javois Lorette , Kindem Mark , Chakraborty Hrishikesh , Dutra Graca , López-Camelo Jorge S , Orioli Iêda M , Murray Jeffrey C
Published: December 2011

Background

Cleft lip and/or palate (CL/P) increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America.

Methods

The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7th and 28th day of life. The primary outcomes were mortality between the 7th and 28th day of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates.

Results

There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group.

Conclusions

Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention.

Trial Registration

ClinicalTrials.gov: NCT00097149
The association between delusional-like experiences, and tobacco, alcohol or cannabis use: a nationwide population-based survey
Authors: Saha Sukanta , Scott James G , Varghese Daniel , Degenhardt Louisa , Slade Tim , McGrath John J
Published: December 2011

Background

Previous population-based studies have found that delusional-like experiences (DLE) are prevalent in the community, and are associated with a wide range of mental health disorders including substance use. The aim of the study was to explore the association between DLE and three commonly used substances - tobacco, alcohol and cannabis.

Methods

Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007. The Composite International Diagnostic Interview was used to identify DLE, common psychiatric disorders, and substance use. We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors.

Results

Of 8 773 participants, 8.4% (n = 776) subjects endorsed one or more DLE. With respect to tobacco use, compared to nonusers, DLE were more common in those who (a) had daily use, (b) commenced usage aged 15 years or less, and (c) those who smoked heavily (23 or more cigarettes per day). Participants with cannabis use disorders were more likely to endorse DLE; this association was most prominent in those with an onset of 16 years or younger. In contrast, the pattern of association between DLE versus alcohol use or dependence was less consistent, however those with early onset alcohol use disorders were more likely to endorse DLE probe items.

Conclusions

While cannabis use disorders have been previously linked with DLE, our findings linking alcohol and tobacco use and DLE suggest that the influence of these substances on psychosis-related outcomes warrants closer scrutiny in longitudinal prospective studies.
Heterogeneity reduces sensitivity of cell death for TNF-Stimuli
Authors: Schliemann Monica , Bullinger Eric , Borchers Steffen , Allgöwer Frank , Findeisen Rolf , Scheurich Peter
Published: December 2011

Background

Apoptosis is a form of programmed cell death essential for the maintenance of homeostasis and the removal of potentially damaged cells in multicellular organisms. By binding its cognate membrane receptor, TNF receptor type 1 (TNF-R1), the proinflammatory cytokine Tumor Necrosis Factor (TNF) activates pro-apoptotic signaling via caspase activation, but at the same time also stimulates nuclear factor κB (NF-κB)-mediated survival pathways. Differential dose-response relationships of these two major TNF signaling pathways have been described experimentally and using mathematical modeling. However, the quantitative analysis of the complex interplay between pro- and anti-apoptotic signaling pathways is an open question as it is challenging for several reasons: the overall signaling network is complex, various time scales are present, and cells respond quantitatively and qualitatively in a heterogeneous manner.

Results

This study analyzes the complex interplay of the crosstalk of TNF-R1 induced pro- and anti-apoptotic signaling pathways based on an experimentally validated mathematical model. The mathematical model describes the temporal responses on both the single cell level as well as the level of a heterogeneous cell population, as observed in the respective quantitative experiments using TNF-R1 stimuli of different strengths and durations. Global sensitivity of the heterogeneous population was quantified by measuring the average gradient of time of death versus each population parameter. This global sensitivity analysis uncovers the concentrations of Caspase-8 and Caspase-3, and their respective inhibitors BAR and XIAP, as key elements for deciding the cell's fate. A simulated knockout of the NF-κB-mediated anti-apoptotic signaling reveals the importance of this pathway for delaying the time of death, reducing the death rate in the case of pulse stimulation and significantly increasing cell-to-cell variability.

Conclusions

Cell ensemble modeling of a heterogeneous cell population including a global sensitivity analysis presented here allowed us to illuminate the role of the different elements and parameters on apoptotic signaling. The receptors serve to transmit the external stimulus; procaspases and their inhibitors control the switching from life to death, while NF-κB enhances the heterogeneity of the cell population. The global sensitivity analysis of the cell population model further revealed an unexpected impact of heterogeneity, i.e. the reduction of parametric sensitivity.
A comparative study of total quality management of health care system in India and Iran
Authors: Heidari Gorji Ali Morad , Farooquie Jamal A
Published: December 2011

Background

Total quality management (TQM) has a great potential to address quality problems in a wide range of industries and improve the organizational performance. The growing need to take initiatives by hospitals in countries like India and Iran to improve the service quality and reduce wastage of resources has inspired the authors to develop a survey instrument to measure health care quality and performance in the two countries.

Methods

Based on the Baldrige health care criteria for performance excellence 2009-2010 and the guidelines proposed by the American Hospitals Association for hospitals in pursuit of excellence, compared health care services in three countries. The data are collected from the capital cities and their nearby places in India and Iran. Using ANOVAs, three groups in quality planning and performance have been compared.

Result

Results showed there is significantly difference between groups and in no case the hospitals from India and Iran are found scoring close to the benchmarks. The average scores of Indian and Iranian hospitals on different constructs of the IHCQPM model are compared with the major results achieved by the recipients of the MBNQ award.

Conclusion

In no case the hospitals from India and Iran are found scoring close to the benchmarks (Baldrige health care criteria for performance excellence 2009-2010 and the guidelines proposed by the American Hospitals Association for hospitals). These results suggested to health care services more attempt to achieve high quality in management and performance.
Failure of non-conventional composite pipes — an experimental and numerical approach
Authors: Wahab M. , Ramachandran P.
Published: December 2011

This paper discusses an experimental and numerical study to investigate the failure behavior of innovative and newly designed non-conventional cross-sectional fiber reinforced composite pipes subjected to internal pressure and bending loads. An adaptive filament winder for non-conventional pipes is exclusively designed and built to fabricate the test samples used in this investigation. Experiments are conducted on triangular and rectangular cross-sectioned samples as per ASTM standards to find the internal burst pressure, bending strength, and failure modes of the pipes. Numerical analysis for the pipe loading process has been developed based on the finite element method for linear orthotropic conditions for composite pipes. The finite element analysis is used to build the model and predict the stresses imposed on the non-conventional pipes. The relationships between the applied internal pressure and peak circumferential stress, bending load, and bending strength with reference to the fillet radius are determined; and generally a good correlation is found between the experimental and numerical results. This study has extended the use of non-conventional composite pipes in structural applications.
Naive and primed murine pluripotent stem cells have distinct miRNA expression profiles
Authors: Jouneau Alice , Ciaudo Constance , Sismeiro Odile , Brochard Vincent , Jouneau Luc , Vandormael-Pournin Sandrine , Coppée Jean-Yves , Zhou Qi , Heard Edith , Antoniewski Christophe , Cohen-Tannoudji Michel
Published: December 2011

Over the last years, the microRNA (miRNA) pathway has emerged as a key component of the regulatory network of pluripotency. Although clearly distinct states of pluripotency have been described in vivo and ex vivo, differences in miRNA expression profiles associated with the developmental modulation of pluripotency have not been extensively studied so far. Here, we performed deep sequencing to profile miRNA expression in naive (embryonic stem cell [ESC]) and primed (epiblast stem cell [EpiSC]) pluripotent stem cells derived from mouse embryos of identical genetic background. We developed a graphical representation method allowing the rapid identification of miRNAs with an atypical profile including mirtrons, a small nucleolar RNA (snoRNA)-derived miRNA, and miRNAs whose biogenesis may differ between ESC and EpiSC. Comparison of mature miRNA profiles revealed that ESCs and EpiSCs exhibit very different miRNA signatures with one third of miRNAs being differentially expressed between the two cell types. Notably, differential expression of several clusters, including miR290-295, miR17-92, miR302/367, and a large repetitive cluster on chromosome 2, was observed. Our analysis also showed that differentiation priming of EpiSC compared to ESC is evidenced by changes in miRNA expression. These dynamic changes in miRNAs signature are likely to reflect both redundant and specific roles of miRNAs in the fine-tuning of pluripotency during development.
Biomarkers in Cardiovascular Clinical Trials: Past, Present, Future
Authors: Halim Sharif A , Newby L Kristin , Ohman E Magnus
Published: December 2011

BACKGROUND

Cardiovascular (CV) clinical trials are instrumental in understanding treatment effects and offer insights into the natural progression of CV disease. Biomarkers are a critical component of patient selection, end point definition, and safety monitoring, and clinical trials provide a platform for the discovery and validation of new biomarkers that may augment the understanding of disease mechanisms, risk stratification, and/or clinical decision-making.

CONTENT

We review the roles that biomarkers have played in CV clinical trials and roles that CV clinical trials have played and will continue to play in the discovery and validation of biomarkers and their implementation in clinical practice. Large biobanks containing multiple specimen types are increasingly being created from patients enrolled in clinical trials, and such biobanks, when coupled with advances in molecular techniques and bioinformatics, promise to accelerate our understanding of CV disease mechanisms and to help fuel the discovery and development of novel therapeutic targets and biomarkers of risk and treatment response.

The past, present, and future of biomarkers and clinical trials have been and will remain intertwined. Biomarkers were once the workhorses of patient selection and end point definition in clinical trials; more recently, clinical trials have been the proving ground for individual biomarkers. Attention to biobanking and the application of modern informatics and molecular techniques to samples collected within clinical trials will usher in the era of stratified and personalized medicine.
Revision of Etyidae Guinot and Tavares, 2001 (Crustacea: Brachyura)
Authors: Schweitzer Carrie E. , Feldmann Rodney M. , Franţescu Ovidiu D. , Klompmaker Adiël
Published: December 2011

Members of the Etyidae and Feldmanniidae new family have unique arrangements of the spermatheca and gonopores that permit placement of each in different families and that differentiate each from all other brachyurans. Spermathecal openings are not always positioned along the sternal suture between sternites 7 and 8, suggesting that reproductive architecture within the Brachyura and what was formerly regarded as the Podotremata is considerably more diverse and disparate than previously thought. Etyidae and Feldmanniidae radiated in the early Cretaceous and survived into the Paleogene. New taxa includeSteorrosianew genus,Bretonianew genus,Faksecarcinusnew genus, and sixteen new combinations.
Multiscale Finite-Volume Formulation for the Saturation Equations
Authors: Zhou H.. , Lee S.H.. H. , Tchelepi H.A.. A.
Published: December 2011

Recent advances in multiscale methods have shown great promise in modeling multiphase flow in highly detailed heterogeneous domains. Existing multiscale methods, however, solve for the flow field (pressure and total velocity) only. Once the fine-scale flow field is reconstructed, the saturation equations are solved on the fine scale. With the efficiency in dealing with the flow equations greatly improved by multiscale formulations, solving the saturation equations on the fine scale becomes the relatively more expensive part. In this paper, we describe an adaptive multiscale finite-volume (MSFV) formulation for nonlinear transport (saturation) equations. A general algebraic multiscale formulation consistent with the operator-based framework proposed by Zhou and Tchelepi (SPE Journal, June 2008, pages 267–273) is presented. Thus, the flow and transport equations are solved in a unified multiscale framework. Two types of multiscale operators—namely, restriction and prolongation—are used to construct the multiscale saturation solution. The restriction operator is defined as the sum of the fine-scale transport equations in a coarse gridblock. Three adaptive prolongation operators are defined according to the local saturation history at a particular coarse block. The three operators have different computational complexities, and they are used adaptively in the course of a simulation run. When properly used, they yield excellent computational efficiency while preserving accuracy. This adaptive multiscale formulation has been tested using several challenging problems with strong heterogeneity, large buoyancy effects, and changes in the well operating conditions (e.g., switching injectors and producers during simulation). The results demonstrate that adaptive multiscale transport calculations are in excellent agreement with fine-scale reference solutions, but at a much lower computational cost.