bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of frontline risk‐adapted strategy on the overall survival of patients with newly diagnosed multiple myeloma: an analysis of the Singapore multiple myeloma study group
Authors: Tan Daryl , Ong Kiat H. , Koh Liang P. , Wong Siew S. , Khin Myat T. , Lee Lai H. , Goh Yeow T. , Chng Wee J.
Published: May 2012

Introduction

Risk stratification is vital for prognostication and informing treatment decisions in multiple myeloma (MM). We study the prognostic values of the International Staging System (ISS) and underlying cytogenetics in the bortezomib era and assess the impacts of an upfront risk‐adapted approach in the treatment ofMM.

Methods

We compare the overall survival (OS) of 221 patients withMMdiagnosed from 2006 to 2009 (era 2) where upfront bortezomib combination was approved for high‐riskMMwith theOSof 262 patients diagnosed from 2000 to 2005 (era 1) where bortezomib could only be administered at relapse. High‐riskMMis defined by the presence ofISS IIIdisease with renal impairment or adverse cytogenetics.

Results

Baseline characteristics were comparable between the 2 eras. At median follow‐up of 20 months, 0% and 26% of patients had received frontline bortezomib in eras 1 and 2, respectively. The medianOSwere 4.2 yrs and not reached for eras 1 and 2, respectively (P = 0.03). On multivariate analysis stratified by era, the most significant prognostic factor shifts from cytogenetics in era 1 to the quality of response in era 2.

Conclusion

Frontline use of bortezomib in a risk‐adapted manner may avert early mortality and is better able to overcome adverse risks compared to its sequential use.
A prospective cohort study on patients treated with anticoagulants for cerebral vein thrombosis
Authors: Sartori Maria T. , Zampieri Paolo , Barbar Sofia , Pasetto Laura , Munari Marina , Carollo Carla , Briani Chiara , Ricchieri Gianluigi , Prandoni Paolo
Published: May 2012

Objectives

Cerebral vein thrombosis (CVT) is a potentially fatal disorder for which treatment guidelines are scanty. To assess the short‐ and long‐term benefit of anticoagulant therapy, we performed a prospective cohort study on CVT patients.

Methods

Forty‐four consecutive CVT patients received conventional anticoagulation with heparin followed by warfarin for at least 3 months. Patients presenting with symptoms suggestive of pulmonary embolism (PE) underwent confirmatory objective tests. Acquired or inherited risk factors for thrombosis were investigated in all patients. Thrombotic and hemorrhagic events occurring during treatment, and the long‐term outcome using the modified Rankin Scale (mRS) were recorded.

Results

Congenital and/or acquired conditions predisposing to thrombosis were detected in 37 patients (84.1%), with a high prevalence of oral contraceptive use (66.7% of females) and thrombophilia (31.8%); more than one risk factor was seen in 31.8% of cases. At referral, six patients (13.6%) presented with symptoms of PE, which was confirmed in all. During the initial treatment period, two patients (4.5%) developed symptomatic progression of CVT, which was fatal in 1, and 2 (4.5%) developed major bleeding complications. A favorable outcome (mRS 0–2) at 6–12 months was recorded in 37 of the 43 patients who survived the acute phase (86%).

Conclusions

The outcome of CVT patients managed with conventional anticoagulation who survive the initial phase is favorable in the vast majority. The prevalence of concomitant PE is considerably high, supporting the need of anticoagulant therapy.
The wound‐healing response and upregulated embryonic mechanisms: brothers‐in‐arms forever
Authors: Aller María‐Angeles , Blanco‐Rivero Javier , Arias Jose‐Ignacio , Balfagon Gloria , Arias Jaime
Published: May 2012

The cutaneous wound‐healing reaction occurs in overlapping but inter‐related phases, which ultimately result in fibrosis. The pathophysiological mechanisms involved in fibrotic diseases, including organ‐related and even systemic diseases, such as systemic sclerosis, could represent the successive systemic upregulation of extraembryonic‐like phenotypes, that is, amniotic and vitelline phenotypes. These two extraembryonic‐like phenotypes act on the injured tissue to induce a process similar to gastrulation, which occurs during the early phases of embryo development. The amniotic‐like phenotype plays a leading role in the development of neurogenic responses with significant hydroelectrolytic alterations that essentially represent the development of open microcirculation within the injured tissue. In turn, through the overlapping expression of a vitelline‐like phenotype, a bone marrow‐related response is produced. Interstitial infiltration by molecular and cellular mediators contributed by amniotic‐ and vitelline‐like functions provides the functional and metabolic autonomy needed for inducing new tissue formation through mechanisms similar to those that act in gastrulation during the early phases of embryonic development. Thus, while a new tissue is formed, it quickly evolves into fibrotic tissue because of premature senescence. Mechanisms related to extraembryonic‐like functions have been suggested in the following physiological and pathological processes: embryonic development; wound‐healing reactions occurring during adult life; and senescence. The existence of this sort of basic self‐organizing fractal‐like functional pattern is an essential characteristic of our way of life.
The CEO's Representation of Demands and the Corporation's Response to External Pressures: Do Politically Affiliated Firms Donate More?
Authors: Jia Ming , Zhang Zhe
Published: May 2012

This study seeks to explain why firms respond in different ways to similar external administrative pressures, such as government demands for charitable giving, particularly in a transitional economy such as China's. Taking the perspective of the CEO's representation on external demands, the study explores the relationship between political affiliation and corporate giving, stimulated by powerful and politically affiliated CEOs, who are the government's natural constituency and who comply with governmental demands for donation. The study introduces contingent factors that influence the CEO's perception of how to satisfy government demands, and that moderate the relationship between political affiliation and corporate giving. Using firm-level data of corporate contributions following the Sichuan earthquake of May 12, 2008, we find that corporations with CEOs who hold political affiliations have a significantly higher probability of donation and also more cash giving. This relationship is moderated by contingent factors such as government ownership, financial condition, and concentration of voting rights.
A TRICKLE‐DOWN MODEL OF ABUSIVE SUPERVISION
Authors: MAWRITZ MARY BARDES , MAYER DAVID M. , HOOBLER JENNY M. , WAYNE SANDY J. , MARINOVA SOPHIA V.
Published: May 2012

Much of the abusive supervision research has focused on the supervisor–subordinate dyad when examining the effects of abusive supervision on employee outcomes. Using data from a large multisource field study, we extend this research by testing a trickle‐down model of abusive supervision across 3 hierarchical levels (i.e., managers, supervisors, and employees). Drawing on social learning theory and social information processing theory, we find general support for the study hypotheses. Specifically, we find that abusive manager behavior is positively related to abusive supervisor behavior, which in turn is positively related to work group interpersonal deviance. In addition, hostile climate moderates the relationship between abusive supervisor behavior and work group interpersonal deviance such that the relationship is stronger when hostile climate is high. The results provide support for our trickle‐down model in that abusive manager behavior was not only related to abusive supervisor behavior but was also associated with employees’ behavior 2 hierarchical levels below the manager.
ASK AND YOU SHALL HEAR (BUT NOT ALWAYS): EXAMINING THE RELATIONSHIP BETWEEN MANAGER CONSULTATION AND EMPLOYEE VOICE
Authors: TANGIRALA SUBRAHMANIAM , RAMANUJAM RANGARAJ
Published: May 2012

The literature on employees’ voice is characterized by 2 influential perspectives on its antecedents—1 that focuses on the importance of managerial behaviors and the other that emphasizes the role of employees’ internal motivational states. In this study, we integrate these perspectives and examine the proposition that (a key managerial behavior) consultation—that is, the extent to which the manager is seen to solicit and listen to suggestions on work issues from the employees, enhances employees’ upward voice by increasing their perceived influence at work (an important motivational state). Using multisource survey data from 640 nurses and their managers, we found that managers’ consultation was positively related to employees’ upward voice, with employees’ perceived influence acting as the mediator. We further delineate key moderators of this mediated relationship and discuss implications for theory and practice.
VLBI and single-dish monitoring of 3C 84 for the period 2009–2011
Authors: Nagai H. , Orienti M. , Kino M. , Suzuki K. , Giovannini G. , Doi A. , Asada K. , Giroletti M. , Kataoka J. , D'Ammando F. , Inoue M. , Lähteenmäki A. , Tornikoski M. , León-Tavares J. , Kameno S. , Bach U.
Published: May 2012

The radio galaxy 3C 84 is a representative of γ-ray-bright misaligned active galactic nuclei (AGNs) and one of the best laboratories to study the radio properties of the subparsec jet in connection with the γ-ray emission. In order to identify possible radio counterparts of γ-ray emissions in 3C 84, we study the change in structure within the central 1 pc and the light curve of subparsec-sized components C1, C2 and C3. We search for any correlation between changes in the radio components and the γ-ray flares by making use of the Very Long Baseline Interferometry (VLBI) and single-dish data. Throughout the radio monitoring spanning over two GeV γ-ray flares detected by the Fermi Large Area Telescope and the MAGIC Cherenkov Telescope during 2009 April–May and 2010 June–August, the total flux density in the radio band increases on average. This flux increase mostly originates in C3. Although γ-ray flares span the time-scale of days to weeks, no clear correlation with the radio light curve on this time-scale is found. No new prominent components and change in morphology associated with the γ-ray flares are found on VLBI images.
11–12 Gyr old white dwarfs 30 pc away
Authors: Kilic Mukremin , Thorstensen John R. , Kowalski P. M. , Andrews J.
Published: May 2012

We present a detailed model atmosphere analysis of two of the oldest stars known in the solar neighbourhood, the high proper motion white dwarfs SDSS J110217.48+411315.4 (hereafter J1102) and WD 0346+246 (hereafter WD0346). We present trigonometric parallax observations of J1102, which places it at a distance of only 33.7 ± 2.0 pc. Based on the state-of-the-art model atmospheres, optical, near-infrared, mid-infrared photometry and distances, we constrain the temperatures, atmospheric compositions, masses and ages for both stars. J1102 is an 11-Gyr-old (white dwarf plus main-sequence age), 0.62 M⊙ white dwarf with a pure H atmosphere and Teff= 3830 K. WD0346 is an 11.5-Gyr-old, 0.77 M⊙ white dwarf with a mixed H/He atmosphere and Teff= 3650 K. Both stars display halo kinematics and their ages agree remarkably well with the ages of the nearest globular clusters, M4 and NGC 6397. J1102 and WD0346 are the closest examples of the oldest halo stars that we know of.
Behavior and Fate of PFOA and PFOS in Sandy Aquifer Sediment
Authors: Ferrey Mark L. , Wilson John T. , Adair Cherri , Su Chunming , Fine Dennis D. , Liu Xuyang , Washington John W.
Published: May 2012

Microcosms were constructed with sediment from beneath a landfill that received waste containing PFOA (perfluorooctanoic acid) and PFOS (perfluorooctane sulfonate). The microcosms were amended with PFOA and PFOS, and sampled after 91, 210, 343, 463, 574, and 740 d of incubation. After 740 d, selected microcosms were extracted to determine the mass of PFOA and PFOS remaining. There was no evidence for degradation of PFOA or PFOS. Over time, the aqueous concentrations of PFOA and PFOS increased in the microcosms, indicating that PFOA and PFOS that had originally sorbed to the sediment was desorbing. At the beginning of the experiment, the adsorption coefficient, Kd, averaged 0.27 L/kg for PFOA and 1.2 L/kg for PFOS. After 740 d of incubation, sorption of PFOA was not detectable and the Kd of PFOS was undetectable in two microcosms and was 0.08 L/kg in a third microcosm. During incubation, the pH of the pore water in the microcosms increased from pH 7.2 to pH ranging from 8.1 to 8.8. The zeta potential of the sediment decreased with increasing pH. These observations suggest that the sorption of PFOA and PFOS at near neutral pH was controlled by the electrostatic sorption on ferric oxide minerals, and not by the sorption to organic carbon. Accurate predictions of PFOA and PFOS mobility in ground water should be based on empirical estimates of sorption using affected aquifer sediment.
δ98/95Mo values and Molybdenum Concentration Data for NIST SRM 610, 612 and 3134: Towards a Common Protocol for Reporting Mo Data
Authors: Greber Nicolas D. , Siebert Christopher , Nägler Thomas F. , Pettke Thomas
Published: May 2012

Molybdenum concentration and δ98/95Mo values for NIST SRM 610 and 612 (solid glass), NIST SRM 3134 (lot 891307; liquid) and IAPSO seawater reference material are presented based on comparative measurements by MC‐ICP‐MS performed in laboratories at the Universities of Bern and Oxford. NIST SRM 3134 and NIST SRM 610 and 612 were found to have identical and homogeneous 98Mo/95Mo ratios at a test portion mass of 0.02 g. We suggest, therefore, that NIST SRM 3134 should be used as reference for the δ–Mo notation and to employ NIST SRM 610 or 612 as solid silicate secondary measurement standards, in the absence of an isotopically homogeneous solid geological reference material for Mo. The δ98/95MoJMC Bern composition (Johnson Matthey ICP standard solution, lot 602332B as reference) of NIST SRM 3134 was 0.25 ± 0.09‰ (2s). Based on five new values, we determined more precisely the mean open ocean δ98/95MoSRM 3134 value of 2.09 ± 0.07‰, which equals the value of δ98/95MoJMC Bern of 2.34 ± 0.07‰. We also refined the Mo concentration data for NIST SRM 610 to 412 ± 9 μg g−1 (2s) and NIST SRM 612 to 6.4 ± 0.7 μg g−1 by isotope dilution. We propose these concentration data as new working values, which allow for more accurate in situ Mo determination using laser ablation ICP‐MS or SIMS.
A model to determine the economic viability of water fluoridation
Authors: Kroon Jeroen , van Wyk Philippus Johannes
Published: May 2012

Objectives: In view of concerns expressed by South African local authorities the aim of this study was to develop a model to determine whether water fluoridation is economically viable to reduce dental caries in South Africa.

Methods: Microsoft Excel software was used to develop a model to determine economic viability of water fluoridation for 17 water providers from all nine South African provinces. Input variables for this model relate to chemical cost, labor cost, maintenance cost of infrastructure, opportunity cost, and capital depreciation. The following output variables were calculated to evaluate the cost of water fluoridation: per capita cost per year, cost‐effectiveness and cost‐benefit. In this model it is assumed that the introduction of community water fluoridation can reduce caries prevalence by an additional 15 percent and that the savings in cost of treatment will be equal to the average fee for a two surface restoration.

Results: Water providers included in the study serve 53.5 percent of the total population of South Africa. For all providers combined chemical cost contributes 64.5 percent to the total cost, per capita cost per year was $0.36, cost‐effectiveness was calculated as $11.41 and cost‐benefit of the implementation of water fluoridation was 0.34.

Conclusions: This model confirmed that water fluoridation is an economically viable option to prevent dental caries in South African communities, as well as conclusions over the last 10 years that water fluoridation leads to significant cost savings and remains a cost‐effective measure for reducing dental caries, even when the caries‐preventive effectiveness is modest.
Mainstreaming ecosystem services through reformed European agricultural policies
Authors: Plieninger Tobias , Schleyer Christian , Schaich Harald , Ohnesorge Bettina , Gerdes Holger , Hernández‐Morcillo Mónica , Bieling Claudia
Published: May 2012

Agroecosystems are vital for supplying ecosystem services to human society, but most modern farming practices impact detrimentally on the environment. Public agricultural support policies have been critically important in influencing the transformation of the farm sectors; however, few of them have been dedicated to enhancing ecosystem services beyond agricultural commodities. The largest agricultural support system worldwide, the European common agricultural policy (CAP), has now come to a critical point, as major decisions concerning its design and implementation after 2013 are about to be taken. The debate on this reform process presents a unique opportunity to trigger a transition from commodity‐based subsidy policies to policies centered on efficient provision of ecosystem services from agricultural land. To prompt such discussion, we formulate key recommendations informed by a review of ecosystem services literature and address verifiable links to human well‐being, nonmarket valuation for balanced services provision, treatment of ecosystem services bundles, site‐specific and regionalized approaches, matching spatial scales for different ecosystem services, funding permanence for payment schemes, strong monitoring and adaptive approaches to tackling uncertainties, and coherent cross‐sectoral policy design. If these issues were to be considered in formulating and implementing future CAP, it might become an exemplar for redirecting agricultural policies elsewhere in the world toward sustainability.
Dose calculation for photon‐emitting brachytherapy sources with average energy higher than 50 keV: Report of the AAPM and ESTRO
Authors: Perez‐Calatayud Jose , Ballester Facundo , Das Rupak K. , DeWerd Larry A. , Ibbott Geoffrey S. , Meigooni Ali S. , Ouhib Zoubir , Rivard Mark J. , Sloboda Ron S. , Williamson Jeffrey F.
Published: May 2012

Purpose:

Recommendations of the American Association of Physicists in Medicine (AAPM) and the European Society for Radiotherapy and Oncology (ESTRO) on dose calculations for high‐energy (average energy higher than 50 keV) photon‐emitting brachytherapy sources are presented, including the physical characteristics of specific192Ir,137Cs, and 60Co source models.

Methods:

This report has been prepared by the High Energy Brachytherapy Source Dosimetry (HEBD) Working Group. This report includes considerations in the application of the TG‐43U1 formalism to high‐energy photon‐emitting sources with particular attention to phantom size effects, interpolation accuracy dependence on dose calculation grid size, and dosimetry parameter dependence on source active length.

Results:

Consensus datasets for commercially available high‐energy photon sources are provided, along with recommended methods for evaluating these datasets. Recommendations on dosimetry characterization methods, mainly using experimental procedures and Monte Carlo, are established and discussed. Also included are methodological recommendations on detector choice, detector energy response characterization and phantom materials, and measurement specification methodology. Uncertainty analyses are discussed and recommendations for high‐energy sources without consensus datasets are given.

Conclusions:

Recommended consensus datasets for high‐energy sources have been derived for sources that were commercially available as of January 2010. Data are presented according to the AAPM TG‐43U1 formalism, with modified interpolation and extrapolation techniques of the AAPM TG‐43U1S1 report for the 2D anisotropy function and radial dose function.
Categorical perception of intonation contrasts: Effects of listeners’ language background
Authors: Liu Chang , Rodriguez Amanda
Published: May 2012

Intonation perception of English speech was examined for English- and Chinese-native listeners. F0 contour was manipulated from falling to rising patterns for the final words of three sentences. Listener’s task was to identify and discriminate the intonation of each sentence (question versus statement). English and Chinese listeners had significant differences in the identification functions such as the categorical boundary and the slope. In the discrimination functions, Chinese listeners showed greater peakedness than English peers. The cross-linguistic differences in intonation perception were similar to the previous findings in perception of lexical tones, likely due to listeners’ language background differences.
B Cell Receptor Signal Transduction in the GC Is Short-Circuited by High Phosphatase Activity
Authors: Khalil Ashraf M. , Cambier John C. , Shlomchik Mark J.
Published: May 2012

So Selective

The key elements for long-lived antibody-mediated immunity—memory B cells and plasmablasts—are generated in germinal centers, where B cells expressing high-affinity antigen receptors are selected for survival and proliferation in a process called affinity maturation. Unexpectedly,

Khalil
et al.

(p.
1178
, published online 3 May; see the Perspective by

Bannard and Cyster

) found that, in contrast to naïve B cells and B cells outside the germinal center, proximal signaling events are impaired downstream of the antigen receptor in mouse germinal center B cells.
Axillary temperature measurement during hypothermia treatment for neonatal hypoxic-ischaemic encephalopathy
Authors: Landry Marc-Antoine , Doyle Lex W , Lee Katherine , Jacobs Susan E
Published: May 2012

Objective

To determine the accuracy of axillary temperature relative to core rectal temperature during whole-body therapeutic hypothermia for moderate-to-severe hypoxic-ischaemic encephalopathy.

Design

Retrospective audit.

Setting

Single tertiary neonatal intensive care unit at The Royal Women's Hospital in Australia.

Patients

Fifty-eight term newborn infants with moderate-to-severe hypoxic-ischaemic encephalopathy. Forty infants were treated with whole-body hypothermia between February 2001 and May 2010, 16 of whom were enrolled in the Infant Cooling Evaluation (ICE) trial, and 18 control infants randomised to normothermia in the ICE trial.

Intervention

Comparison of simultaneous axillary and rectal temperatures measured between 0 and 84 h post randomisation or induction of cooling.

Results

During the initiation of hypothermia (0–<6 h) axillary and rectal temperatures were similar (mean difference rectal-axillary =0.07°C), but with large variability (95% limits of agreement −1.18 to 1.33°C). There was larger variability in measurements between 6 and <72 h in the hypothermic infants (total SD 0.44) than in the normothermic group (total SD 0.24, p<0.001). In the hypothermic infants, the mean difference between the measurements during the rewarming phase (72–<84 h) was −0.19°C (95% limits of agreement −0.95 to 0.57°C).

Conclusion

As there is wide variability in the difference between axillary and rectal temperatures at all stages of whole-body cooling, our data do not support the use of axillary temperature as a surrogate for core rectal temperature during therapeutic hypothermia.
Uterotonic drug quality: an assessment of the potency of injectable uterotonic drugs purchased by simulated clients in three districts in Ghana
Authors: Stanton Cynthia , Koski Alissa , Cofie Patience , Mirzabagi Ellie , Grady Breanne L , Brooke Steve
Published: May 2012

Objectives

Given use of uterotonics for postpartum haemorrhage and other obstetric indications, the importance of potent uterotonics is indisputable. This study evaluated access to and potency of injectable uterotonics in Ghana.

Design

Study design involved research assistants simulating clients to purchase oxytocin and ergometrine from different sources. Drug potency was measured via chemical assay by the Ghana Food and Drugs Board.

Setting

The study was conducted in three contrasting districts in Ghana.

Outcome measure

The per cent of active pharmaceutical ingredient was measured to assess the quality of oxytocin and ergometrine.

Results

69 formal points of sale were visited, from which 55 ergometrine ampoules and 46 oxytocin ampoules were purchased. None of the ergometrine ampoules were within British Pharmacopoeia specification for active ingredient, none were expired and one showed 0% active ingredient, suggestive of a counterfeit drug. Among oxytocin ampoules purchased, only 11 (26%) were within British Pharmacopoeia specification for active ingredient and two (4%) were expired. The median percentages of active ingredients were 64% and 50% for oxytocin and ergometrine, respectively.

Conclusions

The quality of injectable uterotonics in three contrasting districts in Ghana is a serious problem. Restrictions regarding the sale of unregistered drugs, and of registered drugs from unlicensed shops, are inadequately enforced. These problems likely exist elsewhere but are not assessed, as postmarketing drug quality surveillance is generally restricted to well-funded disease-specific programmes relying on antiretroviral, antimalarial and antibiotic drugs. Maternal health programmes must adopt and fund the same approach to drug quality as is standard in programmes addressing infectious disease.
Innovative strategy for effective critical laboratory result management: end-to-end process using automation and manual call centre
Authors: Ti Lian Kah , Ang Sophia Bee Leng , Saw Sharon , Sethi Sunil Kumar , Yip James W L
Published: May 2012

Background

Timely reporting and acknowledgement are crucial steps in critical laboratory results (CLR) management. The authors previously showed that an automated pathway incorporating short messaging system (SMS) texts, auto-escalation, and manual telephone back-up improved the rate and speed of physician acknowledgement compared with manual telephone calling alone. This study investigated if it also improved the rate and speed of physician intervention to CLR and whether utilising the manual back-up affected intervention rates.

Methods

Data from seven audits between November 2007 and January 2011 were analysed. These audits were carried out to assess the robustness of CLR reporting process in the authors' institution. Comparisons were made in the rate and speed of acknowledgement and intervention between the audits performed before and after automation. Using the automation audits, the authors compared intervention data between communication with SMS only and when manual intervention was required.

Results

1680 CLR were reported during the audit periods. Automation improved the rate (100% vs 84.2%; p<0.001) and speed (median 12 min vs 23 min; p<0.001) of CLR acknowledgement. It also improved the rate (93.7% vs 84.0%, p<0.001) and speed (median 21 min vs 109 min; p<0.001) of CLR intervention. From the automation audits, the use of SMS only did not improve physician intervention rates.

Discussion

The automated communication pathway improved physician intervention rate and time in tandem with improved acknowledgement rate and time when compared with manual telephone calling. The use of manual intervention to augment automation did not adversely affect physician intervention rate, implying that an end-to-end pathway was more important than automation alone.
A collaborative project to improve identification and management of patients with chronic kidney disease in a primary care setting in Greater Manchester
Authors: Humphreys John , Harvey Gill , Coleiro Michelle , Butler Brook , Barclay Anna , Gwozdziewicz Maciek , O'Donoghue Donal , Hegarty Janet
Published: May 2012

Problem

Research has demonstrated a knowledge and practice gap in the identification and management of chronic kidney disease (CKD). In 2009, published data showed that general practices in Greater Manchester had a low detection rate for CKD.

Design

A 12-month improvement collaborative, supported by an evidence-informed implementation framework and financial incentives.

Setting

19 general practices from four primary care trusts within Greater Manchester.

Key measures for improvement

Number of recorded patients with CKD on practice registers; percentage of patients on registers achieving nationally agreed blood pressure targets.

Strategies for change

The collaborative commenced in September 2009 and involved three joint learning sessions, interspersed with practice level rapid improvement cycles, and supported by an implementation team from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Greater Manchester.

Effects of change

At baseline, the 19 collaborative practices had 4185 patients on their CKD registers. At final data collection in September 2010, this figure had increased by 1324 to 5509. Blood pressure improved from 34% to 74% of patients on practice registers having a recorded blood pressure within recommended guidelines.

Lessons learnt

Evidence-based improvement can be implemented in practice for chronic disease management. A collaborative approach has been successful in enabling teams to test and apply changes to identify patients and improve care. The model has proved to be more successful for some practices, suggesting a need to develop more context-sensitive approaches to implementation and actively manage the factors that influence the success of the collaborative.
Cultural understanding in the provision of supportive and palliative care: perspectives in relation to an indigenous population
Authors: Johnston Grace , Vukic Adele , Parker Skylan
Published: May 2012

Objectives

The provision of supportive and palliative care for an indigenous people in Nova Scotia, Canada, was examined to further our understanding and thereby improve cultural competency. Most of Nova Scotia's indigenous people are Mi'kmaq. The Mi'kmaq Nation lives in Atlantic Canada as well as New England in the eastern USA.

Methods

Themes were identified in the literature and through discussion with seven experts who have Mi'kmaq health and cultural research expertise. This paper has been reviewed and approved by two Mi'kmaq consultants who frequently speak on behalf of the Mi'kmaq people in relation to health and cultural understanding. Recommendations for non-indigenous care providers are presented.

Results

The themes identified focused on jurisdictional issues and cultural understanding. They are interconnected and grounded in the historic Mi'kmaq context of colonialism. Jurisdictional issues experienced by the Mi'kmaq affect access, continuity and appropriateness of care. Cultural concepts were associated with worldview, spirituality, the role of family and community relationships and communication norms, and thereby with the alignment of values and language in the provision of care. Three Mi'kmaq concepts are noted: apiksiktatulti, nemu'ltus and salite.

Conclusion

Through reflection on the situation of Nova Scotia's Mi'kmaq, non-indigenous healthcare providers can assess how they might increase their cultural understanding in the provision of supportive and palliative care. Recommendations relate to the health system, relationships with individual persons and direction for research.
Seasonal variations in healthcare-associated infection in neonates in Canada
Authors: Shah Prakesh S , Yoon Woojin , Kalapesi Zarin , Bassil Kate , Dunn Michael , Lee Shoo K
Published: May 2012

Objective

To assess the seasonal pattern of healthcare-associated infections (HCAI) among neonates and to describe the trend of HCAI.

Design

Secondary analyses of database.

Setting

The Canadian Neonatal Network database (2003–2009).

Participants

Neonates with HCAI defined as blood/cerebrospinal fluid positive with pathogenic organism in a symptomatic infant after 2 days of age.

Main outcome measure

The incidence rate for HCAI per 1000 days with a 95% CI, for the 4 warmest months (June–September) was compared with the remaining 8 months, to calculate the incidence rate ratio (IRR).

Results

Of 75 629 total infants, 4305 (5.7%) had HCAI (3367 had 1 and 938 had >1 episodes). Infants who had HCAI were of lower gestation, birth weight and Apgar score; but had higher severity of illness scores and clinical chorioamnionitis. There was a borderline increase in all HCAI (IRR 1.05, 95% CI 1.00 to 1.11) and a significant increase in Gram-negative HCAI (IRR 1.20, 95% CI 1.04 to 1.39) during the summer months. Overall, there was a 20% reduction in HCAI from 4.45/1000 days in January 2003 to 3.54/1000 days in December 2009 (mean difference 0.91/1000 days (95% CI 0.89 to 0.92).

Conclusions

Gram-negative infections were significantly increased during the summer months of the year compared with the rest of the year among neonates. Overall, there was a significant temporal reduction in HCAI rates over the study period.
Variability of respiratory parameters and extubation readiness in ventilated neonates
Authors: Kaczmarek Jennifer , Kamlin C Omar Farouk , Morley Colin J , Davis Peter G , Sant'Anna Guilherme M
Published: May 2012

Background

A spontaneous breathing trial (SBT) has been used to guide suitability of extubation in VLBW infants. Respiratory variability (RV) has been used to assess extubation readiness in adults but was never investigated in preterms. The combination of a SBT and RV may further improve prediction of successful extubation.

Study design

Using data previously collected during the SBT, the following respiratory variables were analysed: inspiratory time (TI), expiratory time (TE), TI/total breath time, tidal volume (VT) and mean inspiratory flow (VT/TI). RV was quantified using time-domain analysis for each respiratory variable and expressed as a variability index (VI). The sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the SBT, each VI and combined SBT+VI were calculated. Extubation failure was defined as need of re-intubation within 72 h.

Results

A total of 44 infants were included. Successfully (n=36) and unsuccessfully (n=8) extubated infants had similar baseline characteristics and number of breaths analysed. VI for VT/TIwas significantly decreased in the failure group. The combination of the SBT and VI of either TIor VTwere the most accurate predictors of successful extubation with a sensitivity of 100% and specificity of 75% and a PPV and NPV for extubation success of 95% and 100%, respectively.

Conclusions

A significant decrease in VT/TIvariability occurred in infants requiring re-intubation. The combination of a SBT failure and decreased variability in TIor VTwas highly predictive of failure. This combination is promising but requires prospective evaluation in a larger population.
Transcriptome-level microarray expression profiling implicates IGF-1 and Wnt signalling dysregulation in the pathogenesis of thyroid-associated orbitopathy
Authors: Ezra Daniel G , Krell Jonathan , Rose Geoffrey E , Bailly Maryse , Stebbing Justin , Castellano Leandro
Published: May 2012

Aims

The pathogenesis of thyroid-associated orbitopathy (TAO) remains unclear. The aim of this study is to elucidate the gene expression profile of orbital fat from patients with active, but untreated, TAO.

Methods

A case–control gene expression study was conducted using test samples of orbital fat from TAO patients and control orbital fat specimens; apart from drugs to control thyrotoxicosis, the TAO patients had received no treatment for orbital disease. cDNA expression analysis was performed using the Affymetrix GeneChip Human Genome U133 Plus 2.0 platform and validated using quantitative PCR.

Results

The highest-ranked differentially expressed genes were dominated by IGF-1 signalling genes. These include IGF-1, IGF-1 receptor binding/signalling genes, such as SOCS3 and IRS2, and downstream signalling and transcriptional regulators, such as SGK (PDK/Akt signalling) and c-JUN. Our microarray data also demonstrate dysregulation of wingless-type MMTV (Wnt) signalling gene expression, including Wnt5a, sFRPs and DKK.

Conclusion

Altered Wnt signalling confirms previous array findings. Further investigation of the role of Wnt signalling in TAO pathogenesis is warranted. These data also provide the first evidence of dysregulation of IGF-1 pathway genes in TAO tissue, further strengthening the evidence for the role of IGF-1 signalling in the pathogenesis and potential treatment of TAO.
Neuroendocrine cells associated with neuroendocrine carcinoma of the breast: nature and significance
Authors: Kawasaki Tomonori , Mochizuki Kunio , Yamauchi Hideko , Inoue Shingo , Kondo Tetsuo , Oishi Naoki , Nakazawa Tadao , Yamane Tetsu , Koshimizu Yoshihito , Tsunoda Hiroko , Yagata Hiroshi , Inoue Masayuki , Inoue Ayako , Maruyama Takanori , Fujii Hideki , Katoh Ryohei
Published: May 2012

Background

The developmental mechanisms of breast neuroendocrine carcinoma (B-NEC) have not been sufficiently analysed and are not well understood.

Aims

To investigate NE cells in the background tissues surrounding B-NECs.

Methods

Three cases (four breasts) having many NE cells in the background tissues of multifocal B-NECs were identified at the University of Yamanashi Hospital and St Luke's International Hospital, Japan. These patients were, respectively, 28-, 31- and 38-year-old women with no familial history of NE tumour. The totally-resected breasts were serially studied by immunohistochemistry for specific NE markers (chromogranin A/synaptophysin) and the morphologies and/or localisation of NE cells were investigated.

Results

Immunohistochemical examination showed extensively-distributed NE cells in the background mammary ducts/lobules of the NECs in all breasts. These NE cells were classifiable into three emerging patterns: isolated/scattered, clustered and circumferential. Their distributions were intermingled and were not clearly related to B-NEC foci. NE cells were morphologically polygonal, oval or columnar with sometimes eosinophilic and/or fine-granular cytoplasm and round-to-ovoid nuclei lacking atypia. Some cells were located between epithelial and myoepithelial cells. Apical snouts were occasionally observed in NE cells forming luminal structures.

Conclusions

Benign-appearing NE cells in the parenchyma of a breast with NEC could be regarded as hyperplastic from their emerging patterns and distribution; this NE cell hyperplasia may be associated with the histogenesis of B-NEC as a precancerous condition. These observations might raise questions about the treatment for B-NEC.
Complex adnexal tumours of the skin: a report of three cases and review of literature
Authors: London Vanessa , Saadat Payam , Vadmal Manjunath S
Published: May 2012

Aims

Complex or composite adnexal tumours of the skin (CATS) are unusual neoplasms composed of two or more histopathologically distinct subtypes of appendageal neoplasms coexisting in a single cutaneous lesion. The authors report three examples of CATS, review literature and discuss their probable histogenesis.

Methods and results

Of the three tumours described, one tumour showed a mixture of a proliferating pilar tumour and syringocystadenoma papilliferum, the second lesion was composed of a proliferating pilar tumour and tubulopapillary hidradenoma and the third tumour exhibited a syringocystadenoma papilliferum and tubulopapillary hidradenoma in combination.

Conclusions

CATS are rare tumours. The authors reported three unique cases in addition to the 10 other reported cases. These three cases further strengthen the hypothesis of a ‘folliculosebaceous apocrine’ unit as the most likely point of origin of CATS.
MK-626, a dipeptidyl peptidase-4 inhibitor, does not improve the hyperglycemia or hyperinsulinemia of nonobese diabetic MKR mice
Authors: Bhattacharjee Alpana , Allister Emma M. , Wheeler Michael B.
Published: May 2012

Dipeptidyl peptidase-4 (DPP-4) inhibitors increase circulating levels of incretin hormones, which can enhance insulin secretion and β cell function. The aim of this study was to evaluate the effectiveness of MK-626 (a novel DPP-4 inhibitor) to reduce the hyperglycemia and hyperinsulinemia of nonobese type 2 diabetic MKR mice. Twelve to 14-week-old hyperglycemic MKR mice were gavaged daily with MK-626 (3 mg/kg body weight) or vehicle (0.5% methyl cellulose (MC)) for 2 weeks. MK-626-treated mice displayed no change in body weight or adverse reactions, suggesting good tolerance of the drug. Fed blood glucose was significantly reduced over the 2-week experiment; however, it was also reduced in the MC group, suggesting an effect of gavage alone. Fed plasma insulin and glucagon levels and glucose tolerance of MK-626-treated mice were similar to those of MC mice. Therefore, treatment with MK-626 did not correct the prolonged hyperglycemia and impaired glucose tolerance of MKR mice.
Cardoguard, an Ayurvedic antihypertensive formulation, prevents cardiac remodeling in spontaneously hypertensive rats by inhibition of ERK and PKCε signaling pathways
Authors: Sankar Vandana , Nair Renuka R. , Harikrishnan Vijayakumar S. , Fernandez Adelaide C. , Kumar Cherumanal S. Krishna , Madhavachandran Viswanathamenon
Published: May 2012

Ayurveda is an Indian system of medicine. Despite clinical efficacy, lack of scientific validation has limited the effective use of Ayurvedic drugs. Cardoguard is an Ayurvedic antihypertensive drug formulated by Nagarjuna Herbal Concentrates Ltd., Kerala, India. Left ventricular hypertrophy (LVH) is a modifiable risk factor, and regression of LVH reduces the propensity for adverse cardiovascular events. This study was taken up with the objective of evaluating the efficacy of Cardoguard in the prevention of cardiac remodeling. Cardoguard was administered orally to 2-month-old spontaneously hypertensive rats for 4 months at a dose of 5 mg·day–1. The dose corresponds to the therapeutic dose calculated on the basis of body surface area. Lower hypertrophy index, decrease in cardiomyocyte area, and reduction of interstitial fibrosis in treated spontaneously hypertensive rats indicate amelioration of cardiac hypertrophy by Cardoguard. Cardiac output increased in response to treatment. Immunostaining for the phosphorylated components of major signaling pathways associated with hypertrophy suggests that prevention of LVH by Cardoguard is possibly mediated through inhibition of extracellular signal-regulated kinases and protein kinase C-ε signaling pathways. Reduced expression of 3-nitrotyrosine in response to the treatment suggests that prevention of cardiac remodeling by Cardoguard is mediated by reduction of oxidative stress.
Protective effect of urantide against ischemia–reperfusion injury via protein kinase C and phosphtidylinositol 3′-kinase – Akt pathway
Authors: Zhang Jun-Yan , Chen Zhi-Wu , Yao Hua
Published: May 2012

Urantide is the most potent UT receptor antagonist compound found to date. Our previous studies have shown that it has cardioprotective effect against ischemia–reperfusion injury. However, it is unclear which signal transduction pathways are involved in the urantide-induced cardioprotective effect. This study was designed to investigate whether the effect of urantide on myocardial ischemia–reperfusion injury in rats via the protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K)–Akt signaling pathway. The results showed that urantide at 10 and 30 µg/kg markedly inhibited the increases in serum creatine kinase fraction and lactate dehydrogenase activities and the level of cardiac troponin I, reduced the ratio of myocardial infarct size to area at risk. Urantide significantly decreased the histological damage to the myocardium and modified the ultrastructural damage in cardiac myocytes. In the presence of chelerythrine (an inhibitor of PKC, 1 mg/kg) or LY294002 (an inhibitor of PI3K–Akt, 0.3 mg/kg), the protective effect of urantide was almost completely abolished. Urantide (30 µg/kg) markedly enhanced the expression of p-Akt protein during myocardial ischemia–reperfusion injury, and this enhancement was significantly attenuated by LY294002. Therefore, our results demonstrate that urantide has a potent protective effect against myocardial ischemia–reperfusion injury in rats that may be involved with the PKC and PI3K–Akt signaling pathways.
ON SEMICLASSICAL CALCULATION OF THREE-POINT FUNCTIONS IN AdS5×T1, 1
Authors: MICHALCIK M. , RASHKOV R. C. , SCHIMPF M.
Published: May 2012

Recently there has been progress on the computation of two- and three-point correlation functions with two "heavy" states via semiclassical methods. We extend this analysis to the case of AdS5×T1, 1, and examine the suggested procedure for the case of several simple string solutions. By making use of AdS/CFT duality, we derive the relevant correlation functions of operators belonging to the dual gauge theory.
COMPACTIFIED STRING THEORIES — GENERIC PREDICTIONS FOR PARTICLE PHYSICS
Authors: ACHARYA BOBBY SAMIR , KANE GORDON , KUMAR PIYUSH
Published: May 2012

In recent years it has been realized that in string/M theories compactified to four dimensions which satisfy cosmological constraints, it is possible to make some generic predictions for particle physics and dark matter: a nonthermal cosmological history before primordial nucleosynthesis, a scale of supersymmetry breaking which is "high" as in gravity mediation, scalar superpartners too heavy to be produced at the LHC (although gluino production is expected in many cases), and a significant fraction of dark matter in the form of axions. When the matter and gauge spectrum below the compactification scale is that of the MSSM, a robust prediction of about 125 GeV for the Higgs boson mass, predictions for various aspects of dark matter physics, as well as predictions for future precision measurements, can be made. As a prototypical example, M theory compactified on a manifold of G2holonomy leads to a good candidate for our "string vacuum," with the TeV scale emerging from the Planck scale, a de Sitter vacuum, robust electroweak symmetry breaking, and solutions of the weak and strong CP problems. In this article we review how these and other results were derived, from the key theoretical ideas to the final phenomenological predictions.
ON FERMION MASSES AND MIXING IN A MODEL WITH A4 SYMMETRY
Authors: MACHADO A. C. B. , MONTERO J. C. , PLEITEZ V.
Published: May 2012

In a recently proposed multi-Higgs extension of the standard model in which discrete symmetries, A4 and Z3 are imposed we show that, after accommodating the fermion masses and the mixing matrices in the charged currents, the mixing matrices in the neutral currents induced by neutral scalars are numerically obtained. However, the flavor changing neutral currents are under control mainly by mixing and/or mass suppressions in the neutral scalar sector.
ON NUMBER FIELDS WITH EQUIVALENT INTEGRAL TRACE FORMS
Authors: MANTILLA-SOLER GUILLERMO
Published: May 2012

Let K be a number field. The integral trace form is the integral quadratic form given by tr k/ℚ(x2)|OK. In this article we study the existence of non-conjugated number fields with equivalent integral trace forms. As a corollary of one of the main results of this paper, we show that any two non-totally real number fields with the same signature and same prime discriminant have equivalent integral trace forms. Additionally, based on previous results obtained by the author and the evidence presented here, we conjecture that any two totally real quartic fields of fundamental discriminant have equivalent trace zero forms if and only if they are conjugated.
EXTENDING GAUSSIAN HYPERGEOMETRIC SERIES TO THE p-ADIC SETTING
Authors: MCCARTHY DERMOT
Published: May 2012

We define a function which extends Gaussian hypergeometric series to the p-adic setting. This new function allows results involving Gaussian hypergeometric series to be extended to a wider class of primes. We demonstrate this by providing various congruences between the function and truncated classical hypergeometric series. These congruences provide a framework for proving the supercongruence conjectures of Rodriguez-Villegas.