bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis
Authors: Mattey Derek L , Packham Jonathan C , Nixon Nicola B , Coates Lucy , Creamer Paul , Hailwood Sarah , Taylor Gordon J , Bhalla Ashok K
Published: June 2012

Introduction

The pathology of ankylosing spondylitis (AS) suggests that certain cytokines and matrix metalloproteinases (MMPs) might provide useful markers of disease activity. Serum levels of some cytokines and MMPs have been found to be elevated in active disease, but there is a general lack of information about biomarker profiles in AS and how these are related to disease activity and function. The purpose of this study was to investigate whether clinical measures of disease activity and function in AS are associated with particular profiles of circulating cytokines and MMPs.

Methods

Measurement of 30 cytokines, five MMPs and four tissue inhibitors of metalloproteinases was carried out using Luminex® technology on a well-characterised population of AS patients (n = 157). The relationship between biomarker levels and measures of disease activity (Bath ankylosing spondylitis disease activity index (BASDAI)), function (Bath ankylosing spondylitis functional index) and global health (Bath ankylosing spondylitis global health) was investigated. Principal component analysis was used to reduce the large number of biomarkers to a smaller set of independent components, which were investigated for their association with clinical measures. Further analyses were carried out using hierarchical clustering, multiple regression or multivariate logistic regression.

Results

Principal component analysis identified eight clusters consisting of various combinations of cytokines and MMPs. The strongest association with the BASDAI was found with a component consisting of MMP-8, MMP-9, hepatocyte growth factor and CXCL8, and was independent of C-reactive protein levels. This component was also associated with current smoking. Hierarchical clustering revealed two distinct patient clusters that could be separated on the basis of MMP levels. The high MMP cluster was associated with increased C-reactive protein, the BASDAI and the Bath ankylosing spondylitis functional index.

Conclusions

A profile consisting of high levels of MMP-8, MMP-9, hepatocyte growth factor and CXCL8 is associated with increased disease activity in AS. High MMP levels are also associated with smoking and worse function in AS.
Bone marrow-derived, alternatively activated macrophages enhance solid tumor growth and lung metastasis of mammary carcinoma cells in a Balb/C mouse orthotopic model
Authors: Cho Han Jin , Jung Jae In , Lim Do Young , Kwon Gyoo Taik , Her Song , Park Jong Hoon , Park Jung Han Yoon
Published: June 2012

Introduction

Tumor-associated macrophages, which are derived from the infiltration of circulating bone marrow-derived monocytes, consist primarily of a polarized M2 macrophage (M2-Mϕ) population and are associated with poor prognosis in various cancers. In the present study, we attempted to assess whether M2-Mϕs derived from bone marrow stimulate the promotion and progression of mammary tumors.

Methods

4T1 murine mammary carcinoma cells were injected either alone or coupled with M2-Mϕs into the mammary fat pads of syngeneic female Balb/C mice. M2-Mϕs were prepared by treating monocytes isolated from female Balb/C mouse bone marrow with IL-4. Tumor cell growth was determined using an in vivo imaging system and the expression of cell proliferation-related, angiogenesis-related, and lymphangiogenesis-related proteins in tumor tissues was immunohistochemically analyzed. To evaluate the effects of the crosstalk between 4T1 cells and M2-Mϕs on the secretion and mRNA expression of cytokines and the migration of monocytes, 4T1 cells and M2-Mϕs were co-cultured and cytokine antibody array, real-time RT-PCR, and trans-well migration assays were conducted.

Results

The co-injection of M2-Mϕs into the mammary fat pads of mice increased solid tumor growth and lung metastasis of 4T1 cells as well as the infiltration of CD45+ leukocytes into tumor tissues. The proportions of Ki-67+ proliferating cells and the expression of hypoxia inducible factor-1α, vascular endothelial cell growth factor A, CD31, vascular endothelial cell growth factor C, and lymphatic vessel endothelial receptor-1 were increased significantly in the tumor tissues of mice co-injected with 4T1 cells and M2-Mϕs. The in vitro results revealed that the proliferation of 4T1 cells, the migration of monocytes, and the secretion of granulocyte colony-stimulating factor, IFNγ, IL-1α, IL-2, IL-16, IFNγ-induced protein-10, keratinocyte-derived chemokine, macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, and RANTES were increased when 4T1 cells were co-cultured with M2-Mϕs, as compared with when the 4T1 cells were cultured alone.

Conclusion

The crosstalk between 4T1 cells and M2-Mϕs increased the production of cytokines, which may have induced immune cell infiltration into tumor tissues, tumor cell proliferation, angiogenesis, and lymph angiogenesis, thereby increasing solid tumor growth and lung metastasis.
Implications of constructed biologic subtype and its relationship to locoregional recurrence following mastectomy
Authors: Dominici Laura S , Mittendorf Elizabeth A , Wang Xumei , Liu Jun , Kuerer Henry M , Hunt Kelly K , Brewster Abenaa , Babiera Gildy V , Buchholz Thomas A , Meric-Bernstam Funda , Bedrosian Isabelle
Published: June 2012

Introduction

We examined the prognostic value of biologic subtype on locoregional recurrence (LRR) after mastectomy in a cohort of low risk women who did not receive adjuvant radiation therapy.

Methods

A total of 819 patients with invasive breast cancer underwent mastectomy from January 2000 through December 2005. No patient received preoperative chemotherapy. Estrogen receptor (ER) receptor, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status were used to construct the following 4 subtypes: i) ER+ or PR+ and HER2- (HR+/HER2-), ii) ER+ or PR+ and HER2+ (HR+/HER2+), iii) ER- and PR- and HER2+ (HR-/HER2+)and iv) ER- and PR- and HER2- (HR-/HER2-). LRR-free survival was estimated by the Kaplan-Meier method. Cox proportional hazard models were used to evaluate the association between time-to-event outcomes and patient prognostic factors.

Results

At a median follow-up of 58 months, five-year cumulative incidence of LRR for the entire cohort was 2.5%. Subtype specific LRR rates were 1% for HR+/HER2-, 6.5% in HR+/HER2+, 2% for HR-/HER2+ and 10.9% for HR-/HER2- (P < 0.01). In HER-2+ patients (irrespective of ER/PR status), trastuzumab therapy was not associated with LRR-free survival. On multivariate analysis, one to three positive lymph nodes (HR 4.75 (confidence interval (CI) 1.75 to 12.88, P < 0.01), ≥ 4 positive lymph nodes (HR23.4 (CI 4.64 to 117.94, P < 0.01), HR+/HER2+ (HR 4.26 (CI 1.05 to 17.33), P = 0.04), and HR-/HER2- phenotype (HR 13.87 (CI 4.96 to 38.80), P < 0.01) were associated with shorter LRR-free survival whereas age > 50 at diagnosis (HR 0.31 (CI 0.12 to 0.80), P = 0.02) was associated with improved LRR-free survival. Among the HR-/HER2- subtypes, five-year LRR incidence was 23.4% in patients with positive lymph nodes compared to 7.8% for lymph node negative patients (P = 0.01), although this association did not reach significance when the analysis was limited to HR-/HER2- women with only one to three positive lymph nodes (15.6% versus 7.8%, P = 0.11).

Conclusions

Constructed subtype is a prognostic factor for LRR after mastectomy among low risk women not receiving adjuvant radiation therapy, although rates of LRR remain low across subtypes. Patients with node positive, HR-/HER2- type tumors were more likely to experience LRR following mastectomy alone. Prospective studies to further investigate the potential benefit of adjuvant radiation therapy in these women are warranted.
Early versus late parenteral nutrition in ICU patients: cost analysis of the EPaNIC trial
Authors: Vanderheyden Simon , Casaer Michael P , Kesteloot Katrien , Simoens Steven , De Rijdt Thomas , Peers Guido , Wouters Pieter J , Coenegrachts Jocelijn , Grieten Tine , Polders Katleen , Maes Ann , Wilmer Alexander , Dubois Jasperina , Van den Berghe Greet , Mesotten Dieter
Published: June 2012

Introduction

The EPaNIC randomized controlled multicentre trial showed that postponing initiation of parenteral nutrition (PN) in ICU-patients to beyond the first week (Late-PN) enhanced recovery, as compared with Early-PN. This was mediated by fewer infections, accelerated recovery from organ failure and reduced duration of hospitalization. Now, the trial's preplanned cost analysis (N = 4640) from the Belgian healthcare payers' perspective is reported.

Methods

Cost data were retrieved from individual patient invoices. Undiscounted total healthcare costs were calculated for the index hospital stay. A cost tree based on acquisition of new infections and on prolonged length-of-stay was constructed. Contribution of 8 cost categories to total hospitalization costs was analyzed. The origin of drug costs was clarified in detail through the Anatomical Therapeutic Chemical (ATC) classification system. The potential impact of Early-PN on total hospitalization costs in other healthcare systems was explored in a sensitivity analysis.

Results

ICU-patients developing new infection (24.4%) were responsible for 42.7% of total costs, while ICU-patients staying beyond one week (24.3%) accounted for 43.3% of total costs. Pharmacy-related costs represented 30% of total hospitalization costs and were increased by Early-PN (+608.00 EUR/patient, p = 0.01). Notably, costs for ATC-J (anti-infective agents) (+227.00 EUR/patient, p = 0.02) and ATC-B (comprising PN) (+220.00 EUR/patient, p = 0.006) drugs were increased by Early-PN. Sensitivity analysis revealed a mean total cost increase of 1,210.00 EUR/patient (p = 0.02) by Early-PN, when incorporating the full PN costs.

Conclusions

The increased costs by Early-PN were mainly pharmacy-related and explained by higher expenditures for PN and anti-infective agents. The use of Early-PN in critically ill patients can thus not be recommended for both clinical (no benefit) and cost-related reasons.

Trial registration

ClinicalTrials.gov NCT00512122.
Genomic diversity of the human intestinal parasite Entamoeba histolytica
Authors: Weedall Gareth D , Clark C Graham , Koldkjaer Pia , Kay Suzanne , Bruchhaus Iris , Tannich Egbert , Paterson Steve , Hall Neil
Published: June 2012

Background

Entamoeba histolytica is a significant cause of disease worldwide. However, little is known about the genetic diversity of the parasite. We re-sequenced the genomes of ten laboratory cultured lines of the eukaryotic pathogen Entamoeba histolytica in order to develop a picture of genetic diversity across the genome.

Results

The extreme nucleotide composition bias and repetitiveness of the E. histolytica genome provide a challenge for short-read mapping, yet we were able to define putative single nucleotide polymorphisms in a large portion of the genome. The results suggest a rather low level of single nucleotide diversity, although genes and gene families with putative roles in virulence are among the more polymorphic genes. We did observe large differences in coverage depth among genes, indicating differences in gene copy number between genomes. We found evidence indicating that recombination has occurred in the history of the sequenced genomes, suggesting that E. histolytica may reproduce sexually.

Conclusions

E. histolytica displays a relatively low level of nucleotide diversity across its genome. However, large differences in gene family content and gene copy number are seen among the sequenced genomes. The pattern of polymorphism indicates that E. histolytica reproduces sexually, or has done so in the past, which has previously been suggested but not proven.
A high-throughput approach to identify genomic variants of bacterial metabolite producers at the single-cell level
Authors: Binder Stephan , Schendzielorz Georg , Stäbler Norma , Krumbach Karin , Hoffmann Kristina , Bott Michael , Eggeling Lothar
Published: June 2012

We present a novel method for visualizing intracellular metabolite concentrations within single cells of Escherichia coli and Corynebacterium glutamicum that expedites the screening process of producers. It is based on transcription factors and we used it to isolate new L-lysine producing mutants of C. glutamicum from a large library of mutagenized cells using fluorescence-activated cell sorting (FACS). This high-throughput method fills the gap between existing high-throughput methods for mutant generation and genome analysis. The technology has diverse applications in the analysis of producer populations and screening of mutant libraries that carry mutations in plasmids or genomes.
Temperature-related deaths in people with psychosis, dementia
and substance misuse
Authors: Page Lisa A. , Hajat Shakoor , Kovats R. Sari , Howard Louise M.
Published: June 2012

Background

Climate change is expected to have significant effects on human health,
partly through an increase in extreme events such as heatwaves. People
with mental illness may be at particular risk.

Aims

To estimate risk conferred by high ambient temperature on patients with
psychosis, dementia and substance misuse.

Method

We applied time-series regression analysis to data from a nationally
representative primary care cohort study. Relative risk of death per 1°
increase in temperature was calculated above a threshold.

Results

Patients with mental illness showed an overall increase in risk of death
of 4.9% (95% CI 2.0–7.8) per 1° increase in temperature above the 93rd
percentile of the annual temperature distribution. Younger patients and
those with a primary diagnosis of substance misuse demonstrated greatest
mortality risk.

Conclusions

The increased risk of death during hot weather in patients with
psychosis, dementia and substance misuse has implications for public
health strategies during heatwaves.
Community compulsion in Scotland: a descriptive analysis
Authors: Brown Rachel , Taylor Mark , Mackay Kirsty , Macleod Callum , Lyons Donald
Published: June 2012

Aims and method

Community compulsion via community compulsory treatment orders is used routinely in Scotland. We aimed to describe the common characteristics of individuals subject to community compulsion. We collected standardised information from a national database about individuals subject to community compulsion and compared them with people subject to hospital detention.

Results

Analysis of 499 cases revealed that the majority of individuals subject to community compulsion had a psychotic illness, had a history of non-adherence to services and treatment, and were more likely than not to be in receipt of a long-acting injection of antipsychotic medication. Patients subject to community compulsion were clinically similar to patients subject to hospital-based treatment orders and usually were considered to pose a risk to other people.

Clinical implications

Community compulsion has been widely adopted despite a relative lack of supporting scientific evidence. Our findings are similar to those of other related studies and highlight that individuals with a psychotic illness who are ambivalent about treatment and who pose a risk to self or others are likely to be considered for community compulsion.
Infant mental health: classification and relevance for clinicians
Authors: Ahamat Boolang R. , Minnis Helen
Published: June 2012

Infant mental health is a growing research area, but findings have not generally translated into new service developments. Recognising mental health problems in young infants is relevant for clinicians in all mental health specialties, but it can be a particular challenge to make diagnoses in very young children. Mental health classification systems are fraught with the difficulties of standardising diagnoses for infants, while trying to provide a clinically useful and relevant framework. The diagnostic classification DC:0–3 appears to have strengths, for example, a clear space to consider relationship disorders, and therefore encouraging a broad assessment of the child and family. More information is beginning to gather regarding infant mental health services around the world and assessment of this patient group in clinical practice. This commentary aims to help inform clinicians about this developing field.
Predictors for retention in treatment with a UK community-based naltrexone programme for opioid dependence
Authors: Chaudhry Zubair A. , Sultan Javaid , Alam Farrukh
Published: June 2012

Aims and method

To evaluate the efficacy of naltrexone maintenance therapy in a community-based programme for opioid-dependent patients and to identify predictors for longer-term retention in treatment. A retrospective case-note study was conducted in 142 people dependent on opioids who had undergone detoxification and maintained adherence to naltrexone treatment for a minimum of 4 weeks. Social and clinical demographic factors during treatment were recorded using a standardised naltrexone monitoring scale. Efficacy was measured as retention in treatment, and potential predictors were examined using regression analysis.

Results

Although there was overall low retention of patients in treatment, 55.6% of the patients remained in treatment for 4–8 weeks, and 29.6% of the patients remained in treatment for 17 weeks or more. Enhanced long-term retention in treatment was associated with Asian or other minority ethnic status, employment, parental supervision of naltrexone administration, less boredom, short duration of addiction, younger age, low alcohol intake and no cannabis use in univariate analyses. Short duration of opioid dependence syndrome (3 years) and low alcohol intake (<10 units/week) were significant independent predictors for longer-term retention in treatment in subsequent multivariate analysis.

Clinical implications

Low alcohol intake and shorter duration of addiction were significant independent predictors for longer-term retention in treatment, but retention rates for naltrexone remain low overall. Additional psychosocial support may be needed to address these issues.
Factors affecting the practice of seclusion in an acute mental health service in Southland, New Zealand
Authors: Tyrer Stephen , Beckley Jay , Goel Digvijay , Dennis Brian , Martin Brenda
Published: June 2012

Aims and method

This study examined the frequency of seclusion intervention and factors associated with its use in the acute general adult psychiatric ward serving the Southland area of New Zealand. Details of the use of seclusion and relevant demographic data were collected over a 12-month period in 2007–2008.

Results

During the study period there were 30 seclusion episodes involving 23 patients. The median duration of seclusion was 17 hours. The duration of seclusion was found to be inversely related to the treatment received during the period of isolation. Most patients under seclusion had a diagnosis of psychosis, and the nature of this was directly related to the Mental Health Act order applied.

Clinical implications

The duration of seclusion in this study is long but compares with a similar study from elsewhere in New Zealand. The duration of treatment while in seclusion could be reduced if optimal treatment is given.
Psychiatry in scripture: sacred texts and psychopathology
Authors: Cook Christopher C. H.
Published: June 2012

The engagement of psychiatry with religion is increasingly important for better understanding of the ways in which religious people find resources to cope with mental disorder. An example of how a more critical and constructive engagement might be achieved is found in the psychiatric literature on sacred texts. Articles which engage with the alleged psychopathology of the 6th-century BC Hebrew prophet Ezekiel are examined as an example of this and proposals are made for a more critical yet sensitive and constructive future debate.
The bHLH factors Dpn and members of the E(spl) complex mediate the function of Notch signalling regulating cell proliferation during wing disc development
Authors: San Juan Beatriz P. , Andrade-Zapata Irene , Baonza Antonio
Published: June 2012

The Notch signalling pathway plays an essential role in the intricate control of cell proliferation and pattern formation in many organs during animal development. In addition, mutations in most members of this pathway are well characterized and frequently lead to tumour formation. The Drosophila imaginal wing discs have provided a suitable model system for the genetic and molecular analysis of the different pathway functions. During disc development, Notch signalling at the presumptive wing margin is necessary for the restricted activation of genes required for pattern formation control and disc proliferation. Interestingly, in different cellular contexts within the wing disc, Notch can either promote cell proliferation or can block the G1-S transition by negatively regulating the expression of dmyc and bantam micro RNA. The target genes of Notch signalling that are required for these functions have not been identified. Here, we show that the Hes vertebrate homolog, deadpan (dpn), and the Enhancer-of-split complex (E(spl)C) genes act redundantly and cooperatively to mediate the Notch signalling function regulating cell proliferation during wing disc development.
Anomalous Efficacy of Bimetallic Au/Pd Nanoclusters in C–Cl Bond Activation and Formal Metathesis-type C–B Bond Activation at Room Temperature
Authors: Dhital Raghu Nath , Sakurai Hidehiro
Published: June 2012

Au/Pd alloy nanoclusters stabilized by poly(N-vinylpyrrolidone) catalyze two different reactions of phenylboronic acid with 4-chlorobenzoic acid at room temperature in a single reaction cycle, cross coupling and metathesis-type homocoupling that is normally inaccessible through conventional catalysis.
2-(N-Acyl-N-carboxymethylamino)-1-nitrodibenzo[b,d]thiophene: A New Class of Caging Group for Environmental Selective Photorelease of Carboxylic Acid
Authors: Tanaka Yuji , Momotake Atsuya , Arai Tatsuo
Published: June 2012

The new environment sensitive photolabile protecting group, N-carboxymethyl-1-nitrodibenzo[b,d]thiophen-2-ylamino (CNDT) group, is described. CNDT-caging compound underwent efficient photochemical reaction to produce desired acetic acid in the presence of zwitterionic detergent, CHAPS.
Synthesis of Insulated Pt–Alkynyl Complex Polymer
Authors: Terao Jun , Masai Hiroshi , Fujihara Tetsuaki , Tsuji Yasushi
Published: June 2012

A Pt–alkynyl polymer in which the π-conjugated chain was completely covered with macrocycles was synthesized by intramolecular self-inclusion of an oligomeric phenyleneethynylene as a guest moiety with two permethylated α-cyclodextrins as hosts followed by copolymerization with a Pt(II) complex.
Prognostic value of tumor burden measurement using the number of tumors in non-surgical patients with non-small cell lung cancer
Authors: Zhang Hao , Wroblewski Kristen , Pu Yonglin
Published: June 2012

Background

No study to test the feasibility and prognostic value of the number of primary tumors, the number of positive lymph nodes, and the total number of tumors in the whole body as tumor burden measurements on FDG PET/CT imaging has been reported.

Purpose

To determine whether the number of tumors seen in 18F-FDG PET scans can be a prognostic factor in non-surgical patients with non-small cell lung cancer (NSCLC).

Material and Methods

One hundred and forty patients with histologically proven NSCLC and baseline 18F-FDG PET scan before therapy were identified in this retrospective analysis. The total number of tumors (TTn) in the whole body, the number of primary tumors (Tn), positive lymph nodes (Nn), and distant metastases (Mn), along with the maximum standardized uptake values (SUVmax) of the tumors were measured. Inter-observer variability of the total number of tumors, counted by two radiologists, was assessed. Survival analyses were performed to determine the prognostic value of the number of tumors.

Results

Concordance correlation coefficients for the TTn, Tn, Nn, and Mn were all greater than 0.85. TTn and Nn were strong prognostic factors of NSCLC patients' overall survival (OS). In univariate Cox regression models, gender, stage, TTn, Nn, and Mn were statistically significant factors ( P = 0.016, 0.032, <0.001, <0.001, and 0.006, respectively). In multivariate Cox regression models, TTn and Nn remained as statistically significant predictors for survival with hazard ratios (HR) of 1.06 ( P = 0.001) and 1.11 ( P = 0.002), respectively, after adjusting for clinical stage based 7th edition of TNM staging system, age, gender, and SUVmax. Patients with a TTn ≤4 (cutpoint based on median value) had a median OS of 15.2 months compared with 9.0 months for those with TTn >4.

Conclusion

Measuring the number of tumors on FDG PET imaging is easy to perform with minimal inter-observer variability. The total number of tumors and number of nodal metastases, as metabolic tumor burden measurements in 18F-FDG PET/CT, are prognostic markers independent of clinical stage, age, gender, and SUV measurement in non-surgical patients with NSCLC.
Patient information leaflets for extracorporeal shock wave lithotripsy: questionnaire survey
Authors: Askari A , Shergill I
Published: June 2012

Summary

Objectives

To compare the level of information provided in extracorporeal Shock wave lithotripsy (ESWL) patient information leaflets in the London and East of England Deaneries

Design

All trusts in the London and East of England Deanery who offer an ESWL service were contacted and leaflets were compared

Setting

London and East of England Deanery

Participants

Alan Askari, Iqbal Shergill

Main outcome measures

Examination of key information that was communicated to ESWL patients via leaflets

Results

12 trusts responded across the two deaneries. There was significant variation in the amount of information provided in the leaflets with some leaflets not containing an adequate level of instruction or information to patients

Conclusions

The authors propose that a national standardised information leaflet should be incorporated with the British Association of Urological Surgeons (BAUS) procedure specific information leaflet for ESWL procedures
The Court of Appeals of Virginia Uses Integer Programming and Cloud Computing to Schedule Sessions
Authors: Brooks J. Paul
Published: June 2012

Each spring, a deputy clerk of the Court of Appeals of Virginia manually schedules panel sessions and assigns judges to sessions for the following calendar year. The information technology department for the Supreme Court of Virginia, the head of the judicial branch of government in Virginia, also serves the Court of Appeals of Virginia. In the spring of 2010, the staff of the Court of Appeals of Virginia and the information technology staff contacted Virginia Commonwealth University to explore a computational approach to generating schedules. Together, we developed a tool that uses integer programming to generate schedules; we used the method to generate the 2011 schedule, resulting in savings of up to 150 hours of work annually. The schedule satisfies all the constraints required by the court by properly distributing panel sessions among its districts throughout the year. The court places great importance on its members not becoming parochial; to that end, judges sit in disparate panels to hear litigants, who convene in regions throughout the state, to ensure a more uniform application of the law. The court used industrial-strength integer programming software to generate the 2011 schedule at low cost by using resources available on the Cloud.
Hanover County Improves Its Response to Emergency Medical 911 Patients
Authors: McLay Laura A. , Moore Henri
Published: June 2012

Meeting emergency medical service (EMS) performance measure benchmarks for patient response times is an important factor in saving patient lives. Hanover County Fire and EMS in Virginia initiated a quick-response vehicle (QRV) pilot program in which it replaced some of its ambulances and fire engines with three sport utility vehicles to more effectively coordinate patient response. The decision to use the QRVs is based on an analysis provided by analytical models that estimate the potential improvements in Hanover County's performance measure of responding to patients within nine minutes of dispatch. We use data collected over two years to evaluate the impact of the QRV pilot program. The results report significant improvements to patient response times without increasing personnel costs. When using QRVs, Hanover County Fire and EMS responded to an additional 4.9 percent of high-priority patients within nine minutes compared to its prior operations, which did not use QRVs. The faster response times occurred across all patients, which is an important factor in improving patient survival rates for the most critical classes of patients who are experiencing life-threatening health issues such as cardiac arrest.
Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis
Authors: Yang Xiaokui , Zhou Ying , Peng Sha , Wu Liang , Lin Hai-Yan , Wang Shuyu , Wang Hongmei
Published: June 2012

Recent studies implicate the regulatory function of microRNAs (miRNAs) in oocyte maturation and ovarian follicular development. Differentially expressed miRNAs are found in the plasma of premature ovarian failure (POF) patients and normal cycling women. In this study, miRNA-regulated signaling pathways and related genes were described using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. The effect of mir-23a on granulosa cell apoptosis was also studied by examining the protein expression of X-linked inhibitor of apoptosis protein (XIAP) and caspase-3, followed by subsequent counting of apoptotic cells after Hoechst 33258 staining. Both GO analysis and pathway analysis suggested that many signaling pathways, including the AKT signaling pathway, steroid hormone receptor signaling pathways, and others, were regulated by this group of differentially expressed miRNAs. A decrease in XIAP expression (mRNA and protein level) and caspase-3 protein levels and an increase in cleaved caspase-3 protein were observed in human ovarian granulosa cells transfected with pre-mir-23a, along with an increased occurrence of apoptosis. In conclusion, differentially expressed miRNAs in the plasma of POF patients may have regulatory effects on proliferation and apoptosis of granulosa cells by affecting different signaling pathways. Mir-23a may play important roles in regulating apoptosis via decreasingXIAPexpression in human ovarian granulosa cells.
Identification of miRNAs associated with the follicular–luteal transition in the ruminant ovary
Authors: McBride D , Carré W , Sontakke S D , Hogg C O , Law A , Donadeu F X , Clinton M
Published: June 2012

Little is known about the involvement of microRNAs (miRNAs) in the follicular–luteal transition. The aim of this study was to identify genome-wide changes in miRNAs associated with follicular differentiation in sheep. miRNA libraries were produced from samples collected at defined stages of the ovine oestrous cycle and representing healthy growing follicles, (diameter, 4.0–5.5 mm), pre-ovulatory follicles (6.0–7.0 mm), early corpora lutea (day 3 post-oestrus) and late corpora lutea (day 9). A total of 189 miRNAs reported in sheep or other species and an additional 23 novel miRNAs were identified by sequencing these libraries. miR-21, miR-125b, let-7a and let-7b were the most abundant miRNAs overall, accounting for 40% of all miRNAs sequenced. Examination of changes in cloning frequencies across development identified nine different miRNAs whose expression decreased in association with the follicular–luteal transition and eight miRNAs whose expression increased during this transition. Expression profiles were confirmed by northern analyses, and experimentally validated targets were identified using miRTarBase. A majority of the 29 targets identified represented genes known to be actively involved in regulating follicular differentiation in vivo. Finally, luteinisation of follicular cells in vitro resulted in changes in miRNA levels that were consistent with those identified in vivo, and these changes were temporally associated with changes in the levels of putative miRNA targets in granulosa cells. In conclusion, this is the first study to characterise genome-wide miRNA profiles during different stages of follicle and luteal development. Our data identify a subset of miRNAs that are potentially important regulators of the follicular–luteal transition.
Identification ofInverse Regulator-a(Inr-a) as Synonymous with Pre-mRNA Cleavage Complex II Protein (Pcf11) in Drosophila
Authors: Xie Weiwu , Birchler James A
Published: June 2012

A common modulation of gene expression in aneuploids is an inverse correlation of the monitored gene with the dosage of another segment of the genome. Such effects can be reduced to the action of single genes. One gene previously found to modulate leaky alleles of the white eye color gene in Drosophila is Inverse regulator-a (Inr-a). Heterozygotes of mutations increase the expression of white about 2-fold, and trisomic regions surrounding the gene reduce the expression to about two-thirds of the normal diploid level. Further cytological definition of the location of this gene on the second chromosome led to a candidate pre-mRNA cleavege complex II protein (Pcf11) as the only gene in the remaining region whose mutations exhibit recessive lethality as do alleles of Inr-a. The product of Pcf11 has been implicated in transcriptional initiation, elongation, and termination reactions. Four mutant alleles showed molecular lesions predicted to lead to nonfunctional products of Pcf11. The identification of the molecular lesion of Inr-a provides insight into the basis of this common aneuploidy effect.
Convergent Evolution of Calcineurin Pathway Roles in Thermotolerance and Virulence inCandida glabrata
Authors: Chen Ying-Lien , Konieczka Jay H , Springer Deborah J , Bowen Samantha E , Zhang Jing , Silao Fitz Gerald S , Bungay Alice Alma C , Bigol Ursela G , Nicolas Marilou G , Abraham Soman N , Thompson Dawn A , Regev Aviv , Heitman Joseph
Published: June 2012

Candida glabrata is an emerging human fungal pathogen that is frequently drug tolerant, resulting in difficulties in treatment and a higher mortality in immunocompromised patients. The calcium-activated protein phosphatase calcineurin plays critical roles in controlling drug tolerance, hyphal growth, and virulence in diverse fungal pathogens via distinct mechanisms involving survival in serum or growth at host temperature (37° and higher). Here, we comprehensively studied the calcineurin signaling cascade in C. glabrata and found novel and uncharacterized functions of calcineurin and its downstream target Crz1 in governing thermotolerance, intracellular architecture, and pathogenesis in murine ocular, urinary tract, and systemic infections. This represents a second independent origin of a role for calcineurin in thermotolerant growth of a major human fungal pathogen, distinct from that which arose independently in Cryptococcus neoformans. Calcineurin also promotes survival of C. glabrata in serum via mechanisms distinct from C. albicans and thereby enables establishment of tissue colonization in a murine systemic infection model. To understand calcineurin signaling in detail, we performed global transcript profiling analysis and identified calcineurin- and Crz1-dependent genes in C. glabrata involved in cell wall biosynthesis, heat shock responses, and calcineurin function. Regulators of calcineurin (RCN) are a novel family of calcineurin modifiers, and two members of this family were identified in C. glabrata: Rcn1 and Rcn2. Our studies demonstrate that Rcn2 expression is controlled by calcineurin and Crz1 to function as a feedback inhibitor of calcineurin in a circuit required for calcium tolerance in C. glabrata. In contrast, the calcineurin regulator Rcn1 activates calcineurin signaling. Interestingly, neither Rcn1 nor Rcn2 is required for virulence in a murine systemic infection model. Taken together, our findings show that calcineurin signaling plays critical roles in thermotolerance and virulence, and that Rcn1 and Rcn2 have opposing functions in controlling calcineurin signaling in C. glabrata.
Introgression and Characterization of a Goatgrass Gene for a High Level of Resistance to Ug99 Stem Rust in Tetraploid Wheat
Authors: Klindworth Daryl L , Niu Zhixia , Chao Shiaoman , Friesen Timothy L , Jin Yue , Faris Justin D , Cai Xiwen , Xu Steven S
Published: June 2012

The transfer of alien genes to crop plants using chromosome engineering has been attempted infrequently in tetraploid durum wheat (Triticum turgidum L. subsp. durum). Here, we report a highly efficient approach for the transfer of two genes conferring resistance to stem rust race Pgt-TTKSK (Ug99) from goatgrass (Aegilops speltoides) to tetraploid wheat. The durum line DAS15, carrying the stem rust resistance gene Sr47 derived from Ae. speltoides, was crossed, and backcrossed, to durum 5D(5B) aneuploids to induce homeologous pairing. After a final cross to ‘Rusty’ durum, allosyndetic recombinants were recovered. The Ae. speltoides chromosomal segment carrying Sr47 was found to have two stem rust resistance genes. One gene conditioning an infection type (IT) 2 was located in the same chromosomal region of 2BS as Sr39 and was assigned the temporary gene symbol SrAes7t. Based on ITs observed on a diverse set of rust races, SrAes7t may be the same as Sr39. The second gene conditioned an IT 0; and was located on chromosome arm 2BL. This gene retained the symbol Sr47 because it had a different IT and map location from other stem rust resistance genes derived from Ae. speltoides. Allosyndetic recombinant lines carrying each gene on minimal alien chromosomal segments were identified as were molecular markers distinguishing each alien segment. This study demonstrated that chromosome engineering of Ae. speltoides segments is feasible in tetraploid wheat. The Sr47 gene confers high-level and broad spectrum resistance to stem rust and should be very useful in efforts to control TTKSK.
Improving Neonatal Transition by Giving Ventilatory Support in the Delivery Room
Authors: Roehr Charles C. , Morley Colin J. , Vento Maximo
Published: June 2012

Extremely low gestational age neonates are likely to require help with breathing. Strategies to enhance uncomplicated pulmonary transition are critically evaluated in this article. These strategies include antenatal corticosteroid treatment and different respiratory support options immediately after birth. Important techniques for providing early neonatal support include the careful monitoring of the postnatal progression of heart rate and oxygenation in the delivery room, the provision of continuous distending positive airway pressure with avoidance of high tidal volumes, surfactant treatment without intubation, and options for avoiding endotracheal intubation by giving nasal continuous positive airway pressure from birth. We discuss how the less invasive strategies are likely to reduce iatrogenic neonatal lung injury and may indeed help to reduce the incidence of bronchopulmonary dysplasia.
Empirical Evaluation of Age Groups and Age-Subgroup Analyses in Pediatric Randomized Trials and Pediatric Meta-analyses
Authors: Contopoulos-Ioannidis Despina G. , Seto Iva , Hamm Michele P. , Thomson Denise , Hartling Lisa , Ioannidis John P. A. , Curtis Sarah , Constantin Evelyn , Batmanabane Gitanjali , Klassen Terry , Williams Katrina
Published: June 2012

BACKGROUND:

An important step toward improvement of the conduct of pediatric clinical research is the standardization of the ages of children to be included in pediatric trials and the optimal age-subgroups to be analyzed.

METHODS:

We set out to evaluate empirically the age ranges of children, and age-subgroup analyses thereof, reported in recent pediatric randomized clinical trials (RCTs) and meta-analyses. First, we screened 24 RCTs published in Pediatrics during the first 6 months of 2011; second, we screened 188 pediatric RCTs published in 2007 in the Cochrane Central Register of Controlled Trials; third, we screened 48 pediatric meta-analyses published in the Cochrane Database of Systematic Reviews in 2011. We extracted information on age ranges and age-subgroups considered and age-subgroup differences reported.

RESULTS:

The age range of children in RCTs published in Pediatrics varied from 0.1 to 17.5 years (median age: 5; interquartile range: 1.8–10.2) and only 25% of those presented age-subgroup analyses. Large variability was also detected for age ranges in 188 RCTs from the Cochrane Central Register of Controlled Trials, and only 28 of those analyzed age-subgroups. Moreover, only 11 of 48 meta-analyses had age-subgroup analyses, and in 6 of those, only different studies were included. Furthermore, most of these observed differences were not beyond chance.

CONCLUSIONS:

We observed large variability in the age ranges and age-subgroups of children included in recent pediatric trials and meta-analyses. Despite the limited available data, some age-subgroup differences were noted. The rationale for the selection of particular age-subgroups deserves further study.
Independent Factors and Predictive Score for Extrahepatic Metastasis of Hepatocellular Carcinoma Following Curative Hepatectomy
Authors: Jun Li , Zhenlin Yan , Renyan Gong , Yizhou Wang , Xuying Wan , Feng Xue , Yong Xia , Kui Wang , Jian Liu , Dong Wu , Hongyang Wang , Lehua Shi , Mengchao Wu , Feng Shen
Published: June 2012

Background.

Postoperative extrahepatic metastasis (EHM) contributes to a poor prognosis in patients with hepatocellular carcinoma (HCC) after hepatectomy. This study was aimed to develop a practical method that can be used to predict postoperative EHM.

Methods.

In total, 578 patients were enrolled. We analyzed the clinicopathological features of the tumors and did a long-term follow-up to observe HCC recurrence. Postoperative EHM was detected in 136 patients, and multivariate analysis was used to confirm independent risk factors for postoperative EHM. After the factors were identified, a predictive scoring system was constructed as a weighted sum of these factors. The cutoff value that determines a high risk for EHM was defined by maximizing the Youden's index of the receiver operating characteristic curve.

Results.

Microvascular invasion, incomplete capsule, and larger tumor diameter were the three independent factors predictive for a high risk for EHM. The scoring system was derived with an area under the curve (AUC) of 0.81 for postoperative 10-year EHM prediction. A cutoff value of 43 was derived and validated with a sensitivity >90% and specificity >60% to predict the development of EHM. This system was further verified in a subgroup of Barcelona Clinic Liver Cancer stage 0–A patients with an AUC of 0.82. When the cutoff value was set at 43, the sensitivity and specificity were 90.38% and 64.88%, respectively.

Conclusions.

Our predictive scoring system may be used to identify HCC patients who have a high risk for EHM following curative hepatectomy.
Materials science appraisal for recycling materials in roads
Authors: Ogwuda Olisanwendu I. , Fordyce Derek , Oduyemi Kehinde
Published: June 2012

A novel materials science appraisal that proposes a paradigm shift in the evaluation of recycling materials for road applications has been developed. The appraisal advances materials science thinking in the field of road engineering, has consistent performance criteria for road materials and addresses the concerns about the variable nature of recycled material sources. The appraisal has been realised by reviewing material types, road pavement structures and road pavement distress, and, consequently, conceptual development of the appraisal for materials recycling in roads. The development of the novel materials science appraisal, based on broad fundamental material-types (ceramic-type, metallic-type and polymeric-type), has defined how materials science through a systematic step-by-step procedure can be used to achieve engineering sustainability. The materials science appraisal provides a method for addressing uncertainties in material properties. Thus, the materials science appraisal evaluates recycling of materials in road applications and will be of benefit for various stakeholders (e.g. client, consultant, and contractor) and the environment.
Briefing: The importance of carbon in the conservation of peatlands
Authors: Campen Richard
Published: June 2012

Natural ecosystems provide benefits on which mankind is dependent for sustainable development. Collectively, these benefits are referred to as ecosystem services. Functioning ecosystems are important for sustainable development and the balancing of environmental, social and economic interests. Carbon dioxide is an important greenhouse-enhancing gas and soils in the UK, especially peatlands, represent significant carbon stores and the potential to absorb carbon emissions. The fragile peatland ecosystems have been severely damaged by erosion, caused by a variety of factors such as grazing, burning and drainage. This has adverse impacts on a range of ecosystem services, including the loss of stored carbon. At a landscape scale in the Peak District of England a partnership programme is underway to restore eroded peatlands through revegetation and re-wetting the moorlands to conserve biodiversity, protect the carbon store and re-start peat formation. The experience of large-scale restoration techniques gained in the Peak District can be adapted and applied elsewhere. While there remain many uncertainties about this work, in addition to conserving biodiversity, the majority of peatland restoration work could be deemed a cost-effective means of carbon mitigation.
The American forest pathogen Heterobasidion irregulare colonizes unexpected habitats after its introduction in Italy
Authors: Gonthier Paolo , Lione Guglielmo , Giordano Luana , Garbelotto Matteo
Published: June 2012

Habitat preference of an invasive fungal tree pathogen is here compared with that of a sympatric and native closely related congener to test the hypothesis that the invasive ability of the exotic organism may be linked to its capacity to colonize substrates unavailable to the indigenous relative. We compared the distribution of infectious airspora of the North American Heterobasidion irregulare introduced into Italy with that of the native H. annosum, both regarded to be able to establish only in the presence of conifers. Geostatistical and statistical analyses were employed to test for association between both species and five Mediterranean vegetation types. Results show that H. annosum is positively associated with pines and negatively associated with deciduous oaks. The probability of finding its spores decreases to almost 0 at distances over 500 m from pines, and this species is virtually absent in pure oak forests. Spores of H. irregulare are present irrespective of vegetation type, and this species can be found not only where pines are present, but also in pure oak forests. This knowledge implies that spread of H. irregulare is not limited by the fragmented distribution of pine woodlands in central Italy and is essential to both predict and hinder its progress in Europe.