bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of a continuous educational program on handwashing compliance among healthcare workers in an intensive care unit
Authors: Panhotra BR , Saxena AK , Al-Arabi Al-Ghamdi AM
Published: October 2007

Handwashing is simple, cost-effective and the single most important measure in the prevention of transmission of multiple antibiotic-resistant bacteria, which can spread via the contaminated hands of healthcare workers (HCWs) in intensive care units (ICUs). Despite this simplicity and efficacy, compliance with handwashing protocols is unsatisfactory among HCWs in ICUs. No single interventional measure is successful in improving handwashing compliance.

A continuous educational program was started in February 1998 by the department of infection control, emphasising the importance of handwashing in the prevention of nosocomial infections in the ICU. It took the form of posters, lectures and regular discussions. The posters were pasted in all the strategic areas of the ICU, displaying the indications and precise technique of handwashing. HCWs were directly observed for handwashing compliance, while working in the ICU. Each indication of handwashing was counted as an opportunity of handwashing.

Assessment of handwashing compliance was made once a year during the educational programme. In the final annual assessment in February 2002, out of 1,175 opportunities of handwashing, compliance was observed in 856 (72.8%) among all categories of staff. Highest compliance of 97.5% was recorded among nurses. The compliance among technicians was 47.7%, while the lowest compliance of 37.6% was observed among doctors (RR 2.591, p<0.0001). Opportunities of handwashing utilised with good technique were observed among 98.2% nurses. Handwashing compliance among females was significantly higher (76.2% versus 23.8%) than the male HCWs (RR 3.196, p<0.0001).

A comparative study of the yearly assessments made since the start of the educational program also revealed significant increases in handwashing compliance among nurses (p<0.0001) and technicians (p<0.001), while no statistically significant changes in the handwashing behaviour among doctors was observed during the study period (February 1998 to February 2002).

Disappointing handwashing compliance among doctors visiting and working in the ICU, despite their better understanding of hospital-acquired infections (HAI) and continuous educational programme remains a cause for concern. Additional efforts are required to discover more effective interventional measures to improve handwashing compliance among doctors.
Developing infection control services within primary care
Authors: Judge C. , Hill D.
Published: October 2007

The aim of this paper is to discuss the provision and development of infection control services within primary care during a time of significant change. This will be aided by describing how the use of audit can assist in identifying areas of priority within an under-resourced service.

There have been many changes in the provision of infection control services within primary care since the restructuring of health authorities and the introduction of Primary Care Trusts (PCT) and Health Protection Units (HPU). These changes in service provision have provided a timely opportunity to address the need for adequate infection control services for all areas outside of acute hospital care. The funding and organisation of the infection control services for primary care has been an issue of debate for a significant period of time.

When services are inadequately resourced the need to prioritise activity based on risk is apparent. The use of audit can provide a basis for assessing the main areas of risk. An audit undertaken within a primary care setting, which involved GP practices, identified such priorities requiring infection control input. However the staffing resource available at that time was insufficient to subsequently address the issues identified in a proactive manner.

Infection control services have developed significantly within the acute health care Trusts with infection control teams expanding to include nurse consultants, and audit and surveillance nurses. The primary care environment now needs to follow this model if patients are to receive consistently high standards of care across healthcare boundaries.
Re-emerging infections Part 1: Tuberculosis
Authors: Mayon-White R.
Published: October 2007

n this series of articles on re-emerging infections, we shall be considering infectious diseases that declined in the UK in the past, but which are now an increasing risk for people living here. Any increase of an infectious disease can cause public fear out of proportion to the actual numbers of cases and deaths. This is partly due to a fear of the unfamiliar, but also by the threat of an infection spreading out of control.
Practice development: a concept analysis
Authors: Hanrahan M.
Published: October 2007

Exploration of the term `practice development' is required for the discipline of infection control nursing. Improved understanding of the term would allow practitioners to approach practice development in a more constructive and measurable fashion. A concept analysis based on the model of Walker and Avant is therefore presented. The analysis includes the definition of the term `practice development' and discussion of how it is presented in the literature. Illustrative cases are used to achieve clarification of the concept, culminating in identification of the empirical referents, these being: (1) identified patient need and (2) a change in nursing practice and demonstrably improved care.
Charting CHART's progress
Authors: Harper P. , Jones S.R.L.J. , Curran E.T.
Published: October 2007

The CHART study, a collaboration between the Infection Control Nurses Association (ICNA) and the Richard Wells Research Centre (RWR) at Thames Valley University, is now well underway. This article outlines the progress to date and, for those not familiar with the study, it provides a brief overview of the background to the study and what it involves.
Re-emerging infections
Authors: Mayon-White R.
Published: October 2007

In this, the second of a series of articles on re-emerging infections, we shall be considering sexually transmitted infectious diseases that declined in the UK in the past, but which are now an increasing risk for people living here.
Part 1: Developing systems for surveillance
Authors: Reilly J. , Kilpatrick C.
Published: October 2007

Efforts to establish and maintain surveillance of surgical site infections (SSIs) are underway across the UK and worldwide. Surveillance of SSI is an important element of infection control. The data from surveillance activity can be used at a local level to improve care and are being collated at a national and international level for comparative reasons and allow for sharing of best practice. In order that this data is valid, reliable and comparable, it should be collected in a standardised way and managed in a system that includes quality assurance and reporting mechanisms.

The Scottish Surveillance of Healthcare Associated Infection Programme (SSHAIP) has developed a flexible user-friendly support system for effective SSI surveillance, and the team offers training in data definitions, data management, quality assurance and reporting. This is an important function of any national system of surveillance and the training component of SSHAIP has been highly evaluated by its participants. This article details the components of the surveillance programme including, data management, quality assurance and reporting within SSHAIP.

This article will be followed by second one, which will focus on the training in data definitions component of the surveillance.
The prevention of in-dwelling, catheter-related urinary tract infections — the outcome of a `performance improvement' project
Authors: Roodhouse AJ , Wellsted A.
Published: October 2007

This article aims to show that by making a small change in practice (in this case the introduction of a silver/hydrogel-coated catheter), by using a performance improvement approach a 60.6% reduction in hospital-acquired, catheter-related urinary tract infection was achieved. Apart from the obvious benefits to patients, in an era where bed shortages are an everyday occurrence and budgets are always stretched significant cost savings and reduction in bed occupancy was achieved. The article describes the process of performance improvement, which is an ideal vehicle for any infection control initiative. Without the strict constraints associated with clinical research, performance improvement encourages all grades of staff to participate in projects of varying complexity.
The epic project. Updating the evidence-base for national evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England: a report with recommendations
Authors: Pellowe C.M. , Pratt R.J. , Loveday H.P. , Harper P. , Robinson N. , Jones S.R.L.J.
Published: October 2007

The evidence underpinning infection prevention and control guidelines requires updating at regular intervals as advances in technology and new research findings may influence guideline recommendations. The evidence-base for national guidelines published in 20011 for preventing healthcare-associated infections in hospitals in England has recently been updated using systematic review methods. A critical assessment of the updated evidence indicates that the current guidelines remain robust, relevant and appropriate, but that adjustments need to be made to some guideline recommendations. Periodically updating the evidence base and making necessary adjustments to guideline recommendations is essential, in order to maintain their validity and authority.
Surgical site infection
Authors: Reilly J. , Kilpatrick C.
Published: October 2007

Following the article by Reilly and Kilpatrick (2004) describing a national surveillance system, this second article in the series focuses on the importance of utilising standardised definitions for surgical site infection (SSI) surveillance programmes. By consistently applying recognised, validated definitions across surveillance systems, data can be truly comparable. Furthermore, training in definitions may ensure that they are applied appropriately, therefore ensuring that valid and reliable data are collated and subsequently fed back to all those involved, which is crucial for the success of surveillance.

A training programme in Scotland has been established in order to ensure all clinicians are appropriately engaged and able to participate reliably in the national programme, which was set up following publication of Health Department Letter (HDL) 57 (2001) A Framework for National Surveillance for Hospital Acquired Infection in Scotland. This article outlines the training programme devised to support the Scottish Surveillance of Healthcare Associated Infection Programme (SSHAIP). The SSHAIP team based at the Scottish Centre for Infection and Environmental Health (SCIEH) has been tasked with supporting national surveillance within Scotland following the recommendations given in HDL 57 (2001).
Delivering an infection control link nurse programme: improving practice
Authors: Cooper T.
Published: October 2007

This is the second in a series of articles describing a research study that examined the efficacy of an infection control link nurse programme, which had an educational programme based upon adult learning theory, delivered using an action research approach. This article describes the results of a quantitative study that aimed to identify if the utilisation of this programme led to improvements in infection control practice at clinical level. Implications for practice are discussed.
Outbreaks of influenza: a virus in vaccinated elderly residents
Authors: Etuwewe OM , May H. , Bakhshi S. , Wood A. , Hughes K.
Published: October 2007

Annual influenza immunisation is the recommended practice for people such as the elderly, for whom influenza poses a substantial risk of serious illness and death. Influenza vaccines are effective in preventing, or ameliorating influenza, reducing complications and mortality (Department of Health, 2001, 2002). In long-stay residential accommodation, influenza immunisation should prevent rapid spread of infection causing outbreaks (Communicable Disease Centre, 2003).

This paper reports on two outbreaks of influenza that occurred in vaccinated elderly in residential institutions. In both outbreaks the isolated virus strain was included in the composition of the influenza vaccine for that winter season. Suboptimal protection against influenza may be provided in the vaccinated elderly, due to declining competency of the ageing immune system. Furthermore, the occurrence in the late winter of these outbreaks may demonstrate waning immunity following immunisation early in the season.
Implementing the national influenza vaccine uptake monitoring programme, England
Authors: Joseph C.
Published: October 2007

The national influenza vaccine uptake monitoring programme in England was established in October 2000. It provides cumulative monthly uptake rates for the 65s and over for October, November and December each year. This rapid assessment programme now includes monitoring uptake rates in healthcare workers and at-risk under 65-year-olds. Web-based reporting for the three data sets was introduced as a pilot in October 2004 and when fully implemented will improve the process and completeness of collecting timely data.
Impact toughness of 316 stainless steel weld metal on elevated temperatures aging
Authors: Srinivasan G. , Bhaduri A. K. , Shankar V. , Ray S. K.
Published: October 2007

Shielded metal arc welding electrodes of a modified E316-15 austenitic stainless steel, for service at 673–823 K with delta ferrite in the range of 3–7 ferrite number, have been developed indigenously for welding of 316L(N) stainless steel structural materials for the Indian Prototype Fast Breeder Reactor. Delta ferrite content in weld metals for high temperature service is restricted for limiting the formation of embrittling secondary phases during service. To study the effect of high temperature exposure on microstructure and mechanical properties, the 316 weld metal was aged at three different temperatures of 923, 973 and 1023 K, for various durations up to 500 h. The activation energy for the transformation of delta ferrite has been estimated to analyse the mechanism associated with the micro structural changes that led to the deterioration in toughness on elevated temperature aging of this weld metal.
Tool materials selection for friction stir welding of L80 steel
Authors: Gan W. , Li Z. T. , Khurana S.
Published: October 2007

A numerical analysis framework for evaluating the tool deformation during friction stir welding of steel has been developed. The methodology was developed by using the measured thermomechanical conditions and thermomechanical finite element model. This methodology successfully described the difference in commercially pure tungsten and W–Re tool. Using this technique, the mechanical properties of the candidate tool materials can be evaluated and can be used as a rapid screening tool.
Distortion control in welding by mechanical tensioning
Authors: Price D. A. , Williams S. W. , Wescott A. , Harrison C. J. C. , Rezai A. , Steuwer A. , Peel M. , Staron P. , Koçak M.
Published: October 2007

This paper investigates the potential of mechanical tensioning (MT) to reduce the magnitude of residual stresses in welds and to eliminate buckling distortion. Both friction stir (FSW) and arc welds have been produced from the aluminium alloy AA2024, with different levels of tensile stress applied along the weld line either during or after welding. The resulting welds have been characterised in terms of out of plane distortion, residual stresses and microstructure. Buckling distortion was eliminated by stretching plates to between 35 and 70% of the yield stress of the material during welding. For each set of welding parameters investigated, an optimum tensioning stress has been identified, which eliminates the tensile residual stress peak across the weld zone, along with distortion. This optimum tensioning stress increases in line with the heat input of the welding process. When MT stresses are increased beyond this optimum value, then distortion arises once more and a band of compressive stress is formed across the weld zone.
Improvement of mechanical properties of gas tungsten arc and electron beam welded AA2219 (Al–6 wt-%Cu) alloy
Authors: Nair Biju S. , Phanikumar G. , Prasad Rao K. , Sinha P. P.
Published: October 2007

Despite its excellent weldability characteristics, AA2219 suffers from poor fusion zone strength under the as welded condition. In the present work, it is attempted to increase the mechanical properties of the as welded fusion zone of this alloy by increasing the weld cooling rates and multipass welding. The cooling rate was increased with the use of high intense heat source, namely electron beam in a pulsed current mode. Multipass gas tungsten arc welding was carried out using direct current straight polarity. These techniques resulted in a significant improvement in fusion zone hardness and tensile properties, which is attributed to reduced copper segregation and natural aging as well as aging caused by heat of multipass welding.
Microstructure and mechanical properties of diffusion bonded joints between titanium and stainless steel with copper interlayer
Authors: Kundu S. , Chatterjee S.
Published: October 2007

The solid state joining of titanium to stainless steel with copper interlayer was carried out in the temperature range of 850–950°C for 7·2 ks in vacuum. The interface microstructures and reaction products of the transition joints were investigated with an optical microscope and a scanning electron microscope. The elemental concentration of reaction products at the diffusion interfaces was evaluated by electron probe microanalysis. The occurrence of difference in intermetallics at both interfaces (SS/Cu and Cu/Ti) such as CuTi2, CuTi, Cu4Ti3, χ, FeTi, Fe2Ti, Cr2Ti, α-Fe, α-Ti, β-Ti, T2(Ti40Cu60−xFex; 5< x<17), T4(Ti37Cu63−xFex; 5< x<7) and T5(Ti45Cu55−xFex; 4< x<5) has been predicted from the ternary phase diagrams of Fe–Cu–Ti and Fe–Cr–Ti. These reaction products were detected by X-ray diffraction technique. The maximum tensile strength of ∼91% of Ti strength and shear strength of ∼74% of Ti strength along with ∼ 7·2% ductility were obtained for the joint bonded at 900°C due to better coalescence of mating surfaces. At a lower joining temperature of 850° C, bond strength is poor due to incomplete coalescence of the mating surfaces. With an increase in the joining temperature to 950°C, a decrease in bond strength occurred due to an increase in the volume fraction of brittle Fe–Ti base intermetallics.
Influence of local heat treatment on residual stresses in electron beam welding
Authors: Rosen C.-J. , Gumenyuk A. , Zhao H. , Dilthey U.
Published: October 2007

Electron beam welding (EBW), as a high performance welding method, is also subject to requirements of high integrity welds which particularly include residual stresses affecting distortion and fatigue behaviour. In this context multiple beam technique may provide new applications of specific thermal weld treatment. The present work introduces a promising method of local post-heating in a certain distance to the current welding location applying multiple beams for the reduction in residual stresses in EB welded sheet metals. The conducted investigations include finite element analysis (FEA) and stress measurements in the weld seam area. Using a systematic approach within the FEA decisive process parameters are optimised with reference to the achievable reduction in residual stress. All simulation results are validated by experiments applying strain gauges for the stress measurement. Both simulations and experiments revealed a considerable decrease in residual stress achievable by appropriate positioning of additional heat sources combined with the right power input and beam focusing.
Microcracking susceptibility in dissimilar multipass welds of alloy 690 to type 316L stainless steel using La added filler metals
Authors: Saida Kazuyoshi , Ohta Kenji , Nishimoto Kazutoshi
Published: October 2007

The microcracking susceptibility in dissimilar multipass welds of alloy 690 to type 316L stainless steel was investigated by the Varestraint test and the multipass welding test using the four different stainless steels varying the amounts of impurity elements such as P and S, and using the nine different filler metals of alloy 690 varying the La content. In order to simulate the dissimilar weld metals, stainless steels were gas tungsten arc (GTA) welded using alloy 690 filler metals with varying the dilution ratio. Microcracks occurring in the reheated weld metals were classified into ductility dip, liquation and solidification cracks. The ductility dip cracking susceptibility decreased with increasing the La content in the weld metal, while the liquation and solidification cracking susceptibilities increased contrarily when the La content in the weld metal exceeded ∼0·03 mass-%. The relation among the microcracking susceptibility, the (P + S) and La contents in every weld pass of the multipass welding was investigated. Ductility dip cracks occurred in the compositional range (atomic ratio) of La/(P + S)<0·17 and solidification/liquation cracks occurred in that of La/(P + S)>0·76, while any cracks did not occur at La/(P + S) being between 0·17–0·76. The ductility dip cracking susceptibility could be improved by adding La due to the scavenging of the impurity elements. The excessive La addition to the weld metal resulted in the solidification/liquation cracking alternatively attributed to the formation of Ni–La intermetallic compounds with low eutectic point. The optimal filler metal for the dissimilar multipass welding of alloy 690 to stainless steel was selected as La/(P + S) would be 0·17–0·76 for every weld pass. Microcracking could be completely prevented in the dissimilar multipass weld metal of alloy 690 to type 316L stainless steel by using two kinds of filler metals containing 0·03 mass-%La for the weld passes adjacent to the stainless steel base metal and containing 0·01 mass-%La for other weld passes.
Predicting onset of high speed gas metal arc weld bead defects using dimensional analysis techniques
Authors: Nguyen T. C. , Weckman D. C. , Johnson D. A.
Published: October 2007

The onset of geometric defects such as humping or discontinuous weld beads during gas metal arc welding (GMAW) frequently limits the use of higher welding speeds and increased productivity. In the present study, a dimensional analysis of the GMAW process was performed in order to identify a number of dimensionless groups formulated based on various GMAW process parameters and material properties that could be used to predict when humping or discontinuous weld beads would occur. Experimental data from bead on plate GMA welds in plain carbon steel plate made using argon and two different reactive shielding gases, welding powers between 5 and 12 kW and a range of welding speeds were then used to create dimensionless process maps. These maps showed the limiting welding speed above which the high speed weld defects occurred as a function of all influential process parameters. It was shown that all experimental data for limiting welding speeds could be collapsed onto two collinear dimensionless curves. Also, the transition from spray to rotational metal transfer was found to occur at a well defined value of one of these dimensionless parameters. The effects of work piece preheat temperature on humping were correctly predicted and there was a good correlation between the dimensionless GMAW process map and experimental data from other independent studies. These results suggest that the occurrence of high speed weld bead defects such as humping and discontinuous weld beads as well as the transition from spray to rotational metal transfer can be predicted using these new dimensionless GMAW process maps.
Modelling weld bead geometry using neural networks for GTAW of austenitic stainless steel
Authors: Ghanty P. , Paul S. , Mukherjee D. P. , Vasudevan M. , Pal N. R. , Bhaduri A. K.
Published: October 2007

The authors analyse the importance of different weld control parameters on the weld pool geometry of gas tungsten arc welding using an online feature selection technique that suggests weld voltage and vertex–angle pair as more important than the weld voltage and torch speed pair. Using the selected features multi layer perception and radial basis function networks are developed for prediction of bead width, penetration depth, and bead area. With cross-validation the authors have extensively studied the performance of composite models (one model for all outputs) and individual models (one model for each output). The individual models are found to work better than composite models. Usually, radial basis function networks are found to work better than the multi layer perception networks. To assess the influence of weld control parameters the authors have studied the performance of both networks using different combination of inputs. Overall, the performance of the proposed models is found to be quite satisfactory.
Controlling welding hot cracking based on electromagnetic force
Authors: Xu W. , Fang H. Y. , Xu D. , Xu W. L. , Liu X. S. , Yang J. G.
Published: October 2007

Controlling welding hot cracking based on electromagnetic force was carried out. The results show that the welding cracking can be inhibited with this method, which lies on the voltage of capacitor and the frequency of applying force. The sheet bears the downward axial force and the less radial force of flat spiral coil. The radial force points at the centre of the sheet, so it is able to compress the weld metal. Moreover, the axial force also has the ability to compress the weld metal by means of the backing plate under weldment. Controlling welding hot cracking is mainly due to the improving of mechanical condition of weld metal within brittle temperature range.
Effects of dietary restriction on hematopoietic stem-cell aging are genetically regulated
Authors: Ertl Robin P. , Chen Jichun , Astle Clinton M. , Duffy Theodore M. , Harrison David E.
Published: October 2007

Diminished stem-cell functions with age may be a major cause of anemias and other defects. Unfortunately, treatments that increase stem-cell function can also increase the incidence of cancers. Lifelong dietary restriction (DR) is known to decrease spontaneous cancers and lengthen lifespan. This study examines the effect of DR on the ability of bone marrow cells to repopulate irradiated recipients and produce erythrocytes and lymphocytes. In BALB/cByJ (BALB) mice, repopulating abilities decline with age; DR ameliorates this trend. In C57BL/6J (B6) and (BALB × B6) F1 hybrid (F1) mice, repopulating abilities increase with age; DR maintains this increase. Hematopoietic stem cell (HSC) numbers are highly variable in aged BALB mice; however, the observed loss of marrow function results from a major loss in repopulating ability per HSC. DR greatly ameliorates this loss of function with age. In contrast, function per HSC in B6 mice is affected neither by age nor by DR. Thus, DR increases or maintains increased marrow repopulating ability with age in the 3 different genotypes tested, but effects on function per HSC depend on genotype. That DR increases or maintains stem-cell function with age, while decreasing cancer, has far-reaching health implications.
Mesenchymal stem cells inhibit natural killer–cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2
Authors: Spaggiari Grazia Maria , Capobianco Andrea , Abdelrazik Heba , Becchetti Flavio , Mingari Maria Cristina , Moretta Lorenzo
Published: October 2007

Recently, a number of clinical trials used either mesenchymal stem cells (MSCs) or natural killer (NK) cells in an attempt to improve the effectiveness of hematopoietic stem cell transplantation (HSCT). In view of the relevant role of both MSCs and NK cells in HSCT, we have recently explored the result of possible interactions between the 2 cell types. We found that activated NK cells could kill MSCs, whereas MSCs strongly inhibited interleukin-2 (IL-2)–induced NK-cell proliferation. In this study, we further analyzed the inhibitory effect exerted by MSCs on NK cells. We show that MSCs not only inhibit the cytokine-induced proliferation of freshly isolated NK cells but also prevent the induction of effector functions, such as cytotoxic activity and cytokine production. Moreover, we show that this inhibitory effect is related to a sharp down-regulation of the surface expression of the activating NK receptors NKp30, NKp44, and NKG2D. Finally, we demonstrate that indoleamine 2,3-dioxygenase and prostaglandin E2 represent key mediators of the MSC-induced inhibition of NK cells.
Bortezomib down-regulates the cell-surface expression of HLA class I and enhances natural killer cell–mediated lysis of myeloma
Authors: Shi Jumei , Tricot Guido J. , Garg Tarun K. , Malaviarachchi Priyangi A. , Szmania Susann M. , Kellum Rachel E. , Storrie Brian , Mulder Arend , Shaughnessy John D. , Barlogie Bart , van Rhee Frits
Published: October 2007

Human leukocyte antigen class I molecules expressed by tumor cells play a central role in the regulation of natural killer (NK) cell–mediated immune responses. The proteasome inhibitor bortezomib has demonstrated significant activity in multiple myeloma (MM). We hypothesized that treatment of MM with bortezomib results in the reduction of cell-surface expression of class I and thereby sensitizes MM to NK cell–mediated lysis. Here we report that bortezomib down-regulates class I in a time- and dose-dependent fashion on all MM cell lines and patient MM cells tested. Downregulation of class I can also be induced in vivo after a single dose of 1.0 mg/m2 bortezomib. Bortezomib significantly enhances the sensitivity of patient myeloma to allogeneic and autologous NK cell–mediated lysis. Further, the level of decrease in class I expression correlates with increased susceptibility to lysis by NK cells. Clinically relevant bortezomib concentrations do not affect NK-cell function. Our findings have clear therapeutic implications for MM and other NK cell–sensitive malignancies in the context of both allogeneic and autologous adoptively transferred NK cells.
Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas
Authors: Ding B. Belinda , Yu J. Jessica , Yu Raymond Y.-L. , Mendez Lourdes M. , Shaknovich Rita , Zhang Yonghui , Cattoretti Giorgio , Ye B. Hilda
Published: October 2007

Diffuse large B-cell lymphoma (DLBCL) consists of at least 2 phenotypic subtypes; that is, the germinal center B-cell–like (GCB-DLBCL) and the activated B-cell–like (ABC-DLBCL) groups. It has been shown that GCB-DLBCL responds favorably to chemotherapy and expresses high levels of BCL6, a transcription repressor known to play a causative role in lymphomagenesis. In comparison, ABC-DLBCL has lower levels of BCL6, constitutively activated nuclear factor-κB, and tends to be refractory to chemotherapy. Here, we report that the STAT3 gene is a transcriptional target of BCL6. As a result, high-level STAT3 expression and activation are preferentially detected in ABC-DLBCL and BCL6-negative normal germinal center B cells. Most importantly, inactivating STAT3 by either AG490 or small interference RNA in ABC-DLBCL cells inhibits cell proliferation and triggers apoptosis. These phenotypes are accompanied by decreased expression of several known STAT3 target genes, including c-Myc, JunB, and Mcl-1, and increased expression of the cell- cycle inhibitor p27. In addition to identifying STAT3 as a novel BCL6 target gene, our results define a second oncogenic pathway, STAT3 activation, which operates in ABC-DLBCL, suggesting that STAT3 may be a new therapeutic target in these aggressive lymphomas.
Short sequence motifs, overrepresented in mammalian conserved non-coding sequences
Authors: Minovitsky Simon , Stegmaier Philip , Kel Alexander , Kondrashov Alexey S , Dubchak Inna
Published: October 2007

Background

A substantial fraction of non-coding DNA sequences of multicellular eukaryotes is under selective constraint. In particular, ~5% of the human genome consists of conserved non-coding sequences (CNSs). CNSs differ from other genomic sequences in their nucleotide composition and must play important functional roles, which mostly remain obscure.

Results

We investigated relative abundances of short sequence motifs in all human CNSs present in the human/mouse whole-genome alignments vs. three background sets of sequences: (i) weakly conserved or unconserved non-coding sequences (non-CNSs); (ii) near-promoter sequences (located between nucleotides -500 and -1500, relative to a start of transcription); and (iii) random sequences with the same nucleotide composition as that of CNSs. When compared to non-CNSs and near-promoter sequences, CNSs possess an excess of AT-rich motifs, often containing runs of identical nucleotides. In contrast, when compared to random sequences, CNSs contain an excess of GC-rich motifs which, however, lack CpG dinucleotides. Thus, abundance of short sequence motifs in human CNSs, taken as a whole, is mostly determined by their overall compositional properties and not by overrepresentation of any specific short motifs. These properties are: (i) high AT-content of CNSs, (ii) a tendency, probably due to context-dependent mutation, of A's and T's to clump, (iii) presence of short GC-rich regions, and (iv) avoidance of CpG contexts, due to their hypermutability. Only a small number of short motifs, overrepresented in all human CNSs are similar to binding sites of transcription factors from the FOX family.

Conclusion

Human CNSs as a whole appear to be too broad a class of sequences to possess strong footprints of any short sequence-specific functions. Such footprints should be studied at the level of functional subclasses of CNSs, such as those which flank genes with a particular pattern of expression. Overall properties of CNSs are affected by patterns in mutation, suggesting that selection which causes their conservation is not always very strong.
Establishment of an early liver fibrosis model by the hydrodynamics-based transfer of TGF-β1 gene
Authors: Yang Kun-Lin , Hung Kuo-Chen , Chang Wen-Teng , Li Eric IC
Published: October 2007

Background

Liver fibrosis represents a significant and severe health care problem and there are no efficient drugs for therapy so far. Preventing the progression of fibrogenesis and revival endogenous repair activities is an important strategy for both current and future therapies. Many studies of liver fibrosis consist of animal testing with various hepatotoxins. Although this method is often used, the model at which cirrhosis or extensive fibrosis becomes irreversible has not been well defined and is not representative of early-stage fibrogenesis. We here report the establishment of a transient and reversible liver fibrosis animal model which may better represent an early and natural fibrotic event. We used a high-speed intravenous injection of naked plasmid DNA of transforming growth factor-β1 (TGF-β1) gene which is under the control of a metallothionein-regulated gene in a pPK9A expression vector into the tail vein (the hydrodynamics-based transfer) and fed the mouse with zinc sulfate (ZnSO4)-containing water simultaneously.

Results

Using our hydrodynamics-based gene transfer model we found that upon induction by ZnSO4, the serum TGF-β1 level in Balb/c mice and Sp1 transcription factor binding activity peaked at 48 h and declined thereafter to a normal level on the 5th day. In addition, mRNA and protein levels of TGF-β1 in the liver were also upregulated at 48 h. Furthermore, induction of TGF-β1 increased the α-smooth muscle actin (α-SMA), p-Smad2/3, hydroxyproline and collagen 1A2 (Col 1A2) levels in the liver, suggesting a significant liver fibrosis.

Conclusion

Our results show that TGF-β1 in pPK9a-transferred mice liver with ZnSO4 feeding can achieve a high expression level with significant fibrosis. However, since TGF-β1 induction is transient in our model, the fibrotic level does not reach a large scale (panlobular fibrosis) as seen in the CCl4-treated liver. Our model hence represents a dynamic and reversible liver fibrosis and could be a useful tool for studying early molecular mechanism of fibrogenesis or screening of antifibrotic drugs for clinical use.
Estimating the role of casual contact from the community in transmission of Bordetella pertussis to young infants
Authors: Wendelboe Aaron M , Hudgens Michael G , Poole Charles , Van Rie Annelies
Published: October 2007

The proportion of infant pertussis cases due to transmission from casual contact in the community has not been estimated since before the introduction of pertussis vaccines in the 1950s. This study aimed to estimate the proportion of pertussis transmission due to casual contact using demographic and clinical data from a study of 95 infant pertussis cases and their close contacts enrolled at 14 hospitals in France, Germany, Canada, and the U.S. between February 2003 and September 2004. A complete case analysis was conducted as well as multiple imputation (MI) to account for missing data for participants and close contacts who did not participate. By considering all possible close contacts, the MI analysis estimated 66% of source cases were close contacts, implying the minimum attributable proportion of infant cases due to transmission from casual contact with community members was 34% (95% CI = 24%, 44%). Estimates from the complete case analysis were comparable but less precise. Results were sensitive to changes in the operational definition of a source case, which broadened the range of MI point estimates of transmission from casual community contact to 20%–47%. We conclude that casual contact appears to be responsible for a substantial proportion of pertussis transmission to young infants.

Medical subject headings (MeSH): multiple imputation, pertussis, transmission, casual contact, sensitivity analysis, missing data, community.
Purification of infectious human herpesvirus 6A virions and association of host cell proteins
Authors: Hammarstedt Maria , Ahlqvist Jenny , Jacobson Steven , Garoff Henrik , Fogdell-Hahn Anna
Published: October 2007

Background

Viruses that are incorporating host cell proteins might trigger autoimmune diseases. It is therefore of interest to identify possible host proteins associated with viruses, especially for enveloped viruses that have been suggested to play a role in autoimmune diseases, like human herpesvirus 6A (HHV-6A) in multiple sclerosis (MS).

Results

We have established a method for rapid and morphology preserving purification of HHV-6A virions, which in combination with parallel analyses with background control material released from mock-infected cells facilitates qualitative and quantitative investigations of the protein content of HHV-6A virions. In our iodixanol gradient purified preparation, we detected high levels of viral DNA by real-time PCR and viral proteins by metabolic labelling, silver staining and western blots. In contrast, the background level of cellular contamination was low in the purified samples as demonstrated by the silver staining and metabolic labelling analyses. Western blot analyses showed that the cellular complement protein CD46, the receptor for HHV-6A, is associated with the purified and infectious virions. Also, the cellular proteins clathrin, ezrin and Tsg101 are associated with intact HHV-6A virions.

Conclusion

Cellular proteins are associated with HHV-6A virions. The relevance of the association in disease and especially in autoimmunity will be further investigated.
The impact of the introduction of critical care outreach services in England: a multicentre interrupted time-series analysis
Authors: Gao Haiyan , Harrison David A , Parry Gareth J , Daly Kathleen , Subbe Christian P , Rowan Kathy
Published: October 2007

Introduction

Critical care outreach services (CCOS) have been widely introduced in England with little rigorous evaluation. We undertook a multicentre interrupted time-series analysis of the impact of CCOS, as characterised by the case mix, outcome and activity of admissions to adult, general critical care units in England.

Methods

Data from the Case Mix Programme Database (CMPD) were linked with the results of a survey on the evolution of CCOS in England. Over 350,000 admissions to 172 units between 1996 and 2004 were extracted from the CMPD. The start date of CCOS, activities performed, coverage and staffing were identified from survey data and other sources. Individual patient-level data in the CMPD were collapsed into a monthly time series for each unit (panel data). Population-averaged panel-data models were fitted using a generalised estimating equation approach. Various potential outcomes reflecting possible objectives of the CCOS were investigated in three subgroups of admissions: all admissions to the unit, admissions from the ward, and unit survivors discharged to the ward. The primary comparison was between periods when a formal CCOS was and was not present. Secondary analyses considered specific CCOS activities, coverage and staffing.

Results

In all, 108 units were included in the analysis, of which 79 had formal CCOS starting between 1996 and 2004. For admissions from the ward, CCOS were associated with significant decreases in the proportion of admissions receiving cardiopulmonary resuscitation before admission (odds ratio 0.84, 95% confidence interval 0.73 to 0.96), admission out of hours (odds ratio 0.91, 0.84 to 0.97) and mean Intensive Care National Audit & Research Centre physiology score (decrease in mean 1.22, 0.31 to 2.12). There was no significant change in unit mortality (odds ratio 0.97, 0.87 to 1.08) and no significant, sustained effects on outcomes for unit survivors discharged alive to the ward.

Conclusion

The observational nature of the study limits its ability to infer causality. Although associations were observed with characteristics of patients admitted to critical care units, there was no clear evidence that CCOS have a big impact on the outcomes of these patients, or for characteristics of what should form the optimal CCOS.
Common gene expression strategies revealed by genome-wide analysis in yeast
Authors: García-Martínez José , González-Candelas Fernando , Pérez-Ortín José E
Published: October 2007

Background

Gene expression is a two-step synthesis process that ends with the necessary amount of each protein required to perform its function. Since the protein is the final product, the main focus of gene regulation should be centered on it. However, because mRNA is an intermediate step and the amounts of both mRNA and protein are controlled by their synthesis and degradation rates, the desired amount of protein can be achieved following different strategies.

Results

In this paper we present the first comprehensive analysis of the relationships among the six variables that characterize gene expression in a living organism: transcription and translation rates, mRNA and protein amounts, and mRNA and protein stabilities. We have used previously published data from exponentially growing Saccharomyces cerevisiae cells. We show that there is a general tendency to harmonize the levels of mRNA and protein by coordinating their synthesis rates and that functionally related genes tend to have similar values for the six variables.

Conclusion

We propose that yeast cells use common expression strategies for genes acting in the same physiological pathways. This trend is more evident for genes coding for large and stable protein complexes, such as ribosomes or the proteasome. Hence, each functional group can be defined by a 'six variable profile' that illustrates the common strategy followed by the genes included in it. Genes encoding subunits of protein complexes show a tendency to have relatively unstable mRNAs and a less balanced profile for mRNA than for protein, suggesting a stronger regulation at the transcriptional level.
Comparative genomic analysis of fungal genomes reveals intron-rich ancestors
Authors: Stajich Jason E , Dietrich Fred S , Roy Scott W
Published: October 2007

Background

Eukaryotic protein-coding genes are interrupted by spliceosomal introns, which are removed from transcripts before protein translation. Many facets of spliceosomal intron evolution, including age, mechanisms of origins, the role of natural selection, and the causes of the vast differences in intron number between eukaryotic species, remain debated. Genome sequencing and comparative analysis has made possible whole genome analysis of intron evolution to address these questions.

Results

We analyzed intron positions in 1,161 sets of orthologous genes across 25 eukaryotic species. We find strong support for an intron-rich fungus-animal ancestor, with more than four introns per kilobase, comparable to the highest known modern intron densities. Indeed, the fungus-animal ancestor is estimated to have had more introns than any of the extant fungi in this study. Thus, subsequent fungal evolution has been characterized by widespread and recurrent intron loss occurring in all fungal clades. These results reconcile three previously proposed methods for estimation of ancestral intron number, which previously gave very different estimates of ancestral intron number for eight eukaryotic species, as well as a fourth more recent method. We do not find a clear inverse correspondence between rates of intron loss and gain, contrary to the predictions of selection-based proposals for interspecific differences in intron number.

Conclusion

Our results underscore the high intron density of eukaryotic ancestors and the widespread importance of intron loss through eukaryotic evolution.
Heme carrier protein (HCP-1) spatially interacts with the CD163 hemoglobin uptake pathway and is a target of inflammatory macrophage activation
Authors: Schaer Christian A , Vallelian Florence , Imhof Alexander , Schoedon Gabriele , Schaer Dominik J
Published: October 2007

Macrophages constitute the major cellular compartment for hemoglobin (Hb) degradation and subsequent recycling of heme-iron to erythropoiesis. Dysregulation of macrophage iron and heme metabolism is a major pathophysiologic determinant of anemia of chronic disease. In this study, we show that the heme transporter heme carrier protein 1 (HCP-1) is expressed in human macrophages. Within early endosomes, HCP-1 colocalizes with endocytosed Hb-haptoglobin (Hp) complexes, which are taken up via the CD163 scavenger receptor pathway. Hb-Hp passes the divalent metal transporter 1B/HCP-1-positive endosomal compartment on its route from the cell surface to lysosomes. HCP-1 mRNA and protein expression are down-regulated by stimulation of macrophages with various TLR agonists and IFN-γ. The profound suppression of HCP-1 expression by inflammatory macrophage activation parallels the regulation of the iron exporter ferroportin. In contrast, dexamethasone enhanced HCP-1 expression significantly. Given the spatial relationship, we propose that the Hb scavenger receptor CD163 and HCP-1 constitute a linked pathway for Hb catabolism and heme-iron recycling in human macrophages.