bluuebunny/crossref_metadata_2025 huggingface dataset:
Small nucleolar RNA signatures as biomarkers for non-small-cell lung cancer
Authors: Liao Jipei , Yu Lei , Mei Yuping , Guarnera Maria , Shen Jun , Li Ruiyun , Liu Zhenqiu , Jiang Feng
Published: July 2010

Background

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC will improve its outcome. The current techniques for NSCLC early detection are either invasive or have low accuracy. Molecular analyses of clinical specimens present promising diagnostic approaches. Non-coding RNAs (ncRNAs) play an important role in tumorigenesis and could be developed as biomarkers for cancer. Here we aimed to develop small nucleolar RNAs (snoRNAs), a common class of ncRNAs, as biomarkers for NSCLC early detection. The study comprised three phases: (1) profiling snoRNA signatures in 22 NSCLC tissues and matched noncancerous lung tissues by GeneChip Array, (2) validating expressions of the signatures by RT-qPCR in the tissues, and (3) evaluating plasma expressions of the snoRNAs in 37 NSCLC patients, 26 patients with chronic obstructive pulmonary disease (COPD), and 22 healthy subjects.

Results

In the surgical tissues, six snoRNAs were identified, which were overexpressed in all tumour tissues compared with their normal counterparts. The overexpressions of the genes in tumors were confirmed by RT-qPCR. The snoRNAs were stably present and reliably detectable in plasma. Of the six genes, three (SNORD33, SNORD66 and SNORD76) displayed higher plasma expressions in NSCLC patients compared with the cancer-free individuals (All < 0.01). The use of the three genes produced 81.1% sensitivity and 95.8% specificity in distinguishing NSCLC patients from both normal and COPD subjects. The plasma snoRNA expressions were not associated with stages and histological types of NSCLC (All > 0.05).

Conclusions

The identified snoRNAs provide potential markers for NSCLC early detection.
Proteomic analysis of proteins expressing in regions of rat brain by a combination of SDS-PAGE with nano-liquid chromatography-quadrupole-time of flight tandem mass spectrometry
Authors: Katagiri Tomoki , Hatano Naoya , Aihara Masamune , Kawano Hiroo , Okamoto Mariko , Liu Ying , Izumi Tomonori , Maekawa Tsuyoshi , Nakamura Shoji , Ishihara Tokuhiro , Shirai Mutsunori , Mizukami Yoichi
Published: July 2010

Background

Most biological functions controlled by the brain and their related disorders are closely associated with activation in specific regions of the brain. Neuroproteomics has been applied to the analysis of whole brain, and the general pattern of protein expression in all regions has been elucidated. However, the comprehensive proteome of each brain region remains unclear.

Results

In this study, we carried out comparative proteomics of six regions of the adult rat brain: thalamus, hippocampus, frontal cortex, parietal cortex, occipital cortex, and amygdala using semi-quantitative analysis by Mascot Score of the identified proteins. In order to identify efficiently the proteins that are present in the brain, the proteins were separated by a combination of SDS-PAGE on a C18 column-equipped nano-liquid chromatograph, and analyzed by quadrupole-time of flight-tandem-mass spectrometry. The proteomic data show 2,909 peptides in the rat brain, with more than 200 identified as region-abundant proteins by semi-quantitative analysis. The regions containing the identified proteins are membrane (20.0%), cytoplasm (19.5%), mitochondrion (17.1%), cytoskeleton (8.2%), nucleus (4.7%), extracellular region (3.3%), and other (18.0%). Of the identified proteins, the expressions of glial fibrillary acidic protein, GABA transporter 3, Septin 5, heat shock protein 90, synaptotagmin, heat shock protein 70, and pyruvate kinase were confirmed by immunoblotting. We examined the distributions in rat brain of GABA transporter 3, glial fibrillary acidic protein, and heat shock protein 70 by immunohistochemistry, and found that the proteins are localized around the regions observed by proteomic analysis and immunoblotting. IPA analysis indicates that pathways closely related to the biological functions of each region may be activated in rat brain.

Conclusions

These observations indicate that proteomics in each region of adult rat brain may provide a novel way to elucidate biological actions associated with the activation of regions of the brain.
How 5000 independent rowers coordinate their strokes in order to row into the sunlight: Phototaxis in the multicellular green alga Volvox
Authors: Ueki Noriko , Matsunaga Shigeru , Inouye Isao , Hallmann Armin
Published: July 2010

Background

The evolution of multicellular motile organisms from unicellular ancestors required the utilization of previously evolved tactic behavior in a multicellular context. Volvocine green algae are uniquely suited for studying tactic responses during the transition to multicellularity because they range in complexity from unicellular to multicellular genera. Phototactic responses are essential for these flagellates because they need to orientate themselves to receive sufficient light for photosynthesis, but how does a multicellular organism accomplish phototaxis without any known direct communication among cells? Several aspects of the photoresponse have previously been analyzed in volvocine algae, particularly in the unicellular alga Chlamydomonas.

Results

In this study, the phototactic behavior in the spheroidal, multicellular volvocine green alga Volvox rousseletii (Volvocales, Chlorophyta) was analyzed. In response to light stimuli, not only did the flagella waveform and beat frequency change, but the effective stroke was reversed. Moreover, there was a photoresponse gradient from the anterior to the posterior pole of the spheroid, and only cells of the anterior hemisphere showed an effective response. The latter caused a reverse of the fluid flow that was confined to the anterior hemisphere. The responsiveness to light is consistent with an anterior-to-posterior size gradient of eyespots. At the posterior pole, the eyespots are tiny or absent, making the corresponding cells appear to be blind. Pulsed light stimulation of an immobilized spheroid was used to simulate the light fluctuation experienced by a rotating spheroid during phototaxis. The results demonstrated that in free-swimming spheroids, only those cells of the anterior hemisphere that face toward the light source reverse the beating direction in the presence of illumination; this behavior results in phototactic turning. Moreover, positive phototaxis is facilitated by gravitational forces. Under our conditions, V. rousseletii spheroids showed no negative phototaxis.

Conclusions

On the basis of our results, we developed a mechanistic model that predicts the phototactic behavior in V. rousseletii. The model involves photoresponses, periodically changing light conditions, morphological polarity, rotation of the spheroid, two modes of flagellar beating, and the impact of gravity. Our results also indicate how recently evolved multicellular organisms adapted the phototactic capabilities of their unicellular ancestors to multicellular life.
Characterization of proteinases from the midgut of Rhipicephalus (Boophilus) microplus involved in the generation of antimicrobial peptides
Authors: Cruz Carlos E , Fogaça Andréa C , Nakayasu Ernesto S , Angeli Cláudia B , Belmonte Rodrigo , Almeida Igor C , Miranda Antônio , Miranda Maria Terêsa M , Tanaka Aparecida S , Braz Glória R , Craik Charles S , Schneider Eric , Caffrey Conor R , Daffre Sirlei
Published: July 2010

Background

Hemoglobin is a rich source of biologically active peptides, some of which are potent antimicrobials (hemocidins). A few hemocidins have been purified from the midgut contents of ticks. Nonetheless, how antimicrobials are generated in the tick midgut and their role in immunity is still poorly understood. Here we report, for the first time, the contribution of two midgut proteinases to the generation of hemocidins.

Results

An aspartic proteinase, designated BmAP, was isolated from the midgut of Rhipicephalus (Boophilus) microplus using three chromatographic steps. Reverse transcription-quantitative polymerase chain reaction revealed that BmAP is restricted to the midgut. The other enzyme is a previously characterized midgut cathepsin L-like cysteine proteinase designated BmCL1. Substrate specificities of native BmAP and recombinant BmCL1 were mapped using a synthetic combinatorial peptide library and bovine hemoglobin. BmCL1 preferred substrates containing non-polar residues at P2 subsite and polar residues at P1, whereas BmAP hydrolysed substrates containing non-polar amino acids at P1 and P1'.

Conclusions

BmAP and BmCL1 generate hemocidins from hemoglobin alpha and beta chains in vitro. We postulate that hemocidins may be important for the control of tick pathogens and midgut flora.
Characterisation of the Binding Properties of Bacillus Thuringiensis 18 Toxin on Leukaemic Cells
Authors: Wong Rebecca SY , Mohamed Shar M , Nadarajah Vishna D , Tengku Ibrahim Azmi T
Published: July 2010

Background

Various strains ofBacillus thuringiensis(Bt) have been found to produce parasporal proteins that are cytotoxic to human cancer cells. This study aims to establish the binding affinity of purified Bt 18 toxin for CEM-SS (T lymphoblastic leukaemia cell line), to determine if competition exists between the toxin and commercial anticancer drugs for the binding site on CEM-SS and to localise the binding site of the toxin on CEM-SS.

Methods

In homologous competitive binding study, the purified toxin was labelled with biotin and allowed to compete with unlabelled toxin for binding sites on CEM-SS and its dissociation constant (Kd) was determined. Comparisons were made with CCRF-SB, CCRF-HSB-2 and MCF-7. In heterologous competitive binding study, biotinylated toxin competition was determined with two other Bt toxins (crude Btj and crude Bt 22) and anticancer drugs (cisplatin, doxorubicin, etoposide, navelbine and methotrexate). To localise the binding site under the confocal microscope, the biotinylated toxin was tagged with FITC-conjugated streptavidin.

Results

Homologous competitive binding assays revealed decreasing binding affinity of Bt 18 toxin for CEM-SS, CCRF-SB, and CCRF-HSB-2 with Kd of 8.44 nM, 14.98 nM and 17.71 nM respectively. Kd for MCF-7 was not determined as the inhibitory concentration (IC50) was not reached. Heterologous competitive study showed little competition (< 30%) between biotinylated Bt 18 toxin and all test compounds used. Confocal microscopy revealed binding of toxin at the periphery of the cell.

Conclusions

It was postulated that purified Bt 18 toxin binds on the cell surface of CEM-SS and the mechanism of cell death may differ from that of Btj toxin, Bt 22 toxin and all five anticancer drugs used in this study, since it did not significantly compete with these compounds for the same binding site.
Economic results of a palivizumab seasonal prophylaxis using a cohorting software and vial sharing
Authors: Coletta Elio , Coppolino Salvatore , Federico Febronia , Fulia Francesco
Published: July 2010

Background

Respiratory syncytial virus is the most important pathogen in lower respiratory tract infection in infants and young children. In high-risk populations it may develop severe, sometimes fatal, lower respiratory tract infections. A proportion of these infants require admission to intensive care units due to the severity of the condition and the level of care needed. Furthermore, we must consider the possible increased risk of asthma following RSV infection in infancy.

Methods

The aim of this work is to show how we strictly coordinated, during the 2008-2009 RSV season, the delivery of prophylaxis while minimising drug cost through vial sharing and cohorting infants with a software performed through Visual Basic programming system.

Results

By using this method we have been able to obtain a saving of the 29.2% compared to the theoretical amount. No infant requested hospitalisation for a RSV infection.

Conclusions

Such a model ensures all patients to receive appropriate immunization and thus positively influencing the cost-benefit of palivizumab prophylaxis. We hope that our model of care delivery will be of use to other hospitals.
Trait-stratified genome-wide association study identifies novel and diverse genetic associations with serologic and cytokine phenotypes in systemic lupus erythematosus
Authors: Kariuki Silvia N , Franek Beverly S , Kumar Akaash A , Arrington Jasmine , Mikolaitis Rachel A , Utset Tammy O , Jolly Meenakshi , Crow Mary K , Skol Andrew D , Niewold Timothy B
Published: July 2010

Introduction

Systemic lupus erythematosus (SLE) is a highly heterogeneous disorder, characterized by differences in autoantibody profile, serum cytokines, and clinical manifestations. SLE-associated autoantibodies and high serum interferon alpha (IFN-α) are important heritable phenotypes in SLE which are correlated with each other, and play a role in disease pathogenesis. These two heritable risk factors are shared between ancestral backgrounds. The aim of the study was to detect genetic factors associated with autoantibody profiles and serum IFN-α in SLE.

Methods

We undertook a case-case genome-wide association study of SLE patients stratified by ancestry and extremes of phenotype in serology and serum IFN-α. Single nucleotide polymorphisms (SNPs) in seven loci were selected for follow-up in a large independent cohort of 538 SLE patients and 522 controls using a multi-step screening approach based on novel metrics and expert database review. The seven loci were: leucine-rich repeat containing 20 (LRRC20); protein phosphatase 1 H (PPM1H); lysophosphatidic acid receptor 1 (LPAR1); ankyrin repeat and sterile alpha motif domain 1A (ANKS1A); protein tyrosine phosphatase, receptor type M (PTPRM); ephrin A5 (EFNA5); and V-set and immunoglobulin domain containing 2 (VSIG2).

Results

SNPs in the LRRC20, PPM1H, LPAR1, ANKS1A, and VSIG2 loci each demonstrated strong association with a particular serologic profile (all odds ratios > 2.2 and P < 3.5 × 10-4). Each of these serologic profiles was associated with increased serum IFN-α. SNPs in both PTPRM and LRRC20 were associated with increased serum IFN-α independent of serologic profile (P = 2.2 × 10-6 and P = 2.6 × 10-3 respectively). None of the SNPs were strongly associated with SLE in case-control analysis, suggesting that the major impact of these variants will be upon subphenotypes in SLE.

Conclusions

This study demonstrates the power of using serologic and cytokine subphenotypes to elucidate genetic factors involved in complex autoimmune disease. The distinct associations observed emphasize the heterogeneity of molecular pathogenesis in SLE, and the need for stratification by subphenotypes in genetic studies. We hypothesize that these genetic variants play a role in disease manifestations and severity in SLE.
ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67
Authors: Tuominen Vilppu J , Ruotoistenmäki Sanna , Viitanen Arttu , Jumppanen Mervi , Isola Jorma
Published: July 2010

Introduction

Accurate assessment of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 is essential in the histopathologic diagnostics of breast cancer. Commercially available image analysis systems are usually bundled with dedicated analysis hardware and, to our knowledge, no easily installable, free software for immunostained slide scoring has been described. In this study, we describe a free, Internet-based web application for quantitative image analysis of ER, PR, and Ki-67 immunohistochemistry in breast cancer tissue sections.

Methods

The application, named ImmunoRatio, calculates the percentage of positively stained nuclear area (labeling index) by using a color deconvolution algorithm for separating the staining components (diaminobenzidine and hematoxylin) and adaptive thresholding for nuclear area segmentation. ImmunoRatio was calibrated using cell counts defined visually as the gold standard (training set, n = 50). Validation was done using a separate set of 50 ER, PR, and Ki-67 stained slides (test set, n = 50). In addition, Ki-67 labeling indexes determined by ImmunoRatio were studied for their prognostic value in a retrospective cohort of 123 breast cancer patients.

Results

The labeling indexes by calibrated ImmunoRatio analyses correlated well with those defined visually in the test set (correlation coefficient r = 0.98). Using the median Ki-67 labeling index (20%) as a cutoff, a hazard ratio of 2.2 was obtained in the survival analysis (n = 123, P = 0.01). ImmunoRatio was shown to adapt to various staining protocols, microscope setups, digital camera models, and image acquisition settings. The application can be used directly with web browsers running on modern operating systems (e.g., Microsoft Windows, Linux distributions, and Mac OS). No software downloads or installations are required. ImmunoRatio is open source software, and the web application is publicly accessible on our website.

Conclusions

We anticipate that free web applications, such as ImmunoRatio, will make the quantitative image analysis of ER, PR, and Ki-67 easy and straightforward in the diagnostic assessment of breast cancer specimens.
APCAP - activated protein C in acute pancreatitis: a double-blind randomized human pilot trial
Authors: Pettilä Ville , Kyhälä Lea , Kylänpää Marja-Leena , Leppäniemi Ari , Tallgren Minna , Markkola Antti , Puolakkainen Pauli , Repo Heikki , Kemppainen Esko
Published: July 2010

Introduction

Previous human studies have shown low activity of protein C (APC) in severe acute pancreatitis (SAP). This, together with the findings in animal models, suggests that activated protein C (APC) may protect against pancreatic injury and ameliorate the disease. We, therefore, evaluated its effect on multiple organ dysfunction (MOD) measured by the SOFA (Sequential Organ Failure Assessment) and on organ-failure-free days, and the safety of APC in SAP.

Methods

A prospective double blind randomized pilot study was use. The study occurred in one university hospital tertiary intensive care unit (ICU) with eight beds. The patients were chosen according to the following inclusion criteria: 1) Those admitted to the hospital < 96 h from the onset of pain, 2) Those who had a three-fold increase in serum amylase over normal upper range or/and in whom computed tomography (CT) verification of SAP was noted, 3) Those who had one or more organ dysfunction (OD), and 4) Those in whom less than 48 hours had passed since their first OD. Of a total of 215 adult patients with SAP screened between June 2003 and August 2007, 158 fulfilled the study inclusion criteria. After exclusions 32 patients were randomized to the study. The intervention consisted of APC (N = 16) administered intravenously for 96 hours with a dose of 24 μg/kg/hour or placebo (N = 16) with a similar infusion rate. The sample size for the study was calculated according to the primary end-point: the change in SOFA during study drug infusion (Days 0 and 5). Comparisons between the study groups were performed using patient-related changes and calculation of difference in means (DIM, 95% CIs) and regarding categorical variables with Fisher's exact test. For all comparisons P < 0.05 was considered significant.

Results

No serious bleeding was detected clinically or by CT scans in either group. No significant difference in SOFA score change between the APC and placebo groups was found (difference in means (DIM) +2.3, 95% CI -0.7 to +5.3). Treatment with APC was associated with an increase in serum levels of both total and conjugated bilirubin. No differences in ventilator-free days, in renal replacement therapy-free days, in vasopressor-free days, or in days alive outside the hospital were detected.

Conclusions

No serious bleeding or differences in the evolution of MOD were detected between APC and the placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP.

Trial registration

ClinicalTrials.gov NCT01017107.
Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era
Authors: Gisselbrecht Christian , Glass Bertram , Mounier Nicolas , Singh Gill Devinder , Linch David C. , Trneny Marek , Bosly Andre , Ketterer Nicolas , Shpilberg Ofer , Hagberg Hans , Ma David , Brière Josette , Moskowitz Craig H. , Schmitz Norbert
Published: July 2010

Purpose

Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown.

Patients and Methods

Patients with CD20+DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT.

Results

The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Prognostic Index (IPI) of more than 1 versus 0 to 1 (52% v 71%, respectively), and prior rituximab treatment versus no prior rituximab (51% v 83%, respectively). There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival (EFS) or overall survival. Three-year EFS was affected by prior rituximab treatment versus no rituximab (21% v 47%, respectively), relapse less than versus more than 12 months after diagnosis (20% v 45%, respectively), and IPI of 2 to 3 versus 0 to 1 (18% v 40%, respectively). In the Cox model, these parameters were significant (P < .001).

Conclusion

In patients who experience relapse more than 12 months after diagnosis, prior rituximab treatment does not affect EFS. Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP.
Cytoskeletal dynamics and supracellular organisation of cell shape fluctuations during dorsal closure
Authors: Blanchard Guy B. , Murugesu Sughashini , Adams Richard J. , Martinez-Arias Alfonso , Gorfinkiel Nicole
Published: July 2010

Fluctuations in the shape of amnioserosa (AS) cells during Drosophila dorsal closure (DC) provide an ideal system with which to understand contractile epithelia, both in terms of the cellular mechanisms and how tissue behaviour emerges from the activity of individual cells. Using quantitative image analysis we show that apical shape fluctuations are driven by the medial cytoskeleton, with periodic foci of contractile myosin and actin travelling across cell apices. Shape changes were mostly anisotropic and neighbouring cells were often, but transiently, organised into strings with parallel deformations. During the early stages of DC, shape fluctuations with long cycle lengths produced no net tissue contraction. Cycle lengths shortened with the onset of net tissue contraction, followed by a damping of fluctuation amplitude. Eventually, fluctuations became undetectable as AS cells contracted rapidly. These transitions were accompanied by an increase in apical myosin, both at cell-cell junctions and medially, the latter ultimately forming a coherent, but still dynamic, sheet across cells. Mutants with increased myosin activity or actin polymerisation exhibited precocious cell contraction through changes in the subcellular localisation of myosin. thickveins mutant embryos, which exhibited defects in the actin cable at the leading edge, showed similar timings of fluctuation damping to the wild type, suggesting that damping is an autonomous property of the AS. Our results suggest that cell shape fluctuations are a property of cells with low and increasing levels of apical myosin, and that medial and junctional myosin populations combine to contract AS cell apices and drive DC.
Senior-Friendly Emergency Department Care: An Environmental Assessment
Authors: Kelley Mary Lou , Parke Belinda , Jokinen Nancy , Stones Michael , Renaud Donna
Published: July 2010

Objectives

To assess the environment of an emergency department (ED) and its impact on care of adults aged 75 and over, using a ‘senior-friendly’ conceptual framework that included the physical environment, social climate, hospital policies and procedures, and wider health care system.

Methods

In this focused ethnography, we collected and analysed data from the ED of a regional acute care hospital located in Ontario, Canada from October 2007 to January 2008. Data collection included interviews with seniors or their proxy decision-makers, staff and key community informants; on-site observations; a staff survey; and hospital administrative data. Data sets were individually analysed and a synthesis of findings developed to formulate recommendations for policy, practice and education.

Results

Staff expressed their vision of providing senior-friendly care. However, the ED was fast-paced, overcrowded, chaotic and lacked orientation and wayfinding cues, as well as appropriate equipment and furniture, all of which created barriers to providing appropriate care. Seniors' expectations often went unmet and staff expressed moral angst at recognizing unmet needs. Some hospital policies and procedures compounded these difficulties, including hallway practice, lack of off-hour access to multidisciplinary health care professionals, and the inability of patients to access food and drink. Better communication and coordination between the ED and other components of the health care system are needed.

Conclusions

The ED is an important part of seniors' health care. Changes to policy and practices, and enhanced education must occur to better meet the complex health care needs of seniors. This assessment provides a method that can be replicated elsewhere to generate site-specific recommendations and initiate capacity development processes to enhance senior-friendly care.
‘Not quite Jericho, but more doors than there used to be’. Staff views of the impact of ‘modernization’ on boundaries around adult critical care services in England
Authors: Durand Mary , Hutchings Andrew , Black Nick , Green Judith
Published: July 2010

Objectives:

To explore staff perceptions of the impact of ‘modernization’ on the organization, delivery and culture of adult critical care services in England. ‘Modernization’ policies aimed to alter the boundaries around critical care and create a comprehensive, seamless service.

Methods:

Seven hospitals (three teaching and four district general hospitals) in three critical care networks participated. In-depth interviews were conducted with a purposive sample of 45 critical care staff. Data were analysed thematically.

Results:

The boundaries around critical care were generally perceived to be less fixed than previously. The reframing of ‘internal walls’ within hospitals was associated with the introduction of outreach teams, new hospital-wide remits for intensive care unit (ICU) staff and the greater integration of allied health professionals into the critical care team. Transformation of services was challenged by practicalities including the need for additional staff, and a ‘them and us’ attitude between ICU and ward staff. ‘External walls’ between hospitals were breached where local clinical networks were perceived to have successfully improved communication and joint working. This was facilitated by effective leadership, availability of network-associated funds, the identification of common problems and evidence of benefit from cooperation. However, barriers existed and there was some scepticism among staff as to whether critical care can ever be entirely ‘without walls’.

Conclusions:

Policies to remove boundaries around adult critical care are perceived to have had a dramatic impact on the organization of the service. Considerable progress was reported towards developing comprehensive critical care services both within and between hospitals.
Hospital Mergers: A Panacea?
Authors: Weil Thomas
Published: July 2010

Hospital mergers in Europe and North America have been launched to scale down expenditure, enhance the delivery of health care and elevate quality. However, the outcome of mergers suggest that they neither generated cost savings nor improved the quality of care. Almost all consolidations fall short, since those in leadership positions lack the necessary understanding and appreciation of the differences in culture, values and goals of the existing facilities. In spite of these shortcomings, hospital mergers will continue to be pursued in order to improve market share, eliminate excess capacity, gain access to capital and enhance the personal egos of the organizations’ leaders.
Exploring communities of music in Virginia's Shenandoah Valley
Authors: Dabback William M
Published: July 2010

Community music practices may offer paths to broaden the scope of the music education field by providing meaningful alternatives to traditional approaches found in many formal music education systems. As specific social settings shape and define community music, prominent researchers
have called for further investigation into practices in the local contexts. This pilot study explores community music in the context of Rockingham County in Virginia, which contains rich musical traditions associated with educational institutions, faith communities, organized community ensembles
and informal music making contexts. Dialogue with prominent local practitioners sought to profile their roles and groups, explore the nature and content of their music making, describe interactions in teaching and learning and identify any perceived interrelationships among the communities
of practice.
Music and conflict transformation in the post-Yugoslav era: empowering youth to develop harmonic inter-ethnic relationships in Kumanovo, Macedonia
Authors: Balandina Alexandra
Published: July 2010

In this article I discuss my recent exploration into the operational interface between applied ethnomusicology and peacebuilding in post-conflict states. I explore how a summer youth music festival provides opportunities to transform conflictual interethnic relationship in contemporary
Macedonia (FYROM), a former republic of Yugoslavia. I investigate the role of intercultural music making in promoting ethnic reconciliation and consider how music making processes may motivate young people to engage in an intercultural dialogue through creative and emotional musical engagement.
I consider how young participants negotiate their own ethnic identities and relationships with their peers on and off stage and consider their role in promoting a culture of peace and non-violence. I argue for considering applied ethnomusicology in advocating the primacy of the voices and
goals of the participants themselves and explore the role of the native ethnomusicologist/anthropologist as an applied practitioner.
The Silver Song Club Project: A sense of well-being through participatory singing
Authors: Bungay Hilary , Clift Stephen , Skingley Anne
Published: July 2010

The Silver Song Club Project provides an opportunity for older people to come together regularly and participate in a programme of singing and music making, and is based on the principle that singing and music have the potential to benefit health and well-being. An evaluation was undertaken
to investigate the development of the Silver Song Club Project, and to explore the experiences and benefits gained by participants. A total of 369 participants (in 26 song clubs across the south east) completed a short questionnaire to provide information on personal characteristics, previous
musical experience, anticipation and enjoyment of the clubs and perceived benefits. It was found that those attending enjoy a positive experience; with two-thirds of those participating saying that it makes them feel better. It is argued that the sense of well-being experienced by people attending
the sessions is due to the potential of singing well-known songs to act as a social catalyst, and the inherent physical and psychological characteristics of singing itself.
Connective tissue growth factor expression in endocrine tumors is associated with high stromal expression of α-smooth muscle actin
Authors: Cunningham Janet L , Tsolakis Apostolos V , Jacobson Annica , Janson Eva T
Published: July 2010

Objective

Complications due to fibrosis development are common in patients with well-differentiated endocrine carcinomas in the small intestine (ileal carcinoids). Connective tissue growth factor (CTGF) expression in ileal carcinoids may be related to this fibrosis development. This study aimed to examine CTGF expression in relation to local myofibroblast differentiation in a large series of ileal carcinoids and in different types of endocrine tumors.

Methods

Immunoreactivity (IR) for CTGF and α-smooth muscle actin (α-SMA), a marker for myofibroblasts, was compared in serial tumor tissue sections from 42 patients with ileal carcinoids and from 80 patients with other endocrine tumors. Western blot was performed on an additional 21 patients with ileal carcinoids.

Results

CTGF IR was present in >50% of tumor cells in all 42 ileal carcinoids and in 2 out of 14 endocrine pancreatic tumors, 4 out of 6 rectal carcinoids, and 1 out of 5 lung carcinoids. Tumors with abundant CTGF expression also displayed α-SMA IR in stromal fibroblast-like cells, whereas other endocrine tumors displayed less or no CTGF and α-SMA IR. Protein bands corresponding to full-length CTGF (36–42 kDa) were detected in protein lysates from ileal carcinoids.

Conclusion

CTGF is uniquely prevalent in ileal carcinoids when compared with most other endocrine tumor types. Immunoreactive cells are adjacent areas with increased fibrovascular stroma that express α-SMA. This supports a potential role for CTGF in myofibroblast-mediated fibrosis associated with ileal carcinoids, and indicates that CTGF should be investigated as a target for future therapy.
Statistical Analysis of Nondisjunction Assays in Drosophila
Authors: Zeng Yong , Li Hua , Schweppe Nicole M , Hawley R Scott , Gilliland William D
Published: July 2010

Many advances in the understanding of meiosis have been made by measuring how often errors in chromosome segregation occur. This process of nondisjunction can be studied by counting experimental progeny, but direct measurement of nondisjunction rates is complicated by not all classes of nondisjunctional progeny being viable. For X chromosome nondisjunction in Drosophila female meiosis, all of the normal progeny survive, while nondisjunctional eggs produce viable progeny only if fertilized by sperm that carry the appropriate sex chromosome. The rate of nondisjunction has traditionally been estimated by assuming a binomial process and doubling the number of observed nondisjunctional progeny, to account for the inviable classes. However, the correct way to derive statistics (such as confidence intervals or hypothesis testing) by this approach is far from clear. Instead, we use the multinomial-Poisson hierarchy model and demonstrate that the old estimator is in fact the maximum-likelihood estimator (MLE). Under more general assumptions, we derive asymptotic normality of this estimator and construct confidence interval and hypothesis testing formulae. Confidence intervals under this framework are always larger than under the binomial framework, and application to published data shows that use of the multinomial approach can avoid an apparent type 1 error made by use of the binomial assumption. The current study provides guidance for researchers designing genetic experiments on nondisjunction and improves several methods for the analysis of genetic data.
Parallel Adaptation: One or Many Waves of Advance of an Advantageous Allele?
Authors: Ralph Peter , Coop Graham
Published: July 2010

Models for detecting the effect of adaptation on population genomic diversity are often predicated on a single newly arisen mutation sweeping rapidly to fixation. However, a population can also adapt to a new environment by multiple mutations of similar phenotypic effect that arise in parallel, at the same locus or different loci. These mutations can each quickly reach intermediate frequency, preventing any single one from rapidly sweeping to fixation globally, leading to a “soft” sweep in the population. Here we study various models of parallel mutation in a continuous, geographically spread population adapting to a global selection pressure. The slow geographic spread of a selected allele due to limited dispersal can allow other selected alleles to arise and start to spread elsewhere in the species range. When these different selected alleles meet, their spread can slow dramatically and so initially form a geographic patchwork, a random tessellation, which could be mistaken for a signal of local adaptation. This spatial tessellation will dissipate over time due to mixing by migration, leaving a set of partial sweeps within the global population. We show that the spatial tessellation initially formed by mutational types is closely connected to Poisson process models of crystallization, which we extend. We find that the probability of parallel mutation and the spatial scale on which parallel mutation occurs are captured by a single compound parameter, a characteristic length, which reflects the expected distance a spreading allele travels before it encounters a different spreading allele. This characteristic length depends on the mutation rate, the dispersal parameter, the effective local density of individuals, and to a much lesser extent the strength of selection. While our knowledge of these parameters is poor, we argue that even in widely dispersing species, such parallel geographic sweeps may be surprisingly common. Thus, we predict that as more data become available, many more examples of intraspecies parallel adaptation will be uncovered.
Detection of Heterozygous Mutations in the Genome of Mismatch Repair Defective Diploid Yeast Using a Bayesian Approach
Authors: Zanders Sarah , Ma Xin , RoyChoudhury Arindam , Hernandez Ryan D , Demogines Ann , Barker Brandon , Gu Zhenglong , Bustamante Carlos D , Alani Eric
Published: July 2010

DNA replication errors that escape polymerase proofreading and mismatch repair (MMR) can lead to base substitution and frameshift mutations. Such mutations can disrupt gene function, reduce fitness, and promote diseases such as cancer and are also the raw material of molecular evolution. To analyze with limited bias genomic features associated with DNA polymerase errors, we performed a genome-wide analysis of mutations that accumulate in MMR-deficient diploid lines of Saccharomyces cerevisiae. These lines were derived from a common ancestor and were grown for 160 generations, with bottlenecks reducing the population to one cell every 20 generations. We sequenced to between 8- and 20-fold coverage one wild-type and three mutator lines using Illumina Solexa 36-bp reads. Using an experimentally aware Bayesian genotype caller developed to pool experimental data across sequencing runs for all strains, we detected 28 heterozygous single-nucleotide polymorphisms (SNPs) and 48 single-nt insertion/deletions (indels) from the data set. This method was evaluated on simulated data sets and found to have a very low false-positive rate (∼6 × 10−5) and a false-negative rate of 0.08 within the unique mapping regions of the genome that contained at least sevenfold coverage. The heterozygous mutations identified by the Bayesian genotype caller were confirmed by Sanger sequencing. All of the mutations were unique to a given line, except for a single-nt deletion mutation which occurred independently in two lines. All 48 indels, composed of 46 deletions and two insertions, occurred in homopolymer (HP) tracts [i.e., 47 poly(A) or (T) tracts, 1 poly(G) or (C) tract] between 5 and 13 bp long. Our findings are of interest because HP tracts are present at high levels in the yeast genome (>77,400 for 5- to 20-nt HP tracts), and frameshift mutations in these regions are likely to disrupt gene function. In addition, they demonstrate that the mutation pattern seen previously in mismatch repair defective strains using a limited number of reporters holds true for the entire genome.
Epidemiology of Postconcussion Syndrome in Pediatric Mild Traumatic Brain Injury
Authors: Barlow Karen Maria , Crawford Susan , Stevenson Andrea , Sandhu Sandeep Sona , Belanger François , Dewey Deborah
Published: July 2010

BACKGROUND:

Much disagreement exists as to whether postconcussion syndrome (PCS) is attributable to brain injury or to other factors such as trauma alone, preexisting psychosocial problems, or medicolegal issues. We investigated the epidemiology and natural history of PCS symptoms in a large cohort of children with a mild traumatic brain injury (mTBI) and compared them with children with an extracranial injury (ECI).

METHODS:

This investigation was a prospective, consecutive controlled-cohort study of 670 children who presented to a tertiary referral emergency department with mTBI and 197 children who presented with ECI. For all participants, data were collected by use of a telephone interview of a parent 7 to 10 days after injury. If a change from preinjury symptoms was reported by a parent, follow-up continued monthly until symptom resolution. Outcomes were measured by using the Post Concussion Symptom Inventory, Rivermead Postconcussion Symptom Questionnaire, Brief Symptom Inventory, and Family Assessment Device.

RESULTS:

There was a significant difference between the mTBI and ECI groups in their survival curves for time to symptom resolution (log rank [Mantel-Cox] 11.15, P < .001). Three months after injury, 11% of the children in the mTBI group were symptomatic (13.7% of children older than 6 years) compared with 0.5% of the children in the ECI group. The prevalence of persistent symptoms at 1 year was 2.3% in the mTBI group and 0.01% in the ECI group. Family functioning and maternal adjustment did not differ between groups.

CONCLUSIONS:

Among school-aged children with mTBI, 13.7% were symptomatic 3 months after injury. This finding could not be explained by trauma, family dysfunction, or maternal psychological adjustment. The results of this study provide clear support for the validity of the diagnosis of PCS in children.
Iron Deficiency Anemia and Cognitive Function in Infancy
Authors: Carter R. Colin , Jacobson Joseph L. , Burden Matthew J. , Armony-Sivan Rinat , Dodge Neil C. , Angelilli Mary Lu , Lozoff Betsy , Jacobson Sandra W.
Published: July 2010

OBJECTIVES:

This study examined effects of iron deficiency anemia (IDA) on specific domains of infant cognitive function and the role of IDA-related socioemotional deficits in mediating and/or moderating these effects.

METHODS:

Infants were recruited during routine 9-month visits to an inner-city clinic. IDA was defined as hemoglobin level <110 g/L with ≥2 abnormal iron deficiency indicators (mean corpuscular volume, red cell distribution width, zinc protoporphyrin, transferrin saturation, and ferritin). At 9 and 12 months, the Fagan Test of Infant Intelligence (FTII); A-not-B task; Emotionality, Activity, and Sociability Temperament Survey; and Behavior Rating Scale were administered. Analyses were adjusted for potential confounders, including age and sociodemographic variables.

RESULTS:

Twenty-eight infants met criteria for IDA, 28 had nonanemic iron deficiency (NA ID) and 21 had iron sufficiency (IS). There was a linear effect for object permanence at 9 months: infants with IDA were least likely to exhibit object permanence, IS most likely, and NA ID intermediate. Infants with IDA and those with hemoglobin level ≤105 g/L showed poorer recognition memory on the FTII than infants without IDA. The Behavior Rating Scale orientation/engagement measure partially mediated these effects. Stronger effects of IDA on these outcomes were seen in infants who scored more poorly on the socioemotional measures.

CONCLUSIONS:

These data indicate poorer object permanence and short-term memory encoding and/or retrieval in infants with IDA at 9 months. These cognitive effects were attributable, in part, to IDA-related deficits in socioemotional function. Children with poor socioemotional performance seem to be more vulnerable to the effects of IDA on cognitive function.
The Eye Examination in the Evaluation of Child Abuse
Authors: Levin Alex V. , Christian Cindy W. ,   Committee on Child Abuse and Neglect, Section on Ophthalmology
Published: July 2010

This Clinical Report was revised. See https://doi.org/10.1542/peds.2018-1411.

Retinal hemorrhage is an important indicator of possible abusive head trauma, but it is also found in a number of other conditions. Distinguishing the type, number, and pattern of retinal hemorrhages may be helpful in establishing a differential diagnosis. Identification of ocular abnormalities requires a full retinal examination by an ophthalmologist using indirect ophthalmoscopy through a pupil that has been pharmacologically dilated. At autopsy, removal of the eyes and orbital tissues may also reveal abnormalities not discovered before death. In previously well young children who experience unexpected apparent life-threatening events with no obvious cause, children with head trauma that results in significant intracranial hemorrhage and brain injury, victims of abusive head trauma, and children with unexplained death, premortem clinical eye examination and postmortem examination of the eyes and orbits may be helpful in detecting abnormalities that can help establish the underlying etiology.
Systematic comparison of sporadic and syndromic pancreatic islet cell tumors
Authors: Erlic Zoran , Ploeckinger Ursula , Cascon Alberto , Hoffmann Michael M , von Duecker Laura , Winter Aurelia , Kammel Gerit , Bacher Janina , Sullivan Maren , Isermann Berend , Fischer Lars , Raffel Andreas , Knoefel Wolfram Trudo , Schott Matthias , Baumann Tobias , Schaefer Oliver , Keck Tobias , Baum Richard P , Milos Ioana , Muresan Mihaela , Peczkowska Mariola , Januszewicz Andrzej , Cupisti Kenko , Tönjes Anke , Fasshauer Mathias , Langrehr Jan , von Wussow Peter , Agaimy Abbas , Schlimok Günter , Lamberts Regina , Wiech Thorsten , Schmid Kurt Werner , Weber Alexander , Nunez Mercedes , Robledo Mercedes , Eng Charis , Neumann Hartmut P H , _ _
Published: July 2010

Pancreatic islet cell tumors (ICTs) occur as sporadic neoplasias or as a manifestation of multiple endocrine neoplasia type 1 (MEN1) and von Hippel–Lindau disease (VHL). Molecular classification of ICTs is mandatory for timely diagnosis and surveillance. Systematic comparison of VHL-ICTs and sporadic ICTs has been lacking. Our registry-based approaches used the German NET-Registry with 259 patients with neuroendocrine tumors (NETs), who were primarily diagnosed with NETs, and the German VHL-Registry with 485 molecular genetically confirmed patients who had undergone magnetic resonance imaging or computed tomography of the abdomen. All patients provided blood DNA for testing of the MEN1 and VHL genes for intragenic mutations and large deletions. In the NET-Registry, 9/101 patients (8.9%) with ICTs had germline mutations, 8 in MEN1 and 1 in VHL. In the VHL-Registry, prevalence of NETs was 52/487 (10.6%), and all were ICTs. Interestingly, of those with VHL p.R167W, 47% developed ICTs, compared to 2% of those with p.Y98H. In total, there were 92 truly sporadic, i.e. mutation-negative ICT patients. Comparing these with the 53 VHL-ICT patients, the statistically significant differences were predominance of female gender (P=0.01), multifocal ICTs (P=0.0029), and lower malignancy rate (P<0.001) in VHL-ICTs compared to sporadic cases. VHL was prevalent in <0.5% of NETs, while NETs occur in ∼10% of VHL, virtually exclusively as ICTs, which are rarely the first presentation. Patients with NETs should not be subjected to genetic testing of the VHL gene, unless they have multifocal ICTs, other VHL-associated tumors, and/or a family history for VHL.