bluuebunny/crossref_metadata_2025 huggingface dataset:
An MRI‐based index to measure the severity of Alzheimer's disease‐like structural pattern in subjects with mild cognitive impairment
Authors: Spulber G. , Simmons A. , Muehlboeck J.‐S. , Mecocci P. , Vellas B. , Tsolaki M. , Kłoszewska I. , Soininen H. , Spenger C. , Lovestone S. , Wahlund L.‐O. , Westman E. ,   for the AddNeuroMed consortium and for the Alzheimer Disease Neuroimaging Initiative
Published: April 2013

Background

Structural magnetic resonance imaging (MRI) is sensitive to neurodegeneration and can be used to estimate the risk of converting to Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI). Brain changes in AD and prodromal AD involve a pattern of widespread atrophy. The use of multivariate analysis algorithms could enable the development of diagnostic tools based on structural MRI data. In this study, we investigated the possibility of combining multiple MRI features in the form of a severity index.

Methods

We used baseline MRI scans from two large multicentre cohorts (AddNeuroMed and ADNI). On the basis of volumetric and cortical thickness measures at baseline with AD cases and healthy control (CTL) subjects as training sets, we generated an MRI‐based severity index using the method of orthogonal projection to latent structures (OPLS). The severity index tends to be close to 1 for AD patients and 0 for CTL subjects. Values above 0.5 indicate a more AD‐like pattern. The index was then estimated for subjects with MCI, and the accuracy of classification was investigated.

Results

Based on the data at follow‐up, 173 subjects converted to AD, of whom 112 (64.7%) were classified as AD‐like and 61 (35.3%) as CTL‐like.

Conclusion

We found that joint evaluation of multiple brain regions provided accurate discrimination between progressive and stable MCI, with better performance than hippocampal volume alone, or a limited set of features. A major challenge is still to determine optimal cut‐off points for such parameters and to compare their relative reliability.
Shortening the ‘short‐course’ therapy– insights into host immunity may contribute to new treatment strategies for tuberculosis
Authors: Schön T. , Lerm M. , Stendahl O.
Published: April 2013

Achieving global control of tuberculosis (TB) is a great challenge considering the current increase in multidrug resistance and mortality rate. Considerable efforts are therefore being made to develop new effective vaccines, more effective and rapid diagnostic tools as well as new drugs. Shortening the duration of TB treatment with revised regimens and modes of delivery of existing drugs, as well as development of new antimicrobial agents and optimization of the host response with adjuvant immunotherapy could have a profound impact on TB cure rates. Recent data show that chronic worm infection and deficiencies in micronutrients such as vitamin D and arginine are potential areas of intervention to optimize host immunity. Nutritional supplementation to enhance nitric oxide production and vitamin D‐mediated effector functions as well as the treatment of worm infection to reduce immunosuppressive effects of regulatory T (Treg) lymphocytes may be more suitable and accessible strategies for highly endemic areas than adjuvant cytokine therapy. In this review, we focus mainly on immune control of human TB, and discuss how current treatment strategies, including immunotherapy and nutritional supplementation, could be optimized to enhance the host response leading to more effective treatment.
Sitagliptin improves beta‐cell function in patients with acute coronary syndromes and newly diagnosed glucose abnormalities–the BEGAMI study
Authors: Hage C. , Brismar K. , Efendic S. , Lundman P. , Rydén L. , Mellbin L.
Published: April 2013

Background

Newly detected impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM) are common in patients with acute coronary syndrome (ACS; i.e. unstable angina/myocardial infarction) and related to disturbed beta‐cell function. The aim of this study is to test the hypothesis that treatment with a dipeptidyl peptidase‐4 inhibitor initiated soon after a coronary event improves beta‐cell function.

Methods

Acute coronary syndromeACS patients with IGT or T2DM (n = 71), screened by oral glucose tolerance test (OGTT) 4–23 days (median 6 days) after hospital admission, were randomly assigned to sitagliptin 100 mg (n = 34) or placebo (n = 37) and treated for a duration of 12 weeks. All patients received lifestyle advice but no glucose‐lowering agents other than the study drug. The study end‐point was beta‐cell function assessed using the insulinogenic index (IGI = ΔInsulin30/ΔGlucose30), derived from an OGTT, and acute insulin response to glucose (AIRg) assessed by a frequently sampled intravenous glucose tolerance test.

Results

The IGI and AIRg did not differ at baseline between the sitagliptin and placebo groups (69.9 vs. 66.4 pmol mmol−1 and 1394 vs. 1106 pmol L−1 min−1 respectively). After 12 weeks, the IGI was 85.0 in the sitagliptin and 58.1 pmol/mmol in the placebo group (P = 0.013) and AIRg was 1909 and 1043 pmol L−1 min−1 (P < 0.0001) in the sitagliptin and placebo groups respectively. Fasting glucose at baseline was 6.1 mmol L−1 in sitagliptin‐treated patients and 6.0 mmol L−1 in those who received placebo compared with 5.8 and 5.9 mmol L−1 respectively, after 12 weeks of treatment. Post load glucose metabolism improved in significantly more sitagliptin‐treated patients compared with the placebo group (P = 0.003). Sitagliptin was well tolerated.

Conclusion

Sitagliptin improved beta‐cell function and glucose perturbations in patients with ACS and newly diagnosed glucose disturbances.
Classification and prediction of clinical diagnosis of Alzheimer's disease based on MRI and plasma measures of α‐/γ‐tocotrienols and γ‐tocopherol
Authors: Mangialasche F. , Westman E. , Kivipelto M. , Muehlboeck J.‐S. , Cecchetti R. , Baglioni M. , Tarducci R. , Gobbi G. , Floridi P. , Soininen H. , Kłoszewska I. , Tsolaki M. , Vellas B. , Spenger C. , Lovestone S. , Wahlund L.‐O. , Simmons A. , Mecocci P. ,   The AddNeuroMed consortium
Published: April 2013

Background

The aim of this study was to evaluate the accuracy of combined structural magnetic resonance imaging (MRI) measures and plasma levels of vitamin E forms, including all eight natural vitamin E congeners (four tocopherols and four tocotrienols) and markers of vitamin E oxidative/nitrosative damage, in differentiating individuals with Alzheimer's disease (AD) and mild cognitive impairment (MCI) from cognitively intact control (CTL) subjects.

Methods

Overall, 81 patients with AD, 86 with MCI and 86 CTL individuals were enrolled from the longitudinal multicentre AddNeuroMed study. MRI and plasma vitamin E data were acquired at baseline. MRI scans were analysed using Freesurfer, an automated segmentation scheme which generates regional volume and cortical thickness measures. Orthogonal partial least squares to latent structures (OPLS), a multivariate data analysis technique, was used to analyse MRI and vitamin E measures in relation to AD and MCI diagnosis.

Results

The joint evaluation of MRI and plasma vitamin E measures enhanced the accuracy of differentiating individuals with AD and MCI from CTL subjects: 98.2% (sensitivity 98.8%, specificity 97.7%) for AD versus CTL, and 90.7% (sensitivity 91.8%, specificity 89.5%) for MCI versus CTL. This combination of measures also identified 85% of individuals with MCI who converted to clinical AD at follow‐up after 1 year.

Conclusions

Plasma levels of tocopherols and tocotrienols together with automated MRI measures can help to differentiate AD and MCI patients from CTL subjects, and to prospectively predict MCI conversion into AD. Our results suggest the potential role of nutritional biomarkers detected in plasma–tocopherols and tocotrienols–as indirect indicators of AD pathology, and the utility of a multimodality approach.
Methodology and mental illness: resistance and restorying
Authors: Fisher P. , Freshwater D.
Published: April 2013

Accessible summary

This paper compares two post‐modern methodological approaches, post‐structuralist and narrative, and considers their usefulness in relation to emancipatory research in mental health.

The paper finds that post‐structural analyses can be useful in deconstructing oppressive practices and in indicating emerging forms of resistance.

Narrative approaches potentially offer greater emancipatory scope than post‐structuralism as they enable people with mental health problems to restore their lives and enact their own subjective transformation.

However, narrative templates may perpetuate injustice if they erase the complexity of people's stories. This raises ethical issues in relation to narrative interpretation.

Concerns with social justice have been traditionally associated with a modernist concept of the individual whose actions express an underlying, essential and unified self. This paper compares the usefulness of two methodologies (post‐structuralist and narrative) that are based on a rejection of identity of a unified self and compares their usefulness in relation to the development of a social justice paradigm within mental health. It considers how professional forms of knowledge may be deconstructed by post‐structural analyses, arguing that these have also been used by service users to articulate more enabling discursive alternatives. The notion of agency is central to our understanding of social justice. We question the commonly held assumption that although post‐structuralism deconstructs power and challenges its legitimacy, it is nevertheless unsuited to facilitating the necessary agency to put forward viable alternatives. The second half of the paper considers how narrative research offers greater emancipatory potential by enabling the research subject to author their stories and thereby brings about their own subjective transformation. Nevertheless, the interpretation of people's stories by researchers may result in the imposition of narrative templates that erase complexities and contribute to the perpetuation of oppression. This raises ethical implications in relation to how people's stories are interpreted.
Pediatric allergy and immunology in Brazil
Authors: Rosario‐Filho Nelson A. , Jacob Cristina M. , Sole Dirceu , Condino‐Neto Antonio , Arruda Luisa K. , Costa‐Carvalho Beatriz , Cocco Renata R. , Camelo‐Nunes Inês , Chong‐Neto Herberto J. , Wandalsen Gustavo F. , Castro Ana P. M. , Yang Ariana C. , Pastorino Antonio C. , Sarinho Emanuel S.
Published: April 2013

The subspecialty of pediatric allergy and immunology in Brazil is in its early years and progressing steadily. This review highlights the research developed in the past years aiming to show the characteristics of allergic and immunologic diseases in this vast country. Epidemiologic studies demonstrated the high prevalence of asthma in infants, children, and adolescents. Mortality rates and average annual variation of asthma hospitalization have reduced in all pediatric age groups. Indoor aeroallergen exposure is excessively high and contributes to the high rates of allergy sensitization. Prevalence of food allergy has increased to epidemic levels. Foods (35%), insect stings (30%), and drugs (23%) are the main etiological agents of anaphylaxis in children and adolescents. Molecular diagnosis of primary immunodeficiencies (PID) showed a high incidence of fungal infections including paracoccidioidomycosis in X‐linked hyper‐IgM syndrome, and the occurrence of BCG adverse reactions or other mycobacterial infections in patients with chronic granulomatous disease. Education in pediatric allergy and immunology is deficient for medical students, but residency programs are effective in training internists and pediatricians for the practice of allergy. The field of PID requires further training. Last, this review is a tribute to Prof. Dr. Charles Naspitz, one of the pioneers of our specialty in Brazil.
Dietary polyunsaturated fatty acids and non‐digestible oligosaccharides reduce dermatitis in mice
Authors: Weise Christin , Ernst Dennis , van Tol Eric A. F. , Worm Margitta
Published: April 2013

Background

Oral administration of specific food ingredients can modify mucosal and systemic inflammatory processes. Such food components are fatty acids or carbohydrates. Nevertheless, little is known about the impact of oral administration of polyunsaturated fatty acids (PUFA) and non‐digestible oligosaccharides on allergen‐induced dermatitis.

Method

In this pilot study, skin inflammation was induced by serial epicutaneous OVA applications in OVA‐sensitized mice. In parallel, mice were fed with solid food containing arachidonic acid/docosahexaenoic acid (AA/DHA), galactooligosaccharide/polydextrose (GOS/PDX) or their combination. Skin lesions were assessed by clinical skin score, but also skin barrier parameters, immunohistochemical analyses, and local cytokine expression profile.

Results

Both dietary AA/DHA and GOS/PDX significantly ameliorated the severity of allergen‐induced dermatitis. The clinical improvement upon oral AA/DHA and GOS/PDX supplementation was associated with a reduction in transepidermal water loss and reduced KI‐67 expression in the skin. Lesional CD8+ and mast cells were reduced in all treatment groups, but appeared to be most pronounced in combined AA/DHA/GOS/PDX‐treated mice. Moreover, in GOS/PDX‐treated mice, IFNγ and TGFβ expression was increased in skin lesions.

Conclusion

Dietary supplementation with DHA/AA and GOS/PDX ameliorates symptoms of allergen‐induced dermatitis and may thus be beneficial in the dietary management of human atopic eczema.
Preemptive intravenous immunoglobulin allows safe and timely administration of antineoplastic therapies in patients with multiple myeloma and parvovirus B19 disease
Authors: Katragadda L. , Shahid Z. , Restrepo A. , Muzaffar J. , Alapat D. , Anaissie E.
Published: April 2013

Background

Parvovirus B19 (B19) disease is a rare cause of anemia in cancer patients and often goes unrecognized, causing delays in anticancer therapy.

Methods

A retrospective review was carried out of the records of patients with multiple myeloma who underwent melphalan‐based autologous stem cell transplantation (MEL‐ASCT) and developed B19 infection (January 2009–December 2011). Cases were defined by the presence of clinical and laboratory findings consistent with B19 disease in patients with repeatedly positive plasma quantitative polymerase chain reaction for parvovirus.

Results

Six patients qualified as cases; 5 presented with trilineage cytopenias (chronic in 1) and 1 with anemia later progressing to pancytopenia. Transfusion‐dependent thrombocytopenia led to testing in 5 patients. Two of these patients also had manifestations of autoimmune disease. Therapy with intravenous immunoglobulin (IVIG) resulted in clinical and hematologic response in all; however, 1 patient, whose white blood cell counts and serum hemoglobin levels improved, required splenectomy for persistent thrombocytopenia. All patients required additional IVIG for recurrent B19 disease. Although viral load at diagnosis did not correlate with the severity of cytopenia, its decrease was associated with response during 17 of 20 evaluable episodes (P = 0.02). Preemptive IVIG allowed the safe administration of chemotherapy in 3 patients, including MEL‐ASCT in 1.

Conclusion

Parvovirus B19 can cause severe disease in myeloma patients including ASCT recipients. Thrombocytopenia – not anemia – was the leading presentation and may be associated with autoimmune conditions. Patients with unexplained cytopenias, particularly when prolonged, should undergo testing for circulating parvovirus. A reduction in viral load was associated with response to IVIG, although additional therapy was needed for recurrent disease. Most importantly, preemptive IVIG allowed for safe and timely administration of antineoplastic therapy in patients with ongoing B19 disease.
IMAGING DIAGNOSIS‐INFILTRATIVE LIPOMA CAUSING SPINAL CORD AND LUMBAR NERVE ROOT COMPRESSION IN A DOG
Authors: Agut Amalia , Anson Agustina , Navarro Antonio , Murciano Jose , Soler Marta , Belda Eliseo , Pallares Francisco J. , Laredo Francisco G.
Published: April 2013

A 12‐year‐old, male, fox terrier dog presented with an abnormal gait of the left pelvic limb. Computed tomography revealed a large, homogeneous, hypoattenuating, noncontrast enhancing mass within the left epaxial muscles that invaded the L5–6 vertebral canal and caused spinal cord compression. Imaging findings were consistent with an infiltrative lipoma. The mass was removed and a left hemilaminectomy was performed in the affected area. Histopathology confirmed the mass to be an infiltrative lipoma. The dog recovered and regained neurologic function within 2 weeks. Computed tomography assisted preoperative planning by characterizing the shape, size, and location of the mass.
INVITED REVIEW: STUDY DESIGN CONSIDERATIONS FOR CLINICAL RESEARCH IN VETERINARY RADIOLOGY AND RADIATION ONCOLOGY
Authors: Scrivani Peter V. , Erb Hollis N.
Published: April 2013

High quality clinical research is essential for advancing knowledge in the areas of veterinary radiology and radiation oncology. Types of clinical research studies may include experimental studies, method‐comparison studies, and patient‐based studies. Experimental studies explore issues relative to pathophysiology, patient safety, and treatment efficacy. Method‐comparison studies evaluate agreement between techniques or between observers. Patient‐based studies investigate naturally acquired disease and focus on questions asked in clinical practice that relate to individuals or populations (e.g., risk, accuracy, or prognosis). Careful preplanning and study design are essential in order to achieve valid results. A key point to planning studies is ensuring that the design is tailored to the study objectives. Good design includes a comprehensive literature review, asking suitable questions, selecting the proper sample population, collecting the appropriate data, performing the correct statistical analyses, and drawing conclusions supported by the available evidence. Most study designs are classified by whether they are experimental or observational, longitudinal or cross‐sectional, and prospective or retrospective. Additional features (e.g., controlled, randomized, or blinded) may be described that address bias. Two related challenging aspects of study design are defining an important research question and selecting an appropriate sample population. The sample population should represent the target population as much as possible. Furthermore, when comparing groups, it is important that the groups are as alike to each other as possible except for the variables of interest. Medical images are well suited for clinical research because imaging signs are categorical or numerical variables that might be predictors or outcomes of diseases or treatments.
VARIATIONS IN MAGNETIC RESONANCE VENOGRAPHIC ANATOMY OF THE DORSAL DURAL VENOUS SINUS SYSTEM IN 51 DOGS
Authors: Fenn Joe , Lam Richard , Kenny Patrick J.
Published: April 2013

Variations in intracranial dural venous sinus anatomy have been widely reported in humans, but there have been no studies reporting this in dogs. The purpose of this retrospective study was to describe variations in magnetic resonance (MR) venographic anatomy of the dorsal dural venous sinus system in a sample population of dogs with structurally normal brains. Medical records were searched for dogs with complete phase contrast, intracranialMRvenograms and a diagnosis of idiopathic epilepsy. Magnetic resonance venograms were retrieved for each dog and characteristics of the dorsal dural sinuses, symmetry of the transverse sinuses and other anatomic variations were recorded. A total of 51 dogs were included. Transverse sinus asymmetry was present in 58.8% of the dogs, with transverse sinus hypoplasia seen in 39.2%, and aplasia in 23.5% of dogs. For 70.6% of dogs, at least one anatomic variation in the dorsal sagittal sinus was observed, including deviation from the midline (33.3%) and collateral branches from either the dorsal sagittal sinus or dorsal cerebral veins (54.9%). In 5 dogs (9.8%) a vessel was also identified running from the proximal transverse sinus to the distal sigmoid sinus, in a similar location to the occipital sinus previously reported in children. Findings from this study indicated that, as in humans, anatomic variations are common in the intracranial dural venous sinus system of dogs. These anatomic variations should be taken into consideration for surgical planning or diagnosis of cerebrovascular disease.
Transient extensive hepatic portal venous gas following hypotension in a dialysis patient
Authors: Suzuki Kei , Umaoka Ai , Katayama Naoyuki , Imai Hiroshi
Published: April 2013

A 68-year-old woman developed abdominal pain during a haemodialysis session and was transferred to our hospital. Although initial CT scan at former hospital detected extensive hepatic portal venous gas (HPVG), repeated CT scan on admission performed 2 h after the initial scan demonstrated a marked decrease in HPVG. Although HPVG is associated in some cases with bowel necrosis and high mortality, HPVG completely resolved within 18 h with only conservative treatment in presented case. Because recent increased use of CT scan allows early and highly sensitive detection of HPVG, not only in bowel necrosis, but also in non-life-threatening cases, we usually face a clinical dilemma whether to perform exploratory laparotomy. No previous studies have evaluated the duration of HPVG in detail, although this case suggests the value of CT scan follow-up in relatively stable patient even when the course of HPVG is short.
Toward the modelling of safety violations in healthcare systems
Authors: Catchpole Ken
Published: April 2013

When frontline staff do not adhere to policies, protocols, or checklists, managers often regard these violations as indicating poor practice or even negligence. More often than not, however, these policy and protocol violations reflect the efforts of well intentioned professionals to carry out their work efficiently in the face of systems poorly designed to meet the diverse demands of patient care. Thus, non-compliance with institutional policies and protocols often signals a systems problem, rather than a people problem, and can be influenced among other things by training, competing goals, context, process, location, case complexity, individual beliefs, the direct or indirect influence of others, job pressure, flexibility, rule definition, and clinician-centred design. Three candidates are considered for developing a model of safety behaviour and decision making. The dynamic safety model helps to understand the relationship between systems designs and human performance. The theory of planned behaviour suggests that intention is a function of attitudes, social norms and perceived behavioural control. The naturalistic decision making paradigm posits that decisions are based on a wider view of multiple patients, expertise, systems complexity, behavioural intention, individual beliefs and current understanding of the system. Understanding and predicting behavioural safety decisions could help us to encourage compliance to current processes and to design better interventions.
Contribution of the empirical dispersion correction on the conformation of short alanine peptides obtained by gas-phase QM calculations
Authors: Fadda Elisa , Woods Robert J.
Published: April 2013

In this work we analyze the effect of the inclusion of an empirical dispersion term to standard DFT (DFT-D) in the prediction of the conformational energy of the alanine dipeptide (Ala2) and in assessing the relative stabilities of short polyalanine peptides in helical conformations, i.e., α and 310helices, from Ala4 to Ala16. The Ala2 conformational energies obtained with the dispersion-corrected GGA functional B97-D are compared to previously published high level MP2 data. Meanwhile, the B97-D performance on larger polyalanine peptides is compared to MP2, B3LYP and RHF calculations obtained at a lower level of theory. Our results show that electron correlation affects the conformational energies of short peptides with a weight that increases with the peptide length. Indeed, while the contribution of vdW forces is significant for larger peptides, in the case of Ala2 it is negligible when compared to solvent effects. Even for short peptides, the inclusion of an empirical dispersion term greatly improves accuracy of DFT methods, providing results that correlate very well with the MP2 reference at no additional computational cost.
A LOW OFFSET HIGH SPEED COMPARATOR FOR PIPELINE ADC
Authors: ZHU ZHANGMING , WU HONGBING , YU GUANGWEN , LI YANHONG , LIU LIANXI , YANG YINTANG
Published: April 2013

A low offset and high speed preamplifier latch comparator is proposed for high-speed pipeline analog-to-digital converters (ADCs). In order to realize low offset, both offset cancellation techniques and kickback noise reduction techniques are adopted. Based on TSMC 0.18 μm 3.3 V CMOS process, Monte Carlo simulation shows that the comparator has a low offset voltage 1.1806 mV at 1 sigma at 125 MHz, with a power dissipation of 413.48 μW.
AN IMPROVED RULE-BASED DUMMY METAL FILL METHOD FOR 65 NM ASIC DESIGN
Authors: CHEN XIAOMING , XIN LING , ZHANG JIANWEI , LI SONGSONG
Published: April 2013

Chemical-mechanical polishing (CMP) is an essential process in deep-submicrometer LSI manufacturing to achieve Chip's planarization. It includes two processes: back-end-of-line (BEOL) and front-end-of-line (FEOL). This paper focuses on the problem of BEOL in 65 nm copper process. Although model-based dummy metal fill has become a tendency recently, the proposed improved rule-based dummy fill is appropriate still. A middle scale design is used for simulation. The metal density, oxide thickness, copper thickness, capacitance variation and variation of layout data size were investigated. The results show that improved rule-based dummy fill and model-based dummy fill have the same planarization, and proposed method has small capacitance variation. The GDS file size of the proposed rule-based fill is less than the model-based fill's.
RELATIVISTIC MEAN FIELD STUDY OF ISLANDS OF INVERSION IN NEUTRON-RICH Z = 17–23, 37–40 AND 60–64 NUCLEI
Authors: SINGH S. K. , MAHAPATRO S. , MISHRA R. N.
Published: April 2013

We study the extremely neutron-rich nuclei for Z = 17–23, 37–40 and 60–64 regions of the periodic table by using axially deformed relativistic mean field formalism with NL3* parametrization. Based on the analysis of binding energy, two neutron separation energy, quadrupole deformation and root mean square radii, we emphasized the speciality of these considered regions which are recently predicted islands of inversion.
Dissociation of hemodynamic and electrocardiographic indexes of myocardial ischemia in pigs with hibernating myocardium and sudden cardiac death
Authors: Pizzuto Matthew F. , Suzuki Gen , Banas Michael D. , Heavey Brendan , Fallavollita James A. , Canty John M.
Published: April 2013

Many survivors of sudden cardiac death (SCD) have normal global ventricular function and severe coronary artery disease but no evidence of symptomatic ischemia or infarction before the development of lethal ventricular arrhythmias, and the trigger for ventricular tachycardia (VT)/ventricular fibrillation (VF) remains unclear. We sought to identify the role of spontaneous ischemia and temporal hemodynamic factors preceding SCD using continuous telemetry of left ventricular (LV) pressure and the ECG for periods up to 5 mo in swine ( n = 37) with hibernating myocardium who experience spontaneous VT/VF in the absence of heart failure or infarction. Hemodynamics and ST deviation at the time of VT/VF were compared with survivors with hibernating myocardium as well as sham controls. All episodes of VT/VF occurred during sympathetic activation and were initiated by single premature ventricular contractions, and the VT degenerated into VF in ∼ 30 s. ECG evidence of ischemia was infrequent and no different from those that survived. Baseline hemodynamics were no different among groups, but LV end-diastolic pressure during sympathetic activation was higher at the time of SCD (37 ± 4 vs. 26 ± 4 mmHg, P < 0.05) and the ECG demonstrated QT shortening (155 ± 4 vs. 173 ± 5 ms, P < 0.05). The week before SCD, both parameters were no different from survivors. These data indicate that there are no differences in the degree of sympathetic activation or hemodynamic stress when VT/VF develops in swine with hibernating myocardium. The transiently elevated LV end-diastolic pressure and QT shortening preceding VT/VF raises the possibility that electrocardiographically silent subendocardial ischemia and/or mechanoelectrical feedback serve as a trigger for the development of SCD in chronic ischemic heart disease.
Ex Vivo Expansion of Highly Cytotoxic Human NK Cells by Cocultivation with Irradiated Tumor Cells for Adoptive Immunotherapy
Authors: Lim Seon Ah , Kim Tae-Jin , Lee Jung Eun , Sonn Chung Hee , Kim Kwanghee , Kim Jiyoung , Choi Jong Gwon , Choi Il-Kyu , Yun Chae-Ok , Kim Jae-Hong , Yee Cassian , Kumar Vinay , Lee Kyung-Mi
Published: April 2013

Adoptive natural killer (NK) cell therapy may offer an effective treatment regimen for cancer patients whose disease is refractory to conventional therapy. NK cells can kill a wide range of tumor cells by patterned recognition of target ligands. We hypothesized that tumor targets sensitive to NK lysis would drive vigorous expansion of NK cells from human peripheral blood mononuclear cells (PBMC). Here, we provide the basis for developing a novel ex vivo expansion process. By screening class I–negative or –mismatched tumor cell lines we identified a Jurkat T-lymphoblast subline termed KL-1, which was highly effective in specifically expanding NK cells. KL-1 addition to PBMC cultures achieved approximately 100-fold expansion of NK cells with nearly 90% purity, accompanied by reciprocal inhibition of T-cell growth. Marked elevations in expression of activation receptors, natural cytotoxicity receptors (NKp30, NKp44), and adhesion molecules (CD11a, ICAM-1) were associated with high tumor-lytic capacity, in both in vitro and in vivo models. KL-1–mediated expansion of NK cells was contact dependent and required interactions with CD16, the Fcγ receptor on NK cells, with ligands that are expressed on B cells. Indeed, B-cell depletion during culture abrogated selective NK cell expansion, while addition of EBV-transformed B cells further augmented NK expansion to approximately 740-fold. Together, our studies define a novel method for efficient activation of human NK cells that employs KL-1–lysed tumor cells and cocultured B cells, which drive a robust expansion of potent antitumor effector cells that will be useful for clinical evaluation. Cancer Res; 73(8); 2598–607. ©2012 AACR.
Laparoscopic versus Open Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Single Institute Comparative Analysis
Authors: Aboumarzouk Omar M. , Drewa Tomasz , Olejniczak Pawel , Chlosta Piotr L.
Published: April 2013

Background: Open radical cystectomy (ORC) is the gold standard of treatment for muscle-invasive bladder cancer. Laparoscopic radical cystectomy (LRC) has emerged to provide an alternative. Methods: Between 2006 and 2012, 155 patients who underwent LRC or ORC were compared (mean follow-up 53 months). Results: The ORC group had shorter operative times (p < 0.0001), more blood loss (p < 0.00001), more transfusion requirement (p < 0.00001), longer postoperative length of hospital stay (p < 0.00001) and more morphine requirement (p = 0.02). No difference was found regarding lymph node yield (p = 0.07), positive margins (p = 0.11), cystectomy pathology results (p > 0.05) and positive lymph nodes (p = 0.02). The ORC group had less intraoperative complications (p = 0.03). No difference was found between the two groups regarding 5-year overall survival (p = 0.93), cancer-specific survival (p = 0.7) and recurrence-free survival (p = 0.62). Conclusion: LRC can be considered as an alternative to ORC with good operative and postoperative results in addition to comparable 5-year survival results.
Hypoxia Results in Upregulation and De Novo Activation of Von Willebrand Factor Expression in Lung Endothelial Cells
Authors: Mojiri Anahita , Nakhaii-Nejad Maryam , Phan Wei-Lee , Kulak Stephen , Radziwon-Balicka Aneta , Jurasz Paul , Michelakis Evangelos , Jahroudi Nadia
Published: April 2013

Objective—

Increased von Willebrand factor (VWF) levels in lungs are associated with diseases such as pulmonary hypertension. The objective of our study was to determine the mechanism of increased VWF levels in conditions, such as hypoxia, which contribute to pulmonary hypertension.

Approach and Results—

We have previously reported generation of transgenic mice that express LacZ transgene under the regulation of lung- and brain-specific transcriptional regulatory elements of the VWF gene. Hypoxia exposure of these transgenic mice resulted in increased VWF and LacZ mRNA levels as well as redistribution of their expression from primarily larger vessels in the lungs to microvessels. Exposure of cultured lung microvascular endothelial cells to hypoxia demonstrated that VWF upregulation was accompanied by increased platelet binding. Transcription upregulation was mediated through inhibition of the repressor nuclear factor-IB association with the VWF promoter, and increased nuclear translocation of the transcription factor YY1 and association with its cognate binding site on the VWF gene. Knockdown of YY1 expression abolished the hypoxia-induced upregulation and reduced basal level of VWF.

Conclusions—

These analyses demonstrate that hypoxia induces a phenotypic shift, accompanied by modulation of nuclear factor-IB and YY1 activities, in microvascular endothelial cells of the lungs to support VWF promoter activation.
Characterization of the Left Atrial Neural Network and its Impact on Autonomic Modification Procedures
Authors: Malcolme-Lawes Louisa C. , Lim Phang Boon , Wright Ian , Kojodjojo Pipin , Koa-Wing Michael , Jamil-Copley Shahnaz , Dehbi Hakim-Moulay , Francis Darrel P. , Davies D. Wyn , Peters Nicholas S. , Kanagaratnam Prapa
Published: April 2013

Background—

Left atrial (LA) ganglionated plexi (GP) are part of the intrinsic cardiac autonomic nervous system and implicated in the pathogenesis of atrial fibrillation. High frequency stimulation is used to identify GP sites in humans. The effect of ablation on neural pathways connecting GPs in humans is unknown.

Methods and Results—

Thirty patients undergoing LA ablation with autonomic modification were recruited. In patients with persistent atrial fibrillation, endocardial continuous high frequency stimulation identified GP sites producing AV block. After right lower GP ablation (N=5), 2 of 15 sites remained positive, whereas after ablation of other GPs (N=5), leaving right lower GP intact, all 19 sites remained positive (right lower GP versus other GP,
P
<0.005), indicating that neural pathways between LAGPs and the AV node are via the right lower GP. In 20 patients with paroxysmal atrial fibrillation, synchronized high frequency stimulation identified sites initiating pulmonary vein (PV) ectopy. After PV isolation (N=8), no sites remained positive. After local GP ablation (N=9), 3 of 14 sites remained positive, suggesting neural connections to the PV were disrupted by both PV isolation and GP ablation. Heart rate variability indices reduced significantly after right upper GP ablation alone, suggesting that neural pathways from the LA to the SA node travel via the right upper GP.

Conclusions—

We have demonstrated neural pathways connecting LA GPs with the PVs, AV node, and SA node. The effects of high frequency stimulation at GP sites can be prevented by ablating the GP site or the neural pathway. This further delineates the mechanism via which PV isolation prevents atrial fibrillation and highlights important caveats for autonomic modification end points.
Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation
Authors: Pu Min , Gao Zhaohui , Pu Daniel K. , Davidson William R.
Published: April 2013

Background—

Mitral regurgitation (MR) produces sympathetic nervous system activation which is detrimental in other causes of heart failure. However, whether β-blockade is beneficial in MR has not been determined.

Methods and Results—

Eighty-seven rats with significant organic MR were randomized to the β-blockade group (n=43) or the control group (n=44). Carvedilol was started in week 2 post MR induction and given for 23 to 35 weeks in the β-blockade group. Echocardiography was performed at baseline and at weeks 2, 6, 12, 24, 30, and 36 after MR induction. After 23 weeks of β-blockade, heart rates were significantly reduced by carvedilol (308±25 versus 351±31 beats per minute;
P
<0.001). Left ventricular end-diastolic (2.2±0.7 versus 1.59±0.6 mL;
P
<0.001), end-systolic volumes (0.72±0.42 versus 0.40±0.19 mL;
P
<0.001), and mass index (2.40±0.55 versus 2.06±0.62 g/kg;
P
<0.001) were significantly higher, and left ventricular fraction shortening (33±7% versus 38±7%;
P
<0.001) and ejection fraction (69±11% versus 75±7%;
P
<0.001) were significantly lower in the β-blockade group than in the control group. Systolic blood pressure was lower in the β-blockade group than in the control group (114±10 versus 93±12 mm Hg;
P
<0.005). Survival probability was significantly lower in the early β-blockade group than in the control group (88% versus 96%;
P
=0.03).

Conclusions—

Early and long-term nonselective β-blockade was associated with adverse left ventricular remodeling, systolic dysfunction, and a reduction in survival in the experimental rat model of organic MR.
Surface treatment and adhesive bonding techniques for repair of high-temperature composite materials
Authors: Dillingham R Giles , Oakley Brietta R , Dan-Jumbo Eugene , Baldwin Joel , Keller R , Magato James
Published: April 2013

Adhesive bonding of structural aircraft materials depends upon a thorough understanding of factors that affect bond strength and durability. It is well known that surface preparation is critical to adhesive bond performance. However, little information is available regarding the effect of surface preparation procedures on adhesive bonding of high-temperature polyimide composites. Mechanical treatments such as hand sanding are commonly used for composite materials, and in general are known to improve the wettability of the surface as well as effect contaminant removal. Less is known about the influence of mechanical treatments on the surface chemistry. This article discusses the effects of mechanical surface preparation on the adhesive bond strength, durability, and failure mode of several high-temperature polyimide-based composites and adhesives.
Flexural and impact behaviour of carbon/basalt fibers hybrid laminates
Authors: Dorigato A , Pegoretti A
Published: April 2013

Basalt and E-glass fibers fabrics were combined with carbon fiber fabrics in order to prepare epoxy-based interlaminar hybrid composites and to investigate the hybridization effect on the flexural and impact properties of the resulting laminates. The flexural modulus of the composites depended on their composition according to a rule of mixture, while an important synergistic effect was detected for the ultimate flexural properties. Charpy impact tests evidenced a strength increase as basalt and glass fibers content increased. Interestingly, hybridization with basalt fibers promoted an increase of the adsorbed impact energy due to an enhancement of the fracture propagation component.
Death with dignity from the perspective of the surviving family: A survey study among family caregivers of deceased older adults
Authors: van Gennip Isis E , Roeline H , Pasman W , Kaspers Pam J , Oosterveld-Vlug Mariska G , Willems Dick L , Deeg Dorly JH , Onwuteaka-Philipsen Bregje D
Published: April 2013

Background:

Death with dignity has been identified as important both to patients and their surviving family. While research results have been published on what patients themselves believe may affect the dignity of their deaths, little is known about what family caregivers consider to be a dignified death.

Aim:

(1) To assess the prevalence of death with dignity in older adults from the perspective of family caregivers, (2) to determine factors that diminish dignity during the dying phase according to family caregivers, and (3) to identify physical, psychosocial, and care factors associated with death with dignity.

Design:

A survey study with a self-administered questionnaire.

Participants:

Family caregivers of 163 deceased older (>55 years of age) adults (“patients”) who had participated in the Longitudinal Aging Study Amsterdam.

Results:

Of the family caregivers, 69% reported that their relative had died with dignity. Factors associated with a dignified death in a multivariate regression model were patients feeling peaceful and ready to die, absence of anxiety and depressive mood, presence of fatigue, and a clear explanation by the physician of treatment options during the final months of life.

Conclusions:

The physical and psychosocial condition of the patient in combination with care factors contributed to death with dignity from the perspective of the family caregiver. The patient’s state of mind during the last phase of life and clear communication on the part of the physician both seem to be of particular importance.
Provision of palliative and end-of-life care in stroke units: A qualitative study
Authors: Gardiner Clare , Harrison Madeleine , Ryan Tony , Jones Amanda
Published: April 2013

Background:

Stroke is a leading cause of death; between 20% and 30% of people die within 30 days of a stroke. High-quality palliative and end-of-life care are advocated for patients not expected to recover from stroke.

Aim:

To explore the perspectives of health professionals regarding the provision of palliative and end-of-life care in UK stroke units.

Design and setting:

Qualitative focus groups and individual interviews were held with 66 health professionals working in UK specialist stroke units. Data were analysed thematically.

Results:

Three themes emerged from the data. Palliative care was recognised as an important component of stroke care; however, there was uncertainty when initiating transitions to palliative care in stroke, and issues were identified with the integration of acute stroke care and palliative care.

Conclusions:

The findings provide encouraging evidence that palliative and end-of-life care have been adopted as key components of specialist stroke care in UK stroke units. However, many patients stand to benefit from earlier identification of palliative care need and a consideration of quality-of-life approaches during active care. Encouraging collaboration and partnership when working with specialist palliative care services would optimise palliative care service delivery and may provide patients and their families with greater opportunities for documenting and achieving preferences for care and achieving a better quality of death.
Revisiting the Intercultural Dialogue in the Light of a Culture of Peace
Authors: Himmich Bensalem
Published: April 2013

This paper, originally an address presented before the Executive Council of UNESCO in 2010, presents the author’s views on the possible modalities of an intercultural dialogue, and links them to the somewhat controversial notion of a “culture of peace”.
Traces of Objectivity: Causality and Probabilities in Quantum Physics
Authors: Bitbol Michel
Published: April 2013

Unlike a widespread opinion, the constitution of objectivity (in Kant’s sense) does not require a strict, determinist, application of the category of causality to phenomena manifested in space-time. Some stochastic theories, using probabilities at their fundamental level, are just as able to constitute a domain of objects as determinist theories. In this paper, the conditions to be fulfilled for numbers to be considered as probabilities of intrinsic properties of an object of experience are displayed. These conditions, that synthesize George Boole’s relations and John Bell’s inequalities, are discussed in detail. Where they are not fulfilled, they make us suspect that it is impossible to achieve the detachment of an object from the instruments that give access to it.
From “Pirates” to “Heroes”
Authors: Owen Thomas
Published: April 2013

In the mid-1990s, a transnational civil society campaign emerged to challenge Big Pharma over HIV/AIDS medicines patent protection. In 2001, the dispute crystallized into a dramatic media event as pharmaceutical companies sued the South African government over medicine patent laws. The South African lawsuit has been described as a “public relations disaster” for Big Pharma, and a turning point in HIV/AIDS medicines and intellectual property rights discourse. This article assesses these claims in relation to a corpus-assisted discourse analysis of 1,000 articles from U.S., U.K., and South African press outlets from 1997 to 2003. The study finds that a key discourse change to occur over this period was the elevation of generic HIV/AIDS medicines from an excluded criminal threat to a respected legitimate option. Given subsequent policy developments considerably increasing access to generic HIV/AIDS medicines in majority world countries, this article argues that the news media discourse change was a key transformative moment in addressing the global HIV/AIDS epidemic. The study also notes, however, that an antigeneric discourse persisted throughout the coverage, signifying the ongoing contestation of medicine patent protection that continues to characterize global HIV/AIDS medicines access.
Total Knee Replacement as a Knee Osteoarthritis Outcome
Authors: Raynauld Jean-Pierre , Martel-Pelletier Johanne , Dorais Marc , Haraoui Boulos , Choquette Denis , Abram François , Beaulieu André , Bessette Louis , Morin Frédéric , Wildi Lukas M. , Pelletier Jean-Pierre
Published: April 2013

Objective

To predict, using clinical and qMRI data, the incidence of total knee replacement (TKR) during the long-term follow-up of knee osteoarthritis (OA) patients who formerly received chondroitin sulfate (CS) or placebo treatment.

Design

A post hoc intention-to-treat analysis to evaluate the incidence of TKR was done on knee OA patients who had participated in a 12-month trial evaluating the impact of CS (800 mg/d) versus placebo for 6 months, followed by a 6-month open-phase in which all patients received CS. Additionally, the clinical and qMRI predictors of TKR were determined.

Results

Thirteen TKRs were performed in the population after a 4-year follow-up. More TKRs were performed in the placebo group than in the CS group (69% vs. 31%, P = 0.150, logistic regression). The statistically significant predictors of TKRs were, at baseline, higher WOMAC pain and function scores, presence of bone marrow lesions (BMLs), and higher C-reactive protein levels. Loss of medial cartilage volume and increase in WOMAC pain and function at one-year were also predictors of TKR. Multivariate analyses revealed that baseline presence of BML and higher WOMAC pain score were independent predictors. Time to occurrence of the TKR also favored the CS group versus placebo (log-rank, P = 0.094).

Conclusion

Symptoms such as knee pain and function, presence of BML, and cartilage volume loss predict the long-term occurrence of a “hard” outcome such as TKR.