bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease progression in idiopathic pulmonary fibrosis without pulmonary function impairment
Authors: Kondoh Yasuhiro , Taniguchi Hiroyuki , Ogura Takashi , Johkoh Takeshi , Fujimoto Kiminori , Sumikawa Hiromitsu , Kataoka Kensuke , Baba Tomohisa , Colby Thomas V. , Kitaichi Masanori
Published: March 2013

Background and objective

Despite significant recent progress in the understanding of idiopathic pulmonary fibrosis (IPF), the early phase of the disease is still poorly understood. We studied patients with IPF without pulmonary function impairment in order to determine the clinical features, natural history and key findings for physiological progression.

Methods

Twenty‐five patients without pulmonary function impairment were identified from among patients with previously diagnosed IPF who underwent surgical lung biopsies between January 1997 and December 2006 at our institutions. ‘Without pulmonary function impairment’ was defined as both forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) >80% predicted. Patients diagnosed with IPF through multidisciplinary discussion based on the new IPF guidelines were the subjects of this study.

Results

Sixteen patients had a confirmed diagnosis of IPF. Eleven patients presented with chest X‐ray abnormality found during an annual health examination. Seven patients were asymptomatic. Eleven patients showed physiological disease progression (median time; 19.9 ± 12.3 months) defined by a decline of at least 10% in FVC or at least 15% in DLco. Univariate analysis revealed that both usual interstitial pneumonia pattern and extent of honeycombing on high‐resolution computed tomography (HRCT) were factors associated with disease progression (odds ratio 5.634, 95% confidence interval 1.364–23.278; odds ratio 2.371/5%, 95% confidence interval 1.042–5.395).

Conclusions

IPF patients without pulmonary function impairment have a progressive but slow clinical course. The existence and extent of honeycombing on HRCT are predictive of disease progression.
EXTRAORDINARY WEALTH, GLOBALIZATION, AND CORRUPTION
Authors: TORGLER BENNO , PIATTI MARCO
Published: March 2013

The billionaires of the world attract significant attention from the media and the public. Surprisingly, only a limited number of studies have explored empirically the determinants of extraordinary wealth. Using a large dataset we investigate whether globalization and corruption affect extreme wealth accumulation. We find evidence that an increase in globalization increases super‐affluence. In addition, we also find that an increase in corruption leads to an increase in the creation of super fortune. This supports the argument that in kleptocracies large sums are transferred into the hands of a small group of individuals.
Associations between family characteristics and public health nurses' concerns at children's health examinations
Authors: Poutiainen Hannele , Hakulinen‐Viitanen Tuovi , Laatikainen Tiina
Published: March 2013

Rationale

The family and the way it functions have a key role for the health and well‐being of children and adolescents. Approximately 10–30% of children grow up in families where their health and well‐being may be endangered or weakened. There is very little research data on public health nurses' concerns in connection with children's health examinations related to family characteristics.

Aim

The aim of this study was to investigate the associations of children's gender, age, family structure, mother's employment status and parents' perception on the sufficiency of income with public health nurses' concerns on physical and psychosocial health at children's health examinations.

Methods

In 2007–2009, information about children's health and well‐being and their background factors was collected from the health examinations of altogether 6506 children in Finland using a cross‐sectional design. Associations between family characteristics and nurses concern related to physical and psychosocial health and development of children were assessed using logistic regression analysis.

Results

Physical health and psychosocial issues of school‐age children raised most concern in public health nurses. Especially, public health nurses felt concern for the psychosocial development of boys both under and of school age. Family structure and the family's financial situation were associated with public health nurses' concern for children's physical health, psychosocial development and the presence of at least one concern.

Conclusion

The fact that public health nurses found cause for concern during health examinations was associated with the child's gender, development stage and family characteristic. The research findings may be utilised in planning and targeting health counselling and services in child and school health care. Understanding the role of family characteristics in health and well‐being challenges in children is useful in promoting multidisciplinary work in health care.
Comparative evaluation of efficacy and safety of artesunate–lumefantrine vs. artemether–lumefantrine fixed‐dose combination in the treatment of uncomplicated Plasmodium falciparum malaria
Authors: Pareek Anil , Chandurkar Nitin , Srivastav Vipul , Lakhani Jitendra , Karmakar Partha S. , Basu Subrata , Ray Arnab , Pednekar Sangeeta , Gupta P. B. , Suthar Nilay , Lakhani Sucheta
Published: March 2013

Objective

To establish efficacy and safety of artesunate/lumefantrine fixed‐dose combination (FDC) in comparison with artemether/lumefantrine FDC in treatment of uncomplicated Plasmodium falciparum malaria.

Methods

Confirmed cases of uncomplicated P. falciparum malaria were randomly assigned to receive artesunate (100 mg)/lumefantrine (480 mg) (ASLF FDC) or artemether (80 mg)/lumefantrine (480 mg) (AMLF FDC) tablets for 3 days. Patients were followed up on Day 7, 14, 21 and 28.

Results

Of the 158 enrolled patients, 144 completed the study. Seventy‐three patients (94.8%) from the ASLF group and 71 patients (94.7%) from the AMLF group showed parasite clearance within 48 h. The mean parasite clearance time was 25.40 ± 14.82 h in the ASLF group and 24 ± 13.32 h in the AMLF group (P = 0.542). All patients showed gametocyte clearance by Day 7 and remained gametocyte free till Day 28. Sixty‐five patients (84.4%) from the ASLF group and 56 patients (74.7%) from the AMLF group were afebrile within 24 h. The mean fever clearance time was 17.38 ± 12.33 h in the ASLF group and 17.2 ± 12.01 h in the AMLF group (P = 0.929). There was one early treatment failure in the AMLF group as per WHO criteria. Improvement in haemoglobin and haematocrit was comparable in both the treatment groups. In the ASLF group, of the 25 (32.47%) patients anaemic at baseline, only seven (9.09%) reported anaemia on Day 28, while in the AMLF group, of the 14 (18.67%) patients anaemic at baseline, only four (5.33%) reported anaemia on Day 28. Both study medications were well tolerated.

Conclusion

Artesunate (100 mg)/lumefantrine (480 mg) fixed‐dose combination could add one more option to currently available artemisinin combinations in treatment of uncomplicated P. falciparum malaria.
Declining Distance Effects in International Trade: Some Country‐Level Evidence
Authors: Bleaney Michael , Neaves Abelardo S.
Published: March 2013

Technical progress can be expected to reduce transport costs over time, yet most studies of bilateral trade based on the gravity model find distance effects to be increasing rather than decreasing. We investigate countries' openness to international trade (the ratio of exports plus imports to GDP). We find that trade decreases with geographical remoteness, land area and lack of access to the sea, all of which are likely to be correlated with transport costs. In contrast to the results obtained with log‐linear models of bilateral trade, distance effects (remoteness and land area) have declined over time. Trade decreases with population density and increases with improvements in the terms of trade, investment and a more liberal trade policy.
Credit Support for Export: Robust Evidence from the Czech Republic
Authors: Janda Karel , Michalikova Eva , Skuhrovec Jiri
Published: March 2013

The topic of this paper is quite a novel one – it is one of few empirical academic papers dealing with export credit. Moreover, it is the first analysis of this kind which focuses on transition economies. The paper deals with export credit promotion in the Czech Republic. The development and structure of Czech trade and export support is presented first, followed by an econometric analysis of the gravity model of Czech Republic trade. A panel of 160 countries in 1996–2008 is analysed and two gravity models of exports for the Czech Republic are estimated, the static model by fixed effects (LSDV estimator) and the dynamic model by System GMM. Due to ambiguous conclusions we assume that the behaviour of our explanatory variables is not uniform and our data set behaves as a mixture of countries with heterogeneous behaviour. This means that traditional techniques of estimation which include all observations into one model do not give significant results. Thus, we use robust techniques of estimation that solve the problem of heterogeneous patterns in data sets. Out of several possibilities we use the Least Trimmed Squares estimator (LTS) with a leverage point. We show that guarantees are a significant factor that influences positively the volume of exports in the Czech Republic. Moreover, there exist more variables that affect the size of exports in the Czech Republic. Market forces described by GDP, distance, political risk or gross fix capital formation are significant in our econometric model. We find that higher GDP, shorter distance or lower political risk have a positive impact on Czech exports.
Canine osteosarcoma cell lines from patients with differing serum alkaline phosphatase concentrations display no behavioural differencesin vitro
Authors: Holmes K. E. , Thompson V. , Piskun C. M. , Kohnken R. A. , Huelsmeyer M. K. , Fan T. M. , Stein T. J.
Published: March 2013

Osteosarcoma is an aggressive malignancy and represents the most frequent primary bone malignancy of dogs and humans. Prognostic factors reported for osteosarcoma include tumour size, presence of metastatic disease and serum alkaline phosphatase (ALP) concentration at the time of diagnosis. To date, there have been no studies to determine whether the behaviour of osteosarcoma cells differ based on serumALPconcentration. Here, we report on the generation of six canine osteosarcoma cell lines from osteosarcoma‐bearing dogs with differences in serumALPconcentration. To determine whetherin vitrobehaviour differs between primary osteosarcoma cell lines generated from patients with normal or increased serumALP, assays were performed to evaluate proliferation, migration, invasion and chemosensitivity. There were no significant differences in cell proliferation, migration, invasion or chemosensitivity between cell lines associated with normal or increased serumALPconcentration.
Hind Wings in Basal Birds and the Evolution of Leg Feathers
Authors: Zheng Xiaoting , Zhou Zhonghe , Wang Xiaoli , Zhang Fucheng , Zhang Xiaomei , Wang Yan , Wei Guangjin , Wang Shuo , Xu Xing
Published: March 2013

Four-Winged Birds?

Recently, nonavialan dinosaurs with feathers on their fore- and hindlimbs have been described.

Zheng
et al.

(p.
1309
) describe eleven basal avialan fossils with clear evidence of feathered hindlimbs. Together these fossils show that early avialans possessed four wings, rather than two. A gradual reduction in hindlimb feathering eventually yielded the two-wing condition in today's birds. Such a transition may have accompanied a locomotory decoupling of the fore- and hindlimbs, which facilitated the development of the forelimbs into flight-capable wings.
Evidence for Microbial Carbon and Sulfur Cycling in Deeply Buried Ridge Flank Basalt
Authors: Lever Mark A. , Rouxel Olivier , Alt Jeffrey C. , Shimizu Nobumichi , Ono Shuhei , Coggon Rosalind M. , Shanks Wayne C. , Lapham Laura , Elvert Marcus , Prieto-Mollar Xavier , Hinrichs Kai-Uwe , Inagaki Fumio , Teske Andreas
Published: March 2013

Under the Sea Floor

Microorganisms living in basaltic sea floor buried beneath sediments derive energy from inorganic components from the host rocks that interact with infiltrating seawater, which brings dissolved oxygen and other trace nutrients with it.

Lever
et al.

(p.
1305
) directly sampled the subseafloor community off the eastern flank of the Juan de Fuca Ridge in the Pacific Ocean and found evidence for ongoing microbial sulfate reduction and methanogenesis. Multiyear incubation experiments with samples of host rock confirmed the microbial activities measured in situ.
Planar Photonics with Metasurfaces
Authors: Kildishev Alexander V. , Boltasseva Alexandra , Shalaev Vladimir M.
Published: March 2013

Background

Metamaterials (MMs) are smartly engineered structures with rationally designed, nanostructured building blocks that allow us to build devices with distinct responses to light, acoustic waves, and heat flows that are not attainable with naturally available materials.

Advances

The latest developments have shown that optical metasurfaces comprising a class of optical MMs with a reduced dimensionality can exhibit exceptional abilities for controlling the flow of light; achieve the anomalously large photonic density of states; and, similar to their bulk analog, provide superresolution imaging. Such a planar photonics technology is expected to facilitate new physics and enhanced functionality for devices that are distinctly different from those observed in their three-dimensional MM counterparts. As a result, this technology will enable new applications in imaging, sensing, data storage, quantum information processing, and light harvesting.

Outlook

The recent progress in optical metasurfaces can address the major issues hampering the full-scale development of MM technology, such as high loss, cost-ineffective fabrication, and challenging integration. The studies of new, low-loss, tunable plasmonic materials—such as transparent conducting oxides and intermetallics—that can be used as building blocks for metasurfaces will complement the exploration of smart designs and advanced switching capabilities. This progress in metasurface design and realization will lead to novel functionalities and improved performance and may result in the development of new types of ultrathin metasurface designs with unparalleled properties, including increased operational bandwidths and reduced losses. These new designs would also be compatible with planar, low-cost manufacturing. In turn, these advances will lead to ultrathin devices with unprecedented functionalities, ranging from dynamic spatial light modulation to pulse shaping and from subwavelength imaging or sensing to novel quantum optics devices.
RNA That Gets RAN in Neurodegeneration
Authors: Taylor J. Paul
Published: March 2013

A common neurodegenerative disease is associated with unconventional translation of mutant expanded RNA.

[Also see Report by

Mori
et al.

]
Thymus: Central Role in the Immune System of the Frog
Authors: Volpe E. Peter , Turpen James B.
Published: March 2013

In the leopard frog (
Rana pipiens
), the thymus profoundly influences immunologic development by providing virtually all the progenitor lymphocytic cells for the bone marrow and other peripheral lymphoid organs. The thymus houses a self-perpetuating population of lymphopoietic cells that originally self-differentiated in that gland.
Flavonoid Localization in Epidermal Papillae of Flower Petals: A Specialized Adaptation for Ultraviolet Absorption
Authors: Brehm Bert G. , Krell Douglas
Published: March 2013

In petals of various species of angiosperms that differ in ultraviolet absorption and reflectance, flavonoids were concentrated at surfaces that absorb ultraviolet light. Microscopic examination of intact, dried petals treated with sodium methoxide revealed dense concentrations of flavonoid material in the tips of specialized epidermal papillae. Scanning electron micrographs confirmed this cellular localization and disclosed structural features of the cuticle which are associated with ultraviolet absorption. These papillate epidermal cells have an adaptive complex of chemical and structural features which function in ultraviolet absorbance patterning on the surfaces of flower petals and assist in visual discrimination by insects.
Identification ofIn Vivo-Induced Bacterial Proteins during Human Infection with Salmonella enterica Serotype Paratyphi A
Authors: Alam Mohammad Murshid , Tsai Lillian L. , Rollins Sean M. , Sheikh Alaullah , Khanam Farhana , Bufano Meagan Kelly , Yu Yanan , Wu-Freeman Ying , Kalsy Anuj , Sultana Tania , Sayeed M. Abu , Jahan Nusrat , LaRocque Regina C. , Harris Jason B. , Leung Daniel T. , Brooks W. Abdullah , Calderwood Stephen B. , Charles Richelle C. , Qadri Firdausi , Ryan Edward T.
Published: March 2013

Salmonella entericaserotype Paratyphi A is a human-restricted pathogen and the cause of paratyphoid A fever. Using a high-throughput immunoscreening technique,in vivo-induced antigen technology (IVIAT), we identified 20 immunogenic bacterial proteins expressed in humans who were bacteremic withS. Paratyphi A but not those expressed inS. Paratyphi A grown under standard laboratory conditions. The majority of these proteins have known or potential roles in the pathogenesis ofS. enterica. These include proteins implicated in cell adhesion, fimbrial structure, adaptation to atypical conditions, oxidoreductase activity, proteolysis, antimicrobial resistance, and ion transport. Of particular interest among thesein vivo-expressed proteins wereS. Paratyphi A (SPA)2397, SPA2612, and SPA1604. SPA2397 and SPA2612 are prophage related, and SPA1604 is inSalmonellapathogenicity island 11 (SPI-11). Using real-time quantitative PCR (RT-qPCR), we confirmed increased levels of mRNA expressed by genes identified by IVIAT in a comparison of mRNA levels in organisms in the blood of bacteremic patients to those inin vitrocultures. Comparing convalescent- to acute-phase samples, we also detected a significant increase in the reaction of convalescent-phase antibodies with two proteins identified by IVIAT: SPA2397 and SPA0489. SPA2397 is a phage-related lysozyme, Gp19, and SPA0489 encodes a protein containing NlpC/P60 and cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domains. In a previous study utilizing a different approach, we found that transcripts for 11 and 7 of the genes identified by IVIAT were detectable in organisms in the blood of humans in Bangladesh who were bacteremic withS. Paratyphi A andSalmonella entericaserovar Typhi, respectively.S.Paratyphi A antigens identified by IVIAT warrant further evaluation for their contributions to pathogenesis and might have diagnostic, therapeutic, or preventive relevance.
Neisseria gonorrhoeae False-Positive Result Obtained from a Pharyngeal Swab by Using the Roche cobas 4800 CT/NG Assay in New Zealand in 2012
Authors: Upton Arlo , Bromhead Collette , Whiley David M.
Published: March 2013

The Roche cobas 4800 CT/NG assay is a commonly used commercial system for screening for
Neisseria gonorrhoeae
infection, and previous studies have shown the method to be highly sensitive and specific for urogenital samples. We present the first confirmed clinical
N. gonorrhoeae
false-positive result using the cobas 4800 NG assay, obtained from testing a pharyngeal swab sample and caused by cross-reaction with a commensal
Neisseria
strain.
Methicillin-Resistant Staphylococcus pseudintermedius Infection in a Bone Marrow Transplant Recipient
Authors: Savini Vincenzo , Barbarini Daniela , Polakowska Klaudia , Gherardi Giovanni , Białecka Anna , Kasprowicz Andrzej , Polilli Ennio , Marrollo Roberta , Di Bonaventura Giovanni , Fazii Paolo , D'Antonio Domenico , Międzobrodzki Jacek , Carretto Edoardo
Published: March 2013

Staphylococcus pseudintermedius
is a veterinary pathogen that has seldom been described as an agent of human disease. Features of this probably underreported coagulase-positive
Staphylococcus
species are depicted here through the description of a graft-versus-host disease-related wound infection caused by a multidrug-resistant strain.
Conformation-Dependent Recognition of HIV gp120 by Designed Ankyrin Repeat Proteins Provides Access to Novel HIV Entry Inhibitors
Authors: Mann Axel , Friedrich Nikolas , Krarup Anders , Weber Jacqueline , Stiegeler Emanuel , Dreier Birgit , Pugach Pavel , Robbiani Melissa , Riedel Tina , Moehle Kerstin , Robinson John A. , Rusert Peter , Plückthun Andreas , Trkola Alexandra
Published: March 2013

Here, we applied the designed ankyrin repeat protein (DARPin) technology to develop novel gp120-directed binding molecules with HIV entry-inhibiting capacity. DARPins are interesting molecules for HIV envelope inhibitor design, as their high-affinity binding differs from that of antibodies. DARPins in general prefer epitopes with a defined folded structure. We probed whether this capacity favors the selection of novel gp120-reactive molecules with specificities in epitope recognition and inhibitory activity that differ from those found among neutralizing antibodies. The preference of DARPins for defined structures was notable in our selections, since of the four gp120 modifications probed as selection targets, gp120 arrested by CD4 ligation proved the most successful. Of note, all the gp120-specific DARPin clones with HIV-neutralizing activity isolated recognized their target domains in a conformation-dependent manner. This was particularly pronounced for the V3 loop-specific DARPin 5m3_D12. In stark contrast to V3-specific antibodies, 5m3_D12 preferentially recognized the V3 loop in a specific conformation, as probed by structurally arrested V3 mimetic peptides, but bound linear V3 peptides only very weakly. Most notably, this conformation-dependent V3 recognition allowed 5m3_D12 to bypass the V1V2 shielding of several tier 2 HIV isolates and to neutralize these viruses. These data provide a proof of concept that the DARPin technology holds promise for the development of HIV entry inhibitors with a unique mechanism of action.
Binding of Transmembrane Mucins to Galectin-3 Limits Herpesvirus 1 Infection of Human Corneal Keratinocytes
Authors: Woodward A. M. , Mauris J. , Argüeso P.
Published: March 2013

Epithelial cells lining mucosal surfaces impose multiple barriers to viral infection. At the ocular surface, the carbohydrate-binding protein galectin-3 maintains barrier function by cross-linking transmembrane mucins on the apical glycocalyx. Despite these defense mechanisms, many viruses have evolved to exploit fundamental cellular processes on host cells. Here, we use affinity assays to show that herpes simplex virus type 1 (HSV-1), but not HSV-2, binds human galectin-3. Knockdown of galectin-3 in human corneal keratinocytes by small interfering RNA significantly impaired HSV-1 infection, but not expression of nectin-1, indicating that galectin-3 is a herpesvirus entry mediator. Interestingly, exposure of epithelial cell cultures to transmembrane mucin isolates decreased viral infectivity. Moreover, HSV-1 failed to elute the biological counterreceptor MUC16 from galectin-3 affinity columns, suggesting that association of transmembrane mucins to galectin-3 provides protection against viral infection. Together, these results indicate that HSV-1 exploits galectin-3 to enhance virus attachment to host cells and support a protective role for transmembrane mucins under physiological conditions by masking viral entry mediators on the epithelial glycocalyx.
Systematic Analysis of Enhancer and Critical
cis
-Acting RNA Elements in the Protein-Encoding Region of the Hepatitis C Virus Genome
Authors: Chu Derrick , Ren Songyang , Hu Stacy , Wang Wei Gang , Subramanian Aparna , Contreras Deisy , Kanagavel Vidhya , Chung Eric , Ko Justine , Amirtham Jacob Appadorai Ranjit Singh , Sinha Sanjeev , Jalali Ziba , Hardy David W. , French Samuel W. , Arumugaswami Vaithilingaraja
Published: March 2013

Hepatitis C virus (HCV) causes chronic hepatitis, cirrhosis, and liver cancer.
cis
-acting RNA elements of the HCV genome are critical for translation initiation and replication of the viral genome. We hypothesized that the coding regions of nonstructural proteins harbor enhancer and essential
cis
-acting replication elements (CRE). In order to experimentally identify new
cis
RNA elements, we utilized an unbiased approach to introduce synonymous substitutions. The HCV genome coding for nonstructural proteins (nucleotide positions 3872 to 9097) was divided into 17 contiguous segments. The wobble nucleotide positions of each codon were replaced, resulting in 33% to 41% nucleotide changes. The HCV genome containing one of each of 17 mutant segments (S1 to S17) was tested for genome replication and infectivity. We observed that silent mutations in segment 13 (S13) (nucleotides [nt] 7457 to 7786), S14 (nt 7787 to 8113), S15 (nt 8114 to 8440), S16 (nt 8441 to 8767), and S17 (nt 8768 to 9097) resulted in impaired genome replication, suggesting CRE structures are enriched in the NS5B region. Subsequent high-resolution mutational analysis of NS5B (nt 7787 to 9289) using approximately 51-nucleotide contiguous subsegment mutant viruses having synonymous mutations revealed that subsegments SS8195-8245, SS8654-8704, and SS9011-9061 were required for efficient viral growth, suggesting that these regions act as enhancer elements. Covariant nucleotide substitution analysis of a stem-loop, JFH-SL9098, revealed the formation of an extended stem structure, which we designated JFH-SL9074. We have identified new enhancer RNA elements and an extended stem-loop in the NS5B coding region. Genetic modification of enhancer RNA elements can be utilized for designing attenuated HCV vaccine candidates.
Serum- and Glucocorticoid-Regulated Kinase 1 Is Required for Nuclear Export of the Ribonucleoprotein of Influenza A Virus
Authors: Alamares-Sapuay Judith G. , Martinez-Gil Luis , Stertz Silke , Miller Matthew S. , Shaw Megan L. , Palese Peter
Published: March 2013

We previously performed a small interfering RNA (siRNA) screen and identified serum- and glucocorticoid-regulated kinase 1 (SGK1) as a host factor required for influenza A virus replication. However, the role of SGK1 in the influenza viral life cycle has never been examined. In this study, we demonstrate that SGK1 is required for optimal replication of influenza virus, using the SGK1 inhibitor GSK 650394 and SGK1-specific siRNAs. We also demonstrate that SGK1 is required for viral ribonucleoprotein nuclear export.
Mucosal Priming with a Replicating-Vaccinia Virus-Based Vaccine Elicits Protective Immunity to Simian Immunodeficiency Virus Challenge in Rhesus Monkeys
Authors: Sun Caijun , Chen Zhiwei , Tang Xian , Zhang Yinfeng , Feng Liqiang , Du Yanhua , Xiao Lijun , Liu Li , Zhu Weijun , Chen Ling , Zhang Linqi
Published: March 2013

Mucosal surfaces are not targeted by most human immunodeficiency virus type 1 (HIV-1) vaccines, despite being major routes for HIV-1 transmission. Here we report a novel vaccination regimen consisting of a mucosal prime with a modified replicating vaccinia virus Tiantan strain (MVTT
SIVgpe
) and an intramuscular boost with a nonreplicating adenovirus strain (Ad5
SIVgpe
). This regimen elicited robust cellular immune responses with enhanced magnitudes, sustainability, and polyfunctionality, as well as higher titers of neutralizing antibodies against the simian immunodeficiency virus SIV
mac1A11
in rhesus monkeys. The reductions in peak and set-point viral loads were significant in most animals, with one other animal being protected fully from high-dose intrarectal inoculation of SIV
mac239
. Furthermore, the animals vaccinated with this regimen were healthy, while ∼75% of control animals developed simian AIDS. The protective effects correlated with the vaccine-elicited SIV-specific CD8
+
T cell responses against Gag and Pol. Our study provides a novel strategy for developing an HIV-1 vaccine by using the combination of a replicating vector and mucosal priming.
A Literature Review of de qi in clinical studies
Authors: Park Ji-Eun , Ryu Yeon-Hee , Liu Yan , Jung Hee-Jung , Kim Ae-Ran , Jung So-Young , Choi Sun-Mi
Published: March 2013

Objectives

De qi is a sensation experienced by a patient or an acupuncturist during acupuncture treatment. Although de qi is considered to be important in acupuncture treatment, there are not many studies about de qi and its character. The purpose of this study is to review de qi questionnaires and evaluate the relationship between de qi and acupuncture points, stimulation and treatment effects.

Methods

A search was conducted using three English-language databases (PubMed, Cochrane and ScienceDirect) and seven Korean databases with the keywords ‘ de qi’ and ‘needle sensation’. The included studies were then categorised as following: (1) de qi measurement tools, (2) the relationship between de qi and acupuncture points, (3) the relationship between de qi and stimulation, (4) the relationship between de qi and treatment effects and (5) attitudes and opinions toward de qi.

Results

Several questionnaires have been developed to evaluate de qi, and the most frequent sensation in those questionnaires was ‘heavy’ and ‘numb’. Although a few studies showed specificity to acupuncture points, information is still lacking to be able to draw a clear conclusion about the relationship between de qi and acupuncture points. Also, greater de qi was elicited in real acupuncture than placebo acupuncture in many studies. The relationship between de qi and treatment effects was controversial.

Conclusions

It seems that real acupuncture induced greater de qi than sham acupuncture, and the relationship between de qi, acupuncture points and treatment effects was controversial. However, the current literature evaluating de qi is not sufficient to derive clear conclusions. Further studies with more objective indices and rigorous methodologies are needed.
Development and validation of a brief screening instrument for psychosocial risk associated with genetic testing: a pan-Canadian cohort study
Authors: Esplen Mary Jane , Cappelli Mario , Wong Jiahui , Bottorff Joan L , Hunter Jon , Carroll June , Dorval Michel , Wilson Brenda , Allanson Judith , Semotiuk Kara , Aronson Melyssa , Bordeleau Louise , Charlemagne Nicole , Meschino Wendy
Published: March 2013

Objectives

To develop a brief, reliable and valid instrument to screen psychosocial risk among those who are undergoing genetic testing for Adult-Onset Hereditary Disease (AOHD).

Design

A prospective two-phase cohort study.

Setting

5 genetic testing centres for AOHD, such as cancer, Huntington's disease or haemochromatosis, in ambulatory clinics of tertiary hospitals across Canada.

Participants

141 individuals undergoing genetic testing were approached and consented to the instrument development phase of the study (Phase I). The Genetic Psychosocial Risk Instrument (GPRI) developed in Phase I was tested in Phase II for item refinement and validation. A separate cohort of 722 individuals consented to the study, 712 completed the baseline package and 463 completed all follow-up assessments. Most participants were female, at the mid-life stage. Individuals in advanced stages of the illness or with cognitive impairment or a language barrier were excluded.

Interventions

Phase I: GPRI items were generated from (1) a review of the literature, (2) input from genetic counsellors and (3) phase I participants. Phase II: further item refinement and validation were conducted with a second cohort of participants who completed the GPRI at baseline and were followed for psychological distress 1-month postgenetic testing results.

Primary and secondary outcome measures

GPRI, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Brief Symptom Inventory (BSI) and Impact of Event Scale (IES).

Results

The final 20-item GPRI had a high reliability—Cronbach's α at 0.81. The construct validity was supported by high correlations between GPRI and BSI and IES. The predictive value was demonstrated by a receiver operating characteristic curve of 0.78 plotting GPRI against follow-up assessments using HAM-D and HAM-A.

Conclusions

With a cut-off score of 50, GPRI identified 84% of participants who displayed distress postgenetic testing results, supporting its potential usefulness in a clinical setting.
e-Health preparedness assessment in the context of an influenza pandemic: a qualitative study in China
Authors: Li Junhua , Seale Holly , Ray Pradeep , Wang Quanyi , Yang Peng , Li Shuang , Zhang Yi , MacIntyre C Raina
Published: March 2013

Objective

To assess the preparedness status of a hospital in Beijing, China for implementation of an e-Health system in the context of a pandemic response.

Design

This research project used qualitative methods and involved two phases: (1) group interviews were conducted with key stakeholders to examine how the surveillance system worked with information and communication technology (ICT) support in Beijing, the results of which provided background information for a case study at the second phase and (2) individual interviews were conducted in order to gather a rich data set in relation to e-Health preparedness at the selected hospital.

Setting

In phase 1, group interviews were conducted at Centres for Disease Prevention and Control (CDC) in Beijing. In phase 2, individual interviews were performed at a secondary hospital selected for the case study.

Participants

In phase 1, three group interviews were undertaken with 12 key stakeholders (public health/medical practitioners from the Beijing city CDC, two district CDCs and a tertiary hospital) who were involved in the 2009 influenza A (H1N1) pandemic response in Beijing. In phase 2, individual interviews were conducted with 23 participants (including physicians across medical departments, an IT manager and a general administrative officer).

Primary and secondary measures

For the case study, five areas were examined to assess the hospital's preparedness for implementation of an e-Health system in the context of a pandemic response: (1) motivational forces for change; (2) healthcare providers’ exposure to e-Health; (3) technological preparedness; (4) organisational non-technical ability to support a clinical ICT innovation and (5) sociocultural issues at the organisation in association with e-Health implementation and a pandemic response.

Results

This article reports a small subset of the case study results from which major issues were identified under three main themes in relation to the hospital's preparedness. These issues include a poor sharing of patient health records, prescription errors, unavailability of software tools to assist physicians in answering patient questions, physicians’ concerns about the reliability of ICT and the high monetary cost of e-health implementation and uncertainty over return on investment, and their dissatisfaction with the software in use.

Conclusions

Prior to the implementation of e-Health, planning must be undertaken to ensure the smooth introduction of the system. The assessment of organisational preparedness is an important step in this planning process. On the basis of a case study, deficient areas of organisational preparedness were identified for the prospective implementation of electronic health records. Accordingly, we suggested possible solutions for the areas in need of improvement to facilitate e-Health implementation's success.
Predicting palliative care needs and mortality in end stage renal disease: use of an at-risk register
Authors: Feyi Kennedy , Klinger Sarah , Pharro Georgina , Mcnally Liz , James Ajith , Gretton Kate , Almond Michael K
Published: March 2013

Introduction

The Gold Standard Frameworks (GSF) Committee devised Prognostic Indicator Guidance in November 2007 to ‘aid identification of adult patients with advanced disease, in the last months or year of life, who are in need of supportive or palliative care’.

Methods

This research used the GSF `surprise question' to formulate a list of patients predicted to die within 1 year with end stage renal failure and to establish the specificity and sensitivity of this register.

Results

58 patients were added to the list during the follow-up period of which 28 (48.3%) died during the same period giving an annual mortality of 32.2%. In comparison with the patients who died during the follow-up period but were not added to the at-risk register, those on the register had a much higher mortality rate (32.2% vs 7.8%). Identification of patients with chronic kidney disease and reduced life expectancy by this method appears to have a high sensitivity (66.7%) and specificity (77.9%). In particular, the negative predictive value for mortality for those on the at-risk register appears to be very high (88.3%), indicating the very low mortality among those not on the register.

Conclusions

Patients with chronic kidney disease and a reduced life expectancy can be accurately identified by a multi-disciplinary team using the surprise trigger question with a relatively high sensitivity and specificity. The accurate identification of patients with reduced life expectancy allows appropriate end of life care planning to begin in keeping with patients' wishes and within published guidelines.
The Vulnerable Elders Survey and its prognostic relationship to survival in an older community-based palliative population
Authors: Chapman Michael David , Le Brian H C , Gorelik Alexandra
Published: March 2013

Objectives

Frailty denotes a vulnerability to poor outcomes and is a common risk factor for mortality in older persons. The Vulnerable Elders Survey (VES) is an easy to administer validated screening tool to detect a frail population. Assessment of frailty has the potential to aid in prognostication for the older community dwelling palliative population. This study seeks to evaluate the relationship of the VES to prognosis in this population.

Methods

Prospective cohort study of patients over 65 years old admitted to a community palliative care service. The VES was performed in addition to the usual assessments of physical function. Comorbidity was assessed using the Charlson Comorbidity Index (CCI). Physical function and CCI were assessed to determine whether they improved the prognostic power of the VES. Patients were followed-up for 8 months with the primary endpoint of survival.

Results

197 patients completed the study with a high proportion of malignant diagnoses (87.5%); 98% of patients died during the study with a median survival of 61 days; 93.4% of patients were vulnerable on the VES and high risk scores predicted death within 100 days.

Conclusions

In this study the VES demonstrated high rates of vulnerability and has the potential to improve the accuracy of prognosis in older palliative community dwelling patients. Improving prognostication has potential clinical benefits, including aiding clinical communication and determining the best use of community services. The limitations of this study and the evolving understanding of frailty suggest that further work in this area is required.
Use of immunohistochemistry in the diagnosis of problematic breast lesions
Authors: Lee Andrew H S
Published: March 2013

Most diagnoses in breast pathology can be made with H&E sections. Nevertheless immunohistochemistry plays a useful supplementary role. This article reviews the common uses of immunohistochemistry in diagnostic breast pathology. It is important to be aware of the limitations of individual antibodies. Such problems can often be overcome by using panels of antibodies. Quality control is also essential: internal and external controls should show appropriate staining. Immunohistochemistry must be interpreted in combination with the morphology seen on H&E sections. Myoepithelial markers, such as smooth muscle actin, smooth muscle myosin heavy chain and p63, are useful for distinguishing invasive carcinoma from sclerosing lesions and ductal carcinoma in situ (DCIS), and in the classification of papillary lesions. Basal cytokeratins can help distinguish epithelial hyperplasia of usual type (UEH) and clonal proliferations such as DCIS and lobular carcinoma in situ (LCIS). UEH usually shows patchy expression whereas DCIS and other clonal proliferations are typically negative. E-cadherin can usually separate DCIS and LCIS: DCIS typically shows membrane staining and most LCIS is negative. Cytokeratins can be used to detect small nodal metastases or subtle invasive carcinomas such as invasive lobular carcinomas. Immunohistochemistry plays a useful role in diagnosing spindle cell lesions such as a panel of cytokeratins to identify spindle cell carcinomas. Immunohistochemistry is helpful in recognising metastases to the breast. Different antibodies are useful for different tumours: WT1 for ovarian carcinoma; TTF1 for pulmonary adenocarcinoma; S100, melan-A and HMB45 for melanoma; and lymphoid markers for lymphoma.
Does hormone replacement therapy (HRT) cause breast cancer? An application of causal principles to three studies
Authors: Shapiro Samuel , Farmer Richard D T , Stevenson John C , Burger Henry G , Mueck Alfred O , Gompel Anne
Published: March 2013

Background

Based principally on findings in three studies, the Collaborative Reanalysis (CR), the Women's Health Initiative (WHI), and the Million Women Study, it is claimed that hormone replacement therapy (HRT) is an established cause of breast cancer. The authors have previously reviewed those studies (Parts 1–4). The WHI findings were first published in 2002, following which the use of HRT rapidly declined. A correspondingly rapid decline in the incidence of breast cancer has been reported, and attributed to the drop in the use of HRT. The evidence, however, is conflicting.

Methods

Using generally accepted causal criteria, in this article (Part 5) the authors evaluate reported trends in the incidence of breast cancer.

Results

The evidence to suggest a correlated decline in the incidence of breast cancer following a decline in the use of HRT has not adequately satisfied the criteria of time order, detection bias, confounding, statistical stability and strength of association, internal consistency, and external consistency; biological plausibility is difficult to assess.

Conclusions

Based on the observed trends in the incidence of breast cancer following the decline in HRT use, the ecological evidence is too limited either to support or refute the possibility that HRT causes breast cancer.
The effect of lactic acidosis on the generation and compensation of mixed respiratory‐metabolic acidosis in neonatal calves
Authors: Bleul U. , Götz E.
Published: March 2013

Postnatal mixed respiratory‐metabolic acidosis is common in calves, and depending on its severity can impair vitality or even cause death. Carbon dioxide accounts for the respiratory component and L‐lactate for the metabolic component of the mixed acidosis, but it remains unclear which component determines the severity and duration of the acidosis. In a first attempt to clarify, this was investigated retrospectively in 31 calves during the first two hours of life, and in 13 calves during the first three days of life. Venous blood was collected for blood gas analysis and measurement of acid‐base variables and L‐lactate concentration. pH Was more strongly correlated with L‐lactate concentration (r2 =0.808) than with partial pressure of CO2 (pCO2, r2 =0.418). Duration of parturition had a distinct effect on pH and L‐lactate concentration but not on pCO2 ; calves born within six hours of rupture of the allantoic sac had a higher pH and lower L‐lactate concentration than calves born after a longer duration of parturition (both P<0.01). Normalisation of pCO2 took four hours and normalisation of L‐lactate took 48 hours. It was concluded that L‐lactate is a more important factor in the pathogenesis of acidosis than pCO2, and that the duration of metabolic acidosis exceeds that of respiratory acidosis in perinatal asphyxia of calves.
COMBINED SERIES AND PARALLEL SYSTEMS SUBJECT TO INDIVIDUAL VERSUS OVERARCHING DEFENSE AND ATTACK
Authors: HAUSKEN KJELL
Published: March 2013

A system of components can be in series, parallel, or combined series/parallel. The components and system are protected individually and overarchingly by a defender, and attacked individually and overarchingly by an attacker. Both layers of protection have to be breached for an attack to be successful. Each component, and the system as a whole, have vulnerabilities determined by individual and overarching protection and attack. The agents choose their effort variables simultaneously and independently to maximize their utilities. Each component and the system have unit costs of protection and attack, and a contest intensity. We show for both the parallel and series systems that the defender always prefers overarching and individual protection and attack, while the attacker always prefers individual protection and attack. Analytical expressions are developed for the agents' effort variables, each individual component's vulnerability, and the system vulnerability. The expenditure ratio, between individual protection and attack, and overarching protection and attack, is shown to increase in the number of components for the parallel system, and decrease in the number of components for the series system. Special cases are considered and interpreted. Comparisons are made with only individual protection and attack. The model is applicable to determine how the defender and attacker should strike the balance between choosing efforts to protect and attack components individually versus overarchingly.
CATEGORICAL TINKERTOYS FOR ${\mathcal N} = 2$ GAUGE THEORIES
Authors: CECOTTI SERGIO
Published: March 2013

In view of classification of the quiver 4d [Formula: see text] supersymmetric gauge theories, we discuss the characterization of the quivers with superpotential [Formula: see text] associated to a [Formula: see text] QFT which, in some corner of its parameter space, looks like a gauge theory with gauge group G. The basic idea is that the Abelian category [Formula: see text] of (finite-dimensional) representations of the Jacobian algebra [Formula: see text] should enjoy what we call the Ringel property of type G; in particular, [Formula: see text] should contain a universal "generic" subcategory, which depends only on the gauge group G, capturing the universality of the gauge sector. More precisely, there is a family of "light" subcategories [Formula: see text], indexed by points λ ∈ N, where N is a projective variety whose irreducible components are copies of ℙ1in one-to-one correspondence with the simple factors of G. If λ is the generic point of the ith irreducible component, [Formula: see text] is the universal subcategory corresponding to the ith simple factor of G. Matter, on the contrary, is encoded in the subcategories [Formula: see text] where {λa} is a finite set of closed points in N.

In particular, for a Gaiotto theory there is one such family of subcategories, [Formula: see text], for each maximal degeneration of the corresponding surface Σ, and the index variety N may be identified with the degenerate Gaiotto surface itself: generic light subcategories correspond to cylinders, while closed-point subcategories to "fixtures" (spheres with three punctures of various kinds) and higher-order generalizations. The rules for "gluing" categories are more general than the geometric gluing of surfaces, allowing for a few additional exceptional [Formula: see text] theories which are not of the Gaiotto class. We include several examples and some amusing consequence, as the characterization in terms of quiver combinatorics of asymptotically free theories.