bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Experimental-Numerical Approach to Determine Radiation Properties of Particle Suspensions
Authors: Marti Jan , Roesle Matthew , Steinfeld Aldo
Published: May 2014

A combination of experimental measurements with a numerical model is used to find the volume-averaged radiation properties—extinction coefficient, scattering albedo and approximated scattering phase function—of SiC particle suspensions with varying particle loadings. The experimentally determined angular radiation distribution of irradiated SiC samples is applied to fit a collision-based Monte Carlo (MC) model with a continuous participating media defining the particle suspension. A validation case with glass microspheres and Mie theory is implemented to verify the modeling procedure. Two types of SiC particles with dissimilar optical characteristics are examined and the respective radiation properties are determined for particle loadings between 0.05 and 0.30. The extinction coefficients of both types of SiC particle are in good agreement with the dependent scattering correlation of Kaviany and Singh.
Trefftz Functions Applied to Direct and Inverse Non-Fourier Heat Conduction Problems
Authors: Grysa Krzysztof , Maciag Artur , Adamczyk-Krasa Justyna
Published: May 2014

The paper presents a new approximate method of solving non-Fourier heat conduction problems. The approach described here is suitable for solving both direct and inverse problems. The way of generating Trefftz functions for non-Fourier heat conduction equation has been shown. Obtained functions have been used for solving direct and boundary inverse problems (identification of boundary condition). As a rule, inverse problems are ill-posed. Therefore, each method of solving these problems has to be checked according to disturbance of the input data. Presented examples confirm high usability of the presented approach for solving direct and inverse non-Fourier heat conduction problems.
The Tilted Rocket Rig: A Rayleigh–Taylor Test Case for RANS Models1
Authors: Denissen Nicholas A. , Rollin Bertrand , Reisner Jon M. , Andrews Malcolm J.
Published: May 2014

Reynolds-Averaged Navier–Stokes (RANS) models remain the most common design tool in a wide variety of fluid mixing applications. This includes variable-density turbulent mixing as occurs in inertial confinement fusion. The present work extends validation of the BHR-2 RANS model for variable-density turbulence to a two-dimensional Rayleigh–Taylor test case, the “tilted-rig.” The combined effects of bulk fluid motion and turbulence model behavior are discussed, and several quantities of interest are shown to demonstrate the capability of a four-equation turbulence model to describe this type of two-dimensional turbulent mixing. More generally, the tilted-rig test problem is shown to be a useful exercise for RANS model validation.
The Hermeticity of Compression Seals in Microchannel Hemodialyzers
Authors: Paul Brian K. , Ward Dustin K.
Published: May 2014

Most end stage renal disease patients receive kidney hemodialysis three to four times per week at central medical facilities. At-home kidney dialysis increases the convenience and frequency of hemodialysis treatments which has been shown to produce better patient outcomes. One limiting factor in realizing home hemodialysis treatments is the cost of the hemodialyzer. Microchannel hemodialyzers produced using compression sealing techniques show promise for reducing the size and cost of hemodialyzers. Challenges include the use of a 25 μm thick elastoviscoplastic (EVP) mass transfer membrane for gasketing. This paper provides a framework for understanding the hermeticity of these compression seals. The mechanical properties of a Gambro AN69ST membrane are determined and used to establish limits on the dimensional tolerances of the polycarbonate (PC) laminae containing sealing bosses used to seal the hemodialyzer. The resulting methods are applied to the fabrication of a hemodialysis device showing constraints on the scaling of this method to larger device sizes. The resulting hemodialysis device is used to perform urea mass transfer experiments without leakage.
Sound pressure around dipole source above porous surface
Authors: Prezelj Jurij , Steblaj Peter , Cudina Mirko
Published: May 2014

A technique for in situ measurements of acoustic properties of a fibrous porous material is proposed in this paper. Proposed technique exploits a directivity pattern of a dipole source in its very near field. Theoretical analysis for the proposed technique is based on the Rayleigh integral with a complex reflection included. Results are compared with results of FEM analysis and show that flow resistivity of a porous material placed in the very near field of the dipole source has significant influence on the sound pressure at its ring. Results provide an excellent starting point for the design of the sensor for sound absorption.
Coherent ultrafast charge transfer in an organic photovoltaic blend
Authors: Falke Sarah Maria , Rozzi Carlo Andrea , Brida Daniele , Maiuri Margherita , Amato Michele , Sommer Ephraim , De Sio Antonietta , Rubio Angel , Cerullo Giulio , Molinari Elisa , Lienau Christoph
Published: May 2014

Pull, pull, pulling electrons along

Organic photovoltaics operate by transferring charge from a light-absorbing donor material to a nearby acceptor. Falke
et al.
show that molecular vibrations smooth the way for this charge transfer to proceed. A combination of ultrafast spectroscopy and theoretical simulations revealed an oscillatory signal in a model donor/acceptor blend that implicates carbon-carbon bond stretching in concert with the electronic transition. This vibrational/electronic, or vibronic, process maintains a quantum-mechanical phase relationship that guides the charge more rapidly and directly than an incoherent migration from donor to acceptor.

Science
, this issue p.
1001
Optimal approaches for balancing invasive species eradication and endangered species management
Authors: Lampert Adam , Hastings Alan , Grosholz Edwin D. , Jardine Sunny L. , Sanchirico James N.
Published: May 2014

Conservation vs. eradication

What's an ecologist to do when an endangered bird lives in an invasive grass? Ecosystems are complicated networks, with one species relying on another, and managing one species in isolation may damage other members of a community. Lampert
et al.
(see the Perspective by Buckley and Han) looked at the conflict between eradicating a damaging invasive grass species and protecting an endangered bird species that uses the grass as its home. The most effective management and restoration approach focused not on eradicating the invasive grass as quickly as possible but on making changes slowly enough that the birds could adapt. This approach may prove useful in other situations in which active restoration conflicts with other conservation goals.

Science
, this issue p.
1028
; see also p.
975
A bacterial seek-and-destroy system for foreign DNA
Authors: Vogel Jörg
Published: May 2014

Bacterial argonaute proteins defend the cell against exogenous DNA
X-ray birefringence imaging
Authors: Palmer Benjamin A. , Edwards-Gau Gregory R. , Kariuki Benson M. , Harris Kenneth D. M. , Dolbnya Igor P. , Collins Stephen P.
Published: May 2014

A close-up view of carbon-bromide bonds

Polarizing filters are widely used in optical microscopy to highlight a range of material properties that cause optical path boundaries or birefringence in a material. Palmer
et al.
(see the Perspective by Lidin) developed an analog method for x-ray microscopy using linearly polarized x-ray beams and an area detector inside a synchrotron. The technique revealed the orientation of the C-Br bonds within crystalline materials.

Science
, this issue p.
1013
; see also p.
969
Vibrational spectral signature of the proton defect in the three-dimensional H
+
(H
2
O)
21
cluster
Authors: Fournier Joseph A. , Johnson Christopher J. , Wolke Conrad T. , Weddle Gary H. , Wolk Arron B. , Johnson Mark A.
Published: May 2014

Blackjack water cluster detected

Spectroscopy of protonated water clusters has played a pivotal role in elucidating the molecular arrangement of acid solutions. Whereas bulk liquids manifest broad spectral features, the cluster bands tend to be sharper. The 21-membered water cluster has for decades inspired particular interest on account of its stability and its place in the transition from two-dimensional to three-dimensional hydrogen-bonding network motifs, but the spectral signature of its bound proton has proved elusive. Fournier
et al.
have now detected this long-sought vibrational feature by applying an innovative ion cooling technique.

Science
, this issue p.
1009
Hitting the limit of magnetic anisotropy
Authors: Khajetoorians Alexander Ako , Wiebe Jens
Published: May 2014

Enhancing the magnetic properties of adatoms provides a route toward atom-scale memory

[Also see Report by

Rau
et al.

]
Managing the side effects of invasion control
Authors: Buckley Yvonne M. , Han Yi
Published: May 2014

Efforts to control invasive species must be adapted to avoid unintended damage to native species and ecosystems

[Also see Report by

Lampert
et al.

]
How sulfur beats iron
Authors: Friedrich Michael W. , Finster Kai W.
Published: May 2014

Iron-reducing bacteria switch to sulfur reduction as their main energy source in alkaline environments

[Also see Report by

Flynn
et al.

]
Views of science clash in debate over NSF bill
Authors: Mervis Jeffrey
Published: May 2014

Push for closer oversight of agency alarms university and science groups.
Cytokine Production Assays Reveal Discriminatory Immune Defects in Adults with Recurrent Infections and Noninfectious Inflammation
Authors: ten Oever Jaap , van de Veerdonk Frank L. , Joosten Leo A. B. , Simon Anna , van Crevel Reinout , Kullberg Bart-Jan , Gyssens Inge C. , van der Meer Jos W. M. , van Deuren Marcel , Netea Mihai G.
Published: May 2014

Cytokine production assays have been primarily used in research settings studying novel immunodeficiencies. We sought to determine the diagnostic value of cytokine production assays in patients with recurrent and/or severe infectious diseases (IDs) without known immunodeficiencies and unclassified noninfectious inflammatory disorders (NIIDs). We retrospectively examined cytokine production in whole-blood and peripheral blood mononuclear cell samples from 157 adult patients. A cytokine production rate of <5% of that of healthy controls was considered defective. While monocyte-derived cytokine (tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and IL-6) production was rarely affected, 30% of all included patients had deficient production of interferon gamma (IFN-γ), IL-17A, or IL-22. Twenty-five percent of the NIID patients displayed defective IFN-γ production, whereas IL-17A production was generally unaffected. In the group of ID patients, defective IFN-γ production was found in 19% and 14% of the patients with viral and bacterial infections, respectively, and in 38%, 24%, and 50% of patients with mycobacterial, mucocutaneous, and invasive fungal infections, respectively. Defective IL-17A and IL-22 production was mainly confined to ID patients with mucocutaneous fungal infections. In conclusion, cytokine production assays frequently detect defective Th1 responses in patients with mycobacterial or fungal infections, in contrast to patients with respiratory tract infections or isolated bacterial infections. Defective IL-17A and IL-22 production was primarily found in patients with fungal infections, while monocyte-derived cytokine production was unaffected. Thus, lymphocyte-derived cytokine production assays are helpful in the diagnostic workup of patients with recurrent infections and suspected immunodeficiencies and have the potential to reveal immune defects that might guide adjunctive immunomodulatory therapy.
Adaptation and Attenuation of Duck Tembusu Virus Strain Du/CH/LSD/110128 following Serial Passage in Chicken Embryos
Authors: Sun Ling , Li Yunxia , Zhang Yue , Han Zongxi , Xu Yang , Kong Xiangang , Liu Shengwang
Published: May 2014

Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused massive economic losses to the duck industry in China. In the current study, a virulent strain of DTMUV, designated Du/CH/LSD/110128, was isolated from the livers of diseased ducks and attenuated by serial passage in embryonated chicken eggs. The virus was partially attenuated after 50 and 70 passages and was fully attenuated after 90 passages, based on mortality and morbidity rates and viral loads in inoculated ducklings. Fourteen amino acid substitutions were observed in the capsid, prM, envelope, NS1, NS3, NS4A, NS4B, and NS5 proteins of the fully attenuated strain of Du/CH/LSD/110128, which might be responsible for the observed changes in replication and pathogenicity. A 72-nucleotide deletion was also observed in the 3′ untranslated region of the virus after 30 passages. The fully attenuated virus retained the immunogenicity of the parental strain, providing effective protection to challenge with virulent Du/CH/LSD/110128, and may represent a suitable candidate as a vaccine strain against DTMUV infection in ducks. Our results also lay the foundation for future studies on the replication and pathogenic mechanisms of DTMUV.
Chemically Modified Peptides Based on the Membrane-Proximal External Region of the HIV-1 Envelope Induce High-Titer, Epitope-Specific Nonneutralizing Antibodies in Rabbits
Authors: Venditto Vincent J. , Wieczorek Lindsay , Molnar Sebastian , Teque Fernando , Landucci Gary , Watson Douglas S. , Forthal Donald , Polonis Victoria R. , Levy Jay A. , Szoka Francis C.
Published: May 2014

Broadly neutralizing monoclonal antibodies (bNAbs) 2F5 and 4E10 bind to the membrane proximal external region (MPER) of gp41 and also cross-react with phospholipids. In this study, we investigated if chemical modifications on the MPER adjacent to 2F5 and 4E10 epitopes using mimetics of inflammation-associated posttranslational modifications to induce 2F5- and 4E10-like bNAbs can break tolerance. We synthesized a series of chemically modified peptides spanning the MPER. The serine, threonine, and tyrosine residues in the peptides were modified with sulfate, phosphate, or nitrate moieties and presented in liposomes for rabbit immunizations. All immunizations resulted in high antisera titers directed toward both the modified and unmodified immunogens. Tyrosine modification was observed to significantly suppress antiepitope responses. Sera with strong anti-gp140 titers were purified by affinity chromatography toward the MPER peptide and found to possess a higher affinity toward the MPER than did the bNAbs 2F5 and 4E10. Modest neutralization was observed in the H9 neutralization assay, but neutralization was not observed in the TZM-bl cell or peripheral blood mononuclear cell (PBMC) neutralization assay platforms. Although neutralizing antibodies were not induced by this approach, we conclude that chemical modifications can increase the immune responses to poorly immunogenic antigens, suggesting that chemical modification in an appropriate immunization protocol should be explored further as an HIV-1 vaccine strategy.
Detection of Significant Bacteriuria by Use of the iQ200 Automated Urine Microscope
Authors: Stürenburg Enno , Kramer Jan , Schön Gerhard , Cachovan Georg , Sobottka Ingo
Published: May 2014

In the microbiology laboratory, there is an augmented need for rapid screening methods for the detection of bacteria in urine samples, since about two-thirds of these samples will not yield any bacteria or will yield insignificant growth when cultured. Thus, a reliable screening method can free up laboratory resources and can speed up the reporting of a negative urine result. In this study, we have evaluated the detection of leukocytes, bacteria, and a new sediment indicator, the “all small particles” (ASP), by an automated instrument, the iQ200 urine analyzer, to detect negative urine samples that can be excluded from culture. A coupled automated strip reader (iChem Velocity), enabling the detection of nitrite and leukocyte esterase, was tested in parallel. In total, 963 urine samples were processed through both conventional urine culture and the iQ200/iChem Velocity workstation. Using the data, a multivariate regression model was established, and the predicted specificity and the possible reduction in urine cultures were calculated for the indicators and their respective combinations (leukocytes plus bacteria plus ASP and leukocyte esterase plus nitrite). Among all options, diagnostic performance was best using the whole microscopic content of the sample (leukocytes plus bacteria plus ASP). By using a cutoff value of ≥10
4
CFU/ml for defining a positive culture, a given sensitivity of 95% resulted in a specificity of 61% and a reduction in urine cultures of 35%. By considering the indicators alone, specificity and the culture savings were both much less satisfactory. The regression model was also used to determine possible cutoff values for running the instrument as part of daily routine. By using a graphical representation of all combinations possible, we derived cutoff values for leukocyte, bacterial, and ASP count, which should enable the iQ200 microscope to screen out approximately one-third of the urine samples, significantly reducing the workload in the microbiology laboratory.
Pseudo-Outbreak of Pre-Extensively Drug-Resistant (Pre-XDR) Tuberculosis in Kinshasa: Collateral Damage Caused by False Detection of Fluoroquinolone Resistance by GenoType MTBDR
sl
Authors: Kaswa Michel K. , Aloni Muriel , Nkuku Léontine , Bakoko Brian , Lebeke Rossin , Nzita Albert , Muyembe Jean Jacques , de Jong Bouke C. , de Rijk Pim , Verhaegen Jan , Boelaert Marleen , Ieven Margareta , Van Deun Armand
Published: May 2014

Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-TB). Molecular drug susceptibility testing methods provide considerable advantages for scaling up programmatic management and surveillance of drug-resistant TB. We describe here the misidentification of fluoroquinolone resistance by the GenoType MTBDR
sl
(MTBDR
sl
) (Hain Lifescience GmbH, Nehren, Germany) line probe assay (LPA) encountered during a feasibility and validation study for the introduction of this rapid drug susceptibility test in Kinshasa, Democratic Republic of Congo. The double
gyrA
mutation 80Ala and 90Gly represented 57% of all fluoroquinolone mutations identified from MDR-TB patient sputum samples, as confirmed by DNA sequencing. This double mutation was previously found to be associated with susceptibility to fluoroquinolones, yet it leads to absent hybridization of a wild-type band in the MTBDR
sl
and is thus falsely scored as resistance. Our findings suggest that MTBDR
sl
results must be interpreted with caution when the interpretation is based solely on the absence of a wild-type band without confirmation by visualization of a mutant band. Performance of the MTBDR
sl
LPA might be improved by replacing the
gyrA
wild-type probes by additional probes specific for well-documented
gyrA
mutations that confer clinically relevant resistance.
Cluster of Infections Caused by Methicillin-Resistant Staphylococcus pseudintermedius in Humans in a Tertiary Hospital
Authors: Starlander Gustaf , Börjesson Stefan , Grönlund-Andersson Ulrika , Tellgren-Roth Christian , Melhus Åsa
Published: May 2014

The dog-associated
Staphylococcus pseudintermedius
is a rare pathogen in humans. Here we describe a cluster of infections caused by the methicillin-resistant
S. pseudintermedius
clone ST71-J-t02-II–III. It involved four elderly patients at a tertiary hospital. Three patients had wound infections, and the strain had a tendency to cause bullous skin lesions.
Disseminated Mycobacterium lentiflavum Responsible for Hemophagocytic Lymphohistocytosis in a Man with a History of Heart Transplantation
Authors: Thomas G. , Hraiech S. , Dizier S. , Weiller P. J. , Ene N. , Serratrice J. , Secq V. , Ambrosi P. , Drancourt M. , Roch A. , Papazian L.
Published: May 2014

Mycobacterium lentiflavum
is a nontuberculous, slowly growing mycobacterium usually recognized as a contaminant. Here, we report a case of disseminated
M. lentiflavum
infection responsible for hemophagocytic lymphohistocytosis in a heart-transplanted man.
Clinical Utility of Droplet Digital PCR for Human Cytomegalovirus
Authors: Sedlak Ruth Hall , Cook Linda , Cheng Anqi , Magaret Amalia , Jerome Keith R.
Published: May 2014

Human cytomegalovirus (CMV) has historically been the major infectious cause of morbidity and mortality among patients receiving hematopoietic cell or organ transplant. Standard care in a transplant setting involves frequent monitoring of CMV viral load over weeks to months to determine when antiviral treatment may be required. Quantitative PCR (qPCR) is the standard molecular diagnostic method for monitoring. Recently, digital PCR (dPCR) has shown promise in viral diagnostics, although current dPCR systems have lower throughput than qPCR systems. Here, we compare qPCR and droplet digital PCR (ddPCR) for CMV detection in patient plasma samples. Droplet digital PCR exhibits increased precision over qPCR at viral loads of ≥4 log
10
with equivalent sensitivity. However, retrospective analysis of longitudinal samples from transplant patients with CMV viral loads near therapeutic thresholds did not provide evidence that the improved precision of ddPCR would be of clinical benefit. Given the throughput advantages of current qPCR systems, a widespread switch to dPCR for CMV monitoring would appear premature.
Downregulation of Interleukin-18-Mediated Cell Signaling and Interferon Gamma Expression by the Hepatitis B Virus e Antigen
Authors: Jegaskanda S. , Ahn S. H. , Skinner N. , Thompson A. J. , Ngyuen T. , Holmes J. , De Rose R. , Navis M. , Winnall W. R. , Kramski M. , Bernardi G. , Bayliss J. , Colledge D. , Sozzi V. , Visvanathan K. , Locarnini S. A. , Kent S. J. , Revill P. A.
Published: May 2014

The mechanisms by which hepatitis B virus (HBV) establishes and maintains chronic hepatitis B infection (CHB) are poorly defined. Innate immune responses play an important role in reducing HBV replication and pathogenesis. HBV has developed numerous mechanisms to escape these responses, including the production of the secreted hepatitis B e antigen (HBeAg), which has been shown to regulate antiviral toll-like receptor (TLR) and interleukin-1 (IL-1) signaling. IL-18 is a related cytokine that inhibits HBV replication in hepatoma cell lines and in the liver through the induction of gamma interferon (IFN-γ) by NK cells and T cells. We hypothesized that HBV or HBV proteins inhibit IFN-γ expression by NK cells as an accessory immunomodulatory function. We show that HBeAg protein inhibits the NF-κB pathway and thereby downregulates NK cell IFN-γ expression. Additionally, IFN-γ expression was significantly inhibited by exposure to serum from individuals with HBeAg-positive but not HBeAg-negative chronic HBV infection. Further, we show that the HBeAg protein suppresses IL-18-mediated NF-κB signaling in NK and hepatoma cells via modulation of the NF-κB pathway. Together, these findings show that the HBeAg inhibits IL-18 signaling and IFN-γ expression, which may play an important role in the establishment and/or maintenance of persistent HBV infection.

IMPORTANCEIt is becoming increasingly apparent that NK cells play a role in the establishment and/or maintenance of chronic hepatitis B infection. The secreted HBeAg is an important regulator of innate and adaptive immune responses. We now show that the HBeAg downregulates NK cell-mediated IFN-γ production and IL-18 signaling, which may contribute to the establishment of infection and/or viral persistence. Our findings build on previous studies showing that the HBeAg also suppresses the TLR and IL-1 signaling pathways, suggesting that this viral protein is a key regulator of antiviral innate immune responses.
Activation of c-jun N-Terminal Kinase upon Influenza A Virus (IAV) Infection Is Independent of Pathogen-Related Receptors but Dependent on Amino Acid Sequence Variations of IAV NS1
Authors: Nacken Wolfgang , Anhlan Darisuren , Hrincius Eike R. , Mostafa Ahmed , Wolff Thorsten , Sadewasser Anne , Pleschka Stephan , Ehrhardt Christina , Ludwig Stephan
Published: May 2014

A hallmark cell response to influenza A virus (IAV) infections is the phosphorylation and activation of c-jun N-terminal kinase (JNK). However, so far it is not fully clear which molecules are involved in the activation of JNK upon IAV infection. Here, we report that the transfection of influenza viral-RNA induces JNK in a retinoic acid-inducible gene I (RIG-I)-dependent manner. However, neither RIG-I-like receptors nor MyD88-dependent Toll-like receptors were found to be involved in the activation of JNK upon IAV infection. Viral JNK activation may be blocked by addition of cycloheximide and heat shock protein inhibitors during infection, suggesting that the expression of an IAV-encoded protein is responsible for JNK activation. Indeed, the overexpression of nonstructural protein 1 (NS1) of certain IAV subtypes activated JNK, whereas those of some other subtypes failed to activate JNK. Site-directed mutagenesis experiments using NS1 of the IAV H7N7, H5N1, and H3N2 subtypes identified the amino acid residue phenylalanine (F) at position 103 to be decisive for JNK activation. Cleavage- and polyadenylation-specific factor 30 (CPSF30), whose binding to NS1 is stabilized by the amino acids F103 and M106, is not involved in JNK activation. Conclusively, subtype-specific sequence variations in the IAV NS1 protein result in subtype-specific differences in JNK signaling upon IAV infection.

IMPORTANCE
Influenza A virus (IAV) infection leads to the activation or modulation of multiple signaling pathways. Here, we demonstrate for the first time that the c-jun N-terminal kinase (JNK), a long-known stress-activated mitogen-activated protein (MAP) kinase, is activated by RIG-I when cells are treated with IAV RNA. However, at the same time, nonstructural protein 1 (NS1) of IAV has an intrinsic JNK-activating property that is dependent on IAV subtype-specific amino acid variations around position 103. Our findings identify two different and independent pathways that result in the activation of JNK in the course of an IAV infection.
Progression From IgD+IgM+to Isotype-Switched B Cells Is Site Specific during Coronavirus-Induced Encephalomyelitis
Authors: Phares Timothy W. , DiSano Krista D. , Stohlman Stephen A. , Bergmann Cornelia C.
Published: May 2014

Various infections in the central nervous system (CNS) trigger B cell accumulation; however, the relative dynamics between viral replication and alterations in distinct B cell subsets are largely unknown. Using a glia-tropic coronavirus infection, which is initiated in the brain but rapidly spreads to and predominantly persists in the spinal cord, this study characterizes longitudinal changes in B cell subsets at both infected anatomical sites. The phase of T cell-dependent, antibody-independent control of infectious virus was associated with a similar recruitment of naive/early-activated IgD+IgM+B cells into both the brain and spinal cord. This population was progressively replaced by CD138−IgD−IgM+B cells, isotype-switched CD138−IgD−IgM−memory B cells (Bmem), and CD138+antibody-secreting cells (ASC). A more rapid transition to Bmemand ASC in spinal cord than in brain was associated with higher levels of persisting viral RNA and transcripts encoding factors promoting B cell migration, differentiation, and survival. The results demonstrate that naive/early-activated B cells are recruited early during coronavirus CNS infection but are subsequently replaced by more differentiated B cells. Furthermore, viral persistence, even at low levels, is a driving force for accumulation of isotype-switched Bmemand ASC.

IMPORTANCEAcute and chronic human CNS infections are associated with an accumulation of heterogeneous B cell subsets; however, their influence on viral load and disease is unclear. Using a glia-tropic coronavirus model, we demonstrate that the accumulation of B cells ranging from early-activated to isotype-switched differentiation stages is both temporally and spatially orchestrated. Acutely infected brains and spinal cords indiscriminately recruit a homogeneous population of early-activated B cells, which is progressively replaced by diverse, more differentiated subsets. The latter process is accelerated by elevated proinflammatory responses associated with viral persistence. The results imply that early-recruited B cells do not have antiviral function but may contribute to the inflammatory environment or act as antigen-presenting cells. Moreover, CNS viral persistence is a driving force promoting differentiated B cells with protective potential.
Nucleotide Oligomerization and Binding Domain 2-Dependent Dendritic Cell Activation Is Necessary for Innate Immunity and Optimal CD8+T Cell Responses to Influenza A Virus Infection
Authors: Lupfer Christopher , Thomas Paul G. , Kanneganti Thirumala-Devi
Published: May 2014

Nucleotide oligomerization and binding domain (NOD)-like receptors (NLRs) are important in the innate immune response to viral infection. Recent findings have implicated NLRP3, NOD2, and NLRX1 as important players in the innate antiviral response, but their roles in the generation of adaptive immunity to viruses are less clear. We demonstrate here that NOD2 is critical for both innate and adaptive immune responses necessary for controlling viral replication and survival during influenza A virus (IAV) infection.Nod2−/−mice have reduced beta interferon (IFN-β) levels and fewer activated dendritic cells (DCs), and the DCs are more prone to cell death in the lungs ofNod2−/−mice during IAV infection. In agreement with the role for DCs in priming adaptive immunity, the generation of virus-specific CD8+T cells and their activation and production of IFN-γ were lower inNod2−/−mice. Furthermore,Nod2−/−DCs, when cocultured with T cellsin vitro, have a lower costimulatory capacity. Thus,Nod2−/−DCs are unable to efficiently prime CD8+T cells. These findings demonstrate that Nod2 is critical for the generation of both innate and adaptive immune responses necessary for controlling IAV infection.

IMPORTANCEThe innate immune system is the host's first line of defense against invading pathogens and is also necessary for alerting and activating T and B cells to initiate the adaptive immune response. We demonstrate here that the innate immune receptor NOD2 is required for the production of antiviral type I interferons and the activation and survival of dendritic cells that, in turn, alert T cells to the presence of influenza A virus infection. In mice that are missing NOD2, interferon levels are lower, and the CD8+T cell response is impaired. As a result, the animals cannot control virus replication in their lungs as efficiently. This discovery helps us understand how the body naturally responds to virus infection and may help in the development of vaccines that use NOD2 to stimulate the CD8+T cell response, thus providing better protection against influenza A virus infection.
Restriction of HIV-1 by Rhesus TRIM5α Is Governed by Alpha Helices in the Linker2 Region
Authors: Sastri Jaya , Johnsen Laura , Smolin Nikolai , Imam Sabrina , Mukherjee Santanu , Lukic Zana , Brandariz-Nuñez Alberto , Robia Seth L. , Diaz-Griffero Felipe , Wiethoff Christopher , Campbell Edward M.
Published: May 2014

TRIM5α proteins are a potent barrier to the cross-species transmission of retroviruses. TRIM5α proteins exhibit an ability to self-associate at many levels, ultimately leading to the formation of protein assemblies with hexagonal symmetry
in vitro
and cytoplasmic assemblies when expressed in cells. However, the role of these assemblies in restriction, the determinants that mediate their formation, and the organization of TRIM5α molecules within these assemblies have remained unclear. Here we show that α-helical elements within the Linker2 region of rhesus macaque TRIM5α govern the ability to form cytoplasmic assemblies in cells and restrict HIV-1 infection. Mutations that reduce α-helix formation by the Linker2 region disrupt assembly and restriction. More importantly, mutations that enhance the α-helical content of the Linker2 region, relative to the wild-type protein, also exhibit an increased ability to form cytoplasmic assemblies and restrict HIV-1 infection. Molecular modeling of the TRIM5α dimer suggests a model in which α-helical elements within the Linker2 region dock to α-helices of the coiled-coil domain, likely establishing proper orientation and spacing of protein domains necessary for assembly and restriction. Collectively, these studies provide critical insight into the determinants governing TRIM5α assembly and restriction and demonstrate that the antiviral potency of TRIM5α proteins can be significantly increased without altering the affinity of SPRY/capsid binding.

IMPORTANCE
Many members of the tripartite motif (TRIM) family of proteins act as restriction factors that directly inhibit viral infection and activate innate immune signaling pathways. Another common feature of TRIM proteins is the ability to form protein assemblies in the nucleus or the cytoplasm. However, the determinants in TRIM proteins required for assembly and the degree to which assembly affects TRIM protein function have been poorly understood. Here we show that alpha helices in the Linker2 (L2) region of rhesus TRIM5α govern assembly and restriction of HIV-1 infection. Helix-disrupting mutations disrupt the assembly and restriction of HIV-1, while helix-stabilizing mutations enhance assembly and restriction relative to the wild-type protein. Circular dichroism analysis suggests that that the formation of this helical structure is supported by intermolecular interactions with the coiled-coil (CC) domain in the CCL2 dimer. These studies reveal a novel mechanism by which the antiviral activity of TRIM5α proteins can be regulated and provide detailed insight into the assembly determinants of TRIM family proteins.
Pontine stroke and bladder dysfunction
Authors: Shukla Rakesh , Giri Prithvi , Bhandari Aveg , Shankhwar S N
Published: May 2014

We report the case of a 54-year-old hypertensive woman who presented with sudden onset left hemiparesis with facial asymmetry and inability to pass urine. Her bladder was distended and she had to be catheterised. MRI of her brain showed a large infarct in the right pontine region. Antiplatelet therapy was instituted and the patient showed good recovery and was able to walk with support after a fortnight at the time of discharge. She was discharged with a catheter in situ. After 6 months, she could walk with the support of a stick, but had increased frequency and urgency of micturition along with nocturia. Urodynamic study revealed detrusor hyper-reflexia, possibly due to involvement of the pontine micturition centre.
Mistaken identity: normotensive scleroderma renal crisis
Authors: Aburizik Arwa , Singh Siddharth , Al-Rabadi Laith , Blosser Christopher
Published: May 2014

A patient presented with neuromuscular, respiratory and cardiac symptoms and was initially diagnosed with amyotrophic lateral sclerosis (ALS), myocardial ischaemia and pneumonia. He developed unexplained progressive kidney failure over the ensuing week, and his kidney biopsy showed thrombotic microangiopathy that led to the correct diagnosis of normotensive scleroderma renal crisis. His clinical presentation and course were consistent with systemic sclerosis and normotensive scleroderma renal crisis. He was treated with an ACE inhibitor (ACEi) and haemodialysis with significant functional improvement over the next 3 months to his prior baseline with the exception of kidney failure. This case highlights a diagnostic challenge requiring astute history and physical examination skills, and the value of a kidney biopsy in providing the final diagnosis.
An unusual presentation of endometriosis
Authors: Abu Saadeh Feras , Wahab Nor Azei , Gleeson Noreen
Published: May 2014

A 25-year-old nulliparous woman attended an orthopaedic clinic with a 12-month history of right hip pain and was found to have a hard tender mass in her right groin. Fine-needle aspiration yielded a diagnosis of endometrial glands. The lesion was excised completely and the final diagnosis was round ligament endometriosis. The patient was pain free 3 months postsurgery.
Not your average birth: considering the possibility of denied or concealed pregnancy
Authors: Stammers Kathryn , Long Nicola
Published: May 2014

A 23-year-old woman presented to the emergency department (ED) with a 3-day history of lower back pain. She had seen her general practitioner 2 days previously who prescribed trimethoprim for a confirmed urinary tract infection. Routine admission observations showed she was tachycardic, tachypnoeic and slightly hypotensive but non-feverish with normal oxygen saturations. Her urine sample revealed that she was pregnant but was otherwise negative. The patient maintained that she was unaware she was pregnant. She was reviewed by an ED staff grade who was suspicious of a ruptured ectopic pregnancy. She was subsequently referred to the obstetrics and gynaecology registrar who on examination found she had a gravid uterus and vaginal examination revealed that her cervix was 8 cm dilated. The patient was very promptly admitted onto the labour ward for further assessment. She gave birth to a live male infant in the early hours of the next morning.
Characterisations of adverse events detected in a university hospital: a 4-year study using the Global Trigger Tool method
Authors: Rutberg Hans , Borgstedt Risberg Madeleine , Sjödahl Rune , Nordqvist Pernilla , Valter Lars , Nilsson Lena
Published: May 2014

Objectives

To describe the level, preventability and categories of adverse events (AEs) identified by medical record review using the Global Trigger Tool (GTT). To estimate when the AE occurred in the course of the hospital stay and to compare voluntary AE reporting with medical record reviewing.

Design

Two-stage retrospective record review.

Setting

650-bed university hospital.

Participants

20 randomly selected medical records were reviewed every month from 2009 to 2012.

Primary and secondary outcome measures

AE/1000 patient-days. Proportion of AEs found by GTT found also in the voluntary reporting system. AE categorisation. Description of when during hospital stay AEs occur.

Results

A total of 271 AEs were detected in the 960 medical records reviewed, corresponding to 33.2 AEs/1000 patient-days or 20.5% of the patients. Of the AEs, 6.3% were reported in the voluntary AE reporting system. Hospital-acquired infections were the most common AE category. The AEs occurred and were detected during the hospital stay in 65.5% of cases; the rest occurred or were detected within 30 days before or after the hospital stay. The AE usually occurred early during the hospital stay, and the hospital stay was 5 days longer on average for patients with an AE.

Conclusions

Record reviewing identified AEs to a much larger extent than voluntary AE reporting. Healthcare organisations should consider using a portfolio of tools to gain a comprehensive picture of AEs. Substantial costs could be saved if AEs were prevented.
Is there an association between disease ignorance and self-rated health? The HUNT Study, a cross-sectional survey
Authors: Jørgensen Pål , Langhammer Arnulf , Krokstad Steinar , Forsmo Siri
Published: May 2014

Objective

To explore whether awareness versus unawareness of thyroid dysfunction, diabetes mellitus or hypertension is associated with self-rated health.

Design

Large-scale, cross-sectional population-based study. The association between thyroid function, diabetes mellitus and blood pressure and self-rated health was explored by multiple logistic regression analysis.

Setting

The second survey of the Nord-Trøndelag Health Study, HUNT2, 1995–1997.

Participants

33 734 persons aged 40–70 years.

Primary outcome measures

Logistic regression was used to estimate ORs for good self-rated health as a function of thyroid status, diabetes mellitus status and blood pressure status.

Results

Persons aware of their hypothyroidism, diabetes mellitus or hypertension reported poorer self-rated health than individuals without such conditions. Women with unknown and subclinical hypothyroidism reported better self-rated health than women with normal thyroid status. In women and men, unknown and probable diabetes as well as unknown mild/moderate hypertension was not associated with poorer health. Furthermore, persons with unknown severe hypertension reported better health than normotensive persons.

Conclusions

People with undiagnosed but prevalent hypothyroidism, diabetes mellitus and hypertension often have good self-rated health, while when aware of their diagnoses, they report reduced self-rated health. Use of screening, more sensitive tests and widened diagnostic criteria might have a negative effect on perceived health in the population.
Use of ulipristal acetate and levonorgestrel for emergency contraception: a follow-up study
Authors: Baird Aisling Susan , Trussell James , Webb Anne
Published: May 2014

Objectives

Previously we showed that increasing the choice of emergency contraception (EC) guided by medical eligibility did not result in wholesale large-scale usage of ulipristal acetate (UPA). This further 12-month study aimed to answer three questions. (1) Does offering choice of EC lead to change in methods used? (2) Are women who choose UPA more likely than those who choose levonorgestrel (LNG) to continue using condoms for subsequent contraception or to decline any ongoing contraception? (3) Do more women choosing LNG 'quick start' hormonal contraception?

Methods

A retrospective study of EC episodes (1 April 2012 to 31 March 2013) by quarters. Among women offered all three methods of EC (49.1%) we noted the method chosen, and decisions on ongoing contraception among those choosing either LNG or UPA. Differences were tested for statistical significance.

Results

In 6110 episodes of EC, LNG was issued in 69.2%, UPA in 26.0%, and a copper intrauterine device (Cu-IUD) was fitted in 4.8%. Quarter by quarter, the data show a small decline in LNG use, suggesting plateauing by the last quarter, and a significant increase in UPA use between the first and the other three quarters (p<0.001). Use of the Cu-IUD remained static. The percentage of women offered three methods rose to 54.2%. In women offered full choice (3000; 49.1%) we saw a significant increase in choice of UPA, from 39.3% to 48.6% (p<0.001). Women who chose LNG were more likely to quick start (p=0.02) or be continuing contraception already used (p<0.001). Overall, those choosing UPA were more likely to use condoms (p<0.001) but were no more likely to decline ongoing contraception (p=0.13).

Conclusions

There was a significant increase in women using UPA for EC compared with our previous study, particularly among those wishing to use condoms for continuing contraception. Women choosing LNG were more likely to quick start pills or to continue current hormonal contraception. Detailed attention to continuing contraception following EC may be an important factor in the prevention of unwanted pregnancy.
Anxieties of communication: the limits of narrative in the medical humanities
Authors: McKechnie Claire Charlotte
Published: May 2014

This paper aims to provide an initial response to Angela Woods's endeavour to ‘(re)ignite critical debates around this topic’ in her recent essay ‘The limits of narrative: provocations for the medical humanities’ (Medical Humanities2011). Woods's essay challenges the validity of the notion of the narrative self through her discussion and use of Galen Strawson's seminal ‘Against narrativity’ (2004). To some extent in dialogue with Woods, this article will examine three exploratory concepts connected with the topic. First, it will explore ways in which we might seek to re-place narrative at the centre of the philosophy of good medicine and medical practice by reassessing the role of the narratee in the narrative process. Second, it will reconsider the three alternative forms of expression Woods puts forward as non-narrative—metaphor, phenomenology and photography—as narrative. Finally, and connected to the first two areas of discussion, it will reflect on ways in which narrative might be used to interpret illness and suffering in medical humanities contexts. What I hope to show, in relation to Woods's work on this subject, is that in order to be interpreted (indeed interpretable) the types of non-narrative representation and communication she discusses in fact require a narrative response. We employ narratology to engage with illness experience because narrative is so fundamental to meaning-making that it is not just required, it is an inherent human response to creative outputs we encounter. This is a quite different approach to the question of narrativity in the medical humanities, and it is therefore related to, but not entirely hinged upon, the work that Woods has done, but it is intended to spark further discussion across the emergent discipline.
Aneurysm pressure measurement before and after placement of a Pipeline stent: feasibility study using a 0.014 inch pressure wire for coronary intervention
Authors: Tateshima Satoshi , Jones Jesse G , Mayor Basto Fernando , Vinuela Fernando , Duckwiler Gary R
Published: May 2014

Flow-diverting stents have provided a new endovascular capacity to reconstruct an intracranial aneurysm with its diseased parent artery. The results of first-generation flow diversion stents have been encouraging, with even large or giant treated aneurysms achieving complete angiographic occlusion at 12-month follow-up. Numerous clinical reports have described a slow progressive thrombosis pattern and gradual increase in rate of complete aneurysm obliteration over time. Despite promising early results, some complications specific to flow-diverting stents have been encountered. Chief among them is delayed aneurysm rupture. This complication did not emerge with stent-assisted coil embolization of intracranial aneurysms, and the underlying cause has not been established. However, new evidence suggests that persistent, or even increased, aneurysm pressure after stent placement may play a role in some delayed ruptures. We sought to evaluate this phenomenon by measuring intrasaccular pressure before and after stent placement using two different 0.014 inch coronary pressure measurement wires. Two patients with giant internal carotid artery aneurysms treated with flow-diverting stents were evaluated. Before and after stent deployment, intrasaccular aneurysm and systemic arterial pressures were recorded for 60 s and compared. In both cases, intrasaccular pressure measurement with the use of 0.014 inch pressure wire system was feasible; the pressure wires could be pushed out of the microcatheter placed in the aneurysms without friction or unexpected microcatheter motion. Despite successful flow-diverting stent deployment and angiographic flow diversion effects with excellent wall opposition across the aneurysm necks, there was no significant difference between intrasaccular and systemic pressures.