bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions of Vortices of a Square Cylinder and a Rectangular Vortex Generator Under Couette–Poiseuille Flow
Authors: Maiti Dilip K. , Bhatt Rajesh
Published: January 2015

This study focuses on interactions of vortices generated by a family of eddy-promoting upstream rectangular cylinders (of different heights a* and widths b*) with the shear layers of a downstream square cylinder (of height A*) placed near a plane in an in-line tandem arrangement under the incidence of Couette–Poiseuille flow based nonuniform linear/nonlinear velocity profile. The dimensionless operational parameters are cylinders spacing distance S, ratio of heights r2=a*/A* (≤1), aspect ratio r1=b*/a* (≤1), Reynolds number Re (based on the velocity at height A* for Couette flow), ReU2 (based on the velocity at height 10A* for Couette–Poiseuille flow), and nondimensional pressure gradient P at the inlet. The governing equations are solved numerically through a pressure-correction-based iterative algorithm (SIMPLE) with the quadratic upwind interpolation for convective kinematics (QUICK) scheme for convective terms. The major issue of appearing multiple peaks in the spectrum of the fluctuating lift coefficient of the downstream cylinder is addressed and justified exhibiting the flow patterns. While considering the rectangular shape (for the upstream cylinder) and nonlinear velocity (at the inlet), the possibility of generating the unsteadiness in the steady wake flow of the downstream cylinder at a Re (based on height a*) less than the critical Re for the downstream cylinder is documented here. The dependence of flow characteristics of the downstream cylinder on the angle of incident linear velocity at specific S and r1 is also demonstrated here. It is observed that the discontinuous jump in the aerodynamic characteristics (due to a sudden change from one distinct flow pattern to the other in the critical spacing distance regime) is directly proportional to the height of the vortex generator. Increasing P under the same characteristic velocity causes the steady flow of cylinder(s) to convert to a periodic flow and reduces the critical spacing distance for the vortex generator.
Running-Intensity Fluctuations in Elite Rugby Sevens Performance
Authors: Furlan Nicola , Waldron Mark , Shorter Kathleen , Gabbett Tim J. , Mitchell John , Fitzgerald Edward , Osborne Mark A. , Gray Adrian J.
Published: January 2015

Purpose:

To investigate temporal variation in running intensity across and within halves and evaluate the agreement between match-analysis indices used to identify fluctuations in running intensity in rugby sevens.

Methods:

Data from a 15-Hz global positioning system (GPS) were collected from 12 elite rugby sevens players during the IRB World Sevens Series (N = 21 full games). Kinematic (eg, relative distance [RD]) and energetic (eg, metabolic power [MP]) match-analysis indices were determined from velocity–time curves and used to investigate between-halves variations. Mean MP and RD were used to identify peak 2-minute periods of play. Adjacent 2-minute periods (prepeak and postpeak) were compared with peak periods to identify changes in intensity. MP and RD were expressed relative to maximal oxygen uptake (V̇O2max) and speed at V̇O2max, respectively, and compared in their ability to describe the intensity of peak periods and their temporal occurrence.

Results:

Small to moderate reductions were present for kinematic (RD; 8.9%) and energetic (MP; 6%) indices between halves. Peak periods (RD = 130 m/min, MP =13 W/kg) were higher (P < .001) than the match average (RD = 94 m/min, MP = 9.5 W/kg) and the prepeak and postpeak periods (P < .001). RD underestimated the intensity of peak periods compared with MP (bias 16%, limits of agreement [LoA] ± 6%). Peak periods identified by RD and MP were temporally dissociated (bias 21 s, LoA ± 212 s).

Conclusions:

The findings suggest that running intensity varies between and within halves; however, the index used will influence both the magnitude and the temporal identification of peak periods.
Investigating Strength and Range of Motion of the Hip Complex in Ice Hockey Athletes
Authors: Wilcox Christopher R.J. , Osgood Chad T. , White Hollie S.F. , Vince Rebecca V.
Published: January 2015

Context:

Ice hockey athletes frequently injure the hip complex via a noncontact mechanism. The authors investigated patterns of strength and range of motion (ROM) to establish major differences compared with soccer athletes. Soccer athletes were compared with ice hockey athletes due to similarities between the 2 sports with regard to the intermittent nature and high number of lower-limb injuries.

Objective:

To compare the differences in ROM and strength of the hip for both the dominant (Dom) and nondominant (Ndom) limbs in ice hockey and soccer athletes.

Design:

Case-control study.

Setting:

Bilateral ROM in hip flexion in sitting (FS) and lying (FL), extension, abduction, adduction, and internal rotation (IR) and external rotation (ER) were measured using a goniometer and assessed for strength using a handheld dynamometer on both the Dom and Ndom limbs.

Participants:

24 male, active, uninjured NCAA Division III ice hockey (16) and soccer (8) athletes.

Main Outcome Measures:

ROM and strength for hip FS, FL, extension, abduction, adduction, IR, and ER. A mixed-model ANOVA was used to investigate interactions and main effects.

Results:

Ice hockey athletes exhibited greater hip-adduction ROM than soccer athletes in the Dom leg (both P = .002) and when both limbs were combined (P = .010). Ice hockey athletes had less ROM in ER (P = .042) than soccer athletes. Ice hockey athletes displayed less strength in adduction in their Ndom leg than in their Dom leg (P = .02), along with less adduction than soccer players in their Ndom leg (P = .40). Ice hockey athletes displayed less strength in hip adduction (P = .030), FS (P = .023) and FL (P = .030) than soccer athletes.

Conclusions:

The findings suggest that ice hockey athletes may present an at-risk profile for noncontact hip injuries in comparison with soccer athletes with regard to strength and ROM of the hip.
Draft Genome Sequence of Marine Bacterium Streptomyces sp. Strain CNQ431, a Producer of the Cytokine Inhibitor Splenocin
Authors: Yu Mingjia , Dai Zheng , Qu Xudong , Gao Xu
Published: January 2015

Currently, corticosteroids are the most potent anti-inflammatory drugs on the market. Here, we announce the draft genome sequence of the marine-derived Streptomyces sp. strain CNQ431, which produces cytokine inhibitors, termed splenocins, which display potent suppression of cytokine production at a comparable level to that of corticosteroids. The genome is approximately 498,750 bp with 72.03% G+C content.
Improving Leishmania Species Identification in Different Types of Samples from Cutaneous Lesions
Authors: Cruz-Barrera Mónica L. , Ovalle-Bracho Clemencia , Ortegon-Vergara Viviana , Pérez-Franco Jairo E. , Echeverry Maria C.
Published: January 2015

The discrimination of
Leishmania
species from patient samples has epidemiological and clinical relevance. In this study, different gene target PCR-restriction fragment length polymorphism (RFLP) protocols were evaluated for their robustness as
Leishmania
species discriminators in 61 patients with cutaneous leishmaniasis. We modified the
hsp70
-PCR-RFLP protocol and found it to be the most reliable protocol for species identification.
Comparison of the Sofia and Veritor Direct Antigen Detection Assay Systems for Identification of Influenza Viruses from Patient Nasopharyngeal Specimens
Authors: Leonardi G. P. , Wilson A. M. , Mitrache I. , Zuretti A. R.
Published: January 2015

Influenza antigen detection assays (Sofia fluorescent immunoassay [FIA] and Veritor) yield objective results, which are potentially useful for point-of-care testing. The assays were evaluated with reverse transcriptase PCR (RT-PCR) using 411 nasopharyngeal swab specimens. Sensitivity and specificity values (percentages) of 79.0/99.0 and 64.0/99.4 for influenza A and 92.9/96.7 and 78.6/98.7 for influenza B were obtained for the Sofia and Veritor assays, respectively.
Efficient, Validated Method for Detection of Mycobacterial Growth in Liquid Culture Media by Use of Bead Beating, Magnetic-Particle-Based Nucleic Acid Isolation, and Quantitative PCR
Authors: Plain Karren M. , Waldron Anna M. , Begg Douglas J. , de Silva Kumudika , Purdie Auriol C. , Whittington Richard J.
Published: January 2015

Pathogenic mycobacteria are difficult to culture, requiring specialized media and a long incubation time, and have complex and exceedingly robust cell walls.
Mycobacterium avium
subsp.
paratuberculosis
(MAP), the causative agent of Johne's disease, a chronic wasting disease of ruminants, is a typical example. Culture of MAP from the feces and intestinal tissues is a commonly used test for confirmation of infection. Liquid medium offers greater sensitivity than solid medium for detection of MAP; however, support for the BD Bactec 460 system commonly used for this purpose has been discontinued. We previously developed a new liquid culture medium, M7H9C, to replace it, with confirmation of growth reliant on PCR. Here, we report an efficient DNA isolation and quantitative PCR methodology for the specific detection and confirmation of MAP growth in liquid culture media containing egg yolk. The analytical sensitivity was at least 10
4
-fold higher than a commonly used method involving ethanol precipitation of DNA and conventional PCR; this may be partly due to the addition of a bead-beating step to manually disrupt the cell wall of the mycobacteria. The limit of detection, determined using pure cultures of two different MAP strains, was 100 to 1,000 MAP organisms/ml. The diagnostic accuracy was confirmed using a panel of cattle fecal (
n
= 54) and sheep fecal and tissue (
n
= 90) culture samples. This technique is directly relevant for diagnostic laboratories that perform MAP cultures but may also be applicable to the detection of other species, including
M. avium
and
M. tuberculosis
.
Requirement for Chloride Channel Function during the Hepatitis C Virus Life Cycle
Authors: Igloi Zsofia , Mohl Bjorn-Patrick , Lippiat Jonathan D. , Harris Mark , Mankouri Jamel
Published: January 2015

Hepatocytes express an array of plasma membrane and intracellular ion channels, yet their role during the hepatitis C virus (HCV) life cycle remains largely undefined. Here, we show that HCV increases intracellular hepatic chloride (Cl
−
) influx that can be inhibited by selective Cl
−
channel blockers. Through pharmacological and small interfering RNA (siRNA)-mediated silencing, we demonstrate that Cl
−
channel inhibition is detrimental to HCV replication. This represents the first observation of the involvement of Cl
−
channels during the HCV life cycle.
Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses
Authors: Koel Björn F. , Mögling Ramona , Chutinimitkul Salin , Fraaij Pieter L. , Burke David F. , van der Vliet Stefan , de Wit Emmie , Bestebroer Theo M. , Rimmelzwaan Guus F. , Osterhaus Albert D. M. E. , Smith Derek J. , Fouchier Ron A. M. , de Graaf Miranda
Published: January 2015

The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiencyin vitrocompared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity.

IMPORTANCEInfluenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as a result of increasing population immunity. We show that single amino acid substitutions near the receptor binding site were sufficient to escape from antibodies specific for A(H1N1)pdm09 viruses but not from antibodies elicited in response to infections with seasonal A(H1N1) and A(H1N1)pdm09 viruses. This study identified substitutions in A(H1N1)pdm09 viruses that support escape from population immunity but also suggested that the number of potential escape variants is limited by previous exposure to seasonal A(H1N1) viruses.
Control of Hepatitis C Virus Replication in Mouse Liver-Derived Cells by MAVS-Dependent Production of Type I and Type III Interferons
Authors: Anggakusuma  , Frentzen Anne , Gürlevik Engin , Yuan Qinggong , Steinmann Eike , Ott Michael , Staeheli Peter , Schmid-Burgk Jonathan , Schmidt Tobias , Hornung Veit , Kuehnel Florian , Pietschmann Thomas
Published: January 2015

Hepatitis C virus (HCV) efficiently infects only humans and chimpanzees. Although the detailed mechanisms responsible for this narrow species tropism remain elusive, recent evidence has shown that murine innate immune responses efficiently suppress HCV replication. Therefore, poor adaptation of HCV to evade and/or counteract innate immune responses may prevent HCV replication in mice. The HCV NS3-4A protease cleaves human MAVS, a key cellular adaptor protein required for RIG-I-like receptor (RLR)-dependent innate immune signaling. However, it is unclear if HCV interferes with mouse MAVS function equally well. Moreover, MAVS-dependent signaling events that restrict HCV replication in mouse cells were incompletely defined. Thus, we quantified the ability of HCV NS3-4A to counteract mouse and human MAVS. HCV NS3-4A similarly diminished both human and mouse MAVS-dependent signaling in human and mouse cells. Moreover, replicon-encoded protease cleaved a similar fraction of both MAVS variants. Finally, FLAG-tagged MAVS proteins repressed HCV replication to similar degrees. Depending on MAVS expression, HCV replication in mouse liver cells triggered not only type I but also type III IFNs, which cooperatively repressed HCV replication. Mouse liver cells lacking both type I and III IFN receptors were refractory to MAVS-dependent antiviral effects, indicating that the HCV-induced MAVS-dependent antiviral state depends on both type I and III IFN receptor signaling.

IMPORTANCEIn this study, we found that HCV NS3-4A similarly diminished both human and mouse MAVS-dependent signaling in human and mouse cells. Therefore, it is unlikely that ineffective cleavage of mouse MAVSper seprecludes HCV propagation in immunocompetent mouse liver cells. Hence, approaches to reinforce HCV replication in mouse liver cells (e.g., by expression of essential human replication cofactors) should not be thwarted by the poor ability of HCV to counteract MAVS-dependent antiviral signaling. In addition, we show that mouse MAVS induces both type I and type III IFNs, which together control HCV replication. Characterization of type I or type III-dependent interferon-stimulated genes in these cells should help to identify key murine restriction factors that preclude HCV propagation in immunocompetent mouse liver cells.
Severe Acute Respiratory Syndrome Coronaviruses with Mutations in the E Protein Are Attenuated and Promising Vaccine Candidates
Authors: Regla-Nava Jose A. , Nieto-Torres Jose L. , Jimenez-Guardeño Jose M. , Fernandez-Delgado Raul , Fett Craig , Castaño-Rodríguez Carlos , Perlman Stanley , Enjuanes Luis , DeDiego Marta L.
Published: January 2015

Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a respiratory disease with a mortality rate of 10%. A mouse-adapted SARS-CoV (SARS-CoV-MA15) lacking the envelope (E) protein (rSARS-CoV-MA15-ΔE) is attenuatedin vivo. To identify E protein regions and host responses that contribute to rSARS-CoV-MA15-ΔE attenuation, several mutants (rSARS-CoV-MA15-E*) containing point mutations or deletions in the amino-terminal or the carboxy-terminal regions of the E protein were generated. Amino acid substitutions in the amino terminus, or deletion of regions in the internal carboxy-terminal region of E protein, led to virus attenuation. Attenuated viruses induced minimal lung injury, diminished limited neutrophil influx, and increased CD4+and CD8+T cell counts in the lungs of BALB/c mice, compared to mice infected with the wild-type virus. To analyze the host responses leading to rSARS-CoV-MA15-E* attenuation, differences in gene expression elicited by the native and mutant viruses in the lungs of infected mice were determined. Expression levels of a large number of proinflammatory cytokines associated with lung injury were reduced in the lungs of rSARS-CoV-MA15-E*-infected mice, whereas the levels of anti-inflammatory cytokines were increased, both at the mRNA and protein levels. These results suggested that the reduction in lung inflammation together with a more robust antiviral T cell response contributed to rSARS-CoV-MA15-E* attenuation. The attenuated viruses completely protected mice against challenge with the lethal parental virus, indicating that these viruses are promising vaccine candidates.

IMPORTANCEHuman coronaviruses are important zoonotic pathogens. SARS-CoV caused a worldwide epidemic infecting more than 8,000 people with a mortality of around 10%. Therefore, understanding the virulence mechanisms of this pathogen and developing efficacious vaccines are of high importance to prevent epidemics from this and other human coronaviruses. Previously, we demonstrated that a SARS-CoV lacking the E protein was attenuatedin vivo. Here, we show that small deletions and modifications within the E protein led to virus attenuation, manifested by minimal lung injury, limited neutrophil influx to the lungs, reduced expression of proinflammatory cytokines, increased anti-inflammatory cytokine levels, and enhanced CD4+and CD8+T cell countsin vivo, suggesting that these phenomena contribute to virus attenuation. The attenuated mutants fully protected mice from challenge with virulent virus. These studies show that mutations in the E protein are not well tolerated and indicate that this protein is an excellent target for vaccine development.
High Secretion of Interferons by Human Plasmacytoid Dendritic Cells upon Recognition of Middle East Respiratory Syndrome Coronavirus
Authors: Scheuplein Vivian A. , Seifried Janna , Malczyk Anna H. , Miller Lilija , Höcker Lena , Vergara-Alert Júlia , Dolnik Olga , Zielecki Florian , Becker Björn , Spreitzer Ingo , König Renate , Becker Stephan , Waibler Zoe , Mühlebach Michael D.
Published: January 2015

The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as the causative agent of a severe respiratory disease with a fatality rate of approximately 30%. The high virulence and mortality rate prompted us to analyze aspects of MERS-CoV pathogenesis, especially its interaction with innate immune cells such as antigen-presenting cells (APCs). Particularly, we analyzed secretion of type I and type III interferons (IFNs) by APCs, i.e., B cells, macrophages, monocyte-derived/myeloid dendritic cells (MDDCs/mDCs), and by plasmacytoid dendritic cells (pDCs) of human and murine origin after inoculation with MERS-CoV. Production of large amounts of type I and III IFNs was induced exclusively in human pDCs, which were significantly higher than IFN induction by severe acute respiratory syndrome (SARS)-CoV. Of note, IFNs were secreted in the absence of productive replication. However, receptor binding, endosomal uptake, and probably signaling via Toll-like receptor 7 (TLR7) were critical for sensing of MERS-CoV by pDCs. Furthermore, active transcription of MERS-CoV N RNA and subsequent N protein expression were evident in infected pDCs, indicating abortive infection. Taken together, our results point toward dipeptidyl peptidase 4 (DPP4)-dependent endosomal uptake and subsequent infection of human pDCs by MERS-CoV. However, the replication cycle is stopped after early gene expression. In parallel, human pDCs are potent IFN-producing cells upon MERS-CoV infection. Knowledge of such IFN responses supports our understanding of MERS-CoV pathogenesis and is critical for the choice of treatment options.

IMPORTANCEMERS-CoV causes a severe respiratory disease with high fatality rates in human patients. Recently, confirmed human cases have increased dramatically in both number and geographic distribution. Understanding the pathogenesis of this highly pathogenic CoV is crucial for developing successful treatment strategies. This study elucidates the interaction of MERS-CoV with APCs and pDCs, particularly the induction of type I and III IFN secretion. Human pDCs are the immune cell population sensing MERS-CoV but secrete significantly larger amounts of IFNs, especially IFN-α, than in response to SARS-CoV. A model for molecular virus-host interactions is presented outlining IFN induction in pDCs. The massive IFN secretion upon contact suggests a critical role of this mechanism for the high degree of immune activation observed during MERS-CoV infection.
Simian Retrovirus 4 Induces Lethal Acute Thrombocytopenia in Japanese Macaques
Authors: Yoshikawa Rokusuke , Okamoto Munehiro , Sakaguchi Shoichi , Nakagawa So , Miura Tomoyuki , Hirai Hirohisa , Miyazawa Takayuki
Published: January 2015

In 2001-2002, six of seven Japanese macaques (
Macaca fuscata
) died after developing hemorrhagic syndrome at the Kyoto University Primate Research Institute (KUPRI). While the cause of death was unknown at the time, we detected simian retrovirus 4 (SRV-4) in samples obtained from a similar outbreak in 2008-2011, during which 42 of 43 Japanese macaques died after exhibiting hemorrhagic syndrome. In this study, we isolated SRV-4 strain PRI-172 from a Japanese macaque showing severe thrombocytopenia. When inoculated into four Japanese macaques, the isolate induced severe thrombocytopenia in all within 37 days. We then constructed an infectious molecular clone of strain PRI-172, termed pSR415, and inoculated the clone-derived virus into two Japanese macaques. These animals also developed severe thrombocytopenia in just 31 days after inoculation, and the virus was reisolated from blood, bone marrow, and stool. At necropsy, we observed bleeding from the gingivae and subcutaneous bleeding in all animals. SRV-4 infected a variety of tissues, especially in digestive organs, including colon and stomach, as determined by real-time reverse transcription-PCR (RT-PCR) and immunohistochemical staining. Furthermore, we identified the SRV-4 receptor as ASCT2, a neutral amino acid transporter. ASCT2 mRNA was expressed in a variety of tissues, and the distribution of SRV-4 proviruses in infected Japanese macaques correlated well with the expression levels of ASCT2 mRNA. From these results, we conclude that the causative agent of hemorrhagic syndrome in KUPRI Japanese macaques was SRV-4, and its receptor is ASCT2.

IMPORTANCE
During two separate outbreaks at the KUPRI, in 2001-2002 and 2008-2011, 96% of Japanese macaques (JM) that developed an unknown hemorrhagic syndrome died. Here, we isolated SRV-4 from a JM developing thrombocytopenia. The SRV-4 isolate and a molecularly cloned SRV-4 induced severe thrombocytopenia in virus-inoculated JMs within 37 days. At necropsy, we observed bleeding from gingivae and subcutaneous bleeding in all affected JMs and reisolated SRV-4 from blood, bone marrow, and stool. The distribution of SRV-4 proviruses in tissues correlated with the mRNA expression levels of ASCT2, which we identified as the SRV-4 receptor. From these results, we conclude that SRV-4 was the causative agent of hemorrhagic syndrome in JMs in KUPRI.
Child malnutrition and the Millennium Development Goals: much haste but less speed?
Authors: Oruamabo Raphael S
Published: January 2015

The Millennium Development Goals (MDGs) provide a framework for measuring the progress of nations. Several of these goals relate to child malnutrition, which remains an important contributor to child morbidity and mortality, accounting for approximately 45% of child deaths globally. A high proportion of undernourished children still live in Africa and parts of Asia, and the uneven rate of reduction in the prevalence of various types of child malnutrition among different income groups worldwide is worrying. Attempts to reduce child malnutrition should therefore begin from the grassroots by improving primary healthcare services in developing countries with particular focus on basic requirements. Adequate nutrition should be provided from birth, through infancy, preschool and early childhood to adolescence. The overall strategy should be one of careful and meticulous planning involving all development sectors with an emphasis on a bottom-up approach within a stable and disciplined polity; the MDGs will be only be useful if they are seen not as narrow objectives with unidirectional interventions but as multifaceted and co-ordinated. The setting of deadlines, whether 2015 or 2035, should not be emphasised so as to avoid hasty decision making. The top priority should be the implementation of the essential social services of basic education, primary healthcare, nutrition, reproductive health care, water and sanitation in partnership with the developed economies.
Malaria and the Millennium Development Goals
Authors: Owens Stephen
Published: January 2015

Malaria, as a key disease of poverty, was singled out for special attention in the Millennium Project of 2000. Recent data suggest that malaria incidence and mortality are now declining all over the world. While these figures are cause for celebration, they must be interpreted carefully and with caution, particularly in relation to Africa. There are daunting challenges ahead for those working to achieve malaria eradication, not least of which is the poor quality of the data on which the work is based. In the absence of an affordable and fully effective vaccine, international funding for malaria control needs to be escalated still further. The money is essential to pay for universal access to a set of simple and proven interventions which would save the lives of millions of children over the next 15 years.
Millennium Development Goal 5 and adolescents: looking back, moving forward
Authors: Vogel Joshua P , Pileggi-Castro Cynthia , Chandra-Mouli Venkatraman , Pileggi Vicky Nogueira , Souza João Paulo , Chou Doris , Say Lale
Published: January 2015

Since the Millennium Declaration in 2000, unprecedented progress has been made in the reduction of global maternal mortality. Millennium Development Goal 5 (MDG 5; improving maternal health) includes two primary targets, 5A and 5B. Target 5A aimed for a 75% reduction in the global maternal mortality ratio (MMR), and 5B aimed to achieve universal access to reproductive health. Globally, maternal mortality since 1990 has nearly halved and access to reproductive health services in developing countries has substantially improved. In setting goals and targets for the post-MDG era, the global maternal health community has recognised that ultimate goal of ending preventable maternal mortality is now within reach. The new target of a global MMR of <70 deaths per 100 000 live births by 2030 is ambitious, yet achievable and to reach this target a significantly increased effort to promote and ensure universal, equitable access to reproductive, maternal and newborn services for all women and adolescents will be required. In this article, as we reflect on patterns, trends and determinants of maternal mortality, morbidity and other key MDG5 indicators among adolescents, we aim to highlight the importance of promoting and protecting the sexual and reproductive health and rights of adolescents as part of renewed global efforts to end preventable maternal mortality.
HIV and the Millennium Development Goals
Authors: Prendergast Andrew J , Essajee Shaffiq , Penazzato Martina
Published: January 2015

Millennium Development Goal (MDG) 6 has two HIV/AIDS commitments: to have halted and begun to reverse the spread of HIV/AIDS by 2015 and to ensure access to treatment among all those in need by 2010. Given the almost universal lack of access to HIV testing, prevention and treatment for children in high prevalence countries in 2000, the achievements of the past 15 years have been extraordinary, fuelled by massive donor investment, strong political commitment and ambitious global targets; however, MDG 6 is some way from being attained. Prevention of mother-to-child transmission (PMTCT) services have expanded enormously, with new infections among children falling by 58% between 2002 and 2013. There has been a shift towards initiation of lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women, although low HIV testing rates in pregnancy, suboptimal PMTCT coverage and poor retention in care remain barriers to achieving HIV elimination among children. Early infant diagnosis has expanded substantially but, in 2013, only 44% of all HIV-exposed infants were tested before 2 months of age. Diagnosis of HIV, therefore, frequently occurs late, leading to delays in ART initiation. By the end of 2013, approximately 760 000 children were receiving ART, leading to 40% decline in AIDS-related mortality. However, only 24% of HIV-infected children were receiving ART, compared with 36% of adults, leading to a ‘treatment gap’. In this review, we summarise progress and remaining challenges in reaching MDG 6 and discuss future strategies to achieve the ambitious goals of paediatric HIV elimination and universal access to treatment.
Advancing the newborn and stillbirth global agenda: priorities for the next decade
Authors: Darmstadt Gary L , Shiffman Jeremy , Lawn Joy E
Published: January 2015

Remarkable advances have been made over the past decade in defining the burden of newborn mortality and morbidity and stillbirths, and in identifying interventions to address the major risk factors and causes of deaths. However, progress in saving newborn lives and preventing stillbirths in countries lags behind that for maternal mortality and for children aged 1–59 months. To accelerate progress, greater focus is needed on improving coverage, quality and equity of care at birth—particularly obstetric care during labour and childbirth, and care for small and sick newborns, which gives a triple return on investment, reducing maternal and newborn lives as well as stillbirths. Securing national-level political priority for newborn health and survival and stillbirths, and implementation of the Every Newborn Action Plan are critical to accomplishing the unfinished global agenda for newborns and stillbirths beyond 2015.
Abolishing inequity, a necessity for poverty reduction and the realisation of child mortality targets
Authors: Målqvist Mats
Published: January 2015

The first Millennium Development Goal (MDG 1) due in 2015 concerns poverty reduction. It has been claimed to be fulfilled on a global level, but still more than 1 billion people are living in abject poverty. There is a strong link between the economy and child survival, and only a minority of countries will have reached the MDG target for child mortality reduction by 2015. This paper discusses the relationship between poverty and child survival. It argues that a focus on equity is necessary to further reduce child mortality, through poverty reduction in absolute terms and also through targeting interventions for increased child survival to disadvantaged populations. The political will to actually achieve real change for those in greatest need is crucial but not to be taken for granted, and the distribution rather than the generation of wealth needs to be made a priority in the post-MDG era.
An unusual swelling in the male perineum
Authors: Parnham Arie Stewart , Freeman Alex , Kirkham Alex , Muneer Asif
Published: January 2015

Median raphe cysts are a rare, congenital entity. We present a case and review the literature in respect to a 35-year-old man with a non-visible, painless midline swelling in the anterior perineum initially thought to be a liposarcoma. Subsequent histopathological examination confirmed a median raphe cyst.
Neurosarcoidosis-associated central diabetes insipidus masked by adrenal insufficiency
Authors: Non Lemuel , Brito Daniel , Anastasopoulou Catherine
Published: January 2015

Central diabetes insipidus (CDI) is an infrequent complication of neurosarcoidosis (NS). Its presentation may be masked by adrenal insufficiency (AI) and uncovered by subsequent steroid replacement. A 45-year-old woman with a history of NS presented 2 weeks after abrupt cessation of prednisone with nausea, vomiting, decreased oral intake and confusion. She was diagnosed with secondary AI and intravenous hydrocortisone was promptly begun. Over the next few days, however, the patient developed severe thirst and polyuria exceeding 6 L of urine per day, accompanied by hypernatraemia and hypo-osmolar urine. She was presumed to have CDI due to NS, and intranasal desmopressin was administered. This eventually normalised her urine output and serum sodium. The patient was discharged improved on intranasal desmopressin and oral prednisone. AI may mask the manifestation of CDI because low serum cortisol impairs renal-free water clearance. Steroid replacement reverses this process and unmasks an underlying CDI.
Increase in the oxidised low-density lipoprotein level by smoking and the possible inhibitory effect of statin therapy in patients with cardiovascular disease: a retrospective study
Authors: Ogawa Kazuo , Tanaka Toshikazu , Nagoshi Tomohisa , Sekiyama Hiroshi , Arase Satoshi , Minai Kosuke , Ogawa Takayuki , Yoshimura Michihiro
Published: January 2015

Objectives

Malondialdehyde-modified low-density lipoprotein (MDA-LDL) level is a marker of oxidative stress and is linked to progression of arteriosclerosis; however, the clinical factors affecting the oxidised LDL level have not been elucidated. We investigate various factors to identify correlation with MDA-LDL level in high-risk patients requiring catheter intervention.

Setting

Secondary care (cardiology), single-centre study.

Participants

600 patients who were admitted to our hospital and underwent cardiac catheterisation.

Primary and secondary outcome measures

Blood samples were obtained to measure lipid profiles and MDA-LDL level.

Results

With regard to smoking status, MDA-LDL level was significantly higher in ex-smokers/current smokers compared with non-smokers. Of note, there was no improvement of MDA-LDL level even in patients who had quit smoking. Multiple regression analysis showed that MDA-LDL level was positively correlated with LDL-cholesterol (LDL-C) level, Brinkman index and male gender. The correlation between smoking status and either MDA-LDL or LDL-C level was investigated in two groups: namely, patients with and patients without statin treatment. In the non-statin group, MDA-LDL level and MDA-LDL/LDL-C ratio were significantly higher in ex-smokers/current smokers compared with non-smokers, while no significant correlation was observed between smoking status and LDL-C level. In contrast, in the statin group, there were no significant correlations between smoking status and any of the cholesterol parameters.

Conclusions

We found that MDA-LDL level was affected by multiple factors, such as smoking status, LDL-C level and male gender. The present findings give additional evidence that smoking should be prohibited from a MDA-LDL standpoint. Furthermore, statin therapy might have a beneficial effect on the reduction of MDA-LDL level.
Confusion: delirium and dementia - a smartphone app to improve cognitive assessment
Authors: Sangha Selina , George J , Winthrop Craig , Panchal Sonia
Published: January 2015

Older patients with dementia and delirium are more prone to adverse events in hospital, but formal cognitive assessment to identify these vulnerable patients on admission is often not carried out by junior doctors. A smartphone app was created and provided on hospital wards to facilitate the use of standard cognitive assessments for delirium and dementia. Before the introduction of the app, 36% of patients over 75 years old were assessed cognitively. After the app, the percentage of cognitive assessments improved to 63%. Improvements in cognitive assessments were most marked after individual teaching of the doctors on the wards in the use of the app and on making the app available on the ward tablets. The results of the study suggest that the introduction of a smartphone app for junior doctors can improve performance in cognitive assessment of older people.
How unique is pure erythroid leukaemia? A retrospective analysis of seven cases and review of the literature
Authors: Wong Eric , Ling Victoria , Westerman David , Morgan Susan , Juneja Surender
Published: January 2015

Aims

Pure erythroid leukaemia (PEL) is a rare subtype of acute myeloid leukaemia (AML) and its clinicopathological features are not well-defined. The aim of this study was to describe the immunophenotypic, cytogenetic and clinical features of PEL and to compare these with cases of AML with ≥50% erythroblasts.

Methods

Cases of PEL according to WHO morphological criteria diagnosed at three institutions from 1997 to 2013 were included. A comparison cohort comprised of AML with ≥50% erythroblasts. The clinical, histopathology, immunophenotypic and cytogenetic features of cases were analysed. We also reviewed the existing literature on PEL, and combined our cohort with previously reported cases of PEL in a pooled analysis.

Results

There were seven cases of PEL diagnosed at our institutions. There was a high incidence of either prior chemoradiotherapy exposure or evolution from pre-existing myelodysplastic syndrome (MDS) (71%). The leukaemic blasts frequently expressed glycophorin C (100%), CD117 (83%) and were myeloperoxidase negative (83%). Complex karyotypes were present in 83% of cases. Median overall survival was 2.9 months. Compared with AML with ≥50% erythroblasts, cases of PEL demonstrated a higher incidence of adverse-risk cytogenetics (p=0.01) and prior exposure to chemoradiotherapy (p=0.01).

Conclusions

PEL appears to be a unique entity that is often secondary or therapy related, commonly features a complex karyotype and has a poor prognosis. It is morphologically and immunophenotypically distinct from other cases of AML with erythroid hyperplasia.
Effect of fluoxetine treatment on mitochondrial bioenergetics in central and peripheral rat tissues
Authors: da Silva Aline Isabel , Braz Glauber Ruda Feitoza , Silva-Filho Reginaldo , Pedroza Anderson Apolonio , Ferreira Diorginis Soares , Manhães de Castro Raul , Lagranha Claudia
Published: January 2015

Recent investigations have focused on the mitochondrion as a direct drug target in the treatment of metabolic diseases (obesity, metabolic syndrome). Relatively few studies, however, have explicitly investigated whether drug therapies aimed at changing behavior by altering central nervous system (CNS) function affect mitochondrial bioenergetics, and none has explored their effect during early neonatal development. The present study was designed to evaluate the effects of chronic treatment of newborn male rats with the selective serotonin reuptake inhibitor fluoxetine on the mitochondrial bioenergetics of the hypothalamus and skeletal muscle during the critical nursing period of development. Male Wistar rat pups received either fluoxetine (Fx group) or vehicle solution (Ct group) from the day of birth until 21 days of age. At 60 days of age, mitochondrial bioenergetics were evaluated. The Fx group showed increased oxygen consumption in several different respiratory states and reduced production of reactive oxygen species, but there was no change in mitochondrial permeability transition pore opening or oxidative stress in either the hypothalamus or skeletal muscle. We observed an increase in glutathione S-transferase activity only in the hypothalamus of the Fx group. Taken together, our results suggest that chronic exposure to fluoxetine during the nursing phase of early rat development results in a positive modulation of mitochondrial respiration in the hypothalamus and skeletal muscle that persists into adulthood. Such long-lasting alterations in mitochondrial activity in the CNS, especially in areas regulating appetite, may contribute to permanent changes in energy balance in treated animals.
Environment-specific and sex-specific allocation strategies among gonadal, somatic, and immune indices in a marine fish
Authors: Merrill Loren , Collins Peter M.
Published: January 2015

We examined the relative investment in somatic, gonadal, and liver growth, as well as a measure of immune function, in a marine species of fish (cabezon, Scorpaenichthys marmoratus (Ayres, 1854)) reared under different ambient temperature regimes (mean temperatures: 14.8 °C in Santa Barbara and 12.7 °C in Cayucos; both in California, USA). We predicted that fish reared in colder water would exhibit more pronounced trade-offs among growth, development, and immune parameters than fish in warmer water, and that females would have more pronounced trade-offs than males due to increased energy requirements for ovary development. We found immune function and liver investment were positively related in cold-water fish, but unrelated in warmer water fish. Immune function positively covaried with gonadal investment, but was not associated with somatic investment. Gonadal investment was negatively related to somatic investment, but this was driven by females, as there was no relationship between gonad development and somatic growth in males. We also found that the sexes differed in the relationship between gonadal and liver investments, in which females again exhibited a negative association but males exhibited a positive association. These results indicate that developmental investment strategies in cabezon are flexible and may be both context-specific and sex-specific.
Structure of the positive radial F-solutions of the Matukuma equation
Authors: Sha Yuanchen , Li Yi
Published: January 2015

Our emphasis in this paper lies on the study of the F-solutions (whose existence begins away from r = 0) of Matukuma equation. We describe the structure of F-solution of Matukuma equation by the method Yanagida used to investigate the E-solutions and the key of the investigation in this paper is Pohozaev identity. Here, we prove the uniqueness of F-solution with finite total mass, which make the structure of the F-solutions clear. At the end of this paper, we also give a generalization of Matukuma equation which can be settled by the same method.
A 10-Bit Column-Parallel Single Slope ADC Based on Two-Step TDC with Error Calibration for CMOS Image Sensors
Authors: Xu Jiangtao , Yu Jing , Huang Fujun , Nie Kaiming
Published: January 2015

This paper presents a 10-bit column-parallel single slope analog-to-digital converter (SS ADC) with a two-step time-to-digital converter (TDC) to overcome the long conversion time problem in conventional SS ADC for high-speed CMOS image sensors (CIS). The time interval proportional to the input signal is generated by a ramp generator and a comparator, which is digitized by a two-step TDC consisting of coarse and fine conversions to achieve a high-precision time-interval measurement. To mitigate the impact of propagation delay mismatch, a calibration circuit is also proposed to calibrate the delay skew within -T/2 to T/2. The proposed ADC is designed in 0.18 μm CMOS process. The power dissipation of each column circuit is 232 μW at supply voltages of 3.3 V for the analog circuits and 1.8 V for the digital blocks. The post simulation results indicate that the ADC achieves a SNDR of 60.89 dB (9.82 ENOB) and a SFDR of 79.98 dB at a conversion rate of 2 MS/s after calibration, while the SNDR and SFDR are limited to 41.52 dB and 67.64 dB, respectively before calibration. The differential nonlinearity (DNL) and integral nonlinearity (INL) without calibration are +15.80/-15.29 LSB and +1.68/-15.34 LSB while they are reduced down to +0.75/-0.25 LSB and +0.76/-0.78 LSB with the proposed calibration.
An alternative proof of doubly transitive property of a connected quandle of a prime order
Authors: Watanabe Taisuke
Published: January 2015

In this paper, we study doubly transitive property of a connected quandle of a prime order. In 2011, Ferman, Nowik and Teicher proved that the group of all quandle automorphisms of a connected quandle of a prime order acts sharply doubly transitively on itself. In this paper, we give a simple alternative proof.
MODELING CHOLERA DISEASE WITH EDUCATION AND CHLORINATION
Authors: AL-ARYDAH MO'TASSEM , MWASA ABUBAKAR , TCHUENCHE JEAN M. , SMITH? ROBERT J.
Published: January 2015

Cholera, characterized by severe diarrhea and rapid dehydration, is a water-borne infectious disease caused by the bacterium Vibrio cholerae. Haiti offers the most recent example of the tragedy that can befall a country and its people when cholera strikes. While cholera has been a recognized disease for two centuries, there is no strategy for its effective control. We formulate and analyze a mathematical model that includes two essential and affordable control measures: water chlorination and education. We calculate the basic reproduction number and determine the global stability of the disease-free equilibrium for the model without chlorination. We use Latin Hypercube Sampling to demonstrate that the model is most sensitive to education. We also derive the minimal effective chlorination period required to control the disease for both fixed and variable chlorination. Numerical simulations suggest that education is more effective than chlorination in decreasing bacteria and the number of cholera cases.
A VECTOR-BORNE DISEASE MODEL WITH VECTOR CONTROLLING AND VACCINATION
Authors: LI XUE-ZHI , WANG JUAN , SAUCEDO OMAR , WANG JIAO
Published: January 2015

In this paper, we formulate a vector-borne disease transmission model with a nonlinear incidence and vaccination. The explicit expression of the basic reproduction number R0(ϕ) which is related to the vaccination rate ϕ is obtained. It has been shown that the global dynamical behavior of the model is completely determined by R0(ϕ). If R0(ϕ) < 1, the disease-free equilibrium (DFE) is globally asymptotically stable, and the disease will be eradicated. If R0(ϕ) > 1, the DFE is unstable, and there exists a unique endemic equilibrium (EE). This equilibrium is globally asymptotically stable which in turn causes the disease to persist in vectors and humans. Finally, a series of numerical simulations, such as sensitive analysis on R0(ϕ), are performed in order to support the theoretical results.