bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical and Experimental Analysis of Added Resistance of Ships in Waves
Authors: Moctar Ould el , Sigmund Sebastian , Ley Jens , Schellin Thomas E.
Published: July 2016

Two Reynolds-Averaged Navier–Stokes (RANS) based field methods numerically predicted added resistance in regular head waves for a 14,000 TEU containership and a medium size cruise ship. Long and short waves of different frequencies were considered. Added resistance was decomposed into diffraction and radiation force components, whereby diffraction forces were obtained by restraining the ship in waves and radiation forces by prescribing the motions of the ship in calm water. In short waves, the diffraction part of total resistance was dominant as almost no ship motions were induced. In long waves, the sum of diffraction and radiation forces exceeded total resistance, i.e., the interaction of these two force components, which caused the reduction of total resistance, needed to be accounted for. Predictions were compared with model test measurements. Particular emphasis was placed on the following aspects: discretization errors, frictional resistance as part of total added resistance in waves, and diffraction and radiation components of added resistance in waves. Investigations comprised two steps, namely, a preliminary simulation to determine calm water resistance and a second simulation to compute total resistance in waves, always using the same grids. Added resistance was obtained by subtracting calm water resistance from total averaged wave resistance. When frictional resistance dominated over calm water resistance, which holds for nearly all conventional ships at moderate Froude numbers, high grid densities were required in the neighborhood surrounding the hull as well as prism cells on top of the model's surface.
Discussion: “Comparison of Statistical Methods for Assessing Spatial Correlations Between Maps of Different Arterial Properties” (Rowland, E. M., Mohamied, Y., Chooi, K. Y., Bailey, E. L., and Weinberg, P. D., 2015, ASME J. Biomech. Eng., 137(10), p. 101003): An Alternative Approach Using Segmentation Based on Local Hemodynamics
Authors: Himburg Heather A. , Grzybowski Deborah M. , Hazel Andrew L. , LaMack Jeffrey A. , Friedman Morton H.
Published: July 2016

The biological response of living arteries to mechanical forces is an important component of the atherosclerotic process and is responsible, at least in part, for the well-recognized spatial variation in atherosusceptibility in man. Experiments to elucidate this response often generate maps of force and response variables over the arterial surface, from which the force–response relationship is sought. Rowland et al. discussed several statistical approaches to the spatial autocorrelation that confounds the analysis of such maps and applied them to maps of hemodynamic stress and vascular response obtained by averaging these variables in multiple animals. Here, we point out an alternative approach, in which discrete surface regions are defined by the hemodynamic stress levels they experience, and the stress and response in each animal are treated separately. This approach, applied properly, is insensitive to autocorrelation and less sensitive to the effect of confounding hemodynamic variables. The analysis suggests an inverse relation between permeability and shear that differs from that in Rowland et al. Possible sources of this difference are suggested.
Mechanics of Fibrous Biological Materials With Hierarchical Chirality
Authors: Zhu Huijuan , Shimada Takahiro , Wang Jianshan , Kitamura Takayuki , Feng Xiqiao
Published: July 2016

Chirality simultaneously exists at different length scales in many biological materials, e.g., climbing tendrils and bacterial flagella. It can transfer from lower structural levels to higher structural levels, which is tightly associated with the growth and assembly of biological materials. In this paper, a continuum mechanics model is presented for understanding the bottom–up transfer of chirality in fibrous biological materials. Basic physical mechanisms underlying the chirality transfer in biological world are revealed. It is demonstrated that the chirality of constituent elements at the microscale can induce the twisting of higher-level structures, which may further transfer into the macroscopic morphology in different manners, rendering the formation of hierarchically chiral structures in tissues or organs. The bottom–up transfer mechanism of chirality may provide a limit to the macroscopic size of biological materials through the accumulative contribution of twisting.
Horizontal Inlets of Water Storage Tanks With Low Disturbance of Stratification
Authors: Gwerder Corsin , Lötscher Lukas , Podhradsky Jason , Kaufmann Matthias , Huggenberger Andreas , Boller Simon , Meier Boris , Mojic Igor , Haller Michel Y.
Published: July 2016

Solar combi-storages are used in many countries for storing solar heat for space heating and domestic hot water (DHW) in one device. When a combi-storage is used in combination with a heat pump, the temperature stratification efficiency of the storage is a decisive factor for the overall efficiency and thus, for the consumed end-energy of the system. In particular, fluid that is entering the storage with a high velocity may cause considerable mixing, thus, destroying stratification and leading to poor system performance. This work presents computational fluid dynamics (CFD) simulations of direct horizontal inlets at midheight of a typical solar combi-storage of about 800 L volume. Different inlet diffusor designs were simulated, and laboratory measurements were used to validate CFD experiments. For the given tank geometry, mass flow rates, and inlet position, it is found for a fluid inlet temperature of 30 °C that fluid velocities should be below 0.1 m/s and Reynolds numbers below 3000–5000 at the outlet of the diffusor in order to avoid the disturbance of a hotter 50 °C zone above the inlet. Furthermore, the fluid path within the diffusor must exceed a minimum length that corresponds to three to four times the hydraulic diameter of the diffusor.
A Case Study on the Influence of Selected Parameters on Microexplosion Behavior of Water in Biodiesel Emulsion Droplets
Authors: Yahaya Khan Mohammed , Abdul Karim Z. A. , Aziz A. Rashid A. , Tan Isa M.
Published: July 2016

Microexplosion behavior of water in biodiesel emulsion droplets was studied by suspending a single droplet on a wire type thermocouple. Water in biodiesel emulsion droplets with 9%, 12%, 15%, and 18% water by volume was observed in the Leiden frost regime using a hot plate as the heat source maintained at two different temperatures of 400 °C and 500 °C. The evolution of microexplosion was recorded with a high-speed camera synchronized with a temperature data logger. The emulsions were prepared by an electrical stirrer fitted with customized made blades rotating at 1500 rpm for 15 min. The emulsions were stabilized with two different hydrophilic–lipophilic balance (HLB) values, which were prepared by mixing two different commercial surfactants. It is found that the microexplosion time and temperature were influenced by emulsion stability, water content, surfactant dosage, base plate temperature, and HLB value. All the unstable emulsions developed microexplosion at both plate temperatures. Emulsions stabilized with an HLB value of 6.31 and 18% water content did exhibit microexplosion at both base plate temperatures. Also, the waiting time was found to decrease with increasing surfactant concentrations for a 500 °C plate temperature compared to 400 °C.
Plasma-modified nitric oxide-releasing polymer films exhibit time-delayed 8-log reduction in growth of bacteria
Authors: Mann Michelle N. , Neufeld Bella H. , Hawker Morgan J. , Pegalajar-Jurado Adoracion , Paricio Lindsey N. , Reynolds Melissa M. , Fisher Ellen R.
Published: July 2016

Tygon® and other poly(vinyl chloride)-derived polymers are frequently used for tubing in blood transfusions, hemodialysis, and other extracorporeal circuit applications. These materials, however, tend to promote bacterial proliferation which contributes to the high risk of infection associated with device use. Antibacterial agents, such as nitric oxide donors, can be incorporated into these materials to eliminate bacteria before they can proliferate. The release of the antimicrobial agent from the device, however, is challenging to control and sustain on timescales relevant to blood transport procedures. Surface modification techniques can be employed to address challenges with controlled drug release. Here, surface modification using H2O (v) plasma is explored as a potential method to improve the biocompatibility of biomedical polymers, namely, to tune the nitric oxide-releasing capabilities from Tygon films. Film properties are evaluated pre- and post-treatment by contact angle goniometry, x-ray photoelectron spectroscopy, and optical profilometry. H2O (v) plasma treatment significantly enhances the wettability of the nitric-oxide releasing films, doubles film oxygen content, and maintains surface roughness. Using the kill rate method, the authors determine both treated and untreated films cause an 8 log reduction in the population of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Notably, however, H2O (v) plasma treatment delays the kill rate of treated films by 24 h, yet antibacterial efficacy is not diminished. Results of nitric oxide release, measured via chemiluminescent detection, are also reported and correlated to the observed kill rate behavior. Overall, the observed delay in biocidal agent release caused by our treatment indicates that plasma surface modification is an important route toward achieving controlled drug release from polymeric biomedical devices.
Relationship between sound radiation from sound-induced and force-excited vibration: Analysis using an infinite elastic plate model
Authors: Yairi Motoki , Sakagami Kimihiro , Nishibara Kosuke , Okuzono Takeshi
Published: July 2016

Although sound radiation from sound-induced vibration and from force-excited vibration of solid structures are similar phenomena in terms of radiating from vibrating structures, the general relationship between them has not been explicitly studied to date. In particular, airborne sound transmission through walls and sound radiation from structurally vibrating surfaces in buildings are treated as different issues in architectural acoustics. In this paper, a fundamental relationship is elucidated through the use of a simple model. The transmission coefficient for random-incidence sound and the radiated sound power under point force excitation of an infinite elastic plate are both analyzed. Exact and approximate solutions are derived for the two problems, and the relationship between them is theoretically discussed. A conversion function that relates the transmission coefficient and radiated sound power is obtained in a simple closed form through the approximate solutions. The exact solutions are also related by the same conversion function. It is composed of the specific impedance and the wavenumber, and is independent of any elastic plate parameters. The sound radiation due to random-incidence sound and point force excitation are similar phenomena, and the only difference is the gradient of those characteristics with respect to the frequency.
A nudge toward participation: Improving clinical trial enrollment with behavioral economics
Authors: VanEpps Eric M. , Volpp Kevin G. , Halpern Scott D.
Published: July 2016

Interventions informed by behavioral economics can address barriers to patient enrollment in clinical trials and improve recruitment efforts.
Deciphering the Principles of Bacterial Nitrogen Dietary Preferences: a Strategy for Nutrient Containment
Authors: Wang Jilong , Yan Dalai , Dixon Ray , Wang Yi-Ping
Published: July 2016

A fundamental question in microbial physiology concerns why organisms prefer certain nutrients to others. For example, among different nitrogen sources, ammonium is the preferred nitrogen source, supporting fast growth, whereas alternative nitrogen sources, such as certain amino acids, are considered to be poor nitrogen sources, supporting much slower exponential growth. However, the physiological/regulatory logic behind such nitrogen dietary choices remains elusive. In this study, by engineering
Escherichia coli
, we switched the dietary preferences toward amino acids, with growth rates equivalent to that of the wild-type strain grown on ammonia. However, when the engineered strain was cultured together with wild-type
E. coli
, this growth advantage was diminished as a consequence of ammonium leakage from the transport-and-catabolism (TC)-enhanced (TCE) cells, which are preferentially utilized by wild-type bacteria. Our results reveal that the nitrogen regulatory (Ntr) system fine tunes the expression of amino acid transport and catabolism components to match the flux through the ammonia assimilation pathway such that essential nutrients are retained, but, as a consequence, the fast growth rate on amino acids is sacrificed.

IMPORTANCE
Bacteria exhibit different growth rates under various nutrient conditions. These environmentally related behaviors reflect the coordination between metabolism and the underlying regulatory networks. In the present study, we investigated the intertwined nitrogen metabolic and nitrogen regulatory systems to understand the growth differences between rich and poor nitrogen sources. Although maximal growth rate is considered to be evolutionarily advantageous for bacteria (as remarked by François Jacob, who said that the “dream” of every cell is to become two cells), we showed that negative-feedback loops in the regulatory system inhibit growth rates on amino acids. We demonstrated that in the absence of regulatory feedback, amino acids are capable of supporting fast growth rates, but this results in ammonia leaking out from cells as “waste,” benefiting the growth of competitors. These findings provide important insights into the regulatory logic that controls metabolic flux and ensures nutrient containment but consequently sacrifices growth rate.
Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the
Coxiella
-Containing Vacuole
Authors: Kohler Lara J. , Reed Shawna R. , Sarraf Shireen A. , Arteaga David D. , Newton Hayley J. , Roy Craig R.
Published: July 2016

Coxiella burnetii
replicates in an acidified lysosome-derived vacuole. Biogenesis of the
Coxiella
-containing vacuole (CCV) requires bacterial effector proteins delivered into host cells by the Dot/Icm secretion system. Genetic and cell biological analysis revealed that an effector protein called Cig2 promotes constitutive fusion of autophagosomes with the CCV to maintain this compartment in an autolysosomal stage of maturation. This distinguishes the CCV from other pathogen-containing vacuoles that are targeted by the host autophagy pathway, which typically confers host resistance to infection by delivering the pathogen to a toxic lysosomal environment. By maintaining the CCV in an autolysosomal stage of maturation, Cig2 enabled CCV homotypic fusion and enhanced bacterial virulence in the
Galleria mellonella
(wax moth) model of infection by a mechanism that decreases host tolerance. Thus,
C. burnetii
residence in an autolysosomal organelle alters host tolerance of infection, which indicates that Cig2-dependent manipulation of a lysosome-derived vacuole influences the host response to infection.

IMPORTANCE
Coxiella burnetii
is an obligate, intracellular bacterial pathogen that replicates inside a unique, lysosome-like compartment called the
Coxiella
-containing vacuole (CCV). Over 130 bacterial effector proteins are delivered into the host cell cytosol by the
C. burnetii
Dot/Icm type IV secretion system. Although the Dot/Icm system is essential for pathogenesis, the functions of most effectors remain unknown. Here we show that the effector protein Cig2 is essential for converting the CCV to an organelle that is similar to the autolysosome. Cig2 function promotes constitutive fusion between the CCV and autophagosomes generated by selective autophagy. Cig2-directed biogenesis of an autolysosomal vacuole is essential for the unique fusogenic properties of the CCV and for virulence in an animal model of disease. This work highlights how bacterial subversion of the host autophagy pathway can influence the cell biological properties of the CCV and influence the host response to infection.
16S rRNA Amplicon Sequencing for Epidemiological Surveys of Bacteria in Wildlife
Authors: Galan Maxime , Razzauti Maria , Bard Emilie , Bernard Maria , Brouat Carine , Charbonnel Nathalie , Dehne-Garcia Alexandre , Loiseau Anne , Tatard Caroline , Tamisier Lucie , Vayssier-Taussat Muriel , Vignes Helene , Cosson Jean-François
Published: July 2016

Several recent public health crises have shown that the surveillance of zoonotic agents in wildlife is important to prevent pandemic risks. High-throughput sequencing (HTS) technologies are potentially useful for this surveillance, but rigorous experimental processes are required for the use of these effective tools in such epidemiological contexts. In particular, HTS introduces biases into the raw data set that might lead to incorrect interpretations. We describe here a procedure for cleaning data before estimating reliable biological parameters, such as positivity, prevalence, and coinfection, using 16S rRNA amplicon sequencing on an Illumina MiSeq platform. This procedure, applied to 711 rodents collected in West Africa, detected several zoonotic bacterial species, including some at high prevalence, despite their never before having been reported for West Africa. In the future, this approach could be adapted for the monitoring of other microbes such as protists, fungi, and even viruses.
Persistent slip rate discrepancies in the eastern California (USA) shear zone
Authors: Evans Eileen L. , Thatcher Wayne R. , Pollitz Fred F. , Murray Jessica R.
Published: July 2016

Understanding fault slip rates in the eastern California shear zone (ECSZ) using GPS geodesy is complicated by potentially overlapping strain signals due to many sub-parallel strike-slip faults and by inconsistencies with geologic slip rates. The role of fault system geometry in describing ECSZ deformation may be investigated with total variation regularization, which algorithmically determines a best-fitting geometry from an initial model with numerous faults, constrained by a western United States GPS velocity field. The initial dense model (1) enables construction of the first geodetically constrained block model to include all ECSZ faults with geologic slip rates, allowing direct geologic-geodetic slip rate comparisons, and (2) permits fault system geometries with many active faults that are analogous to distributed interseismic deformation. Beginning with 58 ECSZ blocks, a model containing 10 ECSZ blocks is most consistent with geologic slip rates, reproducing five of 11 within their reported uncertainties. The model fits GPS observations with a mean residual velocity of 1.5 mm/yr. Persistent geologic-geodetic slip rate discrepancies occur on the Calico and Garlock faults, on which we estimate slip rates of 7.6 mm/yr and <2 mm/yr, respectively, indicating that inconsistencies between geology and geodesy may be concentrated on or near these faults and are not due to pervasive distributed deformation in the region. Discrepancies may in part be due to postseismic relaxation following the A.D. 1992 Mw 7.3 Landers and 1999 Mw 7.1 Hector Mine earthquakes. Otherwise, resolving geologic-geodetic discrepancies would require as much as 11.4 mm/yr of off-fault deformation within <10 km of the main ECSZ faults, with ∼5 mm/yr concentrated near the Calico fault.
Avulsion flow-path selection on rivers in foreland basins
Authors: Edmonds Douglas A. , Hajek Elizabeth A. , Downton Nic , Bryk Alexander B.
Published: July 2016

River avulsions help distribute sediment across the floodplain, and the frequency and flow path selected by each avulsion determines flooding and sedimentation patterns. However, rivers avulse infrequently, making it difficult to quantify flow-path behavior and test hypotheses posed by experimental and numerical studies. We used Google Earth Engine to create a novel data set of 55 avulsions that occurred from A.D. 1984 to 2014 in the Andean and Himalayan foreland basins. On each avulsion we measure hop length (the displacement of the avulsion across the floodplain orthogonal to the parent channel) and avulsion length (the length of the parent channel reach). Without controlling for external factors, such as climate or geology, we find that both hop length and avulsion length scale with parent channel-belt width. Avulsion channels tend to hop 2.5 channel-belt widths away from their parent channel and avulsion length is 13.4 parent channel-belt widths. We use these data to test between end-member scenarios where flow paths are randomly selected or steered by floodplain topography. Observed avulsions are inconsistent with flow-path predictions derived from a directed random walk model, and a scaling analysis of alluvial ridge size shows that hop lengths are set by alluvial ridge widths. These results suggest that avulsion flow-path selection in the Andean and Himalayan basins is driven by alluvial ridge topography, which promotes evenly spaced (or compensational) channel sand bodies over decadal time scales. These data and results are important for understanding controls on avulsion flow-path selection and how avulsion processes are represented in the stratigraphic record of foreland basins.
Parathyroid adenoma arising within the sternocleidomastoid muscle: a rare complication of autotransplantation
Authors: Touska Philip , Srikanthan Ahgi , Amarasinghe Kavita , Jawad Susan
Published: July 2016

A 19-year-old patient presented with slowly enlarging, painless, left-sided cervical mass. She had a background of multiple endocrine neoplasia 2B and had undergone a total thyroidectomy for medullary thyroid carcinoma during childhood. A cervical recurrence was therefore suspected. Ultrasonographic and MRI examination revealed a well-defined lesion within the left sternocleidomastoid muscle. Further evaluation with sestamibi and single-photon emission CT revealed elevated tracer uptake within the lesion. Cytological analysis, following ultrasound-guided sampling, revealed absent staining for calcitonin and blood samples confirmed a normal serum calcitonin level; however, the serum parathyroid hormone level was elevated. Overall, summative findings were consistent with a diagnosis of a parathyroid adenoma arising within the left sternocleidomastoid muscle. Given that this is not a location for a physiological parathyroid tissue, the adenoma might have arisen within the autotransplanted parathyroid tissue, injected into the muscular sheath during thyroidectomy. The clinical, radiological and pathological features are considered in this article.
Separate origins of the left internal and external carotid arteries from the aortic arch and cervical internal carotid artery aneurysm in a patient with Noonan syndrome
Authors: Tahir Rizwan Ahmad , Asmaro Karam , Pabaney Aqueel , Kole Max , Nypaver Timothy , Marin Horia
Published: July 2016

Distinct origins of the external carotid artery and the internal carotid artery (ICA) from the aortic arch have been rarely described, and represent an aberrant development of the aortic arches during fetal life. This anatomical variation is usually discovered incidentally; infrequently, an aneurysm of the cervical ICA might accompany this rare configuration. We describe one such case in a patient with Noonan syndrome who presented with pulsatile neck mass. The diagnostic features and management of the aneurysm and a review of the literature are presented.
Unusual presentation of disseminatedNocardia abscessusinfection in a patient with AIDS
Authors: Sherbuk Jacqueline , Saly Danielle , Barakat Lydia , Ogbuagu Onyema
Published: July 2016

A 40-year-old man with AIDS presented with symptoms of a chronic cough, subacute headache, generalised weakness with falls, urinary and faecal incontinence, and acute onset subcutaneous nodules. A chest CT scan showed multiple cavitary and nodular pulmonary infiltrates. MRI of his brain and spinal cord revealed innumerable ring-enhancing lesions. Pathological examination of the purulent material obtained from his subcutaneous lesions, as well as transbronchial tissue specimens obtained by biopsy, revealed beaded and branching Gram-positive rods, subsequently identified by 16S RNA sequencing to beNocardia abscessusspecies. We observed an excellent therapeutic response to a combination antimicrobial therapy with resolution of the subcutaneous, pulmonary and central nervous system (CNS) lesions. Infections caused byN. abscessusare rare and typically occur in immunocompromised patients. In this article, we will review the presentation, diagnosis and treatment ofN. abscessusinfection.
Drug fever induced by piperacillin/tazobactam in an elderly patient with underlying human immunodeficiency virus (HIV) infection
Authors: Swe Thein , Ali Mir , Naing Akari Thein
Published: July 2016

Our search of the literature revealed no detailed case reports about drug fever induced by piperacillin/tazobactam in a patient with HIV infection although there were a few case reports about drug fever due to piperacillin/tazobactam with other comorbidities. A 63-year-old male patient with HIV positive was admitted for acute cholecystitis. He was started on piperacillin/tazobactam. For the next 8 days, he had intermittent fever up to 103°F (39.4°C) with relative bradycardia although he showed clinical improvement. There was no laboratory or imaging findings suggestive of another infectious source and drug fever was suspected. The antibiotics were stopped and after 48 hours no fever was observed until the day of discharge. Piperacillin/tazobactam can induce fever in patients with cystic fibrosis and in patients with other conditions. Drug fever may be more prevalent in patients with HIV infection. It has no characteristic pattern and may not be associated with eosinophilia.
Liraglutide improved glycaemic instability in a patient with diabetes with insulin antibodies
Authors: Kato Takehiro , Iizuka Katsumi , Niwa Hiroyuki , Takeda Jun
Published: July 2016

Insulin antibodies sometimes cause glucose instability. A 52-year-old male patient was admitted to our department for the treatment of diabetes mellitus. From October 2003, he received insulin treatment for autoimmune pancreatitis and diabetes mellitus, but his hemoglobin A1c (HbA1c) levels gradually reached 8.0% (64 mmol/mol IFCC). In January 2010, insulin glargine and insulin aspart were introduced. In April 2010, the insulin antibody titre rose to >13.6 U/mL. In July 2010, treatment was changed to insulin glargine, metformin and miglitol. In November 2011, a further change to insulin glargine, metformin and sitagliptin was made. The insulin antibody titres gradually decreased, but HbA1c levels remained high. In November 2014, liraglutide and insulin glargine were introduced and the HbA1c levels decreased dramatically to ∼7.5% (58 mmol/mol IFCC) despite increasing insulin antibody titres (from 32.6 to >50.0 U/mL). Liraglutide successfully improved glycaemic instability due to insulin antibodies without modulating plasma insulin levels.
Suspected autoimmune myocarditis and cardiac conduction abnormalities with nivolumab therapy for non-small cell lung cancer
Authors: Gibson Robert , Delaune Jess , Szady Anita , Markham Merry
Published: July 2016

Checkpoint inhibitors such as nivolumab represent a novel class of agents that are being increasingly used in the treatment of various cancers. Their toxicities represent unique challenges to the oncologists prescribing them, patients' primary care physicians and other specialists who may encounter these patients during consultations. It is important for physicians to remain vigilant and include autoimmune toxicities in the list of potential differential diagnoses in patients receiving novel cancer therapeutics who present with unusual toxicities. We report the unusual case of a 68-year-old woman with advanced lung cancer on the novel chemotherapeutic Nivolumab whom we suspect developed autoimmune myocarditis with significant cardiac conduction disease as an unintended, and as of yet unrecognised, side effect from this medication.
Non-haemorrhagic, bilateral adrenal infarction in a patient with antiphospholipid syndrome along with lupus myocarditis
Authors: Batt Nicholas Marinus , Malik Dean , Harvie Miranda , Sheth Hemant
Published: July 2016

A 40-year-old woman with antiphospholipid syndrome presented with a 5-day history of right upper quadrant (RUQ) pain, radiating posteriorly, associated with fever and vomiting. She was admitted 1-week prior with an upper respiratory infection and erythema multiforme. Clinical assessment revealed sepsis with RUQ tenderness and positive Murphy's sign. Laboratory results showed raised inflammatory markers, along with renal and liver impairment. CT showed bilateral adrenal infarction and inferior vena cava thrombus. The patient was managed for sepsis and started on heparin. Further immunological investigations revealed a diagnosis of systemic lupus erythematous, an exacerbation of which culminated in lupus myocarditis. This case illustrates the importance of promptly recognising adrenal insufficiency in patients with antiphospholipid syndrome and the possible causative agents, which require careful consideration and exclusion to prevent further thrombotic events. It also highlights the importance of undertaking imaging, namely CT, in patients with antiphospholipid syndrome presenting with abdominal pain as well as considering concomitant autoimmune conditions.
Severe perianal shingles during azathioprine and budesonide treatment for Crohn's disease—preventable with zoster vaccine?
Authors: Elliott Timothy Ross , Miller Charles , Macrae Finlay A
Published: July 2016

Patients with inflammatory bowel disease (IBD), particularly those on immunosuppressive medications, suffer a high incidence of, and worse clinical outcomes relating to, herpes zoster (HZ) reactivation. We report on the presentation and management of a patient with Crohn's disease who developed severe perianal HZ after starting azathioprine and oral budesonide treatment. The zoster vaccine may prevent such zoster reactivation in patients with IBD. The zoster vaccine is effective in decreasing the risk of HZ in older adults but its role in younger adults and those with IBD has not been tested prospectively. A review of the potential risks and benefits of this live vaccine in patients with IBD and an approach to further determining its role in this patient population is discussed.
European multicentre double-blind placebo-controlled trial of Nilvadipine in mild-to-moderate Alzheimer's disease—the substudy protocols: NILVAD frailty; NILVAD blood and genetic biomarkers; NILVAD cerebrospinal fluid biomarkers; NILVAD cerebral blood flow
Authors: Meulenbroek Olga , O'Dwyer Sarah , de Jong Daan , van Spijker Gerrita , Kennelly Sean , Cregg Fiona , Olde Rikkert Marcel , Abdullah Laila , Wallin Anders , Walsh Cathal , Coen Robert , Kenny Rose Anne , Daly Leslie , Segurado Ricardo , Borjesson-Hanson Anne , Crawford Fiona , Mullan Michael , Lucca Ugo , Banzi Rita , Pasquier Florence , Breuilh Laetitia , Riepe Matthias , Kalman Janos , Molloy William , Tsolaki Magda , Howard Robert , Adams Jessica , Gaynor Siobhan , Lawlor Brian
Published: July 2016

Introduction

In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer's disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol was previously published inBMJ Open(2014). The objectives of the NILVAD substudies are to determine whether frailty, cerebrospinal fluid (CSF), blood biomarker profile and Apolipoprotein E (APOE) status predict response to Nilvadipine, and to investigate the effect of Nilvadipine on cerebral blood flow and blood biomarkers.

Methods and analysis

All participants who fulfil criteria for the main NILVAD study are eligible for participation in the NILVAD substudies. Participation is subject to informed consent and whether the substudy is available at a particular NILVAD study site. Each substudy entails extra measurements during the course of the main NILVAD study. For example, in the blood and genetic biomarkers substudy, extra blood (30 mL) will be collected at week 0, week 13, week 52 and week 78, while in the cerebral blood flow substudy, participants will receive an MRI and transcranial Doppler measurements at week 0, week 26 and week 78. In the CSF substudy, 10 mL CSF is collected at week 0 and week 78.

Ethics and dissemination

All NILVAD substudies and all subsequent amendments have received ethical approval within each participating country, according to national regulations. Each participant provides written consent to participate. All participants remain anonymised throughout and the results of each substudy will be published in an international peer reviewed journal.

Trial registration number

EUDRACT 2012-002764-27; Pre-results.
Evaluation of a heat warning system in Adelaide, South Australia, using case-series analysis
Authors: Nitschke Monika , Tucker Graeme , Hansen Alana , Williams Susan , Zhang Ying , Bi Peng
Published: July 2016

Background

Heatwave warning systems aim to assist in reducing health effects during extreme heat. Evaluations of such systems have been limited. This study explored the effect of a heatwave warning programme on morbidity and mortality in Adelaide, South Australia, by comparing extreme events in 2009 and 2014, the latter with exposure to the preventive programme.

Methods

The health outcomes during the two heatwaves were compared using the incidence rate ratios (IRRs) of daily ambulance call-outs, emergency presentations and mortality data during the heatwaves compared with non-heatwave periods during the warm seasons. Excess or reduced numbers of cases were calculated and the differences in cases between the two heatwaves were estimated.

Results

IRRs for total ambulance call-outs and emergency presentations were lower during the 2014 heatwaves compared with the 2009 event. The estimated differences in health-specific outcomes between 2009 and 2014 were statistically significant with 207 (59%) for cardiac-related call-outs, 134 (30%) for renal and 145 (56%) for heat-related emergency presentations. Mortality was not reduced in 2014. There were an estimated 34.5 excess deaths in 2009 and 38.2 in 2014.

Conclusions

Morbidity outcomes were reduced significantly during the 2014 event. The fact that cardiac, renal and heat-related diagnoses were significantly reduced is likely to be associated with the intervention in 2014, which comprised a public warning through media and intense preventive measures directed to individual populations at risk. Further analysis of risk factors of mortality during heatwaves should be explored.
BET 1: Safety and efficacy of colchicine as stand-alone therapy for the prevention of recurrent pericarditis
Authors: Manspeaker Andrew , Andrews-Dickert Rebecca
Published: July 2016

A short cut review was carried out looking for evidence of the benefits of using colchicine as a single therapy for acute pericarditis. A literature search was performed but no papers were found to provide evidence of the efficacy of colchicine without the concurrent use of Non-steriodal anti-inflammatory drugs (NSAIDs) for this condition.
Cognitive and motor abilities of young children and risk of injuries in the home
Authors: Ehrhardt Jennifer , Xu Yingying , Khoury Jane , Yolton Kimberly , Lanphear Bruce , Phelan Kieran
Published: July 2016

Objective

Residential injury is a leading cause of morbidity and mortality in US children. Rates and types of injury vary by child age but little is known about injury risk based on child cognitive and motor abilities. The objective of this study was to determine whether cognitive or motor development in young children is associated with residential injury.

Methods

We employed data from Health Outcomes and Measures of the Environment (HOME) Study. Parent report of medically attended injury was obtained at regular intervals from 0 to 42 months. Child development was assessed at 12, 24 and 36 months using Bayley Scales of Infant and Toddler Development, 2nd edition, which generates both mental developmental index (MDI) and a psychomotor developmental index (PDI). Injury risk was modelled using multivariable logistic regression as function of child's MDI or PDI. Effects of MDI and PDI on injury risk were examined separately and jointly, adjusting for important covariates.

Results

Children with cognitive delay (MDI <77) were at significantly higher risk of injury than children without cognitive delay (OR=3.7, 95% CI 1.4 to 10.5, p=0.012). There was no significant association of PDI with injury. There was, however, significant interaction of MDI and PDI (p=0.02); children with cognitive delay but normal motor development were at significantly higher risk of injury than children with normal cognitive and motor development (OR=9.6, 95% CI 2.6 to 35.8, p=0.001).

Conclusions

Children with cognitive delays, especially those with normal motor development, are at elevated risk for residential injuries. Injury prevention efforts should target children with developmental delays.

Clinical trials number

NCT00129324; post-results.
Assessment of direct versus indirect magnetic bead-based T-cell isolation procedures followed by magnetic bead-based DNA isolation
Authors: Rosenbaum Anna , Bleck Ellen , Schneider Matthias , Pongratz Georg , Vordenbäumen Stefan
Published: July 2016

Objective

To compare direct and indirect bead-based T-cell isolation followed by magnetic bead-based DNA isolation.

Methods

T-cells were isolated by direct or indirect selection with magnetic bead coated antbiodies followed by magnetic bead-based automated DNA isolation in 10 healthy subjects. Purity of T-cells, purity of DNA (by A260/A280 ratio measurement) and DNA concentration were assessed.

Results

Direct and indirect labelling resulted in comparable T-cell purity (93.11±1.47% vs. 94.99±1.54%, p= 0.125) and DNA concentration per cell (50.97±14.15 ng/(mlxcell) vs. 49.53±13.62 ng/(mlxcell), p=0.492), while DNA purity was significantly higher after direct labelling (1.82±0.05 vs. 1.78±0.03, p=0.0488).

Conclusions

Both direct and indirect magnetic bead-based T-cell selection may be used prior to magnetic bead-based DNA isolation procedures.
Republished: Delayed subarachnoid hemorrhage 7 years after cerebellar infarction from traumatic vertebral artery dissection
Authors: Silva Michael A , See Alfred P , Khandelwal Priyank , Patel Nirav J , Aziz-Sultan Mohammad Ali
Published: July 2016

Vertebral artery dissection (VAD) is an important cause of ischemic stroke and subarachnoid hemorrhage (SAH). Dissections presenting with ischemia rarely cause SAH after more than a few hours, especially without radiographic evidence of pseudoaneurysm. We successfully treated a patient for persistent vessel injury presenting with SAH 7 years after presenting with extracranial subocclusive dissection of the right vertebral artery and an associated right posterior inferior cerebellar artery stroke. This is one of only three reported cases of delayed SAH occurring more than 2 weeks after an initial ischemic presentation of a VAD, and the only one without radiographic evidence of pseudoaneurysm at standard follow-up duration.
Long-term efficiency of infliximab in patients with ankylosing spondylitis: real life data confirm the potential for dose reduction
Authors: Baraliakos X , Heldmann F , van den Bosch F , Burmester G , Gaston H , van der Horst-Bruinsma I E , Krause A , Schmidt R , Schneider M , Sieper J , Andermann B , van Tubergen A , Witt M , Braun J
Published: July 2016

Objective

To analyse the treatment outcome of patients with ankylosing spondylitis (AS) in the European AS infliximab cohort (EASIC) study after a total period of 8 years with specific focus on dosage and the duration of intervals between infliximab infusions.

Methods

EASIC included patients with AS who had received infliximab for 2 years as part of the ASSERT trial. After that period, rheumatologists were free to change the dose or the intervals of infliximab. Clinical data were status at baseline, end of ASSERT and for a total of 8 years of follow-up.

Results

Of the initially 71 patients with AS from EASIC, 55 patients (77.5%) had completed the 8th year of anti-tumour necrosis factor (TNF) treatment. Of those, 48 patients (87.3%) still continued on infliximab. The mean infusion interval increased slightly from 6 to 7.1±1.5 weeks, while 45.8% patients had increased the intervals up to a maximum of 12 weeks. The mean infliximab dose remained stable over time, with a minimum of 3.1 mg/kg and a maximum of 6.4 mg/kg. In patients receiving <5 mg/kg infliximab, the mean infusion interval increased to 7.0±1.2 weeks. In total, the mean cumulative dose per patient and per year decreased from 3566.30 to 2973.60 mg.

Conclusions

We could observe that over a follow-up of 8 years of treatment with infliximab, >85% patients still remained on the same treatment, without any major safety events. Furthermore, both the infusion intervals and also the mean infliximab dose were modestly reduced in ≥70% of the patients without the loss of clinical efficiency.
Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines
Authors: Howard Tripp Nadia , Tarn Jessica , Natasari Andini , Gillespie Colin , Mitchell Sheryl , Hackett Katie L , Bowman Simon J , Price Elizabeth , Pease Colin T , Emery Paul , Lanyon Peter , Hunter John , Gupta Monica , Bombardieri Michele , Sutcliffe Nurhan , Pitzalis Costantino , McLaren John , Cooper Annie , Regan Marian , Giles Ian , Isenberg David A , Saravanan Vadivelu , Coady David , Dasgupta Bhaskar , McHugh Neil , Young-Min Steven , Moots Robert , Gendi Nagui , Akil Mohammed , Griffiths Bridget , Lendrem Dennis W , Ng Wan-Fai
Published: July 2016

Objectives

This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS).

Methods

Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels.

Results

14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines—interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)—were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy.

Conclusions

Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.
Dietary assessment is a critical element of health research – Perspective from the Partnership for Advancing Nutritional and Dietary Assessment in Canada
Authors: Labonté Marie-Ève , Kirkpatrick Sharon I. , Bell Rhonda C. , Boucher Beatrice A. , Csizmadi Ilona , Koushik Anita , L’Abbé Mary R. , Massarelli Isabelle , Robson Paula J. , Rondeau Isabelle , Shatenstein Bryna , Subar Amy F. , Lamarche Benoît
Published: July 2016

Challenges and complexities associated with assessing dietary intakes are numerous, but not insurmountable. This opinion paper from Canadian researchers draws attention to the importance of building capacity and providing funding opportunities for research in dietary assessment methods in Canada and elsewhere. Such strategies would contribute to a better understanding of the roles played by diet in human health and better translation of this information into the most meaningful and effective dietary guidelines, policies, and interventions.
A decade of understanding spatio-temporal regulation of DNA repair by the nuclear architecture
Authors: Saad Hicham , Cobb Jennifer A.
Published: July 2016

The nucleus is a hub for gene expression and is a highly organized entity. The nucleoplasm is heterogeneous, owing to the preferential localization of specific metabolic factors, which lead to the definition of nuclear compartments or bodies. The genome is organized into chromosome territories, as well as heterochromatin and euchromatin domains. Recent observations have indicated that nuclear organization is important for maintaining genomic stability. For example, nuclear organization has been implicated in stabilizing damaged DNA, repair-pathway choice, and in preventing chromosomal rearrangements. Over the past decade, several studies have revealed that dynamic changes in the nuclear architecture are important during double-strand break repair. Stemming from work in yeast, relocation of a damaged site prior to repair appears to be at least partially conserved in multicellular eukaryotes. In this review, we will discuss genome and nucleoplasm architecture, particularly the importance of the nuclear periphery in genome stability. We will also discuss how the site of relocation regulates repair-pathway choice.
PPN parameters in gravitational theory with nonminimally derivative coupling
Authors: Yi Zhu , Gong Yungui
Published: July 2016

The nonminimal coupling of the kinetic term to Einstein’s tensor helps the implementation of inflationary models due to the gravitationally enhanced friction. We calculate the parametrized post-Newtonian (PPN) parameters for the scalar–tensor theory of gravity with nonminimally derivative coupling. We find that under experimental constraint from the orbits of millisecond pulsars in our galaxy, the theory deviates from Einstein’s general relativity in the order of [Formula: see text], and the effect of the nonminimal coupling is negligible if we take the scalar field as dynamical dark energy. With the assumed conditions that the background scalar field is spatially homogeneous and evolves only on cosmological timescales and the contribution to stress–energy in the solar system from the background scalar field is subdominant, the scalar field is required to be massless.
Option Hedging with Smooth Market Impact
Authors: Almgren Robert , Li Tianhui Michael
Published: July 2016

We consider intraday hedging of an option position, for a large trader who experiences temporary and permanent market impact. We formulate the general model including overnight risk, and solve explicitly in two cases which we believe are representative. The first case is an option with approximately constant gamma: the optimal hedge trades smoothly towards the classical Black–Scholes delta, with trading intensity proportional to instantaneous mishedge and inversely proportional to illiquidity. The second case is an arbitrary non-linear option structure but with no permanent impact: the optimal hedge trades toward a value offset from the Black–Scholes delta. We estimate the effects produced on the public markets if a large collection of traders all hedge similar positions. We construct a stable hedge strategy with discrete time steps.