bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunolocalization of AQP5 in resting and stimulated normal labial glands and in Sjögren's syndrome
Authors: Gresz V , Horvath A , Gera I , Nielsen S , Zelles T
Published: March 2014

Objective

In our current work, in vivo examination of AQP5 distribution in labial salivary glands following stimulation of secretion has been carried out in normal individuals and in patients with Sjögren's syndrome.

Subjects and Methods

For this study, we selected five patients with primary Sjögren's syndrome (mean age 62.4 ± 10.6 s.d. years) diagnosed in accordance with the European Cooperative Community classification criteria. There were five patients (mean age 27 ± 2.5 s.d. years) in the control group. The subcellular distribution of AQP5 in human labial gland biopsies was determined with light and immunoelectron microscopy before and 30 min after administration of oral pilocarpine.

Results

In unstimulated control and Sjögren's labial glands, AQP5 is about 90% localized in the apical plasma membrane, with only rarely associated gold particles with intracellular membrane structures. We have found no evidence of pilocarpine‐induced changes in localization of AQP5 in either healthy individuals or patients with Sjögren's syndrome.

Conclusions

Our studies indicate that neither Sjögren's syndrome itself, nor muscarinic cholinergic stimulation in vivo caused any significant changes in the distribution of AQP5 in the labial salivary gland cells.
A Japanese Christian Socialist‐Pacifist and His American Supporters: Personal Contacts and Critical Internationalism
Authors: Shaffer Robert
Published: March 2014

Kagawa Toyohiko, the preeminent Japanese Christian leader of the interwar era, exerted influence in the United States as well as in his native Japan, with his support for economic cooperatives, his calls for friendship between the two nations, his protests against racist U.S. immigration policies, and his service as a model for the Social Gospel wing of Protestantism. This paper studies four American missionaries in Japan—William Axling, Helen Topping, T.T. Brumbaugh, and Galen Fisher—whose writings and activities were essential in making Kagawa's views known in the United States. It argues that through the personal bonds they forged with Kagawa, they came to a new understanding of the missionary endeavor, moving away from simply spreading Christianity to the Japanese toward serving as interpreters of Japanese society and attitudes for Americans. In the process, they developed a critical approach toward U.S. policy and society, which the author terms “critical internationalism.”
Korean versions of thePerceivedStressScale (PSS‐14, 10 and 4): psychometric evaluation in patients with chronic disease
Authors: Lee Eun‐Hyun , Chung Bok Yae , Suh Chang‐Hee , Jung Ju‐Yang
Published: March 2014

Background

ThePerceivedStressScale (PSS) is a representative instrument used to measure stress. The originalPSScomprises 14 items (PSS‐14) in two subscales, but 10‐ and 4‐item versions are also available (PSS‐10 and 4, respectively). The target populations of psychometric studies using thePSShave far mainly comprised college students, and the underlying constructs of thePSSversions are controversial: one factor vs. two factors and first order vs. second order.

Objective

The aim of this study was to evaluate the psychometric properties of theKorean versions of thePSS‐14, 10 and 4 (designatedKPSS‐14, 10 and ‐4, respectively) in patients with chronic disease.

Methods

ThePSS‐14, 10 and 4 were translated intoKorean using forward and backward translation. Factorial construct validity was tested using both exploratory and confirmatory factor analyses. Item convergent validity and item discriminant validity were tested. Concurrent validity was examined using theCenter forEpidemiologicStudies–Depression scale. Known‐groups validity was analysed usingt‐test and effect size. Reliability was tested usingCronbach's alpha and the intraclass correlation coefficient.

Results

Exploratory factor analysis supported a two‐factor model for allKorean versions of thePSS, and confirmatory factor analysis indicated that the model fit theKPSS‐10 well and theKPSS‐4 only marginally. The testing of item convergent and discriminant validity revealed a 100% scaling success. As expected, all scores in theKPSS‐14, 10 and 4 were moderately correlated with depression scores and differed significantly according to gender. TheCronbach's alpha for theKPSS‐14 and 10 exceeded the criterion of 0.70. The intraclass correlation coefficient values of all threeKorean versions were satisfied.

Conclusions

TheKPSS‐10 exhibited a first‐order, two‐factor construct, and excellent reliability and validity were established forKorean patients with chronic disease. The psychometric properties of the shortest version,KPSS‐4, were only marginally acceptable.
Right for knowledge – the perspective of significant others of persons with memory disorders
Authors: Suhonen Riitta , Stolt Minna , Koskenniemi Jaana , Leino‐Kilpi Helena
Published: March 2014

Rationale

People have a fundamental right to know about care and services within health care. This right is also important for persons with memory disorders (PwMD) and their significant others (SO) for empowering them to manage with difficult situations at home and in institution.

Aim

This study explores the self‐assessed level of received knowledge about care and services of the SOs of PwMDs and the understandability of that knowledge.

Methods

This study employed an exploratory and correlational survey design in multisite settings for older people. Data were collected in Finland in 2010–2011 from the SOs of PwMDs (N = 304, n = 264, response rate 87%) using questionnaires, including the Knowledge of Care and Services for Persons with Memory Disorders; the level of knowledge and the understandability of the knowledge were assessed using visual analogue scale (VAS 0‐100). Data were analysed statistically using descriptive statistics, independent samples t‐test, one‐way analysis of variance and Pearson's correlations coefficients.

Results

The self‐assessed level of received knowledge of SOs about care and services was low (mean 47.7 ± 25.3 out of 100), with the highest level seen in medication (54.5 ± 31.1) and memory disorder as a disease (54.3 ± 30.3) and the lowest level in the services provided at home for PwMDs (45 ± 30.6) and generally for SOs (38.5 ± 31.7). SOs assessed the received knowledge as being understandable to a moderate degree (53.7 ± 25.5).

Conclusion

More knowledge could be delivered to PwMDs to manage in their homes and especially to SOs to take care of PwMDs. New educational solutions could be created aimed at improving the understandability of the knowledge.
A unique Ni2+ ‐dependent and methylglyoxal‐inducible rice glyoxalase I possesses a single active site and functions in abiotic stress response
Authors: Mustafiz Ananda , Ghosh Ajit , Tripathi Amit K. , Kaur Charanpreet , Ganguly Akshay K. , Bhavesh Neel S. , Tripathi Jayant K. , Pareek Ashwani , Sopory Sudhir K. , Singla‐Pareek Sneh L.
Published: March 2014

The glyoxalase system constitutes the major pathway for the detoxification of metabolically produced cytotoxin methylglyoxal (MG) into a non‐toxic metabolite d‐lactate. Glyoxalase I (GLY I) is an evolutionarily conserved metalloenzyme requiring divalent metal ions for its activity: Zn2+ in the case of eukaryotes or Ni2+ for enzymes of prokaryotic origin. Plant GLY I proteins are part of a multimember family; however, not much is known about their physiological function, structure and metal dependency. In this study, we report a unique GLY I (OsGLYI‐11.2) from Oryza sativa (rice) that requires Ni2+ for its activity. Its biochemical, structural and functional characterization revealed it to be a monomeric enzyme, possessing a single Ni2+ coordination site despite containing two GLY I domains. The requirement of Ni2+ as a cofactor by an enzyme involved in cellular detoxification suggests an essential role for this otherwise toxic heavy metal in the stress response. Intriguingly, the expression of OsGLYI‐11.2 was found to be highly substrate inducible, suggesting an important mode of regulation for its cellular levels. Heterologous expression of OsGLYI‐11.2 in Escherichia coli and model plant Nicotiana tabacum (tobacco) resulted in improved adaptation to various abiotic stresses caused by increased scavenging of MG, lower Na+/K+ ratio and maintenance of reduced glutathione levels. Together, our results suggest interesting links between MG cellular levels, its detoxification by GLY I, and Ni2+ – the heavy metal cofactor of OsGLYI‐11.2, in relation to stress response and adaptation in plants.
Successful use of miniphotopheresis for the treatment of graft‐versus‐host disease
Authors: Hackstein Holger , Amoros Jose Jaime Verdu , Bein Gregor , Woessmann Wilhelm
Published: March 2014

Background

Extracorporeal photopheresis (ECP) is an important cell‐based therapy for graft‐versus‐host disease (GVHD); however, the blood volume required per treatment to achieve a clinical response is unknown.

Study Design and Methods

We developed a mini‐ECP technique (mini‐ECP) using only 100 to 200 mL of whole blood for patients with contraindications for apheresis or low body weight. Sixteen patients (n = 13 acute, n = 3 chronic GVHD) with a median body weight of 19 kg (range, 7‐48 kg) received 460 mini‐ECP treatments with a median duration of 115 days (range, 49‐973 days).

Results

Mini‐ECP was well tolerated, and acute GVHD resolved completely in nine of 13 patients and partially in two patients but not in two patients. Cutaneous chronic GVHD exhibited a mixed response (one complete, one partial, and one no response).

Conclusion

These results indicate mini‐ECP as a novel and less invasive therapy for patients with GVHD and contraindications for apheresis.
The Positive Effects of the Schengen Agreement on European Trade
Authors: Davis Dane , Gift Thomas
Published: March 2014

Enacted in 1985, the Schengen Agreement is widely heralded as both a symbol and major institutional advancement of the European project. By eliminating passport requirements for workers, the compact ostensibly produces gains from travel, ease of market access and economies of scale. Yet despite these optimistic predictions, scholars know little about the actual effects of Schengen on trade. We fill this void by identifying why labour mobility should expand the cross‐country exchange of goods and services and then test our theory with data from Europe spanning the period 1980 to 2011. We argue that labour mobility resulting from Schengen yields positive effects on trade by increasing demand for foreign goods, improving awareness of low‐cost producers abroad and lowering the risks associated with buying and selling outside the country. Using the gravity model of trade, we show empirically that Schengen membership makes European states more robust trading partners.
Diode laser photoablation to correct distal nasolacrimal duct atresia in an adult horse
Authors: Stoppini Riccardo , Tassan Stefano , Barachetti Laura
Published: March 2014

Case description

An 8‐year‐old Hanoverian mare was presented for chronic mucopurulent discharge in the left eye, which was responsive to topical antibiotic therapy.

Clinical findings

The nasolacrimal orifice was absent in the left nasal meatum, and anterograde irrigation of left nasolacrimal duct was not possible. Dacryocystorhinography was performed and revealed about 4‐6 cm of distal nasolacrimal duct atresia.

Surgical treatment and outcome

A novel technique was attempted with the horse under standing sedation using an urinary catheter and a 980 nm diode laser with a 600 μm diameter flexible bare quartz fiber. A nasolacrimal orifice was successfully created by ablating the nasal mucosa directly over the tip of the urinary catheter, and patency was maintained with a soft catheter sutured in place for 4 weeks. At 3 months re‐evaluation, the left nasolacrimal duct was patent and functional.

Conclusion

This case report describes a successful novel surgical technique used to correct congenital distal nasolacrimal duct atresia in an adult horse under standing sedation. Advantages over conventional surgical techniques are shorter operating time and limited hemorrhage.
Novel roles of gastrin
Authors: Dimaline Rod , Varro Andrea
Published: March 2014

The existence of the hormone gastrin in the distal stomach (antrum) has been known for almost 110 years, and the physiological function of this amidated peptide in regulating gastric acid secretion via the CCK2 receptor is now well established. In this brief review we consider important additional roles of gastrin, including regulation of genes encoding proteins such as plasminogen activator inhibitors and matrix metalloproteinases that have important actions on extracellular matrix remodelling. These actions are, at least in part, effected by paracrine signalling pathways and make important contributions to maintaining functional integrity of the gastric epithelium. Recent studies also provide support for the idea that gastrin, in concert with other hormones, could potentially contribute a post‐prandial incretin effect. We also review recent developments in the biology of other gastrin gene products, including the precursor progastrin, which causes proliferation of the colonic epithelium and in certain circumstances may induce cancer formation. Glycine‐extended biosynthetic processing intermediates also have proliferative effects in colonic mucosa and in some oesophageal cancer cell lines. Whether these additional gene products exert their effects through the CCK2 receptor or a separate entity is currently a matter of debate.
The Physics of Equestrian Show Jumping
Authors: Stinner Art
Published: March 2014

This article discusses the kinematics and dynamics of equestrian show jumping. For some time I have attended a series of show jumping events at Spruce Meadows, an international equestrian center near Calgary, Alberta, often referred to as the “Wimbledon of equestrian jumping.” I have always had a desire to write an article such as this one, but when I searched the Internet for information and looked at YouTube presentations, I could only find simplistic references to Newton's laws and the conservation of mechanical energy principle. Nowhere could I find detailed calculations. On the other hand, there were several biomechanical articles with empirical reports of the results of kinetic and dynamic investigations of show jumping using high-speed digital cameras and force plates. They summarize their results in tables that give information about the motion of a horse jumping over high fences (1.40 m) and the magnitudes of the forces encountered when landing. However, they do not describe the physics of these results.
Dietary Supplements for Aquatic Sports
Authors: Derave Wim , Tipton Kevin D.
Published: March 2014

Many athletes use dietary supplements, with use more prevalent among those competing at the highest level. Supplements are often self-prescribed, and their use is likely to be based on an inadequate understanding of the issues at stake. Supplementation with essential micronutrients may be useful when a diagnosed deficiency cannot be promptly and effectively corrected with food-based dietary solutions. When used in high doses, some supplements may do more harm than good: Iron supplementation, for example, is potentially harmful. There is good evidence from laboratory studies and some evidence from field studies to support health or performance benefits from appropriate use of a few supplements. The available evidence from studies of aquatic sports is small and is often contradictory. Evidence from elite performers is almost entirely absent, but some athletes may benefit from informed use of creatine, caffeine, and buffering agents. Poor quality assurance in some parts of the dietary supplements industry raises concerns about the safety of some products. Some do not contain the active ingredients listed on the label, and some contain toxic substances, including prescription drugs, that can cause health problems. Some supplements contain compounds that will cause an athlete to fail a doping test. Supplement quality assurance programs can reduce, but not entirely eliminate, this risk.
Disordered Eating and Eating Disorders in Aquatic Sports
Authors: Melin Anna , Torstveit Monica Klungland , Burke Louise , Marks Saul , Sundgot-Borgen Jorunn
Published: March 2014

Disordered eating behavior (DE) and eating disorders (EDs) are of great concern because of their associations with physical and mental health risks and, in the case of athletes, impaired performance. The syndrome originally known as the Female Athlete Triad, which focused on the interaction of energy availability, reproductive function, and bone health in female athletes, has recently been expanded to recognize that Relative Energy Deficiency in Sport (RED-S) has a broader range of negative effects on body systems with functional impairments in both male and female athletes. Athletes in leanness-demanding sports have an increased risk for RED-S and for developing EDs/DE. Special risk factors in aquatic sports related to weight and body composition management include the wearing of skimpy and tight-fitting bathing suits, and in the case of diving and synchronized swimming, the involvement of subjective judgments of performance. The reported prevalence of DE and EDs in athletic populations, including athletes from aquatic sports, ranges from 18 to 45% in female athletes and from 0 to 28% in male athletes. To prevent EDs, aquatic athletes should practice healthy eating behavior at all periods of development pathway, and coaches and members of the athletes’ health care team should be able to recognize early symptoms indicating risk for energy deficiency, DE, and EDs. Coaches and leaders must accept that DE/EDs can be a problem in aquatic disciplines and that openness regarding this challenge is important.
BRAF Inhibitors Induce Metastasis in RAS Mutant or Inhibitor-Resistant Melanoma Cells by Reactivating MEK and ERK Signaling
Authors: Sanchez-Laorden Berta , Viros Amaya , Girotti Maria Romina , Pedersen Malin , Saturno Grazia , Zambon Alfonso , Niculescu-Duvaz Dan , Turajlic Samra , Hayes Andrew , Gore Martin , Larkin James , Lorigan Paul , Cook Martin , Springer Caroline , Marais Richard
Published: March 2014

When therapy leads to cancer metastasis, knowing where else to target in the pathway may be the key to successful treatment.
MicroRNA Circuits Regulate the Cancer-Inflammation Link
Authors: Iliopoulos Dimitrios
Published: March 2014

Increased inflammatory signaling in breast cancer is explained by the loss of a negative feedback loop.
Pharmacokinetics of Rifampin and Isoniazid in Tuberculosis-HIV-Coinfected Patients Receiving Nevirapine- or Efavirenz-Based Antiretroviral Treatment
Authors: Bhatt N. B. , Barau C. , Amin A. , Baudin E. , Meggi B. , Silva C. , Furlan V. , Grinsztejn B. , Barrail-Tran A. , Bonnet M. , Taburet A. M.
Published: March 2014

This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4
+
T cell count, 104 cells/μl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (
C
max
) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid
C
max
and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when coadministered with nevirapine or efavirenz were not altered to a clinically significant extent in these severely immunosuppressed HIV-infected patients. Patients experienced favorable clinical outcomes. (This study has been registered at ClinicalTrials.gov under registration no. NCT00495326.)
Pharmacokinetics of Cefuroxime in Porcine Cortical and Cancellous Bone Determined by Microdialysis
Authors: Tøttrup Mikkel , Hardlei Tore Forsingdal , Bendtsen Michael , Bue Mats , Brock Birgitte , Fuursted Kurt , Søballe Kjeld , Birke-Sørensen Hanne
Published: March 2014

Traditionally, the pharmacokinetics of antimicrobials in bone have been investigated using bone biopsy specimens, but this approach suffers from considerable methodological limitations. Consequently, new methods are needed. The objectives of this study were to assess the feasibility of microdialysis (MD) for measuring cefuroxime in bone and to obtain pharmacokinetic profiles for the same drug in porcine cortical and cancellous bone. The measurements were conducted in bone wax sealed and unsealed drill holes in cortical bone and in drill holes in cancellous bone and in subcutaneous tissue. As a reference, the free and total plasma concentrations were also measured. The animals received a bolus of 1,500 mg cefuroxime over 30 min. No significant differences were found between the key pharmacokinetic parameters for sealed and unsealed drill holes in cortical bone. The mean ± standard error of the mean area under the concentration-time curve (AUC) values from 0 to 5 h were 6,013 ± 1,339, 3,222 ± 1086, 2,232 ± 635, and 952 ± 290 min · μg/ml for free plasma, subcutaneous tissue, cancellous bone, and cortical bone, respectively (
P
< 0.01, analysis of variance). The AUC for cortical bone was also significantly different from that for cancellous bone (
P
= 0.04). This heterogeneous tissue distribution was also reflected in other key pharmacokinetic parameters. This study validates MD as a suitable method for measuring cefuroxime in bone. Cefuroxime penetration was impaired for all tissues, and bone may not be considered one distinct compartment.
Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease
Authors: Zhao Wei , Zhang Daolun , Fakhoury May , Fahd Mony , Duquesne Frédérique , Storme Thomas , Baruchel André , Jacqz-Aigrain Evelyne
Published: March 2014

An increase in vancomycin dose has been proposed in adults with malignant hematological disease. As pediatric data are limited, our aim was to evaluate the population pharmacokinetics of vancomycin in order to define the appropriate dosing regimen in children with malignant hematological disease. Vancomycin concentrations were collected prospectively during therapeutic monitoring. Population pharmacokinetic analysis was performed using NONMEM software. Seventy children (age range, 0.3 to 17.7 years) were included. With the current recommended dosing regimen of 40 to 60 mg/kg/day, 53 children (76%) had subtherapeutic steady-state trough concentrations (
C
ss/min
of <10 mg/liter). A one-compartment model with first-order elimination was developed. Systematic covariate analysis identified that weight significantly influenced clearance (CL) and volume of distribution (
V
) with power functions of 0.677 for CL and 0.838 for
V
. Vancomycin CL also significantly increased with increases in creatinine clearance and seemed to be higher in children with malignant hematological disease than in the general pediatric population. The model was validated internally. Its predictive performance was further confirmed in an external validation by Bayesian estimation. A patient-tailored dosing regimen was developed based on the final pharmacokinetic model and showed that a higher proportion of patients reached the target
C
ss/min
than with the traditional mg/kg-basis dose (60% versus 49%) and that the risks associated with underdosing or overdosing were reduced. This is the first population pharmacokinetic study of vancomycin in children with malignant hematological disease. An optimized dosing regimen, taking into account patient weight, creatinine clearance, and susceptibility of the pathogens involved, could routinely be used to individualize vancomycin therapy in this vulnerable population.
Interleukin 17A Promotes Pneumococcal Clearance by Recruiting Neutrophils and Inducing Apoptosis through a p38 Mitogen-Activated Protein Kinase-Dependent Mechanism in Acute Otitis Media
Authors: Wang Wei , Zhou Aie , Zhang Xuemei , Xiang Yun , Huang Yifei , Wang Lei , Zhang Shuai , Liu Yusi , Yin Yibing , He Yujuan
Published: March 2014

Streptococcus pneumoniae
is a Gram-positive and human-restricted pathogen colonizing the nasopharynx with an absence of clinical symptoms as well as a major pathogen causing otitis media (OM), one of the most common childhood infections. Upon bacterial infection, neutrophils are rapidly activated and recruited to the infected site, acting as the frontline defender against emerging microbial pathogens via different ways. Evidence shows that interleukin 17A (IL-17A), a neutrophil-inducing factor, plays important roles in the immune responses in several diseases. However, its function in response to
S. pneumoniae
OM remains unclear. In this study, the function of IL-17A in response to
S. pneumoniae
OM was examined using an
in vivo
model. We developed a model of acute OM (AOM) in C57BL/6 mice and found that neutrophils were the dominant immune cells that infiltrated to the middle ear cavity (MEC) and contributed to bacterial clearance. Using IL-17A knockout (KO) mice, we found that IL-17A boosted neutrophil recruitment to the MEC and afterwards induced apoptosis, which was identified to be conducive to bacterial clearance. In addition, our observation suggested that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was involved in the recruitment and apoptosis of neutrophils mediated by IL-17A. These data support the conclusion that IL-17A contributes to the host immune response against
S. pneumoniae
by promoting neutrophil recruitment and apoptosis through the p38 MAPK signaling pathway.
Early Changes by
18
Fluorodeoxyglucose Positron Emission Tomography Coregistered with Computed Tomography Predict Outcome after Mycobacterium tuberculosis Infection in Cynomolgus Macaques
Authors: Coleman M. Teresa , Maiello Pauline , Tomko Jaime , Frye Lonnie James , Fillmore Daniel , Janssen Christopher , Klein Edwin , Lin Philana Ling
Published: March 2014

Cynomolgus macaques infected with low-dose
Mycobacterium tuberculosis
develop both active tuberculosis and latent infection similar to those of humans, providing an opportunity to study the clinically silent early events in infection.
18
Fluorodeoxyglucose radiotracer with positron emission tomography coregistered with computed tomography (FDG PET/CT) provides a noninvasive method to measure disease progression. We sought to determine temporal patterns of granuloma evolution that distinguished active-disease and latent outcomes. Macaques (
n
= 10) were infected with low-dose
M. tuberculosis
with FDG PET/CT performed during infection. At 24 weeks postinfection, animals were classified as having active disease (
n
= 3) or latent infection (
n
= 6), with one “percolator” monkey. Imaging characteristics (e.g., lesion number, metabolic activity, size, mineralization, and distribution of lesions) were compared among active and latent groups. As early as 3 weeks postinfection, more pulmonary granulomas were observed in animals that would later develop active disease than in those that would develop latent infection. Over time, new lesions developed in active-disease animals but not in latent animals. Granulomas and mediastinal lymph nodes from active-disease but not latent animals consistently increased in metabolic activity at early time points. The presence of fewer lesions at 3 weeks and the lack of new lesion development in animals with latent infection suggest that innate and rapid adaptive responses are critical to preventing active tuberculosis. A greater emphasis on innate responses and/or rapid recruitment of adaptive responses, especially in the airway, should be emphasized in newer vaccine strategies.
Paraneoplastic overlap syndrome in non-small squamous cell lung carcinoma
Authors: Hoque Romy , DelRosso Lourdes
Published: March 2014

This is a case of paraneoplastic overlap of limbic encephalitis and opsoclonus myoclonus in a patient with non-small squamous cell lung carcinoma.
Coping with heat stress during match-play tennis: Does an individualised hydration regimen enhance performance and recovery?
Authors: Périard Julien D , Racinais Sebastien , Knez Wade L , Herrera Christopher P , Christian Ryan J , Girard Olivier
Published: March 2014

Objectives

To determine whether an individualised hydration regimen reduces thermal, physiological and perceptual strain during match-play tennis in the heat, and minimises alterations in neuromuscular function and physical performance postmatch and into recovery.

Methods

10 men undertook two matches for an effective playing time (ball in play) of 20 min (∼113 min) in ∼37°C and ∼33% RH conditions. Participants consumed fluids ad libitum during the first match (HOT) and followed a hydration regimen (HYD) in the second match based on undertaking play euhydrated, standardising sodium intake and minimising body mass losses.

Results

HYD improved prematch urine specific gravity (1.013±0.006 vs 1.021±0.009 g/mL; p<0.05). Body mass losses (∼0.3%), fluid intake (∼2 L/h) and sweat rates (∼1.6 L/h) were similar between conditions. Core temperature was higher during the first 10 min of effective play in HOT (p<0.05), but increased similarly (∼39.3°C) on match completion. Heart rate was higher (∼11 bpm) throughout HOT (p<0.001). Thermal sensation was higher during the first 7.5 min of effective play in HOT (p<0.05). Postmatch knee extensor and plantar flexor strength losses, along with reductions in 15 m sprint time and repeated-sprint ability (p<0.05), were similar in both conditions, and were restored within 24 h.

Conclusions

Both the hydration regimen and ad libitum fluid consumption allowed for minimal body mass losses (<1%). However, undertaking match-play in a euhydrated state attenuated thermal, physiological and perceptual strain. Maximal voluntary strength in the lower limbs and repeated-sprint ability deteriorated similarly in both conditions, but were restored within 24 h.
Clinical trial participants’ experiences of completing questionnaires: a qualitative study
Authors: Holmberg Christine , Karner Julia J , Rappenecker Julia , Witt Claudia M
Published: March 2014

Objectives

To improve clinical study developments for elderly populations, we aim to understand how they transfer their experiences into validated, standardised self-completed study measurement instruments. We analysed how women (mean 78±8 years of age) participating in a randomised controlled trial (RCT) cognised study instruments used to evaluate outcomes of the intervention.

Setting

The interview study was nested in an RCT on chronic neck pain using common measurement instruments situated in an elderly community in Berlin, Germany, which comprised of units for independent and assisted-living options.

Participants

The sample (n=20 women) was selected from the RCT sample (n=117, 95% women, mean age 76 (SD±8) years). Interview participants were selected using a purposive sampling list based on the RCT outcomes.

Outcomes

We asked participants about their experiences completing the RCT questionnaires. Interviews were analysed thematically, then compared with the questionnaires.

Results

Interviewees had difficulties in translating complex experiences into a single value on a scale and understanding the relationship of the questionnaires to study aims. Interviewees considered important for the trial that their actual experiences were understood by trial organisers. This information was not transferrable by means of the questionnaires. To rectify these difficulties, interviewees used strategies such as adding notes, adding response categories or skipping an item.

Conclusions

Elderly interview participants understood the importance of completing questionnaires for trial success. This led to strategies of completing the questionnaires that resulted in ‘missing’ or ambiguous data. To improve data collection in elderly populations, educational materials addressing the differential logics should be developed and tested. Pilot testing validated instruments using cognitive interviews may be particularly important in such populations. Finally, when the target of an intervention is a subjective experience, it seems important to create a method by which participants can convey their personal experiences. These could be nested qualitative studies.

Trial registration number

ISRCTN77108101807.
Adapting data collection methods in the Australian Life Histories and Health Survey: a retrospective life course study
Authors: Kendig Hal , Byles Julie E , O'Loughlin Kate , Nazroo James Y , Mishra Gita , Noone Jack , Loh Vanessa , Forder Peta M
Published: March 2014

Objective

Ideally, life course data are collected prospectively through an ongoing longitudinal study. We report adaptive multimethod fieldwork procedures that gathered life history data by mail survey and telephone interview, comparable with the face-to-face methods employed in the English Longitudinal Study on Ageing (ELSA).

Design

The Australian Life Histories and Health (LHH) Survey was a substudy of the Australian 45 and Up Study, with data collection methods modified from the ELSA Study. A self-complete questionnaire and life history calendar were completed by the participants, followed by a computer-assisted telephone interview recording key life events.

Results

The LHH survey developed and tested procedures and instruments that gathered rich life history data within an ongoing Australian longitudinal survey on ageing. Data collection proved to be economical. The use of a self-complete questionnaire in conjunction with a life history calendar and coordinated computer-assisted telephone interview was successful in collecting retrospective life course information, in terms of being thorough, practical and efficient. This study has a diverse collection of data covering the life course, starting with early life experiences and continuing with socioeconomic and health exposures and outcomes during adult life.

Conclusions

Mail and telephone methodology can accurately and economically add a life history dimension to an ongoing longitudinal survey. The method is particularly valuable for surveying widely dispersed populations. The results will facilitate understanding of the social determinants of health by gathering data on earlier life exposures as well as comparative data across geographical and societal contexts.
Cerebral oximetry levels during CPR are associated with return of spontaneous circulation following cardiac arrest: an observational study
Authors: Singer Adam J , Ahn Anna , Inigo-Santiago Loren A , Thode Henry C , Henry Mark C , Parnia Sam
Published: March 2014

Objectives

Cerebral oximetry using near-infrared spectroscopy measures regional cerebral oxygen saturation (rSO2) non-invasively and may provide information regarding the quality of cerebral oxygen perfusion. We determined whether the level of rSO2obtained during cardiopulmonary resuscitation is associated with return of spontaneous circulation (ROSC) and survival in Emergency Department (ED) patients presenting with cardiac arrest.

Methods

We conducted a retrospective, observational study of adult ED patients presenting at an academic medical centre with cardiac arrest in whom continuous cerebral oximetry was performed. Demographic and clinical data including age, gender, presenting rhythm and mean rSO2readings were abstracted. Cerebral oxygenation was measured with a commercially available oximeter.

Results

A convenience study sample included 59 patients ages 18–102 years (mean age 68.7 ± 14.9 years); 50 (84.7%) were men. Presenting rhythms included pulseless electrical activity (21), asystole (20) and ventricular fibrillation/tachycardia (17). 24 patients (40.6%) had ROSC and only 1 (1.7%) survived to hospital discharge. Patients with and without ROSC were similar in age and presenting cardiac rhythms. The mean of mean rSO2levels was higher in patients with ROSC, 43.8 (95% CI 40.1 to 47.6) compared with those without ROSC, 34.2 (95% CI 30.6 to 37.8); p=0.001. 91.7% of patients with ROSC had a rSO2of 30% or greater compared with 62.9% in those without ROSC (p=0.01). The area under the curve for mean rSO2as a predictor of ROSC was 0.76 (95% CI 0.64 to 0.89).

Conclusions

In ED patients with cardiac arrest higher cerebral oxygen saturations are associated with higher rates of ROSC.
Determinants of quality of life in advanced kidney disease: time to screen?
Authors: Iyasere Osasuyi , Brown Edwina A
Published: March 2014

The incidence of older patients with end stage renal disease is on the increase. This group of patients have multiple comorbidities and a high symptom burden. Dialysis can be life sustaining for such patients. But it is often at the expense of quality of life, which starts to decline early in the pathway of chronic kidney disease. Quality of life is also important to patients and is a major determinant in decisions regarding renal replacement. As a result, validated patient-reported outcome measures are increasingly used to assess quality of life in renal patients. Cognitive impairment, depression, malnutrition and function decline are non-renal determinants of quality of life and mortality. They are under-recognised in the renal population but are potentially treatable, if not preventable. This review article discusses aetio-pathogenesis, prevalence and impact of these four outcomes, advocating regular screening for early identification and management.
Estimating long-term settlement of floating stone column groups
Authors: Shahu J.T. , Reddy Y.R.
Published: March 2014

Design charts for estimating long-term drained settlement of floating stone column group foundations are presented based on three-dimensional, elastoplastic, finite element analyses. In the analyses, the soft soil behavior is represented by the modified Cam-clay model while the stone column and mat are represented by the Mohr–Coulomb model. The finite element predictions are calibrated against model test results. A detailed parametric study of prototype stone column group foundations of various configurations is carried out to evaluate the relative importance of various foundation parameters on the group response. Next, finite element analyses of corresponding unit cells and single columns are performed. Reasonable correlations of load responses are found between single column and group behavior. Group and single column responses are then used to investigate Sg/S1 relationship with different foundation parameters, where Sg and S1 represent the settlement of the group and single column, respectively.
Complex and unexpected dynamics in simple genetic regulatory networks
Authors: Borg Yanika , Ullner Ekkehard , Alagha Afnan , Alsaedi Ahmed , Nesbeth Darren , Zaikin Alexey
Published: March 2014

One aim of synthetic biology is to construct increasingly complex genetic networks from interconnected simpler ones to address challenges in medicine and biotechnology. However, as systems increase in size and complexity, emergent properties lead to unexpected and complex dynamics due to nonlinear and nonequilibrium properties from component interactions. We focus on four different studies of biological systems which exhibit complex and unexpected dynamics. Using simple synthetic genetic networks, small and large populations of phase-coupled quorum sensing repressilators, Goodwin oscillators, and bistable switches, we review how coupled and stochastic components can result in clustering, chaos, noise-induced coherence and speed-dependent decision making. A system of repressilators exhibits oscillations, limit cycles, steady states or chaos depending on the nature and strength of the coupling mechanism. In large repressilator networks, rich dynamics can also be exhibited, such as clustering and chaos. In populations of Goodwin oscillators, noise can induce coherent oscillations. In bistable systems, the speed with which incoming external signals reach steady state can bias the network towards particular attractors. These studies showcase the range of dynamical behavior that simple synthetic genetic networks can exhibit. In addition, they demonstrate the ability of mathematical modeling to analyze nonlinearity and inhomogeneity within these systems.
Bifurcations and Chaos of Duffing–van der Pol Equation with Nonsymmetric Nonlinear Restoring and Two External Forcing Terms
Authors: Yang Zhiyan , Jiang Tao , Jing Zhujun
Published: March 2014

Bifurcations and chaos of Duffing–van der Pol equation with nonsymmetric nonlinear restoring and two external forcing terms are investigated. The threshold values of the existence of chaotic motion are obtained under periodic perturbation. By the second-order averaging method, we prove the criteria of the existence of chaos in an averaged system under quasi-periodic perturbation for ω2 = nω1 + εσ, n = 1, 2, 3, 5, and cannot prove the criterion of existence of chaos in an averaged system under quasi-periodic perturbation for ω2 = nω1 + εσ, n = 4, 6, 7, …, where σ is not rational to ω1, but can show the occurrence of chaos in the original system by numerical simulation. Numerical simulation including homoclinic or heteroclinic bifurcation surfaces, bifurcation diagrams, maximal Lyapunov exponents, phase portraits and Poincaré maps, not only show the consistence with the theoretical analysis but also exhibit more new complex dynamical behaviors. We show that cascades of interlocking period-doubling and reverse period-doubling bifurcations lead to interleaving occurrence of chaotic behaviors and quasi-periodic orbits, symmetry-breaking of periodic orbits in chaotic regions, onset of chaos occurring more than once, chaos suddenly disappearing to periodic orbits, strange nonchaotic attractor, nonattracting chaotic set and nice chaotic attractors.
The Maximal Number of Limit Cycles in a Family of Polynomial Systems
Authors: Xiang Guanghui , Hu Zhaoping
Published: March 2014

The main objective of this paper is to study the number of limit cycles in a family of polynomial systems. Using bifurcation methods, we obtain the maximal number of limit cycles in global bifurcation.
Chimera States in Networks of Nonlocally Coupled Hindmarsh–Rose Neuron Models
Authors: Hizanidis Johanne , Kanas Vasileios G. , Bezerianos Anastasios , Bountis Tassos
Published: March 2014

We have identified the occurrence of chimera states for various coupling schemes in networks of two-dimensional and three-dimensional Hindmarsh–Rose oscillators, which represent realistic models of neuronal ensembles. This result, together with recent studies on multiple chimera states in nonlocally coupled FitzHugh–Nagumo oscillators, provide strong evidence that the phenomenon of chimeras may indeed be relevant in neuroscience applications. Moreover, our work verifies the existence of chimera states in coupled bistable elements, whereas to date chimeras were known to arise in models possessing a single stable limit cycle. Finally, we have identified an interesting class of mixed oscillatory states, in which desynchronized neurons are uniformly interspersed among the remaining ones that are either stationary or oscillate in synchronized motion.
A Spatial Frequency Domain Analysis of the Belousov–Zhabotinsky Reaction
Authors: Guo Lingzhong , Guo Yuzhu , Zhao Yifan , Billings Stephen A. , Coca Daniel , Lang Zhiqiang
Published: March 2014

A nonlinear spatio-temporal system identification and analysis approach is used to study the dynamical behavior of the Belousov–Zhabotinsky (BZ) chemical reaction process. In our previous study [Guo et al., 2010],, the dynamical behavior of the BZ reaction in the spatial-temporal domain has been analyzed by identifying a coupled map lattice (CML) model of the process directly from experimental data from a real BZ reaction experiment. In this paper, the frequency domain analysis of the dynamics near equilibrium is carried out by mapping the obtained CML model into higher order spatial frequency response functions to reveal the nonlinear coupling and modulation between the various initial spectral components in the process. As far as we are aware, this is the first study of any real spatio-temporal system using a spatio-temporal domain identification and frequency domain analysis approach.
Keynote Paper — AUTOPOIETIC GENE-ENZYME CYCLES AND THE EMERGENCE OF LIFE
Authors: LAVIOLETTE PAUL A.
Published: March 2014

Systems concepts are applied to solve the problem of how early life could have emerged from an initially abiotic organic environment. Proteinoid or lipid microspheres are proposed to have polymerized from a primordial organic soup and to contain various amino acids and several different nucleobases. A self-replicating "basic set" hypercycle consisting of 10 XNA gene strands and 10 enzymes is proposed that utilizes inorganic phosphates as an energy source. The genes would utilize triplet combinations of adenosine and uracil to code for a replicase enzyme, a polymerase enzyme and eight-code translator (synthetase) enzymes. It is shown that there is a high probability that the basic set genes would emerge. Fissioning of the basic set microspheres into a population of microspheres all containing the basic set, could eliminate the problem of a single gene monopolizing use of the replicator enzyme at the expense of the others and greatly enhance the survivability of the replicating population as a whole. A thermodynamic analysis of such a self-replicating system is also presented. It is shown that genetic mutations will, in the long run allow the basic set to evolve to increased diversity, higher rates of enzyme synthesis and greater rates of entropy production. Long-term evolution could have resulted in organisms similar to contemporary bacteria that utilize RNA genes with a four nucleobase codon system.
A version of the Hörmander–Malliavin theorem in 2-smooth Banach spaces
Authors: Shamarova Evelina
Published: March 2014

We consider a stochastic evolution equation in a 2-smooth Banach space with a densely and continuously embedded Hilbert subspace. We prove that under Hörmander's bracket condition, the image measure of the solution law under any finite-rank bounded linear operator is absolutely continuous with respect to the Lebesgue measure. To obtain this result, we apply methods of the Malliavin calculus.
Relative ergodic properties of C*-dynamical systems
Authors: Duvenhage Rocco , Mukhamedov Farrukh
Published: March 2014

We study various ergodic properties of C*-dynamical systems inspired by unique ergodicity. In particular we work in a framework allowing for ergodic properties defined relative to various subspaces, and in terms of weighted means. Our main results are characterizations of such relative ergodic properties, ergodic theorems resulting from these properties, and examples exhibiting these properties.