On the distinguishability of downconverted modes with orbital angular momentum.
Assuming two quantum states of spontaneous parametric downconversion carrying orbital angular momentum, one may ask the question what is the minimum probability of error in identifying between two of these biphoton states by an arbitrary physical measurement over the biphoton state generated. While correctly chosen geometries may lead to perfect distinguishability of modes, it is worth noticing that experimental subtleties may lead to a poor mode distinguishability. We discuss the case where a restricted range instead of the needed range of wave vectors is collected by the experimental setup. These considerations may be useful for some applications, e.g., cryptography.


Promise in nonparametrics.
This paper proposes the use of nonparametric statistical methods as a way to increase the quality and quantity of research in occupational therapy. Assumptions underlying parametric versus nonparametric methods are compared and the conditions under which nonparametric methods may be preferred are specified. Finally, a synopsis of equivalent nonparametric procedures for common parametric methods is presented.


Gene expression in human fungal pathogen Coccidioides immitis changes as arthroconidia differentiate into spherules and mature.
Coccidioides immitis is a dimorphic fungus that causes disease in mammals, including human beings. It grows as a mycelium containing arthroconidia in the soil and in the host arthroconidia differentiates into a unique structure called a spherule. We used a custom open reading frame oligonucleotide microarray to compare the transcriptome of C. immitis mycelia with early (day 2) and late stage (day 8) spherules grown in vitro. All hybridizations were done in quadruplicate and stringent criteria were used to identify significantly differentially expressed genes. 22% of C. immitis genes were differentially expressed in either day 2 or day 8 spherules compared to mycelia, and about 12% of genes were differentially expressed comparing the two spherule time points. Oxireductases, including an extracellular superoxide dismutase, were upregulated in spherules and they may be important for defense against oxidative stress. Many signal transduction molecules, including pleckstrin domain proteins, protein kinases and transcription factors were downregulated in day 2 spherules. Several genes involved in sulfur metabolism were downregulated in day 8 spherules compared to day 2 spherules. Transcription of amylase and α (1,3) glucan synthase was upregulated in spherules; these genes have been found to be important for differentiation to yeast in Histoplasma. There were two homologs of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD); transcription of one was up- and the other downregulated. We tested the effect of a 4-HPPD inhibitor, nitisinone, on mycelial and spherule growth and found that it inhibited mycelial but not spherule growth. Transcription of many genes was differentially expressed in the process of arthroconidia to spherule conversion and spherule maturation, as would be expected given the magnitude of the morphologic change. The transcription profile of early stage (day 2) spherules was different than late stage (day 8) endosporulating spherules. In addition, very few genes that are important for spore to yeast conversion in other dimorphic fungi are differentially expressed in C. immitis mycelia and spherules suggesting that dimorphic fungi may have evolved different mechanisms to differentiate from mycelia to tissue invasive forms.


The neuropeptide Y Y1 receptor subtype is necessary for the anxiolytic-like effects of neuropeptide Y, but not the antidepressant-like effects of fluoxetine, in mice.
Neuropeptide Y (NPY) is implicated in the pathophysiology of affective illness. Multiple receptor subtypes (Y1R, Y2R, and Y5R) have been suggested to contribute to NPY's effects on rodent anxiety and depression-related behaviors. To further elucidate the role of Y1R in (1) NPY's anxiolytic-like effects and (2) fluoxetine's antidepressant-like and neurogenesis-inducing effects. Mice lacking Y1R were assessed for spontaneous anxiety-like behavior (open field, elevated plus-maze, and light/dark exploration test) and Pavlovian fear conditioning, and for the anxiolytic-like effects of intracerebroventricularly (icv)-administrated NPY (elevated plus-maze). Next, Y1R -/- were assessed for the antidepressant-like effects of acute fluoxetine in the forced swim test and chronic fluoxetine in the novelty-induced hypophagia test, as well as for chronic fluoxetine-induced hippocampal neurogenesis. Y1R -/- exhibited largely normal baseline behavior as compared to +/+ littermate controls. Intraventricular administration of NPY in Y1R -/- mice failed to produce the normal anxiolytic-like effect in the elevated plus-maze test seen in +/+ mice. Y1R mutant mice showed higher immobility in the forced swim test and longer latencies in the novelty-induced hypophagia test. In addition, Y1R -/- mice responded normally to the acute and chronic effects of fluoxetine treatment in the forced swim test and the novelty-induced hypophagia test, respectively, as well as increased neuronal precursor cell proliferation in the hippocampus. These data demonstrate that Y1R is necessary for the anxiolytic-like effects of icv NPY, but not for the antidepressant-like or neurogenesis-inducing effects of fluoxetine. The present study supports targeting Y1R as a novel therapeutic target for anxiety disorders.


Lysophosphatidic acid signals through multiple receptors in osteoclasts to elevate cytosolic calcium concentration, evoke retraction, and promote cell survival.
Lysophosphatidic acid (LPA) is a bioactive phospholipid whose functions are mediated by multiple G protein-coupled receptors. We have shown that osteoblasts produce LPA, raising the possibility that it mediates intercellular signaling among osteoblasts and osteoclasts. Here we investigated the expression, signaling and function of LPA receptors in osteoclasts. Focal application of LPA elicited transient increases in cytosolic calcium concentration ([Ca(2+)](i)), with 50% of osteoclasts responding at approximately 400 nm LPA. LPA-induced elevation of [Ca(2+)](i) was blocked by pertussis toxin or the LPA(1/3) receptor antagonist VPC-32183. LPA caused sustained retraction of osteoclast lamellipodia and disrupted peripheral actin belts. Retraction was insensitive to VPC-32183 or pertussis toxin, indicating involvement of a distinct signaling pathway. In this regard, inhibition of Rho-associated kinase stimulated respreading after LPA-induced retraction. Real-time reverse transcription-PCR revealed transcripts encoding LPA(1) and to a lesser extent LPA(2), LPA(4), and LPA(5) receptor subtypes. LPA induced nuclear translocation of NFATc1 and enhanced osteoclast survival, effects that were blocked by VPC-32183 or by a specific peptide inhibitor of NFAT activation. LPA slightly reduced the resorptive activity of osteoclasts in vitro. Thus, LPA binds to at least two receptor subtypes on osteoclasts: LPA(1), which couples through G(i/o) to elevate [Ca(2+)](i), activate NFATc1, and promote survival, and a second receptor that likely couples through G(12/13) and Rho to evoke and maintain retraction through reorganization of the actin cytoskeleton. These findings reveal a signaling axis in bone through which LPA, produced by osteoblasts, acts on multiple receptor subtypes to induce pleiotropic effects on osteoclast activity and function.


A stem cell-based tool for small molecule screening in adipogenesis.
Techniques for small molecule screening are widely used in biological mechanism study and drug discovery. Here, we reported a novel adipocyte differentiation assay for small molecule selection, based on human mesenchymal stem cells (hMSCs) transduced with fluorescence reporter gene driven by adipogenic specific promoter--adipocyte Protein 2 (aP2; also namely Fatty Acid Binding Protein 4, FABP4). During normal adipogenic induction as well as adipogenic inhibition by Ly294002, we confirmed that the intensity of green fluorescence protein corresponded well to the expression level of aP2 gene. Furthermore, this variation of green fluorescence protein intensity can be read simply through fluorescence spectrophotometer. By testing another two small molecules in adipogenesis--Troglitazone and CHIR99021, we proved that this is a simple and sensitive method, which could be applied in adipocyte biology, drug discovery and toxicological study in the future.


Mechanical Properties of Compact Bone Defined by the Stress-Strain Curve Measured Using Uniaxial Tensile Test: A Concise Review and Practical Guide.
Mechanical properties are crucial parameters for scaffold design for bone tissue engineering; therefore, it is important to understand the definitions of the mechanical properties of bones and relevant analysis methods, such that tissue engineers can use this information to properly design the mechanical properties of scaffolds for bone tissue engineering. The main purpose of this article is to provide a review and practical guide to understand and analyze the mechanical properties of compact bone that can be defined and extracted from the stress-strain curve measured using uniaxial tensile test until failure. The typical stress-strain curve of compact bone measured using uniaxial tensile test until failure is a bilinear, monotonically increasing curve. The associated mechanical properties can be obtained by analyzing this bilinear stress-strain curve. In this article, a computer programming code for analyzing the bilinear stress-strain curve of compact bone for quantifying the associated mechanical properties is provided, such that the readers can use this computer code to perform the analysis directly. In addition to being applied to compact bone, the information provided by this article can also be applied to quantify the mechanical properties of any material having a bilinear stress-strain curve, such as a whole bone, some metals and biomaterials. The information provided by this article can be applied by tissue engineers, such that they can have a reference to properly design the mechanical properties of scaffolds for bone tissue engineering. The information can also be applied by researchers in biomechanics and orthopedics to compare the mechanical properties of bones in different physiological or pathological conditions.


Dynamic approximate entropy electroanatomic maps detect rotors in a simulated atrial fibrillation model.
There is evidence that rotors could be drivers that maintain atrial fibrillation. Complex fractionated atrial electrograms have been located in rotor tip areas. However, the concept of electrogram fractionation, defined using time intervals, is still controversial as a tool for locating target sites for ablation. We hypothesize that the fractionation phenomenon is better described using non-linear dynamic measures, such as approximate entropy, and that this tool could be used for locating the rotor tip. The aim of this work has been to determine the relationship between approximate entropy and fractionated electrograms, and to develop a new tool for rotor mapping based on fractionation levels. Two episodes of chronic atrial fibrillation were simulated in a 3D human atrial model, in which rotors were observed. Dynamic approximate entropy maps were calculated using unipolar electrogram signals generated over the whole surface of the 3D atrial model. In addition, we optimized the approximate entropy calculation using two real multi-center databases of fractionated electrogram signals, labeled in 4 levels of fractionation. We found that the values of approximate entropy and the levels of fractionation are positively correlated. This allows the dynamic approximate entropy maps to localize the tips from stable and meandering rotors. Furthermore, we assessed the optimized approximate entropy using bipolar electrograms generated over a vicinity enclosing a rotor, achieving rotor detection. Our results suggest that high approximate entropy values are able to detect a high level of fractionation and to locate rotor tips in simulated atrial fibrillation episodes. We suggest that dynamic approximate entropy maps could become a tool for atrial fibrillation rotor mapping.


Rapid exchange of metal between Zn(7)-metallothionein-3 and amyloid-β peptide promotes amyloid-related structural changes.
Metal ions, especially Zn(2+) and Cu(2+), are implemented in the neuropathogenesis of Alzheimer's disease (AD) by modulating the aggregation of amyloid-β peptides (Aβ). Also, Cu(2+) may promote AD neurotoxicity through production of reactive oxygen species (ROS). Impaired metal ion homeostasis is most likely the underlying cause of aberrant metal-Aβ interaction. Thus, focusing on the body's natural protective mechanisms is an attractive therapeutic strategy for AD. The metalloprotein metallothionein-3 (MT-3) prevents Cu-Aβ-mediated cytotoxicity by a Zn-Cu exchange that terminates ROS production. Key questions about the metal exchange mechanisms remain unanswered, e.g., whether an Aβ-metal-MT-3 complex is formed. We studied the exchange of metal between Aβ and Zn(7)-MT-3 by a combination of spectroscopy (absorption, fluorescence, thioflavin T assay, and nuclear magnetic resonance) and transmission electron microscopy. We found that the metal exchange occurs via free Cu(2+) and that an Aβ-metal-MT-3 complex is not formed. This means that the metal exchange does not require specific recognition between Aβ and Zn(7)-MT-3. Also, we found that the metal exchange caused amyloid-related structural and morphological changes in the resulting Zn-Aβ aggregates. A detailed model of the metal exchange mechanism is presented. This model could potentially be important in developing therapeutics with metal-protein attenuating properties in AD.


Endothelial Progenitor Cells Produced From Human Pluripotent Stem Cells by a Synergistic Combination of Cytokines, Small Compounds, and Serum-Free Medium.
Human pluripotent stem cells (hPSCs) are a promising source of autologous endothelial progenitor cells (EPCs) that can be used for the treatment of vascular diseases. However, this kind of treatment requires a large amount of EPCs. Therefore, a highly efficient, robust, and easily reproducible differentiation protocol is necessary. We present a novel serum-free differentiation protocol that exploits the synergy of multiple powerful differentiation effectors. Our protocol follows the proper physiological pathway by differentiating EPCs from hPSCs in three phases that mimic in vivo embryonic vascular development. Specifically, hPSCs are differentiated into (i) primitive streak, which is subsequently turned into (ii) mesoderm, which finally differentiates into (iii) EPCs. This differentiation process yields up to 15 differentiated cells per seeded hPSC in 5 days. Endothelial progenitor cells constitute up to 97% of these derived cells. The experiments were performed on the human embryonic stem cell line H9 and six human induced pluripotent stem cell lines generated in our laboratory. Therefore, robustness was verified using many hPSC lines. Two previously established protocols were also adapted and compared to our synergistic three-phase protocol. Increased efficiency and decreased variability were observed for our differentiation protocol in comparison to the other tested protocols. Furthermore, EPCs derived from hPSCs by our protocol expressed the high-proliferative-potential EPC marker CD157 on their surface in addition to the standard EPC surface markers CD31, CD144, CD34, KDR, and CXCR4. Our protocol enables efficient fully defined production of autologous endothelial progenitors for research and clinical applications.


A Mobile Health Intervention for Self-Management and Lifestyle Change for Persons With Type 2 Diabetes, Part 2: One-Year Results From the Norwegian Randomized Controlled Trial RENEWING HEALTH.
Self-management is crucial in the daily management of type 2 diabetes. It has been suggested that mHealth may be an important method for enhancing self-management when delivered in combination with health counseling. The objective of this study was to test whether the use of a mobile phone-based self-management system used for 1 year, with or without telephone health counseling by a diabetes specialist nurse for the first 4 months, could improve glycated hemoglobin A1c (HbA1c) level, self-management, and health-related quality of life compared with usual care. We conducted a 3-arm prospective randomized controlled trial involving 2 intervention groups and 1 control group. Eligible participants were persons with type 2 diabetes with an HbA1c level ≥7.1% (≥54.1 mmol/mol) and aged ≥18 years. Both intervention groups received the mobile phone-based self-management system Few Touch Application (FTA). The FTA consisted of a blood glucose-measuring system with automatic wireless data transfer, diet manual, physical activity registration, and management of personal goals, all recorded and operated using a diabetes diary app on the mobile phone. In addition, one intervention group received health counseling based on behavior change theory and delivered by a diabetes specialist nurse for the first 4 months after randomization. All groups received usual care by their general practitioner. The primary outcome was HbA1c level. Secondary outcomes were self-management (heiQ), health-related quality of life (SF-36), depressive symptoms (CES-D), and lifestyle changes (dietary habits and physical activity). Data were analyzed using univariate methods (t test, ANOVA) and multivariate linear and logistic regression. A total of 151 participants were randomized: 51 to the FTA group, 50 to the FTA-health counseling (FTA-HC) group, and 50 to the control group. Follow-up data after 1 year were available for 120 participants (79%). HbA1c level decreased in all groups, but did not differ between groups after 1 year. The mean change in the heiQ domain skills and technique acquisition was significantly greater in the FTA-HC group after adjusting for age, gender, and education (P=.04). Other secondary outcomes did not differ between groups after 1 year. In the FTA group, 39% were substantial users of the app; 34% of the FTA-HC group were substantial users. Those aged ≥63 years used the app more than their younger counterparts did (OR 2.7; 95% CI 1.02-7.12; P=.045). The change in HbA1c level did not differ between groups after the 1-year intervention. Secondary outcomes did not differ between groups except for an increase in the self-management domain of skill and technique acquisition in the FTA-HC group. Older participants used the app more than the younger participants did.


Trial of Calcium for Preeclampsia Prevention (CPEP): rationale, design, and methods.
The results of ten clinical trials suggest that supplemental calcium may prevent preeclampsia. However, methodologic problems and differences in study design limit the acceptance of the results and their relevance to other patient populations. Many of the trials were conducted in countries where, unlike the United States, the usual daily diet contained little calcium. Moreover, none of the trials has reported the outcome of systematic surveillance for urolithiasis, a potential complication of calcium supplementation. In response to the need for a thorough evaluation of the effects of calcium supplementation for the prevention of preeclampsia in the United States, the trial of Calcium for Preeclampsia Prevention (CPEP) was undertaken at five university medical centers. Healthy nulliparous patients were randomly assigned to receive either 2 g supplemental calcium daily (n = 2295) or placebo (n = 2294) in a double-blind study. Study tablets were administered beginning from 13 to 21 completed weeks of gestation and continued until the termination of pregnancy. CPEP employed detailed diagnostic criteria, standardized techniques of measurement, and systematic surveillance for the major study endpoints and for urolithiasis. The nutrient intake of each patient was assessed at randomization and at 32-33 weeks gestation. This report describes the study rationale, design, and methods.


Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group.
Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospective study. We assessed potential risk factors, including bone mass, in 9516 white women 65 years of age or older who had had no previous hip fracture. We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture. All reports of hip fractures were validated by review of x-ray films. During the follow-up period, 192 women had first hip fractures not due to motor vehicle accidents. In multivariable age-adjusted analyses, a maternal history of hip fracture doubled the risk of hip fracture (relative risk, 2.0; 95 percent confidence interval, 1.4 to 2.9), and the increase in risk remained significant after adjustment for bone density. Women who had gained weight since the age of 25 had a lower risk. The risk was higher among women who had previous fractures of any type after the age of 50, were tall at the age of 25, rated their own health as fair or poor, had previous hyperthyroidism, had been treated with long-acting benzodiazepines or anticonvulsant drugs, ingested greater amounts of caffeine, or spent four hours a day or less on their feet. Examination findings associated with an increased risk included the inability to rise from a chair without using one's arms, poor depth perception, poor contrast sensitivity, and tachycardia at rest. Low calcaneal bone density was also an independent risk factor. The incidence of hip fracture ranged from 1.1 (95 percent confidence interval, 0.5 to 1.6) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 (95 percent confidence interval, 20 to 34) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age. Women with multiple risk factors and low bone density have an especially high risk of hip fracture. Maintaining body weight, walking for exercise, avoiding long-acting benzodiazepines, minimizing caffeine intake, and treating impaired visual function are among the steps that may decrease the risk.


Efficient terahertz detection in a sheet cavity using a nonlinear optical parametric process.
We designed and simulated a GaP-based sheet cavity structure for room-temperature THz wave detection via a nonlinear optical (NLO) parametric process, using photonic conversion from THz frequencies to the optical domain. The sheet cavity structure consisted of a GaP rectangular waveguide for THz waves. Pump enhancement in the cavity and strong confinement of the THz wave in the waveguide resulted in a high power conversion efficiency of 1% (detection at 5 THz). The noise equivalent power for THz wave detection using an optical single-photon detector was estimated to be in the order of a few fW Hz(-1/2), which was higher than that obtained using room-temperature bolometers, field-effect transistors, and other NLO processes.


Improving process-based crop models to better capture genotype×environment×management interactions.
In spite of the increasing expectation for process-based crop modelling to capture genotype (G) by environment (E) by management (M) interactions to support breeding selections, it remains a challenge to use current crop models to accurately predict phenotypes from genotypes or from candidate genes. We use wheat as a target crop and the APSIM farming systems model (Holzworth et al., 2014) as an example to analyse the current status of process-based crop models with a major focus on need to improve simulation of specific eco-physiological processes and their linkage to underlying genetic controls. For challenging production environments in Australia, we examine the potential opportunities to capture physiological traits, and to integrate genetic and molecular approaches for future model development and applications. Model improvement will require both reducing the uncertainty in simulating key physiological processes and enhancing the capture of key observable traits and underlying genetic control of key physiological responses to environment. An approach consisting of three interactive stages is outlined to (i) improve modelling of crop physiology, (ii) develop linkage from model parameter to genotypes and further to loci or alleles, and (iii) further link to gene expression pathways. This helps to facilitate the integration of modelling, phenotyping, and functional gene detection and to effectively advance modelling of G×E×M interactions. While gene-based modelling is not always needed to simulate G×E×M, including well-understood gene effects can improve the estimation of genotype effects and prediction of phenotypes. Specific examples are given for enhanced modelling of wheat in the APSIM framework.


Training safer surgeons: How do patients view the role of simulation in orthopaedic training?
Simulation allows training without posing risk to patient safety. It has developed in response to the demand for patient safety and the reduced training times for surgeons. Whilst there is an increasing role of simulation in orthopaedic training, the perception of patients and the general public of this novel method is yet unknown. Patients and the public were given the opportunity to perform a diagnostic knee arthroscopy on a virtual reality ARTHRO Mentor simulator. After their practice session, participants answered a validated questionnaire based on a 5-point Likert Scale assessing their opinions on arthroscopic simulation. Primary objective was observing perception of patients on orthopaedic virtual reality simulation. There were a total of 159 respondents, of which 86% were of the opinion that simulators are widely used in surgical training and 94% felt that they should be compulsory. 91% would feel safer having an operation by a surgeon trained on simulators, 87% desired their surgeon to be trained on simulators and 72% believed that additional simulator training resulted in better surgeons. Moreover, none of the respondents would want their operation to be performed by a surgeon who had not trained on a simulator. Cronbach's alpha was 0.969. There is also a clear public consensus for this method of training to be more widely utilised and it would enhance public perception of safer training of orthopaedic surgeons. This study of public perception provides a mandate to increase investment and infrastructure in orthopaedic simulation as part of promoting clinical governance.


Silk-inspired polymers and proteins.
The biocompatibility and biodegradability of natural silk fibres and the benign conditions under which they (with impressive mechanical properties) are produced represent a biomimetic ideal. This ideal has inspired people in both academia and industry to prepare silk-mimetic polymers and proteins by chemical and/or biotechnological means. In the present paper, we aim to give an overview of the design principles of such silk-inspired polymers/proteins, their processing into various materials morphologies, their mechanical and biological properties, and, finally, their technical and biomedical applications.


Diagnostic value of N-methyl-D-aspartate receptor antibodies in women with new-onset epilepsy.
In women younger than 45 years, a new form of encephalitis associated with ovarian teratoma and presenting with seizures and psychiatric symptoms has been described. Most patients have antibodies to NR1/NR2 heteromers of the N-methyl-D-aspartate receptor (NMDAR). To assess the frequency and significance of antibodies to NMDAR in otherwise unexplained new-onset epilepsies in young women. Prospective cohort study. University department of epileptology. From January 1, 2005, to June 30, 2007, we identified 19 female patients aged 15 to 45 years with unexplained new-onset epilepsy. In addition, we studied 61 cerebrospinal fluid-serum sample pairs from patients with other cryptogenic epilepsies and 11 cerebrospinal fluid-serum sample pairs from surgically treated patients with epilepsy with no evident encephalitic abnormalities. Antibodies to NMDAR and characteristics of affected patients. Five of the 19 patients had antibodies against NMDAR. These patients had diffuse cerebral dysfunction and seizure origins. Psychiatric symptoms and pleocytosis were significantly associated with this group of patients. The disease course was episodic, in part relapsing-remitting, with full recoveries either spontaneously or after corticosteroid or intravenous immunoglobulin treatments. Only 1 patient had a neoplasm (multiple neuroendocrine tumors that included the ovaries) identified to date. In the control series, one 22-year-old man with a cryptogenic, severely encephalopathic seizure disorder was NMDAR antibody positive, and he also recovered fully. Anti-NMDAR encephalitis accounts for a relevant proportion of otherwise unexplained new-onset epilepsies. Patients harboring NMDAR antibodies usually have prominent psychiatric symptoms and pleocytosis, and they may develop hypoventilation. Anti-NMDAR encephalitis is not always paraneoplastic.


Spectral absorption characteristics of the major components of dust clouds.
It is well known that dust clouds selectively absorb radiation in the 700-1300 cm(-1) atmospheric window region. Studies have shown that dust clouds are composed of the same minerals as surface soils, although in different proportion. We have examined seventy soil samples from a number of locations around the world to determine their compositions and spectral characteristics. The results indicate that there are five major components which selectively absorb radiation in the 700-1300 cm(-1) region. These are three clay minerals, silica, and calcium carbonate. Absorptivity coefficient spectra of representative soil samples are given.


Perceptual expertise effects are not all or none: spatially limited perceptual expertise for faces in a case of prosopagnosia.
We document a seemingly unique case of severe prosopagnosia, L. R., who suffered damage to his anterior and inferior right temporal lobe as a result of a motor vehicle accident. We systematically investigated each of three factors associated with expert face recognition: fine-level discrimination, holistic processing, and configural processing (Experiments 1-3). Surprisingly, L. R. shows preservation of all three of these processes; that is, his performance in these experiments is comparable to that of normal controls. However, L. R. is only able to apply these processes over a limited spatial extent to the fine-level detail within faces. Thus, when the location of a given change is unpredictable (Experiment 3), L. R. exhibits normal detection of features and spatial configurations only for the lower half of each face. Similarly, when required to divide his attention over multiple face features, L. R. is able to determine the identity of only a single feature (Experiment 4). We discuss these results in the context of forming a better understanding of prosopagnosia and the mechanisms used in face recognition and visual expertise. We conclude that these mechanisms are not "all-or-none," but rather can be impaired incrementally, such that they may remain functional over a restricted spatial area. This conclusion is consistent with previous research suggesting that perceptual expertise is acquired in a spatially incremental manner [Gauthier, I., & Tarr, M. J. Unraveling mechanisms for expert object recognition: Bridging brain activity and behavior. Journal of Experimental Psychology: Human Perception & Performance, 28, 431-446, 2002].


Heart-brain interactions during social and cognitive stress in hypertensive disease: A multidimensional approach.
Hypertensive disease (HTD), a prominent risk factor for cardiovascular and cerebrovascular diseases, is characterized by elevated stress-proneness. Since stress levels are underpinned by both cardiac and neural factors, multidimensional insights are required to robustly understand their disruption in HTD. Yet, despite their crucial relevance, heart rate variability (HRV) and multimodal neurocognitive markers of stress in HTD remain controversial and unexplored respectively. To bridge this gap, we studied cardiodynamic as well as electrophysiological and neuroanatomical measures of stress in HTD patients and healthy controls. Both groups performed the Trier Social Stress Test (TSST), a validated stress-inducing task comprising a baseline and a mental stress period. During both stages, we assessed a sensitive HRV parameter (the low frequency/high frequency [LF/HF ratio]) and an online neurophysiological measure (the heartbeat-evoked potential [HEP]). Also, we obtained neuroanatomical data via voxel-based morphometry (VBM) for correlation with online markers. Relative to controls, HTD patients exhibited increased LF/HF ratio and greater HEP modulations during baseline, reduced changes between baseline and stress periods, and lack of significant stress-related HRV modulations associated with the grey matter volume of putative frontrostriatal regions. Briefly, HTD patients presented signs of stress-related autonomic imbalance, reflected in a potential basal stress overload and a lack of responsiveness to acute psychosocial stress, accompanied by neurophysiological and neuroanatomical alterations. These multimodal insights underscore the relevance of neurocognitive data for developing innovations in the characterization, prognosis and treatment of HTD and other conditions with autonomic imbalance. More generally, these findings may offer new insights into heart-brain interactions.


Remapping in Cerebral and Cerebellar Cortices Is Not Restricted by Somatotopy.
A fundamental organizing principle in the somatosensory and motor systems is somatotopy, where specific body parts are represented separately and adjacently to other body parts, resulting in a body map. Different terminals of the sensorimotor network show varied somatotopic layouts, in which the relative position, distance, and overlap between body-part representations differ. Since somatotopy is best characterized in the primary somatosensory (S1) and motor (M1) cortices, these terminals have been the main focus of research on somatotopic remapping following loss of sensory input (e.g., arm amputation). Cortical remapping is generally considered to be driven by the layout of the underlying somatotopy, such that neighboring body-part representations tend to activate the deprived brain region. Here, we challenge the assumption that somatotopic layout restricts remapping, by comparing patterns of remapping in humans born without one hand (hereafter, one-handers, n = 26) across multiple terminals of the sensorimotor pathway. We first report that, in the cerebellum of one-handers, the deprived hand region represents multiple body parts. Importantly, the native representations of some of these body parts do not neighbor the deprived hand region. We further replicate our previous findings, showing a similar pattern of remapping in the deprived hand region of the cerebral cortex in one-handers. Finally, we report preliminary results of a similar remapping pattern in the putamen of one-handers. Since these three sensorimotor terminals (cerebellum, cerebrum, putamen) contain different somatotopic layouts, the parallel remapping they undergo demonstrates that the mere spatial layout of body-part representations may not exclusively dictate remapping in the sensorimotor systems.SIGNIFICANCE STATEMENT When a hand is missing, the brain region that typically processes information from that hand may instead process information from other body parts, a phenomenon termed remapping. It is commonly thought that only body parts whose information is processed in regions neighboring the hand region could "take up" the resources of this now deprived region. Here we demonstrate that information from multiple body parts is processed in the hand regions of both the cerebral cortex and cerebellum. The native brain regions of these body parts have varying levels of overlap with the hand regions of the cerebral cortex and cerebellum, and do not necessarily neighbor the hand regions. We therefore propose that proximity between brain regions does not limit brain remapping.


AEKF-SLAM: A New Algorithm for Robotic Underwater Navigation.
In this work, we focus on key topics related to underwater Simultaneous Localization and Mapping (SLAM) applications. Moreover, a detailed review of major studies in the literature and our proposed solutions for addressing the problem are presented. The main goal of this paper is the enhancement of the accuracy and robustness of the SLAM-based navigation problem for underwater robotics with low computational costs. Therefore, we present a new method called AEKF-SLAM that employs an Augmented Extended Kalman Filter (AEKF)-based SLAM algorithm. The AEKF-based SLAM approach stores the robot poses and map landmarks in a single state vector, while estimating the state parameters via a recursive and iterative estimation-update process. Hereby, the prediction and update state (which exist as well in the conventional EKF) are complemented by a newly proposed augmentation stage. Applied to underwater robot navigation, the AEKF-SLAM has been compared with the classic and popular FastSLAM 2.0 algorithm. Concerning the dense loop mapping and line mapping experiments, it shows much better performances in map management with respect to landmark addition and removal, which avoid the long-term accumulation of errors and clutters in the created map. Additionally, the underwater robot achieves more precise and efficient self-localization and a mapping of the surrounding landmarks with much lower processing times. Altogether, the presented AEKF-SLAM method achieves reliably map revisiting, and consistent map upgrading on loop closure.


Influences on control in diabetes mellitus: patient, doctor, practice, or delivery of care?
To assess patient, doctor, practice, and process of care variables for their effect on glycaemic control in diabetes mellitus, and to quantify their relative effects. Search of general practice medical records, patient questionnaires and examination, doctor questionnaire, videotaping and analysis of consultations, and practice questionnaire. 12 practices with 32 participating general practitioners in Nottinghamshire. 318 patients randomly selected from those with diabetes in each practice, 10 for each participating doctor. Glycaemic control as measured by random glycated haemoglobin A1c estimation (random haemoglobin A1 measurement). Glycaemic control was significantly related to the disease process as measured by years since diagnosis, treatment group, and number of diabetes related clinical events. Females had significantly worse control than males. Other patient factors, such as age, social class, lifestyle, attitudes, satisfaction, and knowledge, had no association with glycaemic control. Of all the doctor factors examined, only doctors who professed a special interest in diabetes achieved significantly better glycaemic control. Bigger and better equipped practices and those with a diabetic miniclinic had patients with significantly better glycaemic control, as did those with access to dietetic advice. Patients attending hospital clinics had worse glycaemic control, but this seemed to be attributable to the case mix and practice characteristics. Shared care did not contribute to the multiple linear regression model. Glycaemic control among diabetic patients in the community is related to such factors as treatment group, sex, and years since diagnosis; it is also related to the organisation and process of care. The findings support concentrating diabetic care on partners with special interests in diabetes in well equipped practices with adequate dietetic support.


Can the intake of antiparasitic secondary metabolites explain the low prevalence of hemoparasites among wild Psittaciformes?
Parasites can exert selection pressure on their hosts through effects on survival, on reproductive success, on sexually selected ornament, with important ecological and evolutionary consequences, such as changes in population viability. Consequently, hemoparasites have become the focus of recent avian studies. Infection varies significantly among taxa. Various factors might explain the differences in infection among taxa, including habitat, climate, host density, the presence of vectors, life history and immune defence. Feeding behaviour can also be relevant both through increased exposure to vectors and consumption of secondary metabolites with preventative or therapeutic effects that can reduce parasite load. However, the latter has been little investigated. Psittaciformes (parrots and cockatoos) are a good model to investigate these topics, as they are known to use biological control against ectoparasites and to feed on toxic food. We investigated the presence of avian malaria parasites (Plasmodium), intracellular haemosporidians (Haemoproteus, Leucocytozoon), unicellular flagellate protozoans (Trypanosoma) and microfilariae in 19 Psittaciformes species from a range of habitats in the Indo-Malayan, Australasian and Neotropical regions. We gathered additional data on hemoparasites in wild Psittaciformes from the literature. We considered factors that may control the presence of hemoparasites in the Psittaciformes, compiling information on diet, habitat, and climate. Furthermore, we investigated the role of diet in providing antiparasitic secondary metabolites that could be used as self-medication to reduce parasite load. We found hemoparasites in only two of 19 species sampled. Among them, all species that consume at least one food item known for its secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, were free from hemoparasites. In contrast, the infected parrots do not consume food items with antimalarial or even general antiparasitic properties. We found that the two infected species in this study consumed omnivorous diets. When we combined our data with data from studies previously investigating blood parasites in wild parrots, the positive relationship between omnivorous diets and hemoparasite infestation was confirmed. Individuals from open habitats were less infected than those from forests. The consumption of food items known for their secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, as well as the higher proportion of infected species among omnivorous parrots, could explain the low prevalence of hemoparasites reported in many vertebrates.


Tailoring supramolecular guest-host hydrogel viscoelasticity with covalent fibrinogen double networks.
Supramolecular chemistry has enabled the design of tunable biomaterials that mimic the dynamic and viscoelastic characteristics of the extracellular matrix. However, the noncovalent nature of supramolecular bonds renders them inherently weak, limiting their applicability to many biomedical applications. To address this, we formulated double network (DN) hydrogels through a combination of supramolecular and covalent networks to tailor hydrogel viscoelastic properties. Specifically, DN hydrogels were formed through the combination of supramolecular guest-host (GH) hyaluronic acid (HA) networks with covalent networks from the photocrosslinking of acrylated poly(ethylene glycol) modified fibrinogen (PEG-fibrinogen) and PEG diacrylate. DN hydrogels exhibited higher compressive moduli, increased failure stresses, and increased toughness when compared to purely covalent networks. While GH concentration had little influence on the compressive moduli across DN hydrogels, an increase in the GH concentration resulted in more viscous behavior of DN hydrogels. High viability of encapsulated bovine mesenchymal stromal cells (MSCs) was observed across groups with enhanced spreading and proliferation in DN hydrogels with increased GH concentration. This combination of supramolecular and covalent chemistries enables the formation of dynamic hydrogels with tunable properties that can be customized towards repair of viscoelastic tissues.


Advances in the measurement of coverage for RMNCH and nutrition: from contact to effective coverage.
Current methods for measuring intervention coverage for reproductive, maternal, newborn, and child health and nutrition (RMNCH+N) do not adequately capture the quality of services delivered. Without information on the quality of care, it is difficult to assess whether services provided will result in expected health improvements. We propose a six-step coverage framework, starting from a target population to (1) service contact, (2) likelihood of services, (3) crude coverage, (4) quality-adjusted coverage, (5) user-adherence-adjusted coverage and (6) outcome-adjusted coverage. We support our framework with a comprehensive review of published literature on effective coverage for RMNCH+N interventions since 2000. We screened 8103 articles and selected 36 from which we summarised current methods for measuring effective coverage and computed the gaps between 'crude' coverage measures and quality-adjusted measures. Our review showed considerable variability in data sources, indicator definitions and analytical approaches for effective coverage measurement. Large gaps between crude coverage and quality-adjusted coverage levels were evident, ranging from an average of 10 to 38 percentage points across the RMNCH+N interventions assessed. We define effective coverage as the proportion of individuals experiencing health gains from a service among those who need the service, and distinguish this from other indicators along a coverage cascade that make quality adjustments. We propose a systematic approach for analysis along six steps in the cascade. Research to date shows substantial drops in effective delivery of care across these steps, but variation in methods limits comparability of the results. Advancement in coverage measurement will require standardisation of effective coverage terminology and improvements in data collection and methodological approaches.


Recurrent community-acquired pneumonia in patients starting acid-suppressing drugs.
Several studies suggest that proton pump inhibitors (PPIs) and histamine 2-receptor antagonists (H2s) increase risk of community-acquired pneumonia. To test this hypothesis, we examined a prospective population-based cohort predisposed to pneumonia: elderly patients (> or =65 years) who had survived hospitalization for pneumonia. This study featured a nested case-control design where cases were patients hospitalized for recurrent pneumonia (> or =30 days after initial episode) and controls were age, sex, and incidence-density sampling matched but never had recurrent pneumonia. PPI/H2 exposure was classified as never, past, or current use before recurrent pneumonia. The association between PPI/H2s and pneumonia was assessed using multivariable conditional logistic regression. During 5.4 years of follow-up, 248 recurrent pneumonia cases were matched with 2476 controls. Overall, 71 of 608 (12%) current PPI/H2 users had recurrent pneumonia, compared with 130 of 1487 (8%) nonusers (adjusted odds ratio [aOR] 1.5; 95% confidence interval [CI], 1.1-2.1). Stratifying the 608 current users according to timing of PPI/H2 initiation revealed incident current-users (initiated PPI/H2 after initial pneumonia hospitalization, n=303) bore the entire increased risk of recurrent community-acquired pneumonia (15% vs 8% among nonusers, aOR 2.1; 95% CI, 1.4-3.0). The 305 prevalent current-users (PPI/H2 exposure before and after initial community-acquired pneumonia hospitalization) were equally likely to develop recurrent pneumonia as nonusers (aOR 0.99; 95% CI, 0.63-1.57). Acid-suppressing drug use substantially increased the likelihood of recurrent pneumonia in high-risk elderly patients. The association was confined to patients initiating PPI/H2s after hospital discharge. Our findings should be considered when deciding to prescribe these drugs in patients with a recent history of pneumonia.


Surgical treatment of a paraspinal abscess with osteomyelitis and spinal cord compression in a rabbit.
CASE DESCRIPTION A 16-month-old neutered male Continental Giant rabbit (Lepus curpaeums) was referred for evaluation of a 7-day history of acute-onset, progressive, symmetric paraparesis. CLINICAL FINDINGS On initial examination, the rabbit was nonambulatory, and results of neurologic examination were consistent with a lesion affecting the T3-L3 spinal cord segments. Thoracic radiography showed irregular widening of the left T11-12 articular process joint. Marked dorsolateral and lateral extradural spinal cord compression with contrast enhancement of the adjacent epaxial muscles was evident on MRI images of the spine. TREATMENT AND OUTCOME A left-sided T11-T12 hemilaminectomy was performed, which revealed an abnormal and hypertrophic T11-12 articular process joint and an osteolytic lesion communicating with the vertebral canal. Copious purulent material causing marked spinal cord compression was evident, and the surgical site was lavaged extensively with sterile (0.9% NaCl) saline solution. Results of aerobic, anaerobic, and enriched bacteriologic cultures of swab specimens obtained from the surgical site were negative. Histologic analysis of biopsy samples revealed chronic purulent osteomyelitis, myositis, and fasciitis with necrosis, fibrosis, and dystrophic mineralization. The rabbit was discharged 48 hours after surgery. Ten weeks after surgery, the rabbit was ambulatory with mild paraparesis. On telephone follow-up 21 months after surgery, the owners indicated that the rabbit was healthy and expressed satisfaction with the treatment and outcome. CLINICAL RELEVANCE Paraspinal abscess with vertebral canal involvement should be considered as a differential diagnosis for rabbits with clinical signs of progressive T3-L3 myelopathy. Outcome for the patient of the present report suggested that surgical treatment including decompression and debridement can result in a favorable long-term outcome.


Effect of cell-cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells.
Heterotypic cell interaction between parenchymal cells and nonparenchymal neighbors has been reported to modulate cell growth, migration, and/or differentiation. In both the developing and adult liver, cell-cell interactions are imperative for coordinated organ function. In vitro, cocultivation of hepatocytes and nonparenchymal cells has been used to preserve and modulate the hepatocyte phenotype. We summarize previous studies in this area as well as recent advances in microfabrication that have allowed for more precise control over cell-cell interactions through 'cellular patterning' or 'micropatterning'. Although the precise mechanisms by which nonparenchymal cells modulate the hepatocyte phenotype remain unelucidated, some new insights on the modes of cell signaling, the extent of cell-cell interaction, and the ratio of cell populations are noted. Proposed clinical applications of hepatocyte cocultures, typically extracorporeal bioartificial liver support systems, are reviewed in the context of these new findings. Continued advances in microfabrication and cell culture will allow further study of the role of cell communication in physiological and pathophysiological processes as well as in the development of functional tissue constructs for medical applications.


NO-Dependent programmed cell death is involved in the formation of Zn-related lesions in tobacco leaves.
A recent study indicated that the development of lesions on the leaf blades of tobacco exposed to zinc (Zn) excess can be considered a manifestation of a Zn-tolerance strategy at the organ level. Here, we investigated whether cell death leading to the formation of localized lesions is destructive in character (necrosis type) or results from programmed self-induced cell death (PCD). Selected parameters, including PCD markers, were determined in the leaves from tobacco plants grown in the presence of 200 μM Zn and compared with control conditions. TUNEL assay results showing internucleosomal DNA fragmentation in the nuclei of the cells from Zn-exposed leaves, together with an enhanced expression of three PCD marker genes (NtBI-1, Ntrboh, and NtSIPK), indicated the involvement of PCD in the formation of Zn-related lesions. It is known that NO is a key factor in the execution of PCD. Interestingly, upon exposure to high Zn, in situ localization of NO (visualized using DAF-2DA fluorescence) was restricted to groups of mesophyll cells, and was correlated with the pattern of Zn localization (determined using the fluorophore Zinpyr-1), similarly limited primarily to groups of "Zn accumulating cells". Furthermore, inhibition of the formation of lesions in the presence of l-NAME (an NO synthase inhibitor) was accompanied by the delayed appearance of Zn and by NO localization limited to these groups of cells. Altogether, we provide the first demonstration that Zn-related lesions in leaves develop from groups of mesophyll cells in which accumulation of high concentrations of Zn contributes to enhancement of the NO level and to initiation of PCD processes.


Lipopolysaccharide induces the interactions of breast cancer and endothelial cells via activated monocytes.
The adhesion of circulating cancer cells to vascular endothelium is a key step in hematogenous metastasis. Cancer cell-endothelium interactions are mediated by cell adhesion molecules that can also be involved in the arrest of monocytes and other circulating leukocytes on endothelium in inflammation. Static and microfluidic flow adhesion assays as well as flow cytometry were conducted in this study to elucidate the role of monocytes, bacterial lipopolysaccharide (LPS), and histamine in breast cancer cell adhesion to vascular endothelial cells. Tumor necrosis factor-α (TNF-α) released from LPS-treated monocytes triggered the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. Histamine augmented the TNF-α effect, leading to a high number of arrested breast cancer cells under both static and shear flow conditions. LPS-treated monocytes were shown to enhance the arrest of breast cancer cells by anchoring the cancer cells to activated endothelial cells. This anchorage was achieved by binding cancer cell ICAM-1 to monocyte β2 integrins and binding endothelial ICAM-1 and VCAM-1 to monocyte β1 and β2 integrins. The results of this study imply that LPS is an important risk factor for cancer metastasis and that the elevated serum level of histamine further increases the risk of LPS-induced cancer metastasis. Preventing bacterial infections is essential in cancer treatment, and it is particularly vital for cancer patients affected by allergy.


Zinc deficiency affects DNA damage, oxidative stress, antioxidant defenses, and DNA repair in rats.
Approximately 12% of Americans do not consume the Estimated Average Requirement for zinc and could be at risk for marginal zinc deficiency. Zinc is an essential component of numerous proteins involved in the defense against oxidative stress and DNA damage repair. Studies in vitro have shown that zinc depletion causes DNA damage. We hypothesized that zinc deficiency in vivo causes DNA damage through increases in oxidative stress and impairments in DNA repair. Sprague-Dawley rats were fed zinc-adequate (ZA; 30 mg Zn/kg) or severely zinc-deficient (ZD; <1 mg Zn/kg) diets or were pair-fed zinc-adequate diet to match the mean feed intake of ZD rats for 3 wk. After zinc depletion, rats were repleted with a ZA diet for 10 d. In addition, zinc-adequate (MZA 30 mg Zn/kg) or marginally zinc-deficient (MZD; 6 mg Zn/kg) diets were given to different groups of rats for 6 wk. Severe zinc depletion caused more DNA damage in peripheral blood cells than in the ZA group and this was normalized by zinc repletion. We also detected impairments in DNA repair, such as compromised p53 DNA binding and differential activation of the base excision repair proteins 8-oxoguanine glycosylase and poly ADP ribose polymerase. Importantly, MZD rats also had more DNA damage and higher plasma F(2)-isoprostane concentrations than MZA rats and had impairments in DNA repair functions. However, plasma antioxidant concentrations and erythrocyte superoxide dismutase activity were not affected by zinc depletion. These results suggest interactions among zinc deficiency, DNA integrity, oxidative stress, and DNA repair and suggested a role for zinc in maintaining DNA integrity.


Efficacy of an experimental toothpaste containing 5% calcium sodium phosphosilicate in the relief of dentin hypersensitivity: An 8-week randomized study (Study 1).
To evaluate the efficacy of an experimental toothpaste containing 5% (w/w) calcium sodium phosphosilicate (CSPS) in relieving dentin hypersensitivity (DH) compared with control toothpastes containing no known anti-sensitivity ingredients. This was the first of two exploratory, randomized, four-treatment, examiner-blind, parallel-design, single-site, 8-week studies in healthy subjects with self-reported and clinically diagnosed DH. The experimental toothpaste contained 5% CSPS with a modified surfactant system, developed to enhance its organoleptic properties. Efficacy was evaluated against an abrasivity-matched placebo formulation (0% CSPS) with additional abrasive silica replacing the CSPS, and two commercially available fluoride toothpastes as controls. After an initial lead-in period, subjects were randomized to one of the four study treatments and instructed to brush twice daily for the next 8 weeks. DH was assessed at baseline and following 4 and 8 weeks of treatment by response to tactile and evaporative (air) stimuli, and using a Dentine Hypersensitivity Experience Questionnaire (DHEQ; a validated quality-of-life measure for DH). A total of 134 subjects were randomized and completed the study. All treatments demonstrated statistically significant reductions in sensitivity from baseline at Week 4 and Week 8 for each clinical measure of sensitivity (all P ≤ 0.001). The 0% CSPS toothpaste demonstrated small but statistically significant reductions in Schiff sensitivity score compared with the other study toothpastes at Week 8 (all P< 0.05), whereas the experimental 5% CSPS toothpaste significantly improved the tactile threshold at Week 4 compared with the 0% CSPS toothpaste (P = 0.0467). The DHEQ responses did not reveal any consistent statistically significant within-treatment changes from baseline or between-treatment differences. Correlation analysis showed weak-to-moderate associations between the DHEQ outcomes and clinical endpoints. Study treatments were well tolerated. The treatment differences observed in this exploratory study were small and inconsistent between measures. The reasons for the inconsistencies are not clear but may be related to the properties of the abrasivity-matched 0% CSPS formulation, with the increased level of dental silica conferring an advantage in terms of reducing DH. The ability of dental silicas to occlude exposed dentin tubules and thereby reduce DH has been demonstrated in previous studies, and may warrant further clinical investigation.


Family structure and breakfast consumption of 11-15 year old boys and girls in Scotland, 1994-2010: a repeated cross-sectional study.
The benefits of breakfast during childhood and adolescence have been reported previously though few studies have considered family structure inequalities in breakfast consumption. The proportion of young people living in non-traditional family types has increased in recent years, strengthening the need to describe and monitor the impact of the changing family unit on adolescent breakfast consumption. This study aimed to describe changes in daily breakfast consumption among adolescents in Scotland between 1994 and 2010, while also considering family structure inequalities, and the degree to which these have changed over time. Data from the 1994, 1998, 2002, 2006 and 2010 Scottish Health Behaviour in School-aged Children (HBSC) surveys were analysed using logistic multilevel regression models for binary outcome variable daily breakfast consumption. Daily breakfast consumption among adolescents increased between 1994 and 2010, although there were differences by age and sex. In fact those aged over 14.5 years saw decreases in breakfast consumption, and girls saw significantly larger increases than boys. Daily breakfast consumption was more prevalent among adolescents from 'both parent' families, with lowest prevalence among those from single parent families. Trends in daily breakfast consumption between 1994 and 2010 also varied by family structure. While prevalence of daily breakfast consumption increased among those living with 'both parents', the largest proportion of the population, prevalence decreased over time among adolescents of single parent families, and particularly among those living with their father. Family structure inequalities in daily breakfast consumption increased between 1994 and 2010, while breakfast consumption across the population as a whole increased. As the proportion of young people living in an alternative family structure continues to grow it is important to understand why these inequalities have increased and how these may be overcome. Possible reasons for family structure inequalities and their increase in recent years are discussed.


Stereochemical course of phospho group transfer by human prostatic acid phosphatase.
The stereochemical course of the phospho transfer catalyzed by homogeneous human prostatic acid phosphatase was investigated using 31P nuclear magnetic resonance spectroscopy. Transphosphorylation from phenyl-(R)-[15O, 17O, 18O]phosphate to (S)-propane-1,2-diol occurs with overall retention of configuration at phosphorus. This stereochemical result is consistent with the interpretation that the hydrolysis of substrates by this enzyme proceeds by way of a covalent phosphoenzyme intermediate. Conditions for optimizing phospho transfer by this and related acid phosphatases have also been explored.


Biological age and sex-related declines in physical activity during adolescence.
Sex differences in the rate of decline in physical activity (PA) are most pronounced during adolescence. However, once boys and girls are aligned on biological age, sex differences in the patterns of PA become attenuated. The aim of this study was to test whether biological maturation can account for sex differences in participation in PA over time from late childhood to early adolescence. A prospective cohort of children (N = 2100; 1064 boys) was followed from ages 11 to 14 yr, with repeated assessments of PA and anthropometry. Self-reported participation in organized and free play activities was used to track participation in PA. Biological age was measured using an estimate of years to attainment of peak height velocity. Mixed-effects models were used to test whether controlling for biological age attenuates the effect of chronological age and sex on PA. As expected, the rate of decline in participation in PA was greater for girls than for boys (B = -1.18, P < 0.01). In multivariable analyses, adjusting for biological age completely attenuated the effect of sex and chronological age for participation in free play activities, but not for participation in organized play. Overall, biological age was a stronger predictor of participation than chronological age. The effect of biological age on sex by chronological age differences may be specific to certain types of PA participation. Given the importance of maturation to participation in activity, it is suggested that public health strategies target biological not chronological age to prevent declines in PA during adolescence particularly when promoting habitual or lifestyle activity.


Gastric mucosal response to Helicobacter pylori.
Since Marshall's discovery before 20 years, Helicobacter pylori (H. pylori) infection is reportedly to be associated with a variety of clinical outcomes including peptic ulcer disease and gastric cancer. The first step of the H. pylori colonization might be its adhesion to the surface epithelial cells, which evokes gastric inflammatory events initiated by neutrophil recruitment from the microcirculation. Mongolian gerbil is one of the suitable animal models for H. pylori infection, which exerts gastric ulcer and cancer with its bacterial infection. In H. pylori-colonized gerbils, extensive levels of microvascular leukocyte adhesion and migration into the parenchymal side and significant levels of inflammatory cell infiltration are encountered. Bacterial urease not only neutralizes gastric luminal acid, but also plays as an adhesion factor to the surface epithelium. Recently, such an adhesion to the epithelium is reported to be important for bacterial type IV secretory system, which intermediates Cag A injection into the epithelial cells. Then, multiple chemokine and cytokine networks are activated and mucosal inflammatory lesion formation would be completed. In the long-term colonization of H. pylori, gastric mucosal cell turnover would be modified due to persistent inflammation and then such deregulation of cell turnover might link to the precancerous lesion formation.


Lymnaea EGF and gigantoxin I, novel invertebrate members of the epidermal growth factor family.
In this review, we compare the sequence and structural relationships of two epidermal growth factor (EGF) family related proteins that have recently been discovered in invertebrate species. The first is L-EGF, a secreted growth factor from the gastropod mollusk Lymnaea stagnalis. The second is a peptide toxin (Gigantoxin I), isolated from the sea anenome Stichodactyla giganteus, which can paralyze crabs. L-EGF and Gigantoxin I share striking sequence similarity with mammalian erbB1 receptor ligands, including most of the essential receptor binding sites. Intriguingly, L-EGF's tertiary structure resembles more the structure of the EGF-like domain of coagulation factors. That is, the secondary and tertiary structure of L-EGF indicates the presence of a double-stranded beta-sheet but also suggests that this protein, in contrast to all other erbB1 ligands, contains a calcium-binding domain. One of the most remarkable features of L-EGF and Gigantoxin I however, is the indication that these protein are synthesized as non-membrane bound secreted peptides. This feature sets L-EGF and Gigantoxin I apart from all other members of the EGF family or EGF-like proteins identified thus far. We discuss sequence similarities and dissimilarities in the light of indications that, despite the more than 600 million years of phylogenetic distance separating both these invertebrates from mammals, Gigantoxin I and L-EGF retain some affinity for the mammalian erbB-family of receptors. Considering that mammalian EGF and its family members are frequently implicated in neoplastic diseases, the increasing number of identified and characterized invertebrate EGF family members may provide valuable leads in the design of erbB receptor antagonists.


Systems analysis and improvement approach to optimize the hypertension diagnosis and care cascade for PLHIV individuals (SAIA-HTN): a hybrid type III cluster randomized trial.
Across sub-Saharan Africa, evidence-based clinical guidelines to screen and manage hypertension exist; however, country level application is low due to lack of service readiness, uneven health worker motivation, weak accountability of health worker performance, and poor integration of hypertension screening and management with chronic care services. The systems analysis and improvement approach (SAIA) is an evidence-based implementation strategy that combines systems engineering tools into a five-step, facility-level package to improve understanding of gaps (cascade analysis), guide identification and prioritization of low-cost workflow modifications (process mapping), and iteratively test and redesign these modifications (continuous quality improvement). As hypertension screening and management are integrated into chronic care services in sub-Saharan Africa, an opportunity exists to test whether SAIA interventions shown to be effective in improving efficiency and coverage of HIV services can be effective when applied to the non-communicable disease services that leverage the same platform. We hypothesize that SAIA-hypertension (SAIA-HTN) will be effective as an adaptable, scalable model for broad implementation. We will deploy a hybrid type III cluster randomized trial to evaluate the impact of SAIA-HTN on hypertension management in eight intervention and eight control facilities in central Mozambique. Effectiveness outcomes include hypertension cascade flow measures (screening, diagnosis, management, control), as well as hypertension and HIV clinical outcomes among people living with HIV. Cost-effectiveness will be estimated as the incremental costs per additional patient passing through the hypertension cascade steps and the cost per additional disability-adjusted life year averted, from the payer perspective (Ministry of Health). SAIA-HTN implementation fidelity will be measured, and the Consolidated Framework for Implementation Research will guide qualitative evaluation of the implementation process in high- and low-performing facilities to identify determinants of intervention success and failure, and define core and adaptable components of the SAIA-HTN intervention. The Organizational Readiness for Implementing Change scale will measure facility-level readiness for adopting SAIA-HTN. SAIA packages user-friendly systems engineering tools to guide decision-making by front-line health workers to identify low-cost, contextually appropriate chronic care improvement strategies. By integrating SAIA into routine hypertension screening and management structures, this pragmatic trial is designed to test a model for national scale-up. ClinicalTrials.gov NCT04088656 (registered 09/13/2019; https://clinicaltrials.gov/ct2/show/NCT04088656).


Cardiac Remodeling After Hypertensive Pregnancy Following Physician-Optimized Blood Pressure Self-Management: The POP-HT Randomized Clinical Trial Imaging Sub-study.
Background: Hypertensive pregnancy disorders are associated with adverse cardiac remodeling, which can fail to reverse postpartum in some women. The Physician Optimized Postpartum Hypertension Treatment trial demonstrated improved blood pressure control, while the cardiovascular system recovers postpartum, associates with persistently reduced blood pressure. We now report the impact on cardiac remodeling. Methods: In this prospective, randomized, open-label, blinded endpoint trial, in a single UK hospital, 220 women were randomly assigned 1:1 to self-monitoring with research physician-optimized antihypertensive titration, or usual postnatal care from primary care physician and midwife. Participants were aged 18 years or over, with pre-eclampsia or gestational hypertension, requiring antihypertensives on hospital discharge postnatally. Pre-specified secondary cardiac imaging outcomes were recorded by echocardiography around delivery, and again at blood pressure primary outcome assessment, around nine months postpartum, when cardiovascular magnetic resonance was also performed. Results: 187 women (101 intervention; 86 usual care) underwent echocardiography at baseline and follow up, at a mean 258+/-14.6 days postpartum, of which 174 (93 intervention; 81 usual care) also had cardiovascular magnetic resonance at follow up. Relative wall thickness by echocardiography was 0.06 (95% CI0.07 to 0.05, P=<0.001) lower in the intervention group between baseline and follow up, and cardiovascular magnetic resonance at follow up demonstrated a lower left ventricular mass (-6.37g/m2 (95% CI -7.99 to -4.74, P<0.001), end diastolic volume (-3.87ml/m2, 95% CI -6.77 to -0.98, P=0.009) and end systolic volume (-3.25ml/m2, 95% CI 4.87 to -1.63, P <0.001) and higher left and right ventricular ejection fraction by 2.6% (95% CI 1.3 to 3.9, P<0.001) and 2.8% (95% CI 1.4 to 4.1, P<0.001) respectively. Echocardiography assessed left ventricular diastolic function demonstrated a mean difference in average E/E' of 0.52 (95% CI -0.97 to -0.07, P=0.024), and a reduction in left atrial volumes of -4.33ml/m2 (95% CI -5.52 to -3.21, P=<0.001) between baseline and follow up, when adjusted for baseline differences in measures. Conclusions: Short-term postnatal optimization of blood pressure control following hypertensive pregnancy, through self-monitoring and physician-guided antihypertensive titration, associates with long term changes in cardiovascular structure and function, in a pattern associated with more favorable cardiovascular outcomes.


Precision Measurement of Cosmic-Ray Nitrogen and its Primary and Secondary Components with the Alpha Magnetic Spectrometer on the International Space Station.
A precision measurement of the nitrogen flux with rigidity (momentum per unit charge) from 2.2 GV to 3.3 TV based on 2.2×10^{6} events is presented. The detailed rigidity dependence of the nitrogen flux spectral index is presented for the first time. The spectral index rapidly hardens at high rigidities and becomes identical to the spectral indices of primary He, C, and O cosmic rays above ∼700 GV. We observed that the nitrogen flux Φ_{N} can be presented as the sum of its primary component Φ_{N}^{P} and secondary component Φ_{N}^{S}, Φ_{N}=Φ_{N}^{P}+Φ_{N}^{S}, and we found Φ_{N} is well described by the weighted sum of the oxygen flux Φ_{O} (primary cosmic rays) and the boron flux Φ_{B} (secondary cosmic rays), with Φ_{N}^{P}=(0.090±0.002)×Φ_{O} and Φ_{N}^{S}=(0.62±0.02)×Φ_{B} over the entire rigidity range. This corresponds to a change of the contribution of the secondary cosmic ray component in the nitrogen flux from 70% at a few GV to <30% above 1 TV.


Experimental evidence for asymmetric mate preference and aggression: behavioral interactions in a woodrat (Neotoma) hybrid zone.
Female mate preferences may be under strong selection in zones of contact between closely related species because of greater variation in available mates and the potential costs of hybridization. We studied female mate preferences experimentally in a zone of secondary contact between Desert and Bryant's Woodrat (Neotoma lepida and N. bryanti) in the southern foothills of the Sierra Nevada of California. We tested female preference for conspecific versus heterospecific males in paired choice trials in which females could interact freely with males, but males could not interact directly with each other. We compared preferences of females from both allopatric and sympatric sites. We did not find evidence of the process of reinforcement as assortative preferences were not stronger in sympatry than in allopatry. Mate preferences, however, were asymmetric, with N. lepida females mating preferentially with conspecifics and N. bryanti females showing no preference by species. Sympatric females were less likely to mate than allopatric females, due in part to an increase in aggressive interactions. However, even in the absence of aggression, courtship led to mating less often in sympatric females, suggesting they were choosier or had lower sexual motivation than allopatric females. Patterns of mate choice in this woodrat system appear to be strongly impacted by body size and aggressive behavior. In particular, females of the smaller-bodied species rarely interact with the relatively large heterospecific males. In contrast females of the larger-bodied species accept the relatively small heterospecific males. For sympatric animals, rates of aggression were markedly higher than for allopatric animals and reduced affiliative and reproductive behavior in our trials. Sympatric animals are larger and more aggressive, traits that are likely under strong ecological selection across the sharp resource gradient that characterizes the contact zone. However, our results suggest that these traits that are likely favored in competitive interactions between the species also impact reproductive interactions. Combined with our previous findings of post-zygotic isolation in this system, this study suggests that multiple isolating mechanisms contribute to the rate of genetic exchange between these species when they come into contact, and that these mechanisms are the result of selection on traits that are important in a range of ecological and reproductive interactions.


The impact of smoking on incident type 2 diabetes in a cohort with hepatitis B but not hepatitis C infection.
Smoking may be a risk factor for diabetes, and it has been suggested that viral hepatitis may predispose to diabetes. We studied diabetes and smoking histories in people with viral hepatitis. From 1997 to 2004, we studied the risk of incident diabetes in a community cohort with hyperendemic HBV and HCV infection in southern Taiwan. The cohort involved 3539 people (40-70 years old) without diabetes. Four hundred and twenty-three individuals developed diabetes. Those who were ≥65 years old, frequently consumed alcohol, had a BMI ≥25, had <9 years of education, were anti-HCV+ or smoked ≥1 pack per day were more likely to develop diabetes (P < 0.05). A cumulative hazard function test showed that the higher the smoking levels, the greater the cumulative incidence rate of diabetes in HBsAg+ participants only (P = 0.03 by log-rank test). A multiple Cox proportional hazards model analysis in different hepatitis statuses showed smoking levels were strong predictors of diabetes with a dose-response relationship for type 2 diabetes in those with HBsAg+ : hazard ratio (HR) = 3.8, (95% CI: 1.2, 12.3) for light smokers (<1 pack per day) and HR = 4.4 (95% CI: 1.5, 13.3) for heavy smokers (≥1 pack per day). Increasing BMI was a common predictor in all people. Smoking is a strong predictor for diabetes with a dose-response relationship in HBsAg+ individuals and a mild predictor for seronegative individuals but not significant in anti-HCV+ individuals.


Comparison of tibial nerve H-reflex excitability after cervical and lumbar spine manipulation.
Previous investigations indicate that spinal manipulation leads to short-term attenuation of alpha-motoneuron excitability, when assessed by means of the Hoffmann reflex. Past studies, however, are limited to regional effects, such as lumbar manipulation effects on lumbar alpha-motoneuron activity. This study compared and contrasted the effects of cervical and lumbar spine manipulation on the excitability of the lumbar alpha-motoneuronal pool in human subjects without low back pain, and compared the effects of cervical (nonregional) and lumbar (regional) spinal manipulation on lumbar alpha-motoneuron pool excitability in healthy subjects. The specific aim of this study was to determine if the inhibitory effects on the lumbar alpha-motoneuron pool associated with spinal manipulation are limited to the specific region in which the manipulative procedure is applied, or if rostral (cervical) manipulation can also influence caudal (lumbar) motoneuron excitability. Thirty-six nonpatient human subjects were used to study the effect of cervical and lumbar spinal manipulation on the amplitude of the tibial nerve Hoffmann reflex, recorded from the gastrocnemius muscle. The Hoffmann reflex (H-reflex) technique allows for an indirect index of motoneuron pool excitability by means of peripheral nerve Ia-afferent fiber stimulation. Reflexes were recorded before and after spinal manipulative procedures. Lumbar spinal manipulation, as measured by amplitude changes of the tibial nerve H-reflex, attenuated lumbar alpha-motoneuronal activity. Suppression of motoneuronal excitability was significant (P <.05) but transient, with a return to baseline within 60 seconds after manipulation. Cervical spinal manipulation had no significant effect on lumbar motoneuron activity. These data indicate that the inhibitory effects of spinal manipulation on motoneuronal excitability are regional, rather than global.


Interventions that Foster Healing Among Sexually Exploited Children and Adolescents: A Systematic Review.
Sexual exploitation of children and adolescents is a pressing, yet largely under-recognized form of child abuse. The goals of this review were to identify interventions that have been implemented with sexually exploited children and adolescents and to better understand their effectiveness for fostering healing with this population. Our systematic search generated 4,358 publications of which 21 met our inclusion criteria. Based on their objectives and delivery, we organized the interventions into five categories: (a) focused health and/or social services, (b) intensive case management models, (c) psychoeducational therapy groups, (d) residential programs, and (e) other. Most programs were gender-specific, targeting girls and young women with just one being for boys and young men only. Studies reported on a range of outcomes including psychosocial outcomes, risky behaviors, trauma responses, mental health, protective factors, and public health outcomes. Despite differences in delivery, most of the interventions did, to some degree, appear to foster healing among sexually exploited children and adolescents. Findings from this review have implications for researchers, policy and program developers, and frontline practitioners who, through partnerships with one another, can advocate for the creation of evidence-informed, purpose-built, and thoughtfully delivered interventions.


Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells.
Vitamin K is essential for the posttranslational modification of various Gla proteins. Although it is widespread in several organs, including the testis, the function of vitamin K in these organs is not well characterized. In this study, we investigated the function of vitamin K in the testis and analyzed its role in steroidogenesis. Eight-week-old male Wistar rats were fed a diet supplemented with menaquinone-4 (MK-4, 75 mg/kg diet), one of the predominant K₂ vitamins present in the testis, for 5 weeks. In vivo testosterone levels of the rats' plasma and testes were measured by enzyme-linked immunosorbent assay, and in vitro testosterone levels of testis-derived tumor cells (I-10 cells) maintained in Ham's F-10 medium with 10% fetal bovine serum were measured following treatment with MK-4 (0 to 100 μM) at several time points. Testosterone and cellular protein levels were analyzed with respect to their effects on steroidogenesis. Testosterone levels in the plasma and testes of MK-4-fed rats were significantly increased compared to those of control rats, with no obvious differences in plasma luteinizing hormone levels. Secreted testosterone levels from I-10 cells were elevated by MK-4, but not by vitamin K₁, in a dose-dependent manner independent of cAMP treatment. Western blot analysis revealed that expression of CYP11A, the rate-limiting enzyme in steroidogenesis, and phosphorylation levels of protein kinase A (PKA) and the cAMP response element-binding protein were all stimulated by the presence of MK-4. Enhancement of testosterone production was inhibited by H89, a specific inhibitor of PKA, but not by warfarin, an inhibitor of γ-glutamylcarboxylation. MK-4 stimulates testosterone production in rats and testis-derived tumor cells via activation of PKA. MK-4 may be involved in steroidogenesis in the testis, and its supplementation could reverse the downregulation of testosterone production in elders.


Comparing focal and global responses on multifocal electroretinogram with retinal nerve fibre layer thickness by spectral domain optical coherence tomography in glaucoma.
To evaluate first and second order responses on multifocal electroretinogram (mfERG) and with retinal nerve fibre layer thickness (RNFL) on Cirrus spectral domain optical coherence tomography (SD-OCT) in glaucoma. Patients (old and new) diagnosed with primary open angle glaucoma, primary angle closure glaucoma or normal tension glaucoma attending glaucoma services from November 2012 to January 2013 were screened. Ninety-seven eyes fulfilling inclusion criteria were evaluated by Humphrey visual field, Cirrus SD-OCT imaging and mfERG (Veris Science 5.1.10X; EDI, Redwood City, California, USA) for this observational cross-sectional study. The global and averaged quadrant-wise peak-to-trough amplitudes and peak implicit times of the first trough (N1), the first peak (P1) and the second trough (N2) of the mfERG were compared with average RNFL-full circle (FC) or quadrant RNFL thickness in early (mean deviation (MD) >-6 dB), moderate (MD -6 to -12 dB) and advanced glaucoma (MD <-12 dB). The RNFL-FC correlated with P1N2 amplitude on univariate analysis (r=0.7, p=0.004) and N2 amplitude (r=-0.4, p<0.001). Comparing relationships in different stages of glaucoma, P1N2 amplitude correlated significantly with RNFL-FC and superotemporal quadrant, RNFL-superior temporal (ST), in early and moderate glaucoma only. In contrast, the implicit time of P1N2 correlated significantly with RNFL-FC and RNFL-ST only in severe glaucoma while in earlier stages, this relationship did not hold true. On multivariate analysis, P1N2 amplitude correlated with age (β=-0.2, p<0.001), RNFL-FC (β=0.05, p=0.05), RNFL-ST (β=0.06, p=0.01) and cup-disc ratio (β=-3.2, p=0.006). Of all responses on mfERG, P1N2 amplitude correlates well with RNFL-FC and RNFL-ST on SD-OCT and can be used for monitoring early and moderate glaucoma. Diffuse structural changes may best be reflected by changes in P1N2 implicit time owing to ceiling effect of the amplitude in all regions in severe glaucoma.


Adipose Tissue Formation Utilizing Fat Flap Distraction Technique.
Co-regulation between adipocytes and supporting vasculature is considered an important process in adipose tissue generation. The objective of this study was to evaluate the mechanical and biological effects of a distraction technique on adipose tissue formation and maintenance. Based on the hypothesis that fat flaps gradually receding from each other can develop an adipose tissue construct, perforated polycarbonate syringe-shaped chambers were implanted in a rabbit model. Latency (1 week) and distraction (3 weeks) periods were followed by a consolidation period in the experimental groups (4, 8, and 12 weeks). In the distraction group, the volume of fat pad gradually increased up to 16 weeks. A transition zone was observed at 8 weeks, indicating the initiation of tissue generation. Histomorphologic analysis showed adipose and collagen connective tissue at 8 weeks. At 16 weeks, the relative composition was altered significantly. Adipose components occupied most of the tissue, and connective tissue was reduced. Blood vessels with endothelial lining were noted adjacent to adipocyte clusters, as well as in inter-adipocyte areas. The vessels had increased in number and were evenly distributed by 16 weeks. Our distraction technique produced more balanced adipose tissue generation than a non-distraction method, with co-development of adipose and vascular tissues.


Discovery of a Ni-Ga catalyst for carbon dioxide reduction to methanol.
The use of methanol as a fuel and chemical feedstock could become very important in the development of a more sustainable society if methanol could be efficiently obtained from the direct reduction of CO2 using solar-generated hydrogen. If hydrogen production is to be decentralized, small-scale CO2 reduction devices are required that operate at low pressures. Here, we report the discovery of a Ni-Ga catalyst that reduces CO2 to methanol at ambient pressure. The catalyst was identified through a descriptor-based analysis of the process and the use of computational methods to identify Ni-Ga intermetallic compounds as stable candidates with good activity. We synthesized and tested a series of catalysts and found that Ni5Ga3 is particularly active and selective. Comparison with conventional Cu/ZnO/Al2O3 catalysts revealed the same or better methanol synthesis activity, as well as considerably lower production of CO. We suggest that this is a first step towards the development of small-scale low-pressure devices for CO2 reduction to methanol.


The effect of antagonist of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas.
The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas, have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [3H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718, a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365, 260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364,718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptors, but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.


Occupational asphalt is not associated with head and neck cancer.
Epidemiologic studies that evaluate the relationship between occupational asphalt exposure and head and neck cancer have had a limited ability to control for known risk factors such as smoking, alcohol and human papillomavirus (HPV). To better elucidate this relationship by including known risk factors in a large case-control study of head and neck squamous cell carcinoma (HNSCC) from the greater Boston area. We analysed the relationship between occupational asphalt exposure and HNSCC among men in the Greater Boston area of Massachusetts. Analyses were conducted using unconditional multivariable logistic regression, performed with adjustments for age, race, education, smoking, alcohol consumption and HPV serology. There were 753 cases and 913 controls. No associations between HNSCC and occupational asphalt exposure (neither among ever-exposed nor by occupational duration) were observed for exposures in any occupation or those restricted to the construction industry. We also observed no associations in subgroup analyses of never-smokers and ever-smokers. Adjusting for known risk factors further reduced the estimated effect of asphalt exposure on HNSCC risk. We found no evidence for an association between occupational asphalt exposure and HNSCC. The null findings from this well-controlled analysis could suggest that the risk estimates stemming from occupational cohort studies may be overestimated due to uncontrolled confounding and enhance the literature available for weighing cancer risk from occupational exposure to bitumen.


Assessment of benzo(a)pyrene-equivalent carcinogenicity and mutagenicity of residential indoor versus outdoor polycyclic aromatic hydrocarbons exposing young children in New York City.
The application of benzo(a)pyrene (BaP)-toxic equivalent factor to polycyclic aromatic hydrocarbons (PAH) concentrations can provide a more accurate risk assessment from environmental exposure to PAH. We hypothesized that BaP-equivalent toxicity determined following residential air monitoring among young urban children may vary by season. Residential indoor and outdoor air levels of PAH measured over two-weeks in a cohort of 5-6 year old children (n = 260) in New York City were normalized to the cancer and mutagen potency equivalent factor of BaP (BaP = 1). Data are presented as carcinogenic equivalents (BaP-TEQ) and mutagenic equivalents (BaP-MEQ) for the sum of 8 PAH (Sigma(8)PAH; MW >or= 228) and individual PAH and compared across heating versus nonheating seasons. Results show that heating compared to nonheating season was associated significantly with higher (BaP-TEQ)(Sigma8PAH) and (BaP-MEQ)(Sigma8PAH) both indoors and outdoors (p < 0.001). Outdoor (BaP-TEQ)(Sigma8)(PAH) and (BaP-MEQ)(Sigma8PAH) were significantly higher than the corresponding indoor measures during the heating season (p < 0.01). These findings suggest that at levels encountered in New York City air, especially during the heating season, residential exposure to PAH may pose an increased risk of cancer and mutation.


Vasopressin and copeptin levels in children with sepsis and septic shock.
Levels of vasopressin and its precursor copeptin in pediatric sepsis and septic shock are not well defined. The main aim of this study is to compare the serum levels of vasopressin and copeptin in children with septic shock or sepsis and in healthy children. We hypothesized that vasopressin and copeptin levels are elevated in early and late stages of pediatric septic shock. Three groups were included: healthy children, children with clinical diagnosis of sepsis, and children admitted to the pediatric intensive care unit (PICU) with diagnosis of sepsis shock. Blood samples were drawn from children in all groups within 24 h of admission. For the septic shock group, additional samples at 24-h intervals were drawn up to 120 h after PICU admission. We used competitive immunoassays to determine vasopressin and copeptin levels. There were 70 children in the control group, 53 children in the sepsis group, and 13 in the septic shock group. At baseline, there was a difference in median vasopressin levels [60.9 (Interquartile range: 32.3, 138.0) vs. 141.1 (45.2, 542) vs. 326 (55.6, 399) pg/mL, p < 0.05], but there was no difference in copeptin levels [1.2 (0.8, 1.8) vs. 1.5 (1.0, 2.2) vs. 0.9 (0.8, 1.2) ng/mL, p = 0.14] between the three groups. There was no difference in vasopressin and copeptin levels in early and late stages of pediatric septic shock. Baseline vasopressin levels were different between the three groups. In pediatric septic shock, vasopressin and copeptin levels are not robust markers for severity and clinical outcomes.


Masculinities and condom use patterns among young rural South Africa men: a cross-sectional baseline survey.
Notions of ideal manhood in South Africa are potentially prescriptive of male sexuality thus accounting for the behaviors which may lead to men being at greater HIV risk. We tested the hypothesis that gender and relationship constructs are associated with condom use among young men living in rural South Africa. 1219 men aged 15-26 years completed a cross-sectional baseline survey from an IsiXhosa questionnaire asking about sexual behaviour and relationships. Univariate and bivariate analyses described condom use patterns and explanatory variables, and multinomial regression modeling assessed the factors associated with inconsistent versus consistent and non-condom use. 47.7% of men never used condoms, when 36.9% were inconsistent and 15.4% were consistent with any partner in the past year. Condom use patterns differed in association with gender relations attitudes: never users were significantly more conservative than inconsistent or consistent users. Three gender positions emerged indicating that inconsistent users were most physically/sexually violent and sexually risky; never users had more conservative gender attitudes but were less violent and sexually risky; and consistent users were less conservative, less violent and sexually risky with notably fewer sexual partners than inconsistent users. The confluence of conservative gender attitudes, perpetration of violence against women and sexual risk taking distinguished inconsistent condom users as the most risky compared to never condom users, and rendered inconsistent use one of the basic negative attributes of dominant masculinities in the Eastern Cape, South Africa. This finding is important for the design of HIV prevention and gender equity interventions and emphasizes the need for a wider roll-out of interventions that promote progressive and healthy masculine practices in the country.


Parasite load effects on sex ratio, size, survival and mating fitness of Heleidomermis magnapapula in Culicoides sonorensis.
Heleidomermis magnapapula parasitizes the blood-feeding midge Culicoides sonorensis. Most (84%) single mermithid infective second stage juveniles (J2) developed into adult females, while parasitism by multiple J2 yielded 97% male adults. Nematodes emerged from the midge larval host as adults and mated immediately; females were ovoviviparous. Host larvae were exposed to nematode J2 and examined intact microscopically to score initial parasite load. Midge hosts were reared individually. Premature midge death, nematode survival within the host, and emerging adult nematode sex ratio and size as a function of load and host size were all tracked. Higher nematode loads produced smaller adult nematode males. The higher loads also increased and accelerated premature host death. Emergence of > 7-9 adult nematode males was rare, but up to 19 tiny males emerged from a single host. Larger midges supported higher parasite loads and a larger total volume of emerged nematode biomass. Virgin adult nematode males then were paired with females of variable, known sizes (volume) and held to determine size effects on fertility (egg hatch), and male survival (longevity). Tested adult males ranged in size from 0.0025 - 0.0334 mm3 and females from 0.0121 - 0.1110 mm3. Logistic regression indicated female nematode fertility was positively influenced by male nematode size, while nematode load and female nematode size had no significant effect. While fertility was reduced statistically in smaller males, even some of the smallest male and female individuals could be fertile. Findings are related to field studies in this system.