Genetic approaches in comparative and evolutionary physiology.
Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology.


The LVV Auger line shape of sulfur on copper studied by Auger photoelectron coincidence spectroscopy.
We have studied the line shapes of Cu(0 0 1)-p (2 × 2)S L2VV and L3VV Auger decay by means of Auger photoelectron coincidence spectroscopy. Measuring the LVV Auger spectrum in coincidence with S 2p1/2 and 2p3/2 photoelectrons respectively, we have been able to separate the two overlapping Auger spectra and determine their intrinsic line shapes. The two Auger transitions, though shifted in energy, display an identical line shape whose main features can be qualitatively understood considering a single particle approximation but are better described within a Cini-Sawatzky (CS) approach. Comparison between the experimental and the CS calculated spectra confirms that a substantial part of the Auger lines (∼20%) can be ascribed to decay events accompanied by the excitation of one additional electron-hole pair in the valence band. For the first time, the locality of the Auger process combined with the surface sensitivity of the APECS technique and its ability to separate overlapping structures are used to study Auger transitions taking place at the the surface states of a S/noble-metal interface.


Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects.
In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.


Perceptual grouping and visual selective attention.
The present study demonstrates that incongruent distractor letters at a constant distance from a target letter produce more response competition and negative priming when they share a target's color than when they have a different color. Moreover, perceptual grouping by means of color, attenuated the effects of spatial proximity. For example, when all items were presented in the same color, near distractors produced more response competition and negative priming than far distractors (Experiment 3A). However, when near distractors were presented in a different color and far distractors were presented in the same color as the target, the response competition x distractor proximity interaction was eliminated and the proximity x negative priming interaction was reversed (Experiment 3B). A final experiment demonstrated that distractors appearing on the same object as a selected target produced comparable amounts of response competition and negative priming whether they were near or far from the target. This suggests that the inhibitory mechanisms of visual attention can be directed to perceptual groups/objects in the environment and not only to unsegmented regions of visual space.


Determination of the level of noise in nurseries and pre-schools and the teachers' level of annoyance.
The aim of this article is to determine the level of noise in nurseries and pre-schools and also to compare measured levels with standard levels and evaluate the teachers' level of annoyance. The level of noise was measured in three different schools. A total of 162 students, whose ages were between 3 and 6 years, and 12 teachers were included the study. Every age groups' level of noise was measured during sleeping, gaming, and eating activity. In addition, teachers' annoyance was assessed in different age groups. The 4- to 6-year-old groups were found to have higher level of sounds than 3-year-old group. Eating period was found to be the highest level of sound whereas sleeping was found the lowest. Furthermore, teachers' annoyance was found higher as the age decreased. Nurseries and pre-schools have noisy environment both for the students and the teachers. High level of noise, which has bad effects on health, is a public health problem. Both the students' families and teachers must be aware of this annoying situation.


diskImageR: quantification of resistance and tolerance to antimicrobial drugs using disk diffusion assays.
Microbial pathogens represent an increasing threat to human health. Although many infections can be successfully treated and cleared, drug resistance is a widespread problem. The existence of subpopulations of 'tolerant' cells (where a fraction of the population is able to grow above the population resistance level) may increase the rate of treatment failure; yet, existing methods to measure subpopulation effects are cumbersome. Here we describe diskImageR, a computational pipeline that analyses photographs of disk diffusion assays to determine the degree of drug susceptibility [the radius of inhibition, (RAD)], and two aspects of subpopulation growth [the fraction of growth (FoG) within the zone of inhibition, (ZOI), and the rate of change in growth from no drug to inhibitory drug concentrations, (SLOPE)]. diskImageR was used to examine the response of the human fungal pathogen Candida albicans to the antifungal drug fluconazole across different strain backgrounds and growth conditions. Disk diffusion assays performed under Clinical and Laboratory Standards Institute (CLSI) conditions led to more susceptibility and less tolerance than assays performed using rich medium conditions. We also used diskImageR to quantify the effects of three drugs in combination with fluconazole, finding that all three combinations affected tolerance, with the effect of one drug (doxycycline) being very strain dependent. The three drugs had different effects on susceptibility, with doxycycline generally having no effect, chloroquine generally increasing susceptibility and pyrvinium pamoate generally reducing susceptibility. The ability to simultaneously quantitate different aspects of microbial drug responses will facilitate the study of mechanisms of subpopulation responses in the presence of antimicrobial drugs.


Special relativistic visualization by local ray tracing.
Special relativistic visualization offers the possibility of experiencing the optical effects of traveling near the speed of light, including apparent geometric distortions as well as Doppler and searchlight effects. Early high-quality computer graphics images of relativistic scenes were created using offline, computationally expensive CPU-side 4D ray tracing. Alternate approaches such as image-based rendering and polygon-distortion methods are able to achieve interactivity, but exhibit inferior visual quality due to sampling artifacts. In this paper, we introduce a hybrid rendering technique based on polygon distortion and local ray tracing that facilitates interactive high-quality visualization of multiple objects moving at relativistic speeds in arbitrary directions. The method starts by calculating tight image-space footprints for the apparent triangles of the 3D scene objects. The final image is generated using a single image-space ray tracing step incorporating Doppler and searchlight effects. Our implementation uses GPU shader programming and hardware texture filtering to achieve high rendering speed.


Proposal of a New Adverse Event Classification by the Society of Interventional Radiology Standards of Practice Committee.
To develop a new adverse event (AE) classification for the interventional radiology (IR) procedures and evaluate its clinical, research, and educational value compared with the existing Society of Interventional Radiology (SIR) classification via an SIR member survey. A new AE classification was developed by members of the Standards of Practice Committee of the SIR. Subsequently, a survey was created by a group of 18 members from the SIR Standards of Practice Committee and Service Lines. Twelve clinical AE case scenarios were generated that encompassed a broad spectrum of IR procedures and potential AEs. Survey questions were designed to evaluate the following domains: educational and research values, accountability for intraprocedural challenges, consistency of AE reporting, unambiguity, and potential for incorporation into existing quality-assurance framework. For each AE scenario, the survey participants were instructed to answer questions about the proposed and existing SIR classifications. SIR members were invited via online survey links, and 68 members participated among 140 surveyed. Answers on new and existing classifications were evaluated and compared statistically. Overall comparison between the two surveys was performed by generalized linear modeling. The proposed AE classification received superior evaluations in terms of consistency of reporting (P < .05) and potential for incorporation into existing quality-assurance framework (P < .05). Respondents gave a higher overall rating to the educational and research value of the new compared with the existing classification (P < .05). This study proposed an AE classification system that outperformed the existing SIR classification in the studied domains.


PastView: a user-friendly interface to explore ancestral scenarios.
Ancestral character states computed from the combination of phylogenetic trees with extrinsic traits are used to decipher evolutionary scenarios in various research fields such as phylogeography, epidemiology, and ecology. Despite the existence of powerful methods and software in ancestral character state inference, difficulties may arise when interpreting the outputs of such inferences. The growing complexity of data (trees, annotations), the diversity of optimization criteria for computing trees and ancestral character states, the combinatorial explosion of potential evolutionary scenarios if some ancestral characters states do not stand out clearly from others, requires the design of new methods to explore associations of phylogenetic trees with extrinsic traits, to ease the visualization and interpretation of evolutionary scenarios. We developed PastView, a user-friendly interface that includes numerical and graphical features to help users to import and/or compute ancestral character states from discrete variables and extract ancestral scenarios as sets of successive transitions of character states from the tree root to its leaves. PastView provides summarized views such as transition maps and integrates comparative tools to highlight agreements or discrepancies between methods of ancestral annotations inference. The main contribution of PastView is to assemble known numerical and graphical methods into a multi-maps graphical user interface dedicated to the computing, searching and viewing of evolutionary scenarios based on phylogenetic trees and ancestral character states. PastView is available publicly as a standalone software on www.pastview.org .


Assessment of human health risks posed by consumption of fish from the Lower Passaic River, New Jersey.
The Lower Passaic River (LPR) in New Jersey has been impacted by variety of human activities over the course of the last two centuries. In this risk assessment, we assessed potential human health risks associated with consumption of fish from the LPR, the human exposure pathway of greatest concern when addressing contaminated sediments. Our risk assessment incorporates fish consumption information gathered during a year-long, intercept-style creel angler survey and representative fish tissue concentrations for 156 chemicals of potential concern (COPCs) obtained from USEPA's public database (OurPassaic website: http://www.ourpassaic.org/projectsites/premis_public/index.cfm?fuseaction=contaminants). Due to the large number of COPCs investigated, this risk assessment was divided into two phases: (1) identification of COPCs that contribute to the majority of overall excess cancer risk and hazard estimates using deterministic and probabilistic methods, and (2) probabilistic characterization of risk using distributions of chemical concentration and cooking loss for those compounds identified in Phase 1. Phase 1 relied on point estimates of COPC concentrations and demonstrated that PCDD/Fs and PCBs (dioxin-like and non-dioxin-like) are the greatest contributors to cancer risk, while non-dioxin-like PCBs are the primary contributors to non-cancer hazard estimates. Total excess cancer risks for adult and child and receptors estimated in Phase 1 were within USEPA's acceptable excess cancer risk range, with the exception of RME child (3.0 x 10(-4) and 1.3 x 10(-4) for deterministic and probabilistic approaches, respectively). Phase 2 focused on PCDD, PCDF, and PCBs and used distributions of chemical concentrations in fish. The results showed that all excess cancer risk estimates were within the acceptable risk range, although non-cancer hazard estimates for PCBs slightly exceeded a Hazard Index of 1. This HHRA of LPR fish ingestion represents the most comprehensive evaluation conducted to date, and demonstrates that measured concentrations of COPCs are not likely to pose a health risk to people who currently consume fish from the LPR.


The role of animal models in understanding feeding behavior in infants.
The common evolutionary history humans share with mammals provides us with a solid basis for understanding normal oropharyngeal anatomy and functions. Physiologically, feeding is a cycle of neurophysiologic activity, where sensory input travels to the CNS which sends motor signals out to the periphery. Research with animal models is valuable because it is possible to disrupt this cycle, and develop predictive models on the causal basis of deviation from normal. Based on work with animal models, normal mammalian infant feeding behavior consists of the tongue functioning as a pump. First, the tongue assists in acquisition of milk from the nipple into the oral cavity, and then it pumps milk from the oral cavity into the valleculae prior to the pharyngeal swallow. Starting with this basic model, feeding in infant pigs was manipulated to determine the impact of variation in sensory input on behavioral output. One set of experiments suggested that chemo- or liquid sensation, in the form of milk is necessary to elicit continuing rhythmic activity. However, the rates of rhythmic suckling are intrinsic to an animal, and variation in rate cannot be entrained. Another set showed that initiation of the swallow does not purely depend on the volume of milk delivered, but also on the sensory stimulation at the mouth. These results support the idea that feeding behavior involves complex sensory integration.


Identification of neural networks that contribute to motion sickness through principal components analysis of fos labeling induced by galvanic vestibular stimulation.
Motion sickness is a complex condition that includes both overt signs (e.g., vomiting) and more covert symptoms (e.g., anxiety and foreboding). The neural pathways that mediate these signs and symptoms are yet to identified. This study mapped the distribution of c-fos protein (Fos)-like immunoreactivity elicited during a galvanic vestibular stimulation paradigm that is known to induce motion sickness in felines. A principal components analysis was used to identify networks of neurons activated during this stimulus paradigm from functional correlations between Fos labeling in different nuclei. This analysis identified five principal components (neural networks) that accounted for greater than 95% of the variance in Fos labeling. Two of the components were correlated with the severity of motion sickness symptoms, and likely participated in generating the overt signs of the condition. One of these networks included neurons in locus coeruleus, medial, inferior and lateral vestibular nuclei, lateral nucleus tractus solitarius, medial parabrachial nucleus and periaqueductal gray. The second included neurons in the superior vestibular nucleus, precerebellar nuclei, periaqueductal gray, and parabrachial nuclei, with weaker associations of raphe nuclei. Three additional components (networks) were also identified that were not correlated with the severity of motion sickness symptoms. These networks likely mediated the covert aspects of motion sickness, such as affective components. The identification of five statistically independent component networks associated with the development of motion sickness provides an opportunity to consider, in network activation dimensions, the complex progression of signs and symptoms that are precipitated in provocative environments. Similar methodology can be used to parse the neural networks that mediate other complex responses to environmental stimuli.


In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection.
Coadministration of pomegranate rind extract (PRE) and zinc (II) ions has recently been reported as a potential new topical treatment for Herpes simplex virus (HSV) infections. In the current work we examined the in vitro topical delivery of punicalagin (major phytochemical of PRE) and zinc from hydrogels across epithelial membranes that can become infected with HSV. Porcine epidermal, buccal and vaginal mucous membranes were excised and mounted in Franz diffusion cells and dosed with a simple hydrogel containing PRE and zinc sulphate (ZnSO4). The permeation of punicalagin and zinc were determined by HPLC and ICPMS respectively; punicalagin was also determined in the basal layers by reverse tape stripping. Receptor phases from the epidermal membrane experiment were also used to challenge HSV-1 in Vero host cells, and ex vivo porcine skin was used to probe COX-2 modulation. Punicalagin and zinc permeated each of the three test membranes, with significantly greater amounts of both delivered across the epidermal membrane. The amounts of punicalagin permeating the buccal and vaginal membranes were similar, although the amount of zinc permeating the vaginal membrane was comparatively very large - it is known that zinc interacts with vaginal mucosa. The punicalagin recovered by reverse tape stripping of the epidermal, buccal and vaginal membranes gave 0.47±0.016, 0.45±0.052 and 0.51±0.048nMcm-2 respectively, and were statistically the same (p<0.05). A 2.5 log reduction was achieved against HSV-1 using diffusion cell receptor phase, and COX-2 expression was reduced by 64% in ex vivo skin after 6h. Overall, a hydrogel containing 1.25mgmL-1 PRE and 0.25M ZnSO4 was able to topically deliver both the major bioactive compound within PRE and Zn (II) across all membranes and into the site specific region of Herpes simplex vesicular clusters, while maintaining potentiated virucidal and anti-inflammatory properties. This novel therapeutic system therefore has potential for the topical treatment of HSV infections.


Psychopathological differences among three groups of school children affected by the war in Croatia.
The consequences of extreme violence such as war torture affect children in different ways and may immediately manifest at the physical and/or psychologic level, or may remain hidden and unrecognized for years. The victims are usually very reluctant to speak about their traumatic experiences, and try to deny the existence of psychological disturbances. They often seek help for somatic problems. Taking these physical complaints seriously helps to progressively reach the psychological effects of violence. Therefore, identification of such children should be directed to more complete evaluation of their symptomatology and functioning. This can be done by: a) individual evaluation to get enough information on the historical events, functioning and symptoms of these children; and b) standardized instruments which may allow the children to disclose more about their psychological experiences during the war. In this study rating scales and assessment instruments for children aged < 15, such as CPRS with General Scoring Sheet (Fish, 1985), were used to assess the broad spectrum of psychopathology in this age group. These questionnaires were used in a large group of school children (N = 1888), 989 girls and 899 boys aged 7-16 years. The sample was divided into 3 groups: 843 non-displaced, 377 displaced and 669 refugee children. Results of statistical analysis (arithmetical mean and standard deviation of discriminative variables transformed in Z-values with F-ratio) showed the three groups of children (non-displaced, displaced and refugees) to significantly differ in 13 out of 15 psychopathologic clusters. Discriminative cannonic analysis of the 3 groups of children (non displaced, displaced and refugees) also showed significant differences. The first discriminative function (80.24% of total variance) indicated depression, violence and antisocial behavior to be rare in non-displaced children, more pronounced in displaced, and most pronounced in refugee children. The second discriminative function (19.76% of total variance) showed hyperactivity, anxiety and psychosomatic disturbances to be rare in non-displaced children; more frequent in refugee, and most expressed in displaced children. According to the results, the authors concluded that war is very painful for a large group of children, among whom the displaced and refugee children are most affected by psychopathologic disturbances.


Baseline factors associated with smoking cessation and relapse. MRFIT Research Group.
Data on smoking cessation and relapse for 6 yers of the Multiple Risk Factor Intervention Trial were evaluated in univariate and multivariate analyses to determine the relationship between variables measured at the beginning of the trial and smoking cessation and relapse for special intervention and usual care participants. The variables positively associated with smoking cessation in both the SI and the UC groups included age, education, and past success in quitting; there was a negative association with the number of cigarettes smoked per day. The expectation of quitting was positively associated with cessation in the special intervention group only, while life events, alcohol, and the presence of a wife who smokes were significant predictors of reduced cessation for the usual care group. The special intervention program may have overcome obstacles which interfered with cessation among the usual care participants. Associations with relapse were generally stronger in the usual care group than in the special intervention group. For usual care participants, multivariate analyses showed that education, past success in quitting smoking, alcohol, and life events were associated with relapse rates. For special intervention participants, only alcohol emerged as a significant predictor. Conclusion. The data are relevant in terms of factors that govern smoking cessation and relapse for adult smokers who take part in formal intervention programs and for those who are left to modify their behavior on their own.


[Influence of scatter factor/hepatocyte growth factor on the growth and transmission of hepatocarcinoma SMMC 7721 cells].
To explore the influence of scatter factor/hepatocyte growth factor (SF/HGF) on the growth and transmission of hepatocarcinoma SMMC 7721 cells by SF/HGF cDNA transfection. Gene transfection was operated by lipofectin method. In vitro, SF/HGF and c-met expression was tested by ELISA and Western blot. Cell proliferation and motility were compared by growth curves and wound healing assays. In vivo, cells before and after transfection were implanted subcutaneously into nude mice respectively to observe tumor growth and metastasis. After transfection, the expression of SF/HGF reached 694 pg/ml, compared with 0.26 pg/ml before transfection; however the expression of c-met protein did not change obviously. Growth curves showed that cells after transfection proliferated more rapidly than those before transfection and had an increased capability of motility together with enlarged morphological changes. In vivo experiment, tumors originated from SF/HGF(+) cells grew faster than those from SF/HGF(-) cells and had embolism formed inside and metastasis in the corresponding lung tissues, whereas no such findings in SF/HGF(-) cell originated tumors. High expression of SF/HGF can stimulate tumor cell proliferation and metastasis in hepatocellular carcinoma


Effect of intracellular expression of antimicrobial peptide LL-37 on growth of escherichia coli strain TOP10 under aerobic and anaerobic conditions.
Antimicrobial peptides (AMPs) can cause lysis of target bacteria by directly inserting themselves into the lipid bilayer. This killing mechanism confounds the identification of the intracellular targets of AMPs. To circumvent this, we used a shuttle vector containing the inducible expression of a human cathelicidin-related AMP, LL-37, to examine its effect on Escherichia coli TOP10 under aerobic and anaerobic growth conditions. Induction of LL-37 caused growth inhibition and alteration in cell morphology to a filamentous phenotype. Further examination of the E. coli cell division protein FtsZ revealed that LL-37 did not interact with FtsZ. Moreover, intracellular expression of LL-37 results in the enhanced production of reactive oxygen species (ROS), causing lethal membrane depolarization under aerobic conditions. Additionally, the membrane permeability was increased after intracellular expression of LL37 under both aerobic and anaerobic conditions. Transcriptomic analysis revealed that intracellular LL-37 mainly affected the expression of genes related to energy production and carbohydrate metabolism. More specifically, genes related to oxidative phosphorylation under both aerobic and anaerobic growth conditions were affected. Collectively, our current study demonstrates that intracellular expression of LL-37 in E. coli can inhibit growth under aerobic and anaerobic conditions. While we confirmed that the generation of ROS is a bactericidal mechanism for LL-37 under aerobic growth conditions, we also found that the intracellular accumulation of cationic LL-37 influences the redox and ion status of the cells under both growth conditions. These data suggest that there is a new AMP-mediated bacterial killing mechanism that targets energy metabolism.


Severe feeding disorder and malnutrition in 2 children with autism.
Leanna, a 10-year-old girl with autism, was hospitalized for severe malnutrition and 20 pound weight loss secondary to reduced intake over 4 months. Her food choices became increasingly restrictive to the point where she only ate certain types and brands of foods. She gradually stopped drinking and developed severe constipation and encopresis. A new behavior of collecting saliva in her mouth and spitting onto napkins also emerged. Vital signs and electrolytes were normal on admission. A nasogastric tube was placed because she refused to eat. A behavior modification plan was implemented that awarded points for completing specific tasks related to feeding, which could later be redeemed for specific rewards, such as computer time. Although her ideal body weight increased from 68% to 75% (due to continuous nasogastric tube feeds), her refusal to eat persisted. Upon further data gathering, the staff learned that she moved and changed schools 5 months ago. She was cared for by either a family friend or paid caregiver while her mother worked. Although she could conduct basic self-care activities without assistance and write and draw at a third-grade level, she functioned cognitively at a 4-year-old level. The behavior plan was modified, breaking the tasks into shorter components with immediate and tangible rewards. She soon began eating small portions of food and spitting less frequently. Toileting was later incorporated into this plan. She was referred to a behavioral therapist in the community to work with her at home and school. Weekly visits with her pediatrician and appointments with a child psychiatrist and dietician were made. Orlando, a 3-year-old boy with autism, was evaluated in the emergency room for lethargy and generalized edema for 6 weeks. The history revealed a restrictive diet of commercial pureed fruit and coconut juice for 2 years. He only ate a particular brand and with specific containers; the limited food intake occurred only with his favorite blanket. He refused to eat other types of food. Outpatient treatments were unsuccessful. On physical examination, he was irritable with an erythematous, scaly rash throughout his body. His hair was thin, coarse, and blonde. He had nonpitting edema in his arms, legs, and periorbital region. The laboratory evaluation was significant for anemia, hypoalbuminemia, and hypoproteinemia. He was admitted to the pediatric service where nutritional formula feedings were initiated through a nasogastric tube. Weight gain was adequate, and the hemoglobin, serum albumen, and protein became normal. The rash improved with zinc supplementation. He was transferred to an inpatient feeding disorders unit where a team of occupational therapists implemented a behavioral modification program to overcome his severe food aversion.


Increase in Self-Injury as a Method of Self-Harm in Ghent, Belgium: 1987-2013.
Self-harm is a major health care problem and changes in its prevalence and characteristics can have important implications for suicide prevention. The objective was to describe trends in the epidemiology of self-harm based on emergency department (A&E departments) visits over a 26-year period in Ghent, Belgium. We analyzed data on all self-harm presentations from the three large general hospitals in Ghent between 1987 and 2013. We investigated trends in prevalence (events by year per 100.000), methods and alcohol use. Rates of self-harm steadily decreased during the 26-year study period. In general female rates of self-harm were higher than male rates. The mean patient age was 35 years. The most commonly used method of self-harm was self-poisoning by means of an overdose of medication (80.8%), followed by cutting (10.2%) and hanging (4.2%). Psychotropics (including antidepressants, benzodiazepines, barbiturates and other tranquilizers) were the most frequently used drugs (74.5%). A proportional increase in the use of self-injurious methods in self-harm was highly significant, more specifically in the use of hanging, jumping from heights and the use of other violent methods such as the use of firearms, jumping before a moving object or other traffic related injury. This epidemiological study showed an increase in the use of high-lethality methods in self-harm which has important implications for suicide prevention. As restrictions in the availability of these methods are difficult or impossible to achieve, prevention programmes will have to emphasize the role of thorough psychosocial assessment and adequate follow-up care of self-harm patients.


Hypertension and Aortic Stenosis: A Review.
Aortic stenosis is a common form of valvular heart disease which often coexists with hypertension. These diseases represent two distinct forms of left ventricular systolic overload and in combination may be associated with disadvantageous left ventricular remodeling, increased mortality and heart failure. The treatment of hypertension in aortic stenosis remains a challenging problem with limited data to guide clinical practice. We performed a comprehensive online literature review to find relevant published literature on the topic of hypertension and aortic stenosis. In the present manuscript, we review the pathophysiology of aortic stenosis in combination with hypertension and the effects on the left ventricle. We also provide general recommendations for medical therapy for treatment of hypertension in aortic stenosis and review the available data on specific antihypertensive agents in this context. Aortic stenosis and hypertension commonly coexist and significantly impact the diagnosis and classification of aortic stenosis severity and symptoms. Treatment of hypertension among patients with severe aortic stenosis can be challenging. Among specific antihypertensive agents studied in this context, ACE-inhibitors are the most well studied.


Participatory approach to flood disaster management in Thohoyandou.
In recent years, there has been a paradigm shift in research from 'top-down' directives to 'bottom-up' planning. Thus, there has been a change from imposing strategies to a participatory approach by indigenous people. This study uses the participatory approach to flood disaster management in Thohoyandou and its environs. The aim of this study is twofold: first, to understand the perception of communities towards floods hazards; and second, to probe how communities respond to flood hazards and how this knowledge can be used in the planning and management of future disasters. In order to achieve these objectives, participatory rural appraisal (PRA), interviews and observation were used as data collection techniques. The study found that there was consensus among the participants that flooding is a natural process, but human activities enhance the risks of flooding. Human activities that were found to be the causes of flood included clearance of vegetation, cultivation in steep slope areas, the effect of relief, urbanisation, poor designs and maintenance of drainage system and settlement in inadequate areas. The study found that local communities did not cope when there was flooding. However, they suggested strategies that should be used to cope with future flood hazards.


Synthesis, structure and paramagnetic NMR analysis of a series of lanthanide-containing [LnTi6O3(OiPr)9(salicylate)6] cages.
The influence of paramagnetic Ln3+ ions on the NMR behaviour is investigated via a series of new isostructural lanthanide-containing cages with the general formula [LnTi6O3(OiPr)9(salicylate)6] (Ln-1, Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho and Er). Compared to conventional coordination compounds containing Ln3+ ions, the peripheral ligands in Ln-1 are separated from the paramagnetic lanthanide centres by oxo-Ti4+ linkages, and therefore experience a weaker paramagnetic influence. As a result, all of the 1H and 13C NMR signals of these Ln-1 cages (except for Gd-1) are observed and can be unambiguously assigned, which provides an excellent platform for the in-depth study of the NMR behaviour of paramagnetic Ln3+ ions. Further analysis of the fully assigned paramagnetic signals suggests that the pseudo-contact component dominates the 1H NMR shifts, whereas both the pseudo-contact and Fermi-contact contributions affect the 13C shifts, although the majority of the resonance environments are at least four bonds distant from the central Ln3+ ion. Our results also show that the use of Bleaney's factors to describe the pseudo-contact shift is inadequate for this Ln-1 cage series.


Validating a Rapid, Automated Test of Spatial Release From Masking.
To evaluate the test-retest reliability of a headphone-based spatial release from a masking task with two maskers (referred to here as the SR2) and to describe its relationship to the same test done over loudspeakers in an anechoic chamber (the SR2A). We explore what thresholds tell us about certain populations (such as older individuals or individuals with hearing impairment) and discuss how the SR2 might be useful in the clinic. Fifty-four participants completed speech intelligibility tests in which a target phrase and two masking phrases from the Coordinate Response Measure corpus (Bolia, Nelson, Ericson, & Simpson, 2000) were presented either via earphones using a virtual spatial array or via loudspeakers in an anechoic chamber. For the SR2, the target sentence was always at 0° azimuth angle, and the maskers were either colocated at 0° or positioned at ± 45°. For the SR2A, the target was located at 0°, and the maskers were colocated or located at ± 15°, ± 30°, ± 45°, ± 90°, or ± 135°. Spatial release from masking was determined as the difference between thresholds in the colocated condition and each spatially separated condition. All participants completed the SR2 at least twice, and 29 of the individuals who completed the SR2 at least twice also participated in the SR2A. In a second experiment, 40 participants completed the SR2 8 times, and the changes in performance were evaluated as a function of test repetition. Mean thresholds were slightly better on the SR2 after the first repetition but were consistent across 8 subsequent testing sessions. Performance was consistent for the SR2A, regardless of the number of times testing was repeated. The SR2, which simulates 45° separations of target and maskers, produced spatially separated thresholds that were similar to thresholds obtained with 30° of separation in the anechoic chamber. Over headphones and in the anechoic chamber, pure-tone average was a strong predictor of spatial release, whereas age only reached significance for colocated conditions. The SR2 is a reliable and effective method of testing spatial release from masking, suitable for screening abnormal listening abilities and for tracking rehabilitation over time. Future work should focus on developing and validating rapid, automated testing to identify the ability of listeners to benefit from high-frequency amplification, smaller spatial separations, and larger spectral differences among talkers.


Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation.
Chronic allergic inflammatory diseases are a major cause of morbidity, with allergic asthma alone affecting over 300 million people worldwide. Epidemiological studies demonstrate that environmental stimuli are associated with either the promotion or prevention of disease. Major reductions in asthma prevalence are documented in European and US farming communities. Protection is associated with exposure of mothers during pregnancy to microbial breakdown products present in farm dusts and unprocessed foods and enhancement of innate immune competence in the children. We sought to develop a scientific rationale for progressing these findings toward clinical application for primary disease prevention. Treatment of pregnant mice with a defined, clinically approved immune modulator was shown to markedly reduce susceptibility of their offspring to development of the hallmark clinical features of allergic airway inflammatory disease. Mechanistically, offspring displayed enhanced dendritic cell-dependent airway mucosal immune surveillance function, which resulted in more efficient generation of mucosal-homing regulatory T cells in response to local inflammatory challenge. We provide evidence that the principal target for maternal treatment effects was the fetal dendritic cell progenitor compartment, equipping the offspring for accelerated functional maturation of the airway mucosal dendritic cell network following birth. These data provide proof of concept supporting the rationale for developing transplacental immune reprogramming approaches for primary disease prevention.


High activity before breeding improves reproductive performance by enhancing mitochondrial function and biogenesis.
Understanding of physiological responses of organisms is typically based on data collected during an isolated event. Although many fundamental insights have been gained from these studies, evaluating the response to a single event ignores the fact that each individual has experienced a unique set of events throughout its life that may have altered its physiology. The idea that prior experiences can influence subsequent performance is known as a carry-over effect. Carry-over effects may explain much of the variation in performance found among individuals. For example, high physical activity has been shown to improve mitochondrial respiratory function and biogenesis and reduce oxidative stress, and has been linked to improved health and longevity. In this study, we asked whether the bioenergetic differences between active and inactive individuals carry over to impact performance in a subsequent reproductive event and alter a female's reproductive outcome. Female mice that had access to a running wheel for a month before mating gave birth to a larger litter and weaned a heavier litter, indicating that high physical activity had a positive carry-over effect to reproduction. Mice that ran also displayed higher mitochondrial respiration and biogenesis with no changes in endogenous antioxidant enzymes. These results provide a mechanistic framework for how the conditions that animals experience before breeding can impact reproductive outcomes.


The neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers for lung cancer development.
Elevated neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) at time of cancer diagnosis have been associated to poor prognosis in various cancers. There is no data on their natural progression before the cancer diagnosis has been established. We aim to evaluate whether or not the annual changes in these ratios could be early indicators of lung cancer development. Participants recruited into the Pamplona International Early Lung Cancer Action Program (P-IELCAP, n=3061) between 2001 and 2015 were considered. Complete blood counts (CBC) were registered at annual intervals between enrolment and time of diagnosis. Linear regression was used to calculate the mean annual change in NLR and PLR in participants with ≥3CBCs. Changes were expressed relative to baseline values. Lung cancer incidence density and lung cancer risk (Cox regression analysis) were calculated for different NLR and PLR annual thresholds (<0%, ≥0%, ≥1%, ≥2%, ≥4%). Results were compared to a matched group of participants who did not develop lung cancer. After a median follow-up of 80 months and a median of 4 (IQR 3-6) CBCs, subjects who developed lung cancer (n=32) showed greater NLR and PLR annual changes than matched controls (n=103) (2.56% vs. 0.27% [p=0.25] per year; and 3.75% vs. 0.33% [p=0.053] per year, respectively). Lung cancer incidence density per 100 person-years increased with higher annual NLR and PLR thresholds. On multivariable analysis (adjusting for emphysema and baseline lung-function), NLR and PLR were not significant lung cancer predictors. However, among individuals with emphysema, for each relative unit increase in PLR, lung cancer risk increased 5% (p=0.03). There was a significant supra-additive risk effect between PLR increase and emphysema. Annual NLR change was not a significant lung cancer predictor. In a lung cancer screening setting, the assessment of annual PLR change could help predict lung cancer development.


Facile Synthesis of Di-Mannitol Adipate Ester-Based Zinc Metal Alkoxide as a Bi-Functional Additive for Poly(Vinyl Chloride).
A new di-mannitol adipate ester-based zinc metal alkoxide (DMAE-Zn) was synthesized as a bi-functional poly(vinyl chloride) (PVC) thermal stabilizer for the first time. The materials were characterized with Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). Characterization results confirmed the formation of Zn-O bonds in DMAE-Zn, and confirmed that DMAE-Zn had a high decomposition temperature and a low melting point. The thermal stability of DMAE-Zn on PVC also was tested by a conductivity test, a thermal aging test, and a UV-visible spectroscopy (UV-VIS) test. PVC stabilized by DMAE-Zn had a good initial color and excellent long-term stability. UV-VIS also showed that the conjugated structure in PVC stabilized by DMAE-Zn was almost all of the triene, suggesting that the addition of DMAE-Zn would suppress the formation of conjugated structures above tetraene. The dynamic processing performance of PVC samples tested by torque rheometer indicated that, having a good compatibility with PVC chains in the amorphous regions, DMAE-Zn contributed a good plasticizing effect to PVC. DMAE-Zn thus effectively demonstrates bi-functional roles, e.g., thermal stabilizers and plasticizers to PVC. Furthermore, FT-IR, a HCl absorption capacity test, and a complex ZnCl2 test were also used to verify the thermal stability mechanism of DMAE-Zn for PVC.


Junction-type photonic crystal waveguides for notch- and pass-band filtering.
Evolution of the mode gap and the associated transmission mini stop-band (MSB) as a function of photonic crystal (PhC) waveguide width is theoretically and experimentally investigated. The change of line-defect width is identified to be the most appropriate way since it offers a wide MSB wavelength tuning range. A high transmission narrow-band filter is experimentally demonstrated in a junction-type waveguide composed of two PhC waveguides with slightly different widths. The full width at half maximum is 5.6 nm; the peak transmission is attenuated by only ~5 dB and is ~20 dB above the MSBs. Additionally, temperature tuning of the filter were also performed. The results show red-shift of the transmission peak and the MSB edges with a gradient of dλ/dT = 0.1 nm/°C. It is proposed that the transmission MSBs in such junction-type cascaded PhC waveguides can be used to obtain different types of filters.


Assessing observer variability: a user's guide.
Some form of the assessment of observer variability may be the most frequent statistical task in medical literature. Still, very little attempt is made to make the reported methods uniform and clear to the reader. This paper provides overview of various measures of observer variability, and a rationale of why using standard error of measurement (SEM) is preferable to other measures of observer variability. The supplemental file contains examples on how to design a proper repeatability and reproducibility assessment, determine appropriate sample size, and test for significance of its findings.


Interprofessional competencies in the curriculum: Interpretations of educators from five health professions.
Interprofessional (IP) practice embraces a range of collaborations among health professionals that includes referral networks, case management, and simultaneous co-management models of healthcare. How IP competencies are interpreted and enacted in the curriculum falls to health educators. The aim of this research was to examine health educators' interpretations of IP competencies in five health professions (chiropractic, naturopathy, osteopathy, physiotherapy, and podiatry) in Australia. Semi-structured interviews were conducted with six educators. Transcripts were analysed using constant comparison to identify emergent themes. A number of interpretations of IP practice were evident (e.g. knowing professional scopes of practice and when to refer, and co-assessing and co-managing patients). Lack of resources limited IP practice enactment in the curriculum, including complementary medicine participation in IP teams.


The Varieties of the Psychedelic Experience: A Preliminary Study of the Association Between the Reported Subjective Effects and the Binding Affinity Profiles of Substituted Phenethylamines and Tryptamines.
Classic psychedelics are substances of paramount cultural and neuroscientific importance. A distinctive feature of psychedelic drugs is the wide range of potential subjective effects they can elicit, known to be deeply influenced by the internal state of the user ("set") and the surroundings ("setting"). The observation of cross-tolerance and a series of empirical studies in humans and animal models support agonism at the serotonin (5-HT)2A receptor as a common mechanism for the action of psychedelics. The diversity of subjective effects elicited by different compounds has been attributed to the variables of "set" and "setting," to the binding affinities for other 5-HT receptor subtypes, and to the heterogeneity of transduction pathways initiated by conformational receptor states as they interact with different ligands ("functional selectivity"). Here we investigate the complementary (i.e., not mutually exclusive) possibility that such variety is also related to the binding affinity for a range of neurotransmitters and monoamine transporters including (but not limited to) 5-HT receptors. Building on two independent binding affinity datasets (compared to "in silico" estimates) in combination with natural language processing tools applied to a large repository of reports of psychedelic experiences (Erowid's Experience Vaults), we obtained preliminary evidence supporting that the similarity between the binding affinity profiles of psychoactive substituted phenethylamines and tryptamines is correlated with the semantic similarity of the associated reports. We also showed that the highest correlation was achieved by considering the combined binding affinity for the 5-HT, dopamine (DA), glutamate, muscarinic and opioid receptors and for the Ca+ channel. Applying dimensionality reduction techniques to the reports, we linked the compounds, receptors, transporters and the Ca+ channel to distinct fingerprints of the reported subjective effects. To the extent that the existing binding affinity data is based on a low number of displacement curves that requires further replication, our analysis produced preliminary evidence consistent with the involvement of different binding sites in the reported subjective effects elicited by psychedelics. Beyond the study of this particular class of drugs, we provide a methodological framework to explore the relationship between the binding affinity profiles and the reported subjective effects of other psychoactive compounds.


Adrenalectomy and coat color in deer mice.
Adrenalectomy in prairie deer mice is followed by a profound darkening of the fur which occurs with in 1 to 3 months. The phenomenon is most noticeable on the normally unpigmented ventral surfaces which turn dark gray or black. A possible mechanism for such hyperpigmentation would involve increased release of inelanocyte-stimulating hormones.


Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3.
Skin lies at the interface between the complex physiology of the body and the external environment. This essential epidermal barrier, composed of cornified proteins encased in lipids, prevents both water loss and entry of infectious or toxic substances. We uncover that the transcription factor GATA-3 is required to establish the epidermal barrier and survive in the ex utero environment. Analysis of Gata-3 mutant transcriptional profiles at three critical developmental stages identifies a specific defect in lipid biosynthesis and a delay in differentiation. Genomic analysis identifies highly conserved GATA-3 binding sites bound in vivo by GATA-3 in the first intron of the lipid acyltransferase gene AGPAT5. Skin from both Gata-3-/- and previously characterized barrier-deficient Kruppel-like factor 4-/- newborns up-regulate antimicrobial peptides, effectors of innate immunity. Comparison of these animal models illustrates how impairment of the skin barrier by two genetically distinct mechanisms leads to innate immune responses, as observed in the common human skin disorders psoriasis and atopic dermatitis.


Animal Models for Heart Valve Research and Development.
Valvular heart disease is the third-most common cause of heart problems in the United States. Malfunction of the valves can be acquired or congenital and each may lead either to stenosis or regurgitation, or even both in some cases. Heart valve disease is a progressive disease, which is irreversible and may be fatal if left untreated. Pharmacological agents cannot currently prevent valvular calcification or help repair damaged valves, as valve tissue is unable to regenerate spontaneously. Thus, heart valve replacement/repair is the only current available treatment. Heart valve research and development is currently focused on two parallel paths; first, research that aims to understand the underlying mechanisms for heart valve disease to emerge with an ultimate goal to devise medical treatment; and second, efforts to develop repair and replacement options for a diseased valve. Studies that focus on developmental malformation, genetic and disease epigenetics usually employ small animal models that are easy to access for in vivo imaging that minimally disturbs their environment during early stages of development. Alternatively, studies that aim to develop novel device for replacement and repair of diseased valves often employ large animals whose heart size and anatomy closely replicate human's. This paper aims to briefly review the current state-of-the-art animal models, and justification to use an animal model for a particular heart valve related project.


Understanding the influence of contextual factors and individual social capital on American public mask wearing in response to COVID-19.
The COVID-19 pandemic poses unprecedented risks to the health and well-being of the entire population in the U.S. To control the pandemic, it is imperative for individuals to take precautionary behaviors (e.g., wearing a mask, keeping social distance, washing hands frequently, etc.). The factors that influence individual behavioral response thus warrants a close examination. Using survey data for respondents from 10 states merged with state-level data, our study represents a pioneering effort to reveal contextual and individual social capital factors that explain public mask wearing in response to COVID-19. Findings of logistic multilevel regression show that the COVID-19 death rate and political control of government at the state level along with one's social capital at the individual level altogether influence whether people decide to wear face masks. These findings contribute to the rapidly growing literature and have policy implications for mitigating the pandemic's devastating impact on the American public.


Combining MAD and CPAP as an effective strategy for treating patients with severe sleep apnea intolerant to high-pressure PAP and unresponsive to MAD.
This study aimed to determine the effect of combining positive airway pressure (PAP) therapy and mandibular advancement device (MAD) in patients with severe obstructive sleep apnea (OSA) who were pressure intolerant for PAP and were unresponsive to MAD. This retrospective study reviewed the medical records of severe OSA patients with apnea-hypopnea index (AHI) ≥ 30/hr who were diagnosed between October 1, 2008 and June 30, 2014. Patients were initially treated with 2 weeks of PAP, and those who were intolerant to high-pressure PAP (≥15 cm H2O) were switched to 12 weeks of MAD, which is a monobloc designed at 75% of maximum protrusion. Patients who had high residual AHI (≥15/hr) on MAD underwent 12 weeks of combination therapy (CT) with MAD and CPAP and were enrolled in the present study. Enrolled subjects who completed the 12-week CT were followed-up until June 30, 2016. A total of 14 male patients were included. All three treatments effectively reduced AHI, oxygen desaturation index (ODI), and total sleep time with SpO2 <90% (% TST-SpO2<90%) compared to pretreatment values. The residual AHI and ODI on CT was lower than that on MAD or PAP. The residual % TST-SpO2<90% was lower than that on MAD and similar to that on PAP. The therapeutic pressure on CT was on average 9.2 cm H2O lower than that on PAP. For the 11 patients who completed CT, only CT reduced ESS compared to pretreatment value. No treatment had significant impact on % slow wave sleep or overnight change of blood pressure. For patients who completed CT, the average usage was 5.9±1.7 hr/night at 12th week and 6.4±1.5 hr/night at a median follow-up of 36.5-months. Combining MAD and CPAP showed additive effects on reducing AHI and ODI, and lowered the therapeutic pressures.


Phase I trial of toll-like receptor 9 agonist PF-3512676 with and following rituximab in patients with recurrent indolent and aggressive non Hodgkin's lymphoma.
PF-3512676 (formerly CpG 7909) is a novel Toll-like receptor 9-activating oligonucleotide with single-agent antitumor activity that augments preclinical rituximab efficacy. This Phase I trial was designed to investigate the safety, tolerability, and preliminary antitumor activity of PF-3512676 in combination with rituximab. Patients with relapsed/refractory CD20+ B cell non-Hodgkin's lymphoma received i.v. rituximab (375 mg/m2/week for 4 weeks) and PF-3512676 weekly for 4 weeks either i.v. (0.04, 0.16, 0.32, or 0.48 mg/kg) or s.c. (0.01, 0.04, 0.08, or 0.16 mg/kg). An additional extended-treatment cohort received 4 weeks of 0.24 mg/kg s.c. PF-3512676 in combination with rituximab followed by s.c. PF-3512676 alone weekly for 20 weeks. Patients (N = 50) had received a median of three prior therapies (range, 1-11) including rituximab in 80% of patients. Treatment-related adverse events occurred in 11 of 19 (58%) i.v. patients, 15 of 19 (79%) s.c. patients, and all 12 patients in the extended-treatment cohort. Most common adverse events were mild to moderate systemic flu-like symptoms and injection-site reactions (s.c. cohorts only). Grade 3/4 neutropenia occurred in four patients. Objective responses occurred in 12 of 50 (24%) patients overall and in 6 of 12 (50%) patients in the extended-treatment cohort, including 2 patients with rituximab-refractory disease. Brief or extended-duration PF-3512676 can be safely administered in combination with rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.


Fast Implementation of the Nudged Elastic Band Method in AMBER.
We present a fast implementation of the nudged elastic band (NEB) method into the particle mesh Ewald molecular dynamics module of the Amber software package for both central processing units (CPU) and graphics processing units (GPU). The accuracy of the new implementation has been validated for three cases: a conformational change of alanine dipeptide, the α-helix to β-sheet transition in polyalanine, and a large conformational transition in the human 8-oxoguanine-DNA glycosylase with DNA complex (OGG1-DNA). Timing benchmark tests were performed on the explicitly solvated OGG1-DNA system containing ∼50 000 atoms. The GPU-optimized implementation of NEB achieves a more than two orders of magnitude speedup compared with the previous CPU implementation performed with a two-core CPU processor. The speed and scalable features of this implementation will enable NEB applications on larger and more complex systems.


On the performance of voltage stepping for the simulation of adaptive, nonlinear integrate-and-fire neuronal networks.
In traditional event-driven strategies, spike timings are analytically given or calculated with arbitrary precision (up to machine precision). Exact computation is possible only for simplified neuron models, mainly the leaky integrate-and-fire model. In a recent paper, Zheng, Tonnelier, and Martinez (2009) introduced an approximate event-driven strategy, named voltage stepping, that allows the generic simulation of nonlinear spiking neurons. Promising results were achieved in the simulation of single quadratic integrate-and-fire neurons. Here, we assess the performance of voltage stepping in network simulations by considering more complex neurons (quadratic integrate-and-fire neurons with adaptation) coupled with multiple synapses. To handle the discrete nature of synaptic interactions, we recast voltage stepping in a general framework, the discrete event system specification. The efficiency of the method is assessed through simulations and comparisons with a modified time-stepping scheme of the Runge-Kutta type. We demonstrated numerically that the original order of voltage stepping is preserved when simulating connected spiking neurons, independent of the network activity and connectivity.


Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass.
Micropuncture and morphologic studies were performed in four groups of male Munich-Wistar rats after removal of the right kidney and segmental infarction of two-thirds of the left kidney. Groups 1 and 3 received no specific therapy. Groups 2 and 4 were treated with the angiotensin I converting enzyme inhibitor, enalapril, 50 mg/liter of which was put in their drinking water. All rats were fed standard chow. Groups 1 and 2 underwent micropuncture study 4 wk after renal ablation. Untreated group 1 rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR) due to high average values for the mean glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 rats, treatment with enalapril prevented systemic hypertension and maintained the mean glomerular transcapillary hydraulic pressure gradient at near-normal levels without significantly compromising SNGFR and the glomerular capillary plasma flow rate, as compared with untreated group 1 rats. Groups 3 and 4 were studied 8 wk after renal ablation. Untreated group 3 rats demonstrated persistent systemic hypertension, progressive proteinuria, and glomerular structural lesions, including mesangial expansion and segmental sclerosis. In group 4 rats, treatment with enalapril maintained systemic blood pressure at normal levels over the 8-wk period and significantly limited the development of proteinuria and glomerular lesions. These studies suggest that control of glomerular hypertension effectively limits glomerular injury in rats with renal ablation, and further support the view that glomerular hemodynamic changes mediate progressive renal injury when nephron number is reduced.


Detection of dengue virus infection in children presenting with fever in Hawassa, southern Ethiopia.
Dengue fever is a mosquito-borne viral infection, with rising incidence globally. Eastern Ethiopia has had dengue fever outbreaks in recent years. However, the extent to which the infection contributes to hospital presentation among children with fever in southern Ethiopia is unknown. We examined 407 stored plasma samples collected to investigate the aetiology of fever in children aged at least 2 months and under 13 years presenting to the outpatient of the largest tertiary hospital in southern Ethiopia. We analyzed samples for dengue virus non-structural 1 antigen using enzyme-linked immunosorbent assay. The median (interquartile range) age of the 407 children examined was 20 (10-48) months, and 166 (40.8%) of the children were females. Of 407 samples analyzed, 9 (2.2%) were positive for dengue virus non-structural 1 antigen, of whom 2 were initially treated with antimalarial drugs despite having negative malaria microscopy, and 1 of the 8 patients had a persistent fever at the seventh day of follow-up time. The presence of active dengue virus infection in the study area highlights the need for studies at the community level as well as the integration of dengue diagnostics into fever-management strategies. Further research to characterize circulating strains is warranted.


Altruism in dental students.
Altruistic dentists play a central role in treating minority populations, the poor, the uninsured, and those living in underserved communities. This study examines factors associated with graduating dental students' altruistic attitudes. We use a nationally representative dataset, the 2007 American Dental Education Association Survey of Dental School Seniors (n=3,841), and a comprehensive framework to investigate individual, school, and community characteristics that may influence altruism. Student characteristics were the most significant predictors: women, African Americans, Hispanics, Asian/Pacific Islanders, and students with low socioeconomic status expressed greater altruism than their counterparts. These results inform dental educators and administrators to expand efforts to recruit underrepresented racial/ethnic and low-income students into dentistry. Additionally, we found that students with altruistic personalities attend schools where the social context is more accepting and respectful of diversity. This suggests that schools can promote altruism in their students by creating a positive culture and environment for diverse populations.


Efficacy of levetiracetam for reducing rolandic discharges in comparison with carbamazepine and valproate sodium in rolandic epilepsy.
The main purpose of this study was to compare the efficacy of levetiracetam (LEV) with the older antiepileptic drugs (AEDs) for preventing atypical evolution in children with Rolandic epilepsy (RE). Accordingly, the present study compared the efficacy of older AEDs (carbamazepine (CBZ) and valproate sodium (VPA)) with LEV in reducing rolandic discharges (RDs) on interictal electroencephalogram (EEG) in children with RE. Patients in this heterogenous study were subdivided into CBZ, VPA and LEV groups in accordance with the initial monotherapy. The CBZ and VPA groups were studied retrospectively, but the LEV group was studied prospectively. Appearances of discharges were counted and these rates were computed. In comparison with the baseline RD frequency, EEG response to AED treatment was classified such as complete disappearance and response (≥50% reduction in RD frequency). The time taken to attain complete disappearance or response in EEG responders was assessed for each AED treatment group. Responders comprised 10 (11.2%) of the 89 patients treated with CBZ, 41 (56.2%) of the 73 patients with VPA, and 25 (71.4%) of the 35 patients with LEV. Mean interval to achievement of EEG response in the CBZ, VPA, and LEV groups were 36.3, 23.1, and 14.7 months, respectively. EEG response was achieved significantly more rapidly with LEV than with CBZ (p < 0.001) or VPA (p < 0.005). Seizure control was not significantly different in all 3 investigated drugs. LEV seems to be superior to CBZ and VPA in its ability to suppress RDs in children with RE.


The human lagging strand DNA polymerase δ holoenzyme is distributive.
Polymerase δ is widely accepted as the lagging strand replicative DNA polymerase in eukaryotic cells. It forms a replication complex in the presence of replication factor C and proliferating cell nuclear antigen to perform efficient DNA synthesis in vivo. In this study, the human lagging strand holoenzyme was reconstituted in vitro. The rate of DNA synthesis of this holoenzyme, measured with a singly primed ssM13 DNA substrate, is 4.0 ± 0.4 nucleotides. Results from adenosine 5'-(3-thiotriphosphate) tetralithium salt (ATPγS) inhibition experiments revealed the nonprocessive characteristic of the human DNA polymerase (Pol δ) holoenzyme (150 bp for one binding event), consistent with data from chase experiments with catalytically inactive mutant Pol δ(AA). The ATPase activity of replication factor C was characterized and found to be stimulated ∼10-fold in the presence of both proliferating cell nuclear antigen and DNA, but the activity was not shut down by Pol δ in accord with rapid association/dissociation of the holoenzyme to/from DNA. It is noted that high concentrations of ATP inhibit the holoenzyme DNA synthesis activity, most likely due to its inhibition of the clamp loading process.


The effects of psychotherapy for adult depression are overestimated: a meta-analysis of study quality and effect size.
No meta-analytical study has examined whether the quality of the studies examining psychotherapy for adult depression is associated with the effect sizes found. This study assesses this association. We used a database of 115 randomized controlled trials in which 178 psychotherapies for adult depression were compared to a control condition. Eight quality criteria were assessed by two independent coders: participants met diagnostic criteria for a depressive disorder, a treatment manual was used, the therapists were trained, treatment integrity was checked, intention-to-treat analyses were used, N >or= 50, randomization was conducted by an independent party, and assessors of outcome were blinded. Only 11 studies (16 comparisons) met the eight quality criteria. The standardized mean effect size found for the high-quality studies (d=0.22) was significantly smaller than in the other studies (d=0.74, p<0.001), even after restricting the sample to the subset of other studies that used the kind of care-as-usual or non-specific controls that tended to be used in the high-quality studies. Heterogeneity was zero in the group of high-quality studies. The numbers needed to be treated in the high-quality studies was 8, while it was 2 in the lower-quality studies. We found strong evidence that the effects of psychotherapy for adult depression have been overestimated in meta-analytical studies. Although the effects of psychotherapy are significant, they are much smaller than was assumed until now, even after controlling for the type of control condition used.


Clinical Features of CADASIL.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks, strokes, and vascular dementia. Various mutations in the Notch3 gene cause the disease, whereas the mechanism of how they cause the disorder remains unknown. We recently identified two Japanese CADASIL families with an R141C mutation. The mean age of onset was 44.6, and the main symptoms were recurrent strokes and progressive motor disturbances in extremities, as well as pseudobulbar palsy. Besides those in white matter and basal ganglia, ischemic lesions in temporal edge and corpus callosum were present on magnetic resonance images, which seemed to be characteristic of CADASIL. Moreover, in our cases, nocturnal arterial blood pressure fall was significantly lower in patients compared with control subjects, suggesting that it might be partly associated with ischemic lesions in deep white matter in CADASIL. We also compared Japanese and Caucasian CADASIL cases and found that dementia and pseudobulbar palsy were observed more frequently in Japanese patients, although typical migraine was rather rare. In the present study, we describe the clinical features of CADASIL, hoping to help reveal the mechanism of chronic ischemic brain diseases, including leukoaraiosis or Binswanger's disease.


The birth of convulsive therapy revisited: a reappraisal of László Meduna's first cohort of patients.
The introduction of convulsive therapy (COT) was undoubtedly one of the milestones in the history of psychiatry. Its originator, László Meduna, has become one of the founding fathers of biological psychiatry. In his first major publication on COT, Meduna described the short-term treatment outcome of the first 26 schizophrenia patients who underwent camphor- or cardiazol-induced COT; 10 improved significantly, 3 appeared slightly improved, and 13 were unimproved. The original medical notes of 23 of the 26 patients were recently recovered and the patients re-diagnosed by the authors employing ICD-10 criteria. The diagnosis of schizophrenia was confirmed in 15 cases (all but two of them involving prominent catatonic symptomatology), while 2 cases met diagnostic criteria for schizoaffective disorder, 3 for Bipolar Affective Disorder (BAD) with psychotic features, 1 for psychotic depression, and 1 for Acute and Transient Psychotic Disorder (ATPD). In a final case, the most probable diagnosis was schizophrenia. Scrutiny of the notes revealed that 4 schizophrenia patients evidenced slight improvement on COT and in one case the improvement was only transient. A limitation of this study is that the quality of the original files varied considerably and the re-evaluation was done retrospectively. A very broad concept of schizophrenia in the 1930s explains the discrepancy between the original and the revised results. In line with the current views on the effectiveness of electroconvulsive therapy, catatonic symptoms, but not the core schizophrenic process, showed some improvement while all ATPD, BAD and depressed patients responded to COT.


CD4/CD8 double negative mycosis fungoides with PD-1 (CD279) expression--a disease of follicular helper T-cells?
CD4/CD8 double negative mycosis fungoides (MF) is a rare phenotypic variant of this epidermotropic cutaneous T-cell lymphoma. Clinically, this MF form manifests with unusual appearances such as annular lesions confined to one body region as in our patient in whom the lesions were found on the left lower leg. The cellular origin of CD4/CD8 double negative MF is unknown. In our case, the intraepidermal CD4/CD8 double negative clonal T-lymphocytes (CD2+, CD4-, CD8-, CD30-, beta-F1+) expressed programmed death-1 but were negative for CXCL-13 and cytotoxic molecules (TIA-1, granzyme B, perforin). Our observation may give an insight into the histogenesis of this unique MF variant and may also be of therapeutic significance because programmed death-1 may serve as a target for therapeutic intervention.


[Mental health policies and changes in emergency service demand].
To verify the modifications observed in a school hospital psychiatric emergency unit in Ribeirão Preto - SP, Brazil (EP-RP), due to alterations in the mental health policies implemented in this region. Data about attendances was collected from university hospital files of the EP-RP, from 1988 to 1997. The following variables were studied: sex, age, origin and main diagnosis. Data about changes in mental health policies of the region was obtained from documents of the city and state departments of health. The yearly increase in the number of attendances followed the progressive involvement of EP-RP with the mental health service network, as the number of patients who looked for the service in 1995 was 2.3 times greater than in 1988. During this period, attendance at the EP-RP gave support to the modifications in the mental health policies in this region, resulting in a reduction of 654 psychiatry beds. In 1996 and 1997, a reduction of about 20% was observed in the total of attendance, as compared to 1995, result from an increase in the attendance capacity and number of the extra-hospital services. Since 1990, the EP-RP started to attend a higher proportion of older, male patients, with drug dependency and psychotic disorders and a lower proportion of non-psychotic patients. The changes observed in the EP-RP are related to modifications in the Ribeirão Preto region mental health policies, like the psychiatric beds control, installed in 1990, the reduction of psychiatric beds after 1993, and the creation and/or amplification of extra-hospital services, in 1995.


Determination of thickness of thin turbid painted over-layers using micro-scale spatially offset Raman spectroscopy.
We present a method for estimating the thickness of thin turbid layers using defocusing micro-spatially offset Raman spectroscopy (micro-SORS). The approach, applicable to highly turbid systems, enables one to predict depths in excess of those accessible with conventional Raman microscopy. The technique can be used, for example, to establish the paint layer thickness on cultural heritage objects, such as panel canvases, mural paintings, painted statues and decorated objects. Other applications include analysis in polymer, biological and biomedical disciplines, catalytic and forensics sciences where highly turbid overlayers are often present and where invasive probing may not be possible or is undesirable. The method comprises two stages: (i) a calibration step for training the method on a well characterized sample set with a known thickness, and (ii) a prediction step where the prediction of layer thickness is carried out non-invasively on samples of unknown thickness of the same chemical and physical make up as the calibration set. An illustrative example of a practical deployment of this method is the analysis of larger areas of paintings. In this case, first, a calibration would be performed on a fragment of painting of a known thickness (e.g. derived from cross-sectional analysis) and subsequently the analysis of thickness across larger areas of painting could then be carried out non-invasively. The performance of the method is compared with that of the more established optical coherence tomography (OCT) technique on identical sample set.This article is part of the themed issue 'Raman spectroscopy in art and archaeology'.


Direct Nitrous Oxide Emissions From Tropical And Sub-Tropical Agricultural Systems - A Review And Modelling Of Emission Factors.
There has been much debate about the uncertainties associated with the estimation of direct and indirect agricultural nitrous oxide (N2O) emissions in developing countries and in particular from tropical regions. In this study, we report an up-to-date review of the information published in peer-review journals on direct N2O emissions from agricultural systems in tropical and sub-tropical regions. We statistically analyze net-N2O-N emissions to estimate tropic-specific annual N2O emission factors (N2O-EFs) using a Generalized Additive Mixed Model (GAMM) which allowed the effects of multiple covariates to be modelled as linear or smooth non-linear continuous functions. Overall the mean N2O-EF was 1.2% for the tropics and sub-tropics, thus within the uncertainty range of IPCC-EF. On a regional basis, mean N2O-EFs were 1.4% for Africa, 1.1%, for Asia, 0.9% for Australia and 1.3% for Central &South America. Our annual N2O-EFs, estimated for a range of fertiliser rates using the available data, do not support recent studies hypothesising non-linear increase N2O-EFs as a function of applied N. Our findings highlight that in reporting annual N2O emissions and estimating N2O-EFs, particular attention should be paid in modelling the effect of study length on response of N2O.


Murine OKT4A immunosuppression in cadaver donor renal allograft recipients: a Cooperative Clinical Trials in Transplantation pilot study.
A phase I study of anti-CD4 immunosuppression of cadaver donor renal allograft recipients was conducted by the NIH Cooperative Clinical Trials in Transplantation to assess safety, tolerability, immunoactivity, and pharmacokinetics of multiple infusions of murine anti-human CD4 monoclonal antibody OKT4A. Thirty patients were enrolled (August 1992 to October 1993) and received OKT4A at dosages of 0.5 mg/kg (24 patients), 1.0 mg/kg (3 patients), and 2.0 mg/kg (3 patients), beginning and continuing for 12 consecutive days with a standard regimen of cyclosporine, azathioprine, and prednisone. OKT4A treatment was continued after surgery if serum creatinine 24 hr after transplantation was <85% of pretransplantation baseline creatinine. Ninety-three percent of patients treated at 0.5 mg/kg OKT4A and all patients at higher doses had mean peak CD4 saturations in excess of 90%. A human anti-mouse antibody response of >3 times pretreatment levels was observed in 84% of patients. There was no evidence of CD4 T cell depletion. OKT4A was well tolerated without first-dose side effects. For the 19 eligible patients treated with 0.5 mg/kg OKT4A with initial graft function, the 3-month treated rejection rate was 37%. The 2-year graft survival rate for all 30 patients enrolled was 83%, and for the 19 eligible patients, 95%. The high percentage of CD4 saturation, the minimal side effects, the observation of a low 3-month rejection rate, and an excellent 2-year graft survival rate in patients treated with 0.5 mg/kg OKT4A support the continued investigation of an anti-CD4 approach to immunosuppressive therapy.


Dutch COVID-19 lockdown measures increased trust in government and trust in science: A difference-in-differences analysis.
Many governments have implemented strict lockdown measures to prevent the transmission of the new coronavirus (SARS-CoV-2). Compliance with these restrictions is vital and depends greatly on the level of trust in the institutions central to their development and implementation. The objectives of this study were to assess: (1) the effects of the Dutch lockdown measures imposed in March 2020 on trust in government and trust in science; and (2) whether these differ across social groups. We draw on unique data from the high-quality Longitudinal Internet Studies for the Social Sciences panel, which comprises a true probability sample of Dutch households (average participation rate: 80.4%). Our data were collected on an ongoing basis from December 2017 to March 2020 (n = 2219). Using the implementation of lockdown measures in mid-March as a natural experiment, we employed difference-in-differences analyses to assess the causal effect of the Dutch lockdown measures on trust in government and trust in science. We estimated that the imposition of the measures caused an 18% increase (95% confidence interval (CI):15%-21%)) in trust in government and a 6% increase (95% CI: 4%-8%) in trust in science. The impact on trust in government was greater among the participants aged 65 and older and those with poor self-assessed health, although the relevant CIs were wide and, in the case of self-assessed health, included the null. No differential effects were observed for trust in science. Our study indicates that the strict public-health measures imposed in the Netherlands during an acute phase of the COVID-19 pandemic generated trust in the institutions involved in drafting and implementing them, especially among those with a higher risk of serious health outcomes. This suggests that, to prevent a major public-health crisis, people appreciate firm government intervention during the acute phase of an infectious disease pandemic.


Branched Poly(ethylene imine)s as Anti-algal and Anti-cyanobacterial Agents with Selective Flocculation Behavior to Cyanobacteria over Algae.
Poly(ethylene imine)s (PEIs) have been widely studied for biomedical applications, including antimicrobial agents against potential human pathogens. The interactions of branched PEIs (B-PEIs) with environmentally relevant microorganisms whose uncontrolled growth in natural or engineered environments causes health, economic, and technical issues in many sectors of water management are studied. B-PEIs are shown to be potent antimicrobials effective in controlling the growth of environmentally relevant algae and cyanobacteria with dual-functionality and selectivity. Not only did they effectively inhibit growth of both algae and cyanobacteria, mostly without causing cell death (static activity), but they also selectively flocculated cyanobacteria over algae. Thus, unmodified B-PEIs provide a cost-effective and chemically facile framework for the further development of effective and selective antimicrobial agents useful for control of growth and separation of algae and cyanobacteria in natural or engineered environments.


Attitudes and Beliefs Pertaining to Sexual and Reproductive Health Among Unmarried, Female Bhutanese Refugee Youth in Philadelphia.
We explored attitudes and beliefs pertaining to sexual and reproductive health (SRH) among unmarried, female, resettled Bhutanese refugees 16-20 years. Fourteen interviews were analyzed using the constant comparison method, and major themes were identified. SRH was stigmatized for unmarried youth, making seeking information about SRH or accessing family planning difficult. There were many misconceptions about access to SRH. Universal, culturally, and linguistically appropriate comprehensive SRH education is recommended for female Bhutanese refugee youth. Terminology used should take into account differences in conceptualization of concepts like dating. Educators and health care providers should clearly describe consent and confidentiality laws regarding adolescent SRH services.


Predicting hospital costs among older decedents over time.
To explain the variation in total real hospital costs among elderly patients who died between 1984 and 1991, a cohort analytic study of the nationally representative sample of elderly subjects included in the Longitudinal Study on Aging (N = 7,527) was carried out. The cohort comprised the subset of 1,778 community-dwelling Americans who were age 70 years and older in 1984, had one or more subsequent hospital episodes, and died by 1991. Hospital charges for 1984 through 1991 were taken from the Medicare Automated Data Retrieval System. Annual hospital charges were adjusted for inflation (restated in 1984 dollars) using the hospital market basket component of the consumer price index. The natural logarithm of aggregated real charges was used in the analysis. Mean total real hospital charges were $24,956 (SD = $27,847). A standard multivariable regression model explained 9.7% of the variance in real total hospital charges. After incorporating additional measures reflecting a respondent's distribution (mean and standard deviation) of comorbidities (as measured by the number of ICD-9-CM codes [truncated at five]) during all hospitalizations in the observation window, the cause of death, and the concentration of charges in the last year of life, the explained variance increased to 29.3%. The most important explanatory factors were the two variables controlling for the distribution of comorbidity, the variable controlling for population density, and the dichotomous variable indicating that the patient's death was related to an acute myocardial infarction. Total real hospital resources consumed by elderly decedents vary substantially. The concentration of resources consumed in the last year of a respondent's life was only marginally significant in predicting total real hospital charges over an 8-year observation window.


Mind-Wandering as a Natural Kind: A Family-Resemblances View.
As empirical research on mind-wandering accelerates, we draw attention to an emerging trend in how mind-wandering is conceptualized. Previously articulated definitions of mind-wandering differ from each other in important ways, yet they also maintain overlapping characteristics. This conceptual structure suggests that mind-wandering is best considered from a family-resemblances perspective, which entails treating it as a graded, heterogeneous construct and clearly measuring and describing the specific aspect(s) of mind-wandering that researchers are investigating. We believe that adopting this family-resemblances approach will increase conceptual and methodological connections among related phenomena in the mind-wandering family and encourage a more nuanced and precise understanding of the many varieties of mind-wandering.


Molecular imprinted opal closest-packing photonic crystals for the detection of trace 17β-estradiol in aqueous solution.
A novel opal closest-packing (OCP) photonic crystal (PC) was prepared by the introduction of molecular imprinting technique into the OCP PC. This molecular imprinted (MI)-OCP PC was fabricated via a vertical convective self-assembly method using 17β-estradiol (E2) as template molecules for monitoring E2 in aqueous solution. Morphology characterization showed that the MI-OCP PC possessed a highly ordered three-dimensional (3D) periodically-ordered structure, showing the desired structural color. The proposed PC material displayed a reduced reflection intensity when detecting E2 in water environment, because the molecular imprinting recognition events make the optical characteristics of PC change. The Bragg diffraction intensity decreased by 19.864 a.u. with the increase of E2 concentration from 1.5 ng mL(-1) to 364.5 ng mL(-1) within 6 min, whereas there were no obvious peak intensity changes for estriol, estrone, cholesterol, testosterone and diethylstilbestrol, indicating that the MI-OCP PC had selective and rapid response for E2 molecules. The adsorption results showed that the OCP structure and homogeneous layers were created in the MI-OCP PC with higher adsorption capacity. Thus, it was learned the MI-OCP PC is a simple prepared, sensitive, selective, and easy operative material, which shows promising use in routine supervision for residue detection in food and environment.


Attachment of DNA to the nucleoskeleton of HeLa cells examined using physiological conditions.
Although it is widely believed that eukaryotic DNA is looped by attachment to a nucleoskeleton, there is controversy about its composition and which sequences are attached to it. As most nuclear derivatives are isolated using unphysiological conditions, the criticism that attachments seen in vitro are generated artifactually has been difficult to rebut. Therefore we have re-investigated attachments of chromatin to the skeleton using physiological conditions. HeLa cells are encapsulated in agarose microbeads and lysed using Triton in a 'physiological' buffer. Then, most chromatin can be electroeluted after treatment with a restriction enzyme to leave some at the base of the loops still attached. Analysis of the size and amounts of these residual fragments indicates that the loops are 80-90kbp long. The residual fragments are stably attached, with about 1kbp of each fragment protected from nuclease attack. This is very much longer than a typical protein-binding site of 10-20bp.


Effect of change in P50 on exercise tolerance at high altitude: a theoretical study.
Acclimatization to altitude often results in a rightward shift of the O2 dissociation curve (ODC). However, a left-shifted ODC is reported to increase exercise tolerance in humans at medium altitude and increase survival in rats breathing hypoxic gas mixtures. We examined this paradox using a computer model of pulmonary gas exchange. A Bohr integration procedure allowed for alveolar-capillary diffusion. When diffusion equilibration was complete, mixed venous (PVO2) and arterial PO2 fell as O2 consumption (VO2) was increased, but PVO2 approached a plateau. Under these conditions a right-shifted ODC is advantageous (higher PVO2) at all but very high altitudes. However, diffusion limitation of O2 transfer may occur at any altitude if VO2 is increased sufficiently. If this occurs, a left-shifted ODC results in higher calculated VO2max (compared with the standard ODC). Further, diffusion limitation always occurs at a lower VO2 with a right-shifted ODC than with a left-shifted ODC. We conclude that whether a leftward or rightward shift in the ODC is advantageous to gas exchange at altitude depends on the presence or absence of diffusion limitation.


Malposition of peripherally inserted central catheter: Experience from 3,012 patients with cancer.
The aim of this study was to observe and analyze the causes of misplacement of peripherally inserted central catheters (PICCs) in patients with cancer. A total of 3,012 patients who underwent insertion of a PICC were reviewed from August 2000 to March 2012. The locations of the tube tips were recorded by chest X-ray examination. Malposition of the PICC was observed in 237 cases (7.87%), with the most frequently occurring site of misplacement being the jugular vein, followed by the axillary vein. By taking different remedies, all the malpositioned PICCs were relocated back to the superior vena cava or subclavian vein. In order to ensure the safe usage of PICCs, strict placement guidelines, skilled and experienced healthcare professionals and the cooperation of the patient is necessary.


Simultaneous stratospheric gas and aerosol retrievals from broadband infrared occultation measurements.
The inversion method for simultaneous gas (O3, NO2, HNO3, N2O, CH4, H2O, CFC-11, CFC-12, N2O5, and ClONO2) and aerosol retrievals from broadband continuous IR spectra of occultation measurements is described. Both gas and aerosol physical modeling with consideration of the multicomponent character of aerosol and polar stratospheric clouds (PSCs) are used to minimize the difference between measured and modeled transmittance spectra under smoothness constraints imposed on particle-size distributions for each PSC component and positive constraints on all gas and aerosol parameters. The method is tested by numerical simulations in which synthetic occultation measurements inherent to the improved limb atmospheric spectrometer are used. The study reveals that the method has significant advantages over other approaches based on offset or gas-window-channel aerosol correction for accurate gas retrievals and provides additional information on the particle-size composition, volume density, and chemical component character of PSCs.


Cloning, sequencing, and expression of the Escherichia coli cytolethal distending toxin genes.
A limited number of Escherichia coli isolates which produce an apparently novel toxin, termed cytolethal distending toxin (CDT), have been reported. The toxic activity produced by these strains causes certain cultured cell lines to become slowly distended and then disintegrate. DNA was isolated from the CDT-producing E. coli strain, 9142-88, and cloned into a cosmid vector. Plasmid DNA from a toxin-positive transductant was further subcloned until a plasmid with a 4-kb insert which still encoded the toxin activity was obtained. Nucleotide sequencing of a portion of this insert revealed the presence of three adjacent open reading frames. Further subcloning and deletion analysis suggested that the products of all three open reading frames may be required for toxin activity. Minicell experiments identified the products of all three open reading frames. The three proteins had predicted sizes of 27,753,29,531, and 19,938 Da, and all three appeared to have strong consensus leader sequences. None of the three predicted proteins had significant homology to known proteins.


Effects of expert testimony and interrogation tactics on perceptions of confessions.
Evidence obtained through the process of interrogation is frequently undermined by what can be perceived as overzealous interrogation tactics. Although the majority of psychologically oriented tactics are legally permissible, they nonetheless contribute to innocent suspects confessing to crimes they did not commit. The present study examined the effect of expert testimony and interrogation tactics on perceptions of a confession. 182 undergraduates read a transcript of a homicide trial that varied based on interrogation tactic: implicit threat of punishment (maximization) or leniency (minimization) and expert witness testimony (presence or absence of expert testimony). Analysis indicated that the type of interrogation tactic used in obtaining the confession affected participants' perceptions of the coerciveness of the interrogation process.


A facile synthesis of sulfonylureas via water assisted preparation of carbamates.
A novel and simple approach to the synthesis of sulfonylureas has been reported. It involved the reaction of various amines with diphenyl carbonate to yield the corresponding carbamates, which subsequently reacted with different sulphonamides to produce different sulfonylureas in excellent yields. The first reaction of diphenyl carbonate with amines was carried out in aqueous : organic (H2O : THF, 90 : 10) medium at room temperature to produce carbamates that paved a straightforward route to sulfonylureas after reaction with sulfonamides. The above process avoided traditional multistep protocols and the use of hazardous, irritant, toxic and moisture sensitive reagents such as phosgene, isocyanates and/or chloroformates.