"The way the country has been carved up by researchers": ethics and power in north-south public health research.
Despite the recognition of power as being central to health research collaborations between high income countries and low and middle income countries, there has been insufficient detailed analysis of power within these partnerships. The politics of research in the global south is often considered outside of the remit of research ethics. This article reports on an analysis of power in north-south public health research, using Zambia as a case study. Primary data were collected in 2011/2012, through 53 in-depth interviews with: Zambian researchers (n = 20), Zambian national stakeholders (n = 8) and northern researchers who had been involved in public health research collaborations involving Zambia and the global north (n = 25). Thematic analysis, utilising a situated ethics perspective, was undertaken using Nvivo 10. Most interviewees perceived roles and relationships to be inequitable with power remaining with the north. Concepts from Bourdieu's theory of Power and Practice highlight new aspects of research ethics: Northern and southern researchers perceive that different habituses exist, north and south - habituses of domination (northern) and subordination (Zambian) in relation to researcher relationships. Bourdieu's hysteresis effect provides a possible explanation for why power differentials continue to exist. In some cases, new opportunities have arisen for Zambian researchers; however, they may not immediately recognise and grasp them. Bourdieu's concept of Capitals offers an explanation of how diverse resources are used to explain these power imbalances, where northern researchers are often in possession of more economic, symbolic and social capital; while Zambian researchers possess more cultural capital. Inequities and power imbalances need to be recognised and addressed in research partnerships. A situated ethics approach is central in understanding this relationship in north-south public health research.


Electron transfer by domain movement in cytochrome bc1.
The cytochrome bc1 is one of the three major respiratory enzyme complexes residing in the inner mitochondrial membrane. Cytochrome bc1 transfers electrons from ubiquinol to cytochrome c and uses the energy thus released to form an electrochemical gradient across the inner membrane. Our X-ray crystal structures of the complex from chicken, cow and rabbit in both the presence and absence of inhibitors of quinone oxidation, reveal two different locations for the extrinsic domain of one component of the enzyme, an iron-sulphur protein. One location is close enough to the supposed quinol oxidation site to allow reduction of the Fe-S protein by ubiquinol. The other site is close enough to cytochrome c1 to allow oxidation of the Fe-S protein by the cytochrome. As neither location will allow both reactions to proceed at a suitable rate, the reaction mechanism must involve movement of the extrinsic domain of the Fe-S component in order to shuttle electrons from ubiquinol to cytochrome c1. Such a mechanism has not previously been observed in redox protein complexes.


Pathophysiology of protracted acute renal failure in man.
Postischemic acute renal failure (ARF) induced by cardiac surgery is commonly prolonged and may be irreversible. To examine whether persistence of postischemic, tubular cell injury accounts for delayed recovery from ARF, we studied 10 patients developing protracted (36 +/- 4 d) ARF after cardiac surgery. The differential clearance and excretion dynamics of probe solutes of graded size were determined. Inulin clearance was depressed (5.0 +/- 1.7 ml/min), while the fractional urinary clearance of dextrans (radii 17-30 A) were elevated above unity. Employing a model of conservation of mass, we calculated that 44% of filtered inulin was lost via transtubular backleak. The clearance and fractional backleak of technetium-labeled DTPA ([99mTc]DTPA, radius = 4 A) were identical to those of inulin (radius 15 A). The time at which inulin or DTPA excretion reached a maximum after an intravenous bolus injection was markedly delayed when compared with control subjects with ARF of brief duration, 102 vs. 11 min. Applying a three-compartment model of inulin/DTPA kinetics (which takes backleak into account) revealed the residence time of intravenously administered inulin/DTPA in the compartment occupied by tubular fluid and urine to be markedly prolonged, 20 vs. 6 min in controls, suggesting reduced velocity of tubular fluid flow. We conclude that protracted human ARF is characterized by transtubular backleak of glomerular ultrafiltrate, such that inulin clearance underestimates true glomerular filtration rate by approximately 50%, and by sluggish tubular fluid flow, which strongly suggests the existence of severe and generalized intraluminal tubular obstruction. Because all patients also exhibited extreme hyperreninemia (16 +/- 2 ng/ml per h) that was inversely related to inulin clearance (r value = -0.83) and urine flow (r value = -0.70), we propose that persistent, angiotensin II-mediated renal vasoconstriction may have delayed healing of the injured tubular epithelium.


Methods and feasibility of collecting occupational data for a large population-based cohort study in the United States: the reasons for geographic and racial differences in stroke study.
Coronary heart disease and stroke are major contributors to preventable mortality. Evidence links work conditions to these diseases; however, occupational data are perceived to be difficult to collect for large population-based cohorts. We report methodological details and the feasibility of conducting an occupational ancillary study for a large U.S. prospective cohort being followed longitudinally for cardiovascular disease and stroke. Current and historical occupational information were collected from active participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. A survey was designed to gather quality occupational data among this national cohort of black and white men and women aged 45 years and older (enrolled 2003-2007). Trained staff conducted Computer-Assisted Telephone Interviews (CATI). After a brief pilot period, interviewers received additional training in the collection of narrative industry and occupation data before administering the survey to remaining cohort members. Trained coders used a computer-assisted coding system to assign U.S. Census codes for industry and occupation. All data were double coded; discrepant codes were independently resolved. Over a 2-year period, 17,648 participants provided consent and completed the occupational survey (87% response rate). A total of 20,427 jobs were assigned Census codes. Inter-rater reliability was 80% for industry and 74% for occupation. Less than 0.5% of the industry and occupation data were uncodable, compared with 12% during the pilot period. Concordance between the current and longest-held jobs was moderately high. The median time to collect employment status plus narrative and descriptive job information by CATI was 1.6 to 2.3 minutes per job. Median time to assign Census codes was 1.3 minutes per rater. The feasibility of conducting high-quality occupational data collection and coding for a large heterogeneous population-based sample was demonstrated. We found that training for interview staff was important in ensuring that narrative responses for industry and occupation were adequately specified for coding. Estimates of survey administration time and coding from digital records provide an objective basis for planning future studies. The social and environmental conditions of work are important understudied risk factors that can be feasibly integrated into large population-based health studies.


Veterinary and human biobanking practices: enhancing molecular sample integrity.
Animal models have historically informed veterinary and human pathophysiology. Next-generation genomic sequencing and molecular analyses using analytes derived from tissue require integrative approaches to determine macroanalyte integrity as well as morphology for imaging algorithms that can extend translational applications. The field of biospecimen science and biobanking will play critical roles in tissue sample collection and processing to ensure the integrity of macromolecules, aid experimental design, and provide more accurate and reproducible downstream genomic data. Herein, we employ animal experiments to combine protein expression analysis by microscopy with RNA integrity number and quantitative measures of morphologic changes of autolysis. These analyses can be used to predict the effect of preanalytic variables and provide the basis for standardized methods in tissue sample collection and processing. We also discuss the application of digital imaging with quantitative RNA and tissue-based protein measurements to show that genomic methods augment traditional in vivo imaging to support biospecimen science. To make these observations, we have established a time course experiment of murine kidney tissues that predicts conventional measures of RNA integrity by RIN analysis and provides reliable and accurate measures of biospecimen integrity and fitness, in particular for time points less than 3 hours post-tissue resection.


Automated virtual reality therapy to treat agoraphobic avoidance and distress in patients with psychosis (gameChange): a multicentre, parallel-group, single-blind, randomised, controlled trial in England with mediation and moderation analyses.
Automated delivery of psychological therapy using immersive technologies such as virtual reality (VR) might greatly increase the availability of effective help for patients. We aimed to evaluate the efficacy of an automated VR cognitive therapy (gameChange) to treat avoidance and distress in patients with psychosis, and to analyse how and in whom it might work. We did a parallel-group, single-blind, randomised, controlled trial across nine National Health Service trusts in England. Eligible patients were aged 16 years or older, with a clinical diagnosis of a schizophrenia spectrum disorder or an affective diagnosis with psychotic symptoms, and had self-reported difficulties going outside due to anxiety. Patients were randomly assigned (1:1) to either gameChange VR therapy plus usual care or usual care alone, using a permuted blocks algorithm with randomly varying block size, stratified by study site and service type. gameChange VR therapy was provided in approximately six sessions over 6 weeks. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 6 (primary endpoint), and 26 weeks after randomisation. The primary outcome was avoidance of, and distress in, everyday situations, assessed using the self-reported Oxford Agoraphobic Avoidance Scale (O-AS). Outcome analyses were done in the intention-to-treat population (ie, all participants who were assigned to a study group for whom data were available). We performed planned mediation and moderation analyses to test the effects of gameChange VR therapy when added to usual care. This trial is registered with the ISRCTN registry, 17308399. Between July 25, 2019, and May 7, 2021 (with a pause in recruitment from March 16, 2020, to Sept 14, 2020, due to COVID-19 pandemic restrictions), 551 patients were assessed for eligibility and 346 were enrolled. 231 (67%) patients were men and 111 (32%) were women, 294 (85%) were White, and the mean age was 37·2 years (SD 12·5). 174 patients were randomly assigned to the gameChange VR therapy group and 172 to the usual care alone group. Compared with the usual care alone group, the gameChange VR therapy group had significant reductions in agoraphobic avoidance (O-AS adjusted mean difference -0·47, 95% CI -0·88 to -0·06; n=320; Cohen's d -0·18; p=0·026) and distress (-4·33, -7·78 to -0·87; n=322; -0·26; p=0·014) at 6 weeks. Reductions in threat cognitions and within-situation defence behaviours mediated treatment outcomes. The greater the severity of anxious fears and avoidance, the greater the treatment benefits. There was no significant difference in the occurrence of serious adverse events between the gameChange VR therapy group (12 events in nine patients) and the usual care alone group (eight events in seven patients; p=0·37). Automated VR therapy led to significant reductions in anxious avoidance of, and distress in, everyday situations compared with usual care alone. The mediation analysis indicated that the VR therapy worked in accordance with the cognitive model by reducing anxious thoughts and associated protective behaviours. The moderation analysis indicated that the VR therapy particularly benefited patients with severe agoraphobic avoidance, such as not being able to leave the home unaccompanied. gameChange VR therapy has the potential to increase the provision of effective psychological therapy for psychosis, particularly for patients who find it difficult to leave their home, visit local amenities, or use public transport. National Institute of Health Research Invention for Innovation programme, National Institute of Health Research Oxford Health Biomedical Research Centre.


Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring.
The preimplantation embryo is sensitive to culture conditions in vitro and poor maternal diet in vivo. Such environmental perturbations can have long-lasting detrimental consequences for offspring health and physiology. However, early embryo susceptibility to other aspects of maternal health and their potential long-term influence into adulthood is relatively unexplored. In this study, we established an in vivo mouse model of maternal periconceptional systemic inflammation by intraperitoneal lipopolysaccharide (LPS) administration on the day of zygote formation and investigated the consequences into adulthood. In the short term, maternal LPS challenge induced a transient and typical maternal sickness response (elevated serum proinflammatory cytokines and hypoactive behaviour). Maternal LPS challenge altered preimplantation embryo morphogenesis and cell lineage allocation, resulting in reduced blastocyst inner cell mass (ICM) cell number and a reduced ICM:trophectoderm cell ratio. In the long term, diverse aspects of offspring physiology were affected by maternal LPS treatment. Whilst birthweight, growth and adult blood pressure were unaltered, reduced activity in an open-field behaviour test, increased fat pad:body weight ratio and increased body mass index were observed in male, but not female, offspring. Most importantly, the maternal LPS challenge caused corticosterone-independent blunting of the serum proinflammatory cytokine response to innate immune challenge in both male and female offspring. The suppressed state of innate immunity in challenged offspring was dose-dependent with respect to the maternal LPS concentration administered. These results demonstrate for the first time that the preimplantation embryo in vivo is sensitive to maternal systemic inflammation, with effects on blastocyst cell lineage allocation and consequences for behaviour, adiposity and innate immune response in adult offspring. Critically, we identify a novel mechanism mediated through maternal-embryonic interactions that confers plasticity in the development of the innate immune system, which is potentially important in setting postnatal tolerance to environmental pathogens. Our study extends the concept of developmental programming of health and disease to include maternal health at the time of conception.


Costs for households and community perception of meningitis epidemics in burkina faso.
Bacterial meningitis in the African meningitis belt remains 1 of the most serious threats to health. The perceptions regarding meningitis in local populations and the cost of illness for households are not well described. We conducted an anthropologic and economic study in Burkina Faso, in the heart of the meningitis belt. Respondents reported combining traditional and modern beliefs regarding disease etiology, which in turn influenced therapeutic care-seeking behavior. Households spent US $90 per meningitis case, or 34% of the annual gross domestic product per capita, and up to US $154 more when meningitis sequelae occurred. Much of this cost was attributable to direct medical expenses, which in theory are paid by the government. Preventive immunization against meningitis will overcome limitations imposed by traditional beliefs and contribute to poverty reduction goals.


Initial evaluation of a real-world Internet smoking cessation system.
To significantly reduce smoking prevalence, treatments must balance reach, efficacy, and cost. The Internet can reach millions of smokers cost-effectively. Many cessation Web sites exist, but few have been evaluated. As a result, the potential impact of the Internet on smoking prevalence remains unknown. The present study reports the results, challenges, and limitations of a preliminary, large-scale evaluation of a broadly disseminated smoking cessation Web site used worldwide (QuitNet). Consecutive registrants (N=1,501) were surveyed 3 months after they registered on the Web site to assess 7-day point prevalence abstinence. Results must be interpreted cautiously because this is an uncontrolled study with a 25.6% response rate. Approximately 30% of those surveyed indicated they had already quit smoking at registration. Excluding these participants, an intention-to-treat analysis yielded 7% point prevalence abstinence (for the responders only, abstinence was 30%). A range of plausible cessation outcomes (9.8%-13.1%) among various subgroups is presented to illustrate the strengths and limitations of conducting Web-based evaluations, and the tensions between clinical and dissemination research methods. Process-to-outcome analyses indicated that sustained use of QuitNet, especially the use of social support, was associated with more than three times greater point prevalence abstinence and more than four times greater continuous abstinence. Despite its limitations, the present study provides useful information about the potential efficacy, challenging design and methodological issues, process-to-outcome mechanisms of action, and potential public health impact of Internet-based behavior change programs for smoking cessation.


Introduction of Mobile Health Tools to Support Ebola Surveillance and Contact Tracing in Guinea.
Challenges in data availability and quality have contributed to the longest and deadliest Ebola epidemic in history that began in December 2013. Accurate surveillance data, in particular, has been difficult to access, as it is often collected in remote communities. We describe the design, implementation, and challenges of implementing a smartphone-based contact tracing system that is linked to analytics and data visualization software as part of the Ebola response in Guinea. The system, built on the mobile application CommCare and business intelligence software Tableau, allows for real-time identification of contacts who have not been visited and strong accountability of contact tracers through timestamps and collection of GPS points with their surveillance data. Deployment of this system began in November 2014 in Conakry, Guinea, and was expanded to a total of 5 prefectures by April 2015. To date, the mobile system has not replaced the paper-based system in the 5 prefectures where the program is active. However, as of April 30, 2015, 210 contact tracers in the 5 prefectures were actively using the mobile system to collectively monitor 9,162 contacts. With proper training, some investment in technical hardware, and adequate managerial oversight, there is opportunity to improve access to surveillance data from difficult-to-reach communities in order to inform epidemic control strategies while strengthening health systems to reduce risk of future disease outbreaks.


The human disease network.
A network of disorders and disease genes linked by known disorder-gene associations offers a platform to explore in a single graph-theoretic framework all known phenotype and disease gene associations, indicating the common genetic origin of many diseases. Genes associated with similar disorders show both higher likelihood of physical interactions between their products and higher expression profiling similarity for their transcripts, supporting the existence of distinct disease-specific functional modules. We find that essential human genes are likely to encode hub proteins and are expressed widely in most tissues. This suggests that disease genes also would play a central role in the human interactome. In contrast, we find that the vast majority of disease genes are nonessential and show no tendency to encode hub proteins, and their expression pattern indicates that they are localized in the functional periphery of the network. A selection-based model explains the observed difference between essential and disease genes and also suggests that diseases caused by somatic mutations should not be peripheral, a prediction we confirm for cancer genes.


Lung cancer in women: a single institution experience with 50 patients.
Lung cancer is the most common cause of cancer-related death worldwide. The incidence of lung cancer is aproximately 7-8 thousand percent in Turkish women. In this study, we aimed to evaluate the clinical, pathological properties and survival data of female patients with lung cancer who were treated in our center. From 2007 to 2012, 50 women with lung cancer were enrolled. Patient data were evaluated retrospectively. The median age was 61 (40-81). Forty patients (80%) were diagnosed with non small cell lung cancer (NSCLC), 10 patients (20%) were small cell carcinoma (SCC). Twelve (24%) patients were smokers and 13 of 16 non-smokers had a history of exposure to asbestos. The most common histologic subtype was adenocarcinoma (46%) and this accounted for 71% in patients with exposure to asbestos. The most common initial Eastern Cooperative Oncology Group (ECOG) performance score was 1 (24 patients, 48%) and initial stage was IV (25 patients, 50%) in the study group. During the median 15 months (1-96 months) followup period: 1 year overall survival (OS) was 68%, 2year overall survival was 36% and the median survival time was 19 months. According to univariate analysis, poor ECOG performance status, advanced stage, anemia and weight loss at time of diagnosis were negative prognostic factors. However, adenocarcinoma sub-type was a positive prognostic factor. In this study NSCLC sub-type, poor ECOG performance score, advanced stage, anemia and weight loss were prognostic factors in Turkish women with lung cancer.


Microarray gene expression profiling of a human glioblastoma cell line exposed in vitro to a 1.9 GHz pulse-modulated radiofrequency field.
The widespread use of mobile phones has led to public concerns about the health effects associated with exposure to radiofrequency (RF) fields. The paramount concern of most persons relates to the potential of these fields to cause cancer. Unlike ionizing radiation, RF fields used for mobile telecommunications (800-1900 MHz) do not possess sufficient energy to directly damage DNA. Most rodent bioassay and in vitro genotoxicity/mutation studies have reported that RF fields at non-thermal levels have no direct mutagenic, genotoxic or carcinogenic effects. However, some evidence has suggested that RF fields may cause detectable postexposure changes in gene expression. Therefore, the purpose of this study was to assess the ability of exposure to a 1.9 GHz pulse-modulated RF field for 4 h at specific absorption rates (SARs) of 0.1, 1.0 and 10.0 W/kg to affect global gene expression in U87MG glioblastoma cells. We found no evidence that non-thermal RF fields can affect gene expression in cultured U87MG cells relative to the nonirradiated control groups, whereas exposure to heat shock at 43 degrees C for 1 h up-regulated a number of typical stress-responsive genes in the positive control group. Future studies will assess the effect of RF fields on other cell lines and on gene expression in the mouse brain after in vivo exposure.


A myosin heavy-chain-like polypeptide is associated with the nuclear envelope in higher eukaryotic cells.
A high molecular weight polypeptide, identified as an ATPase subunit by direct ultraviolet photoaffinity labeling, has been shown to be a component of nuclear envelope-enriched fractions prepared from a variety of higher eukaryotes (Berrios, M., G. Blobel, and P. A. Fisher, 1983, J. Biol. Chem., 258:4548-4555). In rat liver as well as Drosophila melanogaster embryos, this polypeptide appears to be a form of myosin heavy chain. This conclusion is based on both immunochemical and immunocytochemical data, as well as on the results of CNBr and chymotryptic peptide map analyses. In Drosophila, the identification of this myosin heavy chain-like polypeptide as a nuclear envelope component has been corroborated in situ by indirect immunofluorescence analyses using permeabilized whole cells, mechanically extruded nuclei, and cryosections obtained from a number of larval tissues. Localization appears to be restricted to the nuclear periphery in a manner similar to that observed for the nuclear lamins and the pore complex glycoprotein. Antibodies directed against the Drosophila nuclear envelope ATPase have also been shown to decorate mammalian and higher plant cell nuclei in situ. Implications for intracellular nuclear mobility and for nucleocytoplasmic exchange of macromolecules in vivo are discussed.


Assessment of interaction-strength interpolation formulas for gold and silver clusters.
The performance of functionals based on the idea of interpolating between the weak- and the strong-interaction limits the global adiabatic-connection integrand is carefully studied for the challenging case of noble-metal clusters. Different interpolation formulas are considered and various features of this approach are analyzed. It is found that these functionals, when used as a correlation correction to Hartree-Fock, are quite robust for the description of atomization energies, while performing less well for ionization potentials. Future directions that can be envisaged from this study and a previous one on main group chemistry are discussed.


Pharmacological characterization of the discriminative-stimulus effects of GBR 12909.
Squirrel monkeys were trained to discriminate the selective dopamine uptake inhibitor GBR 12909 (1-[2-[bis(4-fluorophenyl)-methoxy] ethyl]-4-(3-phenylpropyl)piperazine) from saline in a two-lever drug-discrimination procedure. After i.v. injections of GBR 12909, 10 consecutive responses on one lever produced food, whereas after i.v. saline, 10 consecutive responses on the other lever produced food. By using a cumulative-dosing procedure, several inhibitors of monoamine uptake as well as dopamine receptor agonists and antagonists were evaluated for their ability to substitute for, or attenuate, the discriminative-stimulus effects of GBR 12909. Dopamine uptake inhibitors, including GBR 12909, cocaine, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane, mazindol, bupropion and methylphenidate, as well as the dopamine releasing drug (+)-amphetamine substituted fully (greater than 80% drug-lever responding) for the training dose of GBR 12909. In contrast, the selective norepinephrine uptake inhibitors, desipramine and talsupram, and the selective serotonin uptake inhibitor, citalopram, occasioned averages of only 13 to 19% drug-lever responding. The dopamine D1 agonist SKF 81297 (6-chloro-7,8-ddhydroxy-1-phenyl-2,3,4,5-tetrahydro-[1H]-3- benzazepine), the D2 agonists, (+)-4-propyl-9-hydroxynaphthoxazine and quinpirole, and the nonselective dopamine agonist, (-)-apomorphine, all occasioned a majority of responses (mean = 56-82%) on the drug-appropriate lever. The D1 partial agonists, R-SKF 38393 (R-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro- [1H]-3-benzazepine) and SKF 75670 (7,8-dihydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-[1H]-3-benzazepine), however, occasioned an average of no more than 21% drug-appropriate responding.(ABSTRACT TRUNCATED AT 250 WORDS)


Automatic entry point planning for robotic post-mortem CT-based needle placement.
Post-mortem computed tomography guided placement of co-axial introducer needles allows for the extraction of tissue and liquid samples for histological and toxicological analyses. Automation of this process can increase the accuracy and speed of the needle placement, thereby making it more feasible for routine examinations. To speed up the planning process and increase safety, we developed an algorithm that calculates an optimal entry point and end-effector orientation for a given target point, while taking constraints such as accessibility or bone collisions into account. The algorithm identifies the best entry point for needle trajectories in three steps. First, the source CT data is prepared and bone as well as surface data are extracted and optimized. All vertices of the generated surface polygon are considered to be potential entry points. Second, all surface points are tested for validity within the defined hard constraints (reachability, bone collision as well as collision with other needles) and removed if invalid. All remaining vertices are reachable entry points and are rated with respect to needle insertion angle. Third, the vertex with the highest rating is selected as the final entry point, and the best end-effector rotation is calculated to avoid collisions with the body and already set needles. In most cases, the algorithm is sufficiently fast with approximately 5-6 s per entry point. This is the case if there is no collision between the end-effector and the body. If the end-effector has to be rotated to avoid collision, calculation times can increase up to 24 s due to the inefficient collision detection used here. In conclusion, the algorithm allows for fast and facilitated trajectory planning in forensic imaging.


Normal body perception despite the loss of right fusiform gyrus.
Human extrastriate cortex contains functional regions that are selective for particular categories such as faces, bodies, and places, but it is unclear whether these category-selective regions are necessary for normal perception of their preferred stimuli. One of these regions is the right fusiform body area (FBA), which is selectively involved in body perception. Do loss of the right fusiform gyrus and the absence of the right FBA necessarily lead to deficits in body perception? Here we report the performance of Galen, a brain-damaged patient who lost the right fusiform gyrus and has no right FBA, on eight tasks of body perception. Despite his lesion, Galen showed normal performance on all tasks. Galen's results demonstrate that damage to the right fusiform gyrus and the lack of the right FBA do not necessarily lead to persisting deficits in body perception.


A study of a method for distribution analysis of skin color.
The objective and quantitative assessment of the skin is important in medical and cosmeceutical research. Assessment of color is an important element for analyzing the surface of the skin, which is usually determined subjectively by a doctor or using color analysis devices. These devices, however, cannot provide correct color information because color is construed from the mean value of the observation region, and analysis of color distribution is impossible. The purpose of this paper is to develop an objective analysis method to permit skin color measurement of each pixel unit of an image and analyze the distribution of skin surface color. The Skin Color Distribution Analyzer (SCDA) is an analysis method newly developed at the Research Institute for Skin Image at Korea University. The SCDA system presented in this paper performed a novel form of quantitative and objective analysis of skin color distribution using each pixel color model parameter found in image wavelength information. In this paper, distribution analysis was conducted on normal skin and skin lesions and skin affected by artificially induced irritant contact dermatitis and pigmented nevous. The method selected a grade using a color model parameter. Twenty healthy Korean males participated in this study. A comparative study of the eight anatomical areas was performed, including the exposure and non-exposure parts and the medial aspect and the lateral aspect of the forearm. A reliability test for the SCDA system was also conducted with a spectrometer (SPEC) using the color analysis method. Each skin lesion was precisely segmented by grade and each parameter had a different statistical significance for results of analysis of distribution in pigmented nevous and the artificially induced irritant contact dermatitis. Parameters L(*), b(*), a(*), and EI showed salient traits. Showed resemble measured result in the SCDA system and the SPEC of normal skin. The exposed site, in comparison with the non-exposed site, showed a notable difference in the L(*) parameter and a significant statistical difference in the x and z parameters, except b(*). The comparison of the medial and lateral aspects of the forearm showed a notable difference in the L(*) parameter and a significant statistical difference in the parameters except y and b(*). In the reliability test result using the SCDA system and the SPEC, the SCDA system was highly reliable in terms of the CV value in all color model parameters. The color distribution analysis method using the SCDA system has revealed an aspect that the existent method of medical research has not shown, and is considered to be more reliable than other methods. This method can provide better study findings because it can be applied to other fields in addition to the medical science field and the ripple effect is thought to be bigger in other science field too.


Total synthesis and structural elucidation of spongosoritin A.
Two putative structures of spongosoritin A, with syn (6R,8R) and anti (6S,8R) configurations, were each synthesised in a total of 11 linear steps with only 8 purification procedures. The key steps in our strategy included Evans alkylation and olefin dihydroxylation to install the C8 and C6 stereocentres, a transacetalisation/dehydration cascade to construct the furanylidene core, and chromatographic separation of 9E- and 9Z-isomers of the final compounds with silver nitrate impregnated silica. Comparison of the 1H and 13C NMR data for the synthetic syn- and anti-isomers to that reported for the natural product revealed that the relative configuration of spongosoritin A is syn. The absolute stereochemistry was also confirmed as 6R,8R based on optical rotation measurements where the synthetic syn (6R,8R) and natural product had the same sign of optical rotation (negative).


A noninvasive isotopic approach to estimate the bone lead contribution to blood in children: implications for assessing the efficacy of lead abatement.
Lead hazard control measures to reduce children's exposure to household lead sources often result in only limited reductions in blood lead levels. This may be due to incomplete remediation of lead sources and/or to the remobilization of lead stores from bone, which may act as an endogenous lead source that buffers reductions in blood lead levels. Here we present a noninvasive isotopic approach to estimate the magnitude of the bone lead contribution to blood in children following household lead remediation. In this approach, lead isotopic ratios of a child's blood and 5-day fecal samples are determined before and after a household intervention aimed at reducing the child's lead intake. The bone lead contribution to blood is estimated from a system of mass balance equations of lead concentrations and isotopic compositions in blood at the different times of sample collection. The utility of this method is illustrated with three cases of children with blood lead levels in the range of 18-29 microg/dL. In all three cases, the release of lead from bone supported a substantial fraction of the measured blood lead level postintervention, up to 96% in one case. In general, the lead isotopic compositions of feces matched or were within the range of the lead isotopic compositions of the household dusts with lead loadings exceeding U.S. Environmental Protection Agency action levels. This isotopic agreement underscores the utility of lead isotopic measurements of feces to identify household sources of lead exposure. Results from this limited number of cases support the hypothesis that the release of bone lead into blood may substantially buffer the decrease in blood lead levels expected from the reduction in lead intake.


Design and functionality of colloidal-crystal-templated materials--chemical applications of inverse opals.
Templating with colloidal crystals composed of monodisperse spheres is a convenient chemical method to obtain porous materials with well-ordered periodicity and interconnected pore systems. The three-dimensionally ordered macroporous (3DOM) products or inverse opals are of interest for numerous applications, both for the optical properties related to structural color of these photonic crystal materials and because of their bicontinuous nanostructure, i.e., a continuous nanostructured skeleton with large interfacial area and a three-dimensionally interconnected pore system with low tortuosity. This review outlines various synthetic methods used to control the morphology of 3DOM materials with different compositions. It highlights aspects of the choice of colloidal particles, assembly of the colloidal crystal template, infiltration and processing, template removal, and other necessary modifications to enhance the functionality of the materials. It also considers syntheses within the confinement of 3DOM materials and summarizes characterization methods that are particularly useful in the analysis of 3DOM materials. The review then discusses chemical applications of 3DOM materials, namely sorption and controlled release, optical and electrochemical sensors, solar cells, lithium ion batteries, supercapacitors, fuel cells, and environmental and chemical fuel catalysis. A focus is on structural features and materials properties that enable these applications.


Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1.
To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model. SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated. The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB. These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB.


The effects of hyperventilation; individual variability and its relation to personality.
Self-reported affective and somatic disturbances and heart rate changes resulting from a brief period of voluntary hyperventilation are presented and related to individuals' Eysenck Personality Questionnaire (E.P.Q.) scores. Considerable individual variability was observed in the effects of hyperventilation. Neuroticism was significantly correlated with affective but not self-reported somatic or objectively measured heart rate changes. Other possible determinants of observed variability and its possible relevance to the etiology of panic attacks are discussed.


Probiotics for the treatment of eczema: a systematic review.
Probiotics have been proposed as a treatment for eczema, but the results of intervention trials have been mixed. To evaluate the efficacy of probiotics for treating eczema by performing a systematic review of randomized-controlled trials (RCTs). We searched the Cochrane Skin Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, AMED, LILACS, ISI Web of Science, the reference lists of articles, ongoing clinical trial registers and conference proceedings. RCTs of live orally ingested microorganisms for the treatment of eczema were eligible for inclusion. Twelve trials (781 participants) were identified. Meta-analysis of data from five of these trials showed that there was no significant reduction in eczema symptoms with probiotic treatment compared with placebo (mean difference -0.90 points on a 20-point visual analogue scale; 95% confidence interval -2.84, 1.04). Meta-analysis of data from seven trials showed no significant difference in investigator rated eczema severity between probiotic and placebo treatments. Subgroup analysis by eczema severity or presence of atopy did not identify a specific population in which probiotic treatment was effective. There was significant heterogeneity between studies; however, the results of three studies that used the same probiotic strain were concordant. The adverse events search identified case reports of sepsis and bowel ischaemia caused by probiotics. Currently, probiotics cannot be recommended for treating eczema. The heterogeneity between studies may be attributable to probiotic strain-specific effects, which means that novel probiotic strains may still have a role in eczema management.


Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children.
Acute otitis media (AOM) is one of the most common childhood infectious diseases and a significant reason for antibiotic prescriptions in children worldwide. Pain from middle ear infection and pressure behind the eardrum is the key symptom of AOM. Ear pain is central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management in children. Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs compared with paracetamol in children with AOM. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 7, July 2016; MEDLINE (Ovid, from 1946 to August 2016), Embase (from 1947 to August 2016), CINAHL (from 1981 to August 2016), LILACS (from 1982 to August 2016) and Web of Science (from 1955 to August 2016) for published trials. We screened reference lists of included studies and relevant systematic reviews for additional trials. We searched WHO ICTRP, ClinicalTrials.gov, and the Netherlands Trial Registry (NTR) for completed and ongoing trials (search date 19 August 2016). We included randomised controlled trials (RCTs) comparing the effectiveness of paracetamol or NSAIDs, alone or combined, for pain relief in children with AOM. We also included trials of paracetamol or NSAIDs, alone or combined, for children with fever or upper respiratory tract infections (URTIs) if we were able to extract subgroup data on pain relief in children with AOM either directly or after obtaining additional data from study authors. Two review authors independently assessed methodological quality of the included trials and extracted data. We used the GRADE approach to rate the overall quality of evidence for each outcome of interest. We included three RCTs (327 children) which were assessed at low to moderate risk of bias.One RCT included 219 children with AOM, and used a three-arm, parallel group, double-blind design to compare paracetamol versus ibuprofen versus placebo. All children also received antibiotics and those with fever > 39 °C could have received paracetamol (30 mg to 60 mg) additionally to the studied treatments.Another RCT involved 156 febrile children (26 of whom had AOM). The study design was a three-arm, parallel group, double-blind design and compared paracetamol versus ibuprofen versus ibuprofen plus paracetamol.The third RCT included 889 children with respiratory tract infections (82 of whom had AOM). This study applied a 3 x 2 x 2 factorial, open-label design and compared paracetamol versus ibuprofen versus ibuprofen plus paracetamol. Study participants were randomised to one of the three treatment groups as well as two dosing groups (regular versus as required) and two steam inhalation groups (steam versus no steam).Authors of two RCTs provided crude subgroup data on children with AOM. We used data from the remaining trial to inform comparison of paracetamol versus placebo (148 children) and ibuprofen versus placebo (146 children) assessments. Data from all included RCTs informed comparison of ibuprofen versus paracetamol (183 children); data from the two RCTs informed comparison of ibuprofen plus paracetamol versus paracetamol alone (71 children).We found evidence, albeit of low quality, that both paracetamol and ibuprofen as monotherapies were more effective than placebo in relieving pain at 48 hours (paracetamol versus placebo: proportion of children with pain 10% versus 25%, RR 0.38, 95% CI 0.17 to 0.85; number needed to treat to benefit (NNTB) 7; ibuprofen versus placebo: proportion of children with pain 7% versus 25%, RR 0.28, 95% CI 0.11 to 0.70; NNTB 6). Very low quality evidence suggested that adverse events did not significantly differ between children treated with either paracetamol, ibuprofen or placebo.We found insufficient evidence of a difference between ibuprofen and paracetamol in relieving ear pain at 24 hours (2 RCTs, 39 children; RR 0.83, 95% CI 0.59 to 1.18; very low quality evidence), 48 to 72 hours (3 RCTs, 183 children; RR 0.91, 95% CI 0.54 to 1.54; low quality evidence) and four to seven days (2 RCTs, 38 children; RR 0.74, 95% CI 0.17 to 3.23; very low quality evidence).Data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone came from two RCTs that provided crude subgroup data for 71 children with AOM. The small sample provided imprecise effect estimates and we were consequently unable to draw any firm conclusions (very low quality evidence). Despite explicit guideline recommendations on its use, current evidence on the effectiveness of paracetamol or NSAIDs, alone or combined, in relieving pain in children with AOM is limited. Low quality evidence indicates that both paracetamol and ibuprofen as monotherapies are more effective than placebo in relieving short-term ear pain in children with AOM. There is insufficient evidence of a difference between ibuprofen and paracetamol in relieving short-term ear pain in children with AOM, whereas data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone were insufficient to draw any firm conclusions. Further research is needed to provide insights into the role of ibuprofen as adjunct to paracetamol, and other analgesics such as anaesthetic eardrops, for children with AOM.


Zika virus outbreak on Yap Island, Federated States of Micronesia.
In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented. We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus. We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified. This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission.


Components of the full blood count as risk factors for colorectal cancer detection: a systematic review protocol.
Colorectal cancer is the fourth most common type of cancer and the second most common cause of cancer-related deaths in the UK. The full blood count (FBC) is a blood test that may play a role in early detection of the disease. Previous studies have aimed to identify how levels of individual components, such as haemoglobin, can be used to assist the diagnosis. We aim to systematically review studies to identify whether components of the FBC are risk factors for diagnosis of colorectal cancer, critically appraise the methods used to assess the association and assess performance of the components. The MEDLINE (via OVID), EMBASE (via OVID), CINAHL (via EBSCOhost) and Web of Science databases will be searched to identify studies reporting the association between the levels of at least one FBC component and the risk of a future diagnosis of colorectal cancer in undiagnosed individuals. Clincialtrials.gov and the WHO registry will be searched to identify relevant ongoing research. Search terms will include relevant Medical Subject Headings and Emtree headings, and free-text terms relating to FBC, colorectal cancer and diagnosis. No date or language restrictions will be applied. Two reviewers will independently identify the studies for inclusion and perform data extraction. Time intervals between the blood tests and diagnosis will form the subgroups for analysis. There is no direct patient involvement and only published articles will be reviewed; no ethical approval is required. Results from this review will set a foundation for intended future work on developing a new risk score for early detection of colorectal cancer, derived using FBC data. This systematic review will also provide guidance on the analysis of time to diagnosis. The model will be freely available to UK primary care practices. CRD42019134400.


Comparative effectiveness of sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in patients on kidney replacement therapy: observational study using the OpenSAFELY-UKRR and SRR databases.
Due to limited inclusion of patients on kidney replacement therapy (KRT) in clinical trials, the effectiveness of coronavirus disease 2019 (COVID-19) therapies in this population remains unclear. We sought to address this by comparing the effectiveness of sotrovimab against molnupiravir, two commonly used treatments for non-hospitalised KRT patients with COVID-19 in the UK. With the approval of National Health Service England, we used routine clinical data from 24 million patients in England within the OpenSAFELY-TPP platform linked to the UK Renal Registry (UKRR) to identify patients on KRT. A Cox proportional hazards model was used to estimate hazard ratios (HRs) of sotrovimab versus molnupiravir with regards to COVID-19-related hospitalisations or deaths in the subsequent 28 days. We also conducted a complementary analysis using data from the Scottish Renal Registry (SRR). Among the 2367 kidney patients treated with sotrovimab (n = 1852) or molnupiravir (n = 515) between 16 December 2021 and 1 August 2022 in England, 38 cases (1.6%) of COVID-19-related hospitalisations/deaths were observed. Sotrovimab was associated with substantially lower outcome risk than molnupiravir {adjusted HR 0.35 [95% confidence interval (CI) 0.17-0.71]; P = .004}, with results remaining robust in multiple sensitivity analyses. In the SRR cohort, sotrovimab showed a trend toward lower outcome risk than molnupiravir [HR 0.39 (95% CI 0.13-1.21); P = .106]. In both datasets, sotrovimab had no evidence of an association with other hospitalisation/death compared with molnupiravir (HRs ranged from 0.73 to 1.29; P > .05). In routine care of non-hospitalised patients with COVID-19 on KRT, sotrovimab was associated with a lower risk of severe COVID-19 outcomes compared with molnupiravir during Omicron waves.


Scattering of the transverse magnetic modes from an abruptly ended strongly asymmetrical slab waveguide by an accelerated integral equation technique.
We study the problem of the scattering of the first TM guided mode from an abruptly ended strongly asymmetrical slab waveguide by an improved iteration technique, which is based on the integral equation method with "accelerating" parameters. We demonstrate that the values of these parameters are related to the variational principle, and we save approximately 1-2 iterations compared with the case in which these parameters are not employed. The tangential electric-field distribution on the terminal plane, the reflection coefficient of the first TM guided mode, and the far-field radiation pattern are computed. Furthermore, a simple technique based on the Aitken extrapolation procedure is employed for faster computation of the higher-order solutions of the reflection coefficient. Numerical results are presented for several cases of abruptly ended waveguides, including systems with variational profile, while special attention is given to the far-field radiation pattern rotation and its explanation.


Efficacy of sulbactam and its combination with imipenem, colistin and tigecycline in an experimental model of carbapenem-resistant Acinetobacter baumannii sepsis.
In recent years, multidrug-resistant Acinetobacter baumannii has been reported as an important nosocomial pathogen, and treatment options are limited. The aim of this study was to investigate the additional effect of sulbactam on monotherapy with colistin, tigecycline and imipenem in experimental sepsis with carbapenem-resistant A. baumannii in mice. Sepsis was developed in 8- to 10-week-old BALB/c mice by an intraperitoneal injection of A. baumannii. Antibiotic was given intraperitoneally 2 h after bacterial inoculation. Each experimental group had 15 mice and was divided into 3 subgroups. Mice were sacrificed at 24, 48 or 72 h. Lung, liver, heart and spleen samples were cultured, and homogenates of lung and liver were used to detect the number of colony-forming units per gram. Bacterial clearance was compared in lung and liver at different time points. Imipenem did not decrease the bacterial load, but the other antibiotics showed significant bactericidal activity compared with the control group, and the combination of imipenem with sulbactam decreased the bacterial load in lung and liver. However, the addition of sulbactam to colistin and tigecycline had no significant effect on bacterial counts. Only the addition of sulbactam to imipenem showed better bactericidal activity compared to imipenem alone. These results suggested that combining sulbactam with tigeycline or colistin does not increase the efficiency of these antibiotics.


Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?
Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.


Shared governance in a clinic system.
Shared governance in health care empowers nurses to share in the decision-making process, which results in decentralized management and collective accountability. Share governance practices have been present in hospitals since the late 1970s. However, shared governance in ambulatory care clinics has not been well established. The subjects of this quality project included staff and administrative nurses in a clinic system. The stakeholder committee chose what model of shared governance to implement and educated clinic staff. The Index of Professional Nursing Governance measured a shared governance score pre- and postimplementation of the Clinic Nursing Council. The Clinic Nursing Council met bimonthly for 3 months during this project to discuss issues and make decisions related to nursing staff. The Index of Professional Nursing Governance scores indicated traditional governance pre- and postimplementation of the Clinic Nursing Council, which is to be expected. The stakeholder committee was beneficial to the initial implementation process and facilitated staff nurse involvement. Shared governance is an evolutionary process that develops empowered nurses and nurse leaders.


Double dissociation of dopamine genes and timing in humans.
A number of lines of evidence implicate dopamine in timing [Rammsayer, T. H. Neuropharmacological approaches to human timing. In S. Grondin (Ed.), Psychology of time (pp. 295-320). Bingley, UK: Emerald, 2008; Meck, W. H. Neuropharmacology of timing and time perception. Brain Research, Cognitive Brain Research, 3, 227-242, 1996]. Two human genetic polymorphisms are known to modulate dopaminergic activity. DRD2/ANKK1-Taq1a is a D(2) receptor polymorphism associated with decreased D(2) density in the striatum [Jönsson, E. G., Nothen, M. M., Grunhage, F., Farde, L., Nakashima, Y., Propping, P., et al. Polymorphisms in the dopamine D(2) receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Molecular Psychiatry, 4, 290-296, 1999]; COMT Val158Met is a functional polymorphism associated with increased activity of the COMT enzyme such that catabolism of synaptic dopamine is greater in pFC [Meyer-Lindenberg, A., Kohn, P. D., Kolachana, B., Kippenhan, S., McInerney-Leo, A., Nussbaum, R., et al. Midbrain dopamine and prefrontal function in humans: Interaction and modulation by COMT genotype. Nature Neuroscience, 8, 594-596, 2005]. To investigate the role of dopamine in timing, we genotyped 65 individuals for DRD2/ANKK1-Taq1a, COMT Val158Met, and a third polymorphism, BDNF Val66Met, a functional polymorphism affecting the expression of brain-derived neurotrophic factor [Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 112, 257-269, 2003]. Subjects were tested on a temporal discrimination task with sub- and supra-second intervals (500- and 2000-msec standards) as well as a spontaneous motor tempo task. We found a double dissociation for temporal discrimination: the DRD2/ANKK1-Taq1a polymorphism (A1+ allele) was associated with significantly greater variability for the 500-msec duration only, whereas the COMT Val158Met polymorphism (Val/Val homozygotes) was associated with significantly greater variability for the 2000-msec duration only. No differences were detected for the BDNF Vall66Met variant. Additionally, the DRD2/ANKK1-Taq1a polymorphism was associated with a significantly slower preferred motor tempo. These data provide a potential biological basis for the distinctions between sub- and supra-second timing and suggest that BG are integral for the former whereas pFC is implicated in the latter.


When government agencies turn to unregulated drug sources: Implications for the drug supply chain and public health are grave.
To highlight how sourcing practices for lethal injections drugs are undermining state and federal regulatory structures established to preserve the security and integrity of the medicines supply chain in the United States. Unable to find sources for execution products approved by the U.S. Food and Drug Administration (FDA), some states have started sourcing the required drugs or active ingredients from unapproved foreign manufacturers or have contracted with small compounding pharmacists to compound them. Many states have passed legislation barring the disclosure of information regarding the origin and chain of custody for prisons' stocks of compounded lethal injection drugs. This creates a regulatory vacuum and prevents the responsible authorities (e.g., FDA, Drug Enforcement Agency, state boards of pharmacy) from performing their crucial roles to ensure quality and supply chain transparency for medicines in circulation. By purchasing medicines from non-FDA-approved suppliers and enacting lethal injection sourcing secrecy laws, states are undermining the robust enforcement of chain of custody and pharmaceutical supply chain transparency. The secrecy surrounding the execution drug procurement risks creating illicit supply channels. Once an illicit supply channel is established with a supplier, it creates risks that other drug products move through it, particularly in a context where the FDA, Drug Enforcement Agency, and state boards of pharmacy are prevented from performing their usual regulatory duties. Lawmakers have the obligation and authority to step in and close this regulatory gap to promote public health and safety.


Tailoring wave chaos in vertical-cavity surface-emitting lasers via polarization control.
We demonstrate that polarization control in combination with the geometrical shape affects wave chaos phenomena in vertical-cavity surface-emitting lasers (VCSELs). In a grating-polarization-stabilized VCSEL, we demonstrate wave chaos in one polarization mode and a transition from wave chaos to regular behavior in the other orthogonal polarization mode. We quantify the amount of chaoticity via the Brody nearest-neighbor distribution. Comparing with a reference VCSEL without a surface-grating, we explain these results and their injection current dependence by the surface-grating-induced mode selection and a change in the effective resonator shape.


Serology-enabled discovery of genetically diverse hepaciviruses in a new host.
Genetic and biological characterization of new hepaciviruses infecting animals contributes to our understanding of the ultimate origins of hepatitis C virus (HCV) infection in humans and dramatically enhances our ability to study its pathogenesis using tractable animal models. Animal homologs of HCV include a recently discovered canine hepacivirus (CHV) and GB virus B (GBV-B), both viruses with largely undetermined natural host ranges. Here we used a versatile serology-based approach to determine the natural host of the only known nonprimate hepacivirus (NPHV), CHV, which is also the closest phylogenetic relative of HCV. Recombinant protein expressed from the helicase domain of CHV NS3 was used as antigen in the luciferase immunoprecipitation system (LIPS) assay to screen several nonprimate animal species. Thirty-six samples from 103 horses were immunoreactive, and viral genomic RNA was present in 8 of the 36 seropositive animals and none of the seronegative animals. Complete genome sequences of these 8 genetically diverse NPHVs showed 14% (range, 6.4% to 17.2%) nucleotide sequence divergence, with most changes occurring at synonymous sites. RNA secondary structure prediction of the 383-base 5' untranslated region of NPHV was refined and extended through mapping of polymorphic sites to unpaired regions or (semi)covariant pairings. Similar approaches were adopted to delineate extensive RNA secondary structures in the coding region of the genome, predicted to form 27 regularly spaced, thermodynamically stable stem-loops. Together, these findings suggest a promising new nonprimate animal model and provide a database that will aid creation of functional NPHV cDNA clones and other novel tools for hepacivirus studies.


Molecular Characterization of a Date Palm Vascular Highway 1-Interacting Kinase (PdVIK) Under Abiotic Stresses.
The date palm (Khalas) is an extremophile plant that can adapt to various abiotic stresses including drought and salinity. Salinity tolerance is a complex trait controlled by numerous genes. Identification and functional characterization of salt-responsive genes from the date palm is fundamental to understand salinity tolerance at the molecular level in this plant species. In this study, a salt-inducible vascular highway 1-interacting kinase (PdVIK) that is a MAP kinase kinase kinase (MAPKKK) gene from the date palm, was functionally characterized using in vitro and in vivo strategies. PdVIK, one of the 597 kinases encoded by the date palm genome possesses an ankyrin repeat domain and a kinase domain. The recombinant PdVIK protein exhibited phosphotyrosine activity against myelin basic protein (MBP) substrate. Overexpression of PdVIK in yeast significantly improved its tolerance to salinity, LiCl, and oxidative stresses. Transgenic Arabidopsis seedlings overexpressing PdVIK displayed improved tolerance to salinity, osmotic, and oxidative stresses as assessed by root growth assay. The transgenic lines grown in the soil also displayed modulated salt response, compared to wild-type controls as evaluated by the overall plant growth and proline levels. Likewise, the transgenic lines exhibited drought tolerance by maintaining better relative water content (RWC) compared to non-transgenic control plants. Collectively, these results implicate the involvement of PdVIK in modulating the abiotic stress response of the date palm.


Standards-Based Procedural Phenotyping: The Arden Syntax on i2b2.
Phenotyping, or the identification of patient cohorts, is a recurring challenge in medical informatics. While there are open source tools such as i2b2 that address this problem by providing user-friendly querying interfaces, these platforms lack semantic expressiveness to model complex phenotyping algorithms. The Arden Syntax provides procedural programming language construct, designed specifically for medical decision support and knowledge transfer. In this work, we investigate how language constructs of the Arden Syntax can be used for generic phenotyping. We implemented a prototypical tool to integrate i2b2 with an open source Arden execution environment. To demonstrate the applicability of our approach, we used the tool together with an Arden-based phenotyping algorithm to derive statistics about ICU-acquired hypernatremia. Finally, we discuss how the combination of i2b2's user-friendly cohort pre-selection and Arden's procedural expressiveness could benefit phenotyping.


Cellulose Nanocrystal Reinforced Chitosan Coatings for Improving the Storability of Postharvest Pears Under Both Ambient and Cold Storages.
Cellulose nanocrystal (CNC, 0%, 5%, and 10% w/w, in chitosan, dry basis) reinforced 2% chitosan aqueous coatings were evaluated for delaying the ripening and quality deterioration of postharvest green D'Anjou (Pyrus communis L.) and Bartlett (Pyrus communis L.) pears during 3 wk of ambient storage (20 ± 2 °C and 30 ± 2% RH) or 5 mo of cold storage (-1.1 °C and 90% RH), respectively. Ethylene and CO2 production, color, firmness, and internal fruit quality were monitored during both storage conditions. Moisture and gas barrier, antibacterial activity, and surface morphology of the derived films were also evaluated to investigate the mechanisms of delayed fruit ripening and quality deterioration. In the ambient storage study, the 5% CNC reinforced chitosan coating significantly (P < 0.05) delayed green chlorophyll degradation of pear peels, prevented internal browning, reduced senescence scalding, and improved retained fruit firmness. During cold storage, the 5% CNC reinforced chitosan coating showed a competitive effect on delaying fruit postharvest quality deterioration compared to a commercial product (Semperfresh™, Pace International, Wapato, Wash., U.S.A.). The 5% CNC coating strongly adhered to the pear surface, provided a superior gas barrier and a more homogenous matrix in comparison with the other coatings tested. Hence, it was effective in delaying ripening and improving the storability of postharvest pears during both ambient and cold storage.


Selenium as a predictor of metabolic syndrome in middle age women.
Selenium plays an important role in metabolic homeostasis. It has been suggested that it may also affect the expression and activity of PPAR-γ. The aim of study was to analyze the relationships between these variables in the context of the health of women, for whom the risk of MetS increases with age. The study involved 390 women in middle age. The stages of study: a survey-based part; anthropometric measurements; analysis of biological material (blood) in terms of glycemia, triglyceride, HDL, and selenium levels, as well as genetic analysis of the PPAR-γ polymorphisms. It was found that selenium may moderate the effect of the G allele of the PPAR-γ gene on the occurrence of elevated waist circumference (OR=1.030, 95%CI 1.005-1.057, p=0.020); and the effect of the C (OR=1.077, 95%CI 1.009-1.149, p=0.026) and the G alleles (OR=1.052, 95%CI 1.025-1.080, p<0.000) on the odds of elevated blood pressure. Women in whom HDL levels were not significantly reduced, had higher selenium levels (p=0.007). 1. The effect of selenium on MetS and its components has not been demonstrated. 2. The effect of individual alleles of the PPAR-γ gene on MetS and its components was not demonstrated. 3. The concentration of selenium may affect waist circumference in carriers of the G allele, and arterial hypertension in carriers of the C and G alleles by affecting the expression of PPAR-γ. 4. Higher selenium concentrations increased the odds of higher HDL levels in the group of subjects meeting the MetS criteria.


Neuromechanical characterization of in vivo lumbar spinal manipulation. Part I. Vertebral motion.
To quantify in vivo spinal motions and coupling patterns occurring in human subjects in response to mechanical force, manually assisted, short-lever spinal manipulative thrusts (SMTs) applied to varying vertebral contact points and utilizing various excursion (force) settings. Triaxial accelerometers were attached to intraosseous pins rigidly fixed to the L1, L3, or L4 lumbar spinous process of 4 patients (2 male, 2 female) undergoing lumbar decompressive surgery. Lumbar spine acceleration responses were recorded during the application of 14 externally applied posteroanterior (PA) impulsive SMTs (4 force settings and 3 contact points) in each of the 4 subjects. Displacement time responses in the PA, axial (AX), and medial-lateral (ML) axes were obtained, as were intervertebral (L3-4) motion responses in 1 subject. Statistical analysis of the effects of facet joint (FJ) contact point and force magnitude on peak-to-peak displacements was performed. Motion coupling between the 3 coordinate axes of the vertebrae was examined using a least squares linear regression. SMT forces ranged from 30 N (lowest setting) to 150 N (maximum setting). Peak-to-peak ML, PA, and AX vertebral displacements increased significantly with increasing applied force. For thrusts delivered over the FJs, pronounced coupling was observed between all axes (AX-ML, AX-PA, PA-ML) (linear regression, R(2) = 0.35-0.52, P <.001), whereas only the AX and PA axes showed a significant degree of coupling for thrusts delivered to the spinous processes (SPs) (linear regression, R(2) = 0.82, P <.001). The ML and PA motion responses were significantly (P <.05) greater than the AX response for all SMT force settings. PA vertebral displacements decreased significantly (P <.05) when the FJ contact point was caudal to the pin compared with FJ contact cranial to the pin. FJ contact at the level of the pin produced significantly greater ML vertebral displacements in comparison with contact above and below the pin. SMTs over the spinous processes produced significantly (P <.05) greater PA and AX displacements in comparison with ML displacements. The combined ML, PA, and AX peak-to-peak displacements for the 4 force settings and 2 contact points ranged from 0.15 to 0.66 mm, 0.15 to 0.81 mm, and 0.07 to 0.45 mm, respectively. Intervertebral motions were of similar amplitude as the vertebral motions. In vivo kinematic measurements of the lumbar spine during the application of SMTs over the FJs and SPs corroborate previous spinous process measurements in human subjects. Our findings demonstrate that PA, ML, and AX spinal motions are coupled and dependent on applied force and contact point.


Differential attractiveness of human foot odours to Anopheles gambiae Giles sensu stricto (Diptera: Culicidae) and variation in their chemical composition.
Counter flow geometry (CFG) traps (American Biophysics) baited with foot odours (adsorbed overnight on a combination of a nylon and a cotton socks) from 4 groups of 4 male volunteers were initially used in a screen-house to compare and grade the attractiveness of Anopheles gambiae Giles sensu stricto to these odours. Ten individuals were then selected from the 4 groups for further grading in which mosquito attractiveness to odours adsorbed on socks worn by each of the individuals was compared against a control (clean, un-worn cotton and nylon socks). A gradation of attractiveness was found, with the most attractive foot odour catching 8-fold more mosquitoes than the least attractive one (t-test, p=0.001). For comparison of the chromatographic profiles of the foot odours and identification of their constituents, six adsorbents (tenax, chromsorb, porapak Q, activated charcoal, reverse phase octadecyl and octyl bonded silica) were evaluated for their suitability in trapping the volatiles in a static mode. Of these, porapak Q was found to be the most effective. Comparison of the gas-chromatographic (GC) and gas chromatography-linked mass spectrometry (GC-MS) profiles of blends collected from the most and least attractive feet on porapak Q adsorbent revealed both qualitative and quantitative differences. The implication of our finding on differential attraction of An. gambiae to their preferred feeding site of different human subjects is highlighted.


Deletion mutagenesis during polymerase chain reaction: dependence on DNA polymerase.
Polymerase chain reaction (PCR) was performed with two polymerases. Thermus aquaticus DNA polymerase (Taq), and modified T7 DNA polymerase (Sequenase). Both polymerases were used to amplify the same portion of the human 18S rRNA gene. We report a PCR artifact, namely a deletion of 54 bp, when Taq polymerase was used to amplify a portion of the human 18S rRNA gene. PCR performed with Sequenase did not produce this artifact. The deletion eliminated a potentially stable hairpin loop. Our data are consistent with the following model for generation of the deletion: (i) the formation of an intrastrand hairpin, and (ii) polymerization across the base of the hairpin, thus deleting the nucleotide sequence in the hairpin. Furthermore, we show that the deletion occurs mainly during synthesis of the (-)DNA strand. Our observations suggest that similar artifacts may occur in other sequences containing stable secondary structures.


The histidine effect. Electron transfer and capture cause different dissociations and rearrangements of histidine peptide cation-radicals.
Electron-transfer and -capture dissociations of doubly protonated peptides gave dramatically different product ions for a series of histidine-containing pentapeptides of both non-tryptic (AAHAL, AHAAL, AHADL, AHDAL) and tryptic (AAAHK, AAHAK, AHAAK, HAAAK, AAAHR, AAHAR, AHAAR, HAAAR) type. Electron transfer from gaseous Cs atoms and fluoranthene anions triggered backbone dissociations of all four N-C(alpha) bonds in the peptide ions in addition to loss of H and NH(3). Substantial fractions of charge-reduced cation-radicals did not dissociate on an experimental time scale ranging from 10(-6) to 10(-1) s. Multistage tandem mass spectrometric (MS(n)) experiments indicated that the non-dissociating cation-radicals had undergone rearrangements. These were explained as being due to proton migrations from N-terminal ammonium and COOH groups to the C-2' position of the reduced His ring, resulting in substantial radical stabilization. Ab initio calculations revealed that the charge-reduced cation-radicals can exist as low-energy zwitterionic amide pi* states which were local energy minima. These states underwent facile exothermic proton migrations to form aminoketyl radical intermediates, whereas direct N-C(alpha) bond cleavage in zwitterions was disfavored. RRKM analysis indicated that backbone N-C(alpha) bond cleavages did not occur competitively from a single charge-reduced precursor. Rather, these bond cleavages proceeded from distinct intermediates which originated from different electronic states accessed by electron transfer. In stark contrast to electron transfer, capture of a free electron by the peptide ions mainly induced radical dissociations of the charge-carrying side chains and loss of a hydrogen atom followed by standard backbone dissociations of even-electron ions. The differences in dissociation are explained by different electronic states being accessed upon electron transfer and capture.


A third-generation lentivirus vector with a conditional packaging system.
Vectors derived from human immunodeficiency virus (HIV) are highly efficient vehicles for in vivo gene delivery. However, their biosafety is of major concern. Here we exploit the complexity of the HIV genome to provide lentivirus vectors with novel biosafety features. In addition to the structural genes, HIV contains two regulatory genes, tat and rev, that are essential for HIV replication, and four accessory genes that encode critical virulence factors. We previously reported that the HIV type 1 accessory open reading frames are dispensable for efficient gene transduction by a lentivirus vector. We now demonstrate that the requirement for the tat gene can be offset by placing constitutive promoters upstream of the vector transcript. Vectors generated from constructs containing such a chimeric long terminal repeat (LTR) transduced neurons in vivo at very high efficiency, whether or not they were produced in the presence of Tat. When the rev gene was also deleted from the packaging construct, expression of gag and pol was strictly dependent on Rev complementation in trans. By the combined use of a separate nonoverlapping Rev expression plasmid and a 5' LTR chimeric transfer construct, we achieved optimal yields of vector of high transducing efficiency (up to 10(7) transducing units [TU]/ml and 10(4) TU/ng of p24). This third-generation lentivirus vector uses only a fractional set of HIV genes: gag, pol, and rev. Moreover, the HIV-derived constructs, and any recombinant between them, are contingent on upstream elements and trans complementation for expression and thus are nonfunctional outside of the vector producer cells. This split-genome, conditional packaging system is based on existing viral sequences and acts as a built-in device against the generation of productive recombinants. While the actual biosafety of the vector will ultimately be proven in vivo, the improved design presented here should facilitate testing of lentivirus vectors.


Identity and mechanisms of alkane-oxidizing metalloenzymes from deep-sea hydrothermal vents.
Six aerobic alkanotrophs (organism that can metabolize alkanes as their sole carbon source) isolated from deep-sea hydrothermal vents were characterized using the radical clock substrate norcarane to determine the metalloenzyme and reaction mechanism used to oxidize alkanes. The organisms studied were Alcanivorax sp. strains EPR7 and MAR14, Marinobacter sp. strain EPR21, Nocardioides sp. strains EPR26w, EPR28w, and Parvibaculum hydrocarbonoclasticum strain EPR92. Each organism was able to grow on n-alkanes as the sole carbon source and therefore must express genes encoding an alkane-oxidizing enzyme. Results from the oxidation of the radical-clock diagnostic substrate norcarane demonstrated that five of the six organisms (EPR7, MAR14, EPR21, EPR26w, and EPR28w) used an alkane hydroxylase functionally similar to AlkB to catalyze the oxidation of medium-chain alkanes, while the sixth organism (EPR92) used an alkane-oxidizing cytochrome P450 (CYP)-like protein to catalyze the oxidation. DNA sequencing indicated that EPR7 and EPR21 possess genes encoding AlkB proteins, while sequencing results from EPR92 confirmed the presence of a gene encoding CYP-like alkane hydroxylase, consistent with the results from the norcarane experiments.


Nutrient regulation of inflammatory signalling in obesity and vascular disease.
Despite obesity and diabetes markedly increasing the risk of developing cardiovascular diseases, the molecular and cellular mechanisms that underlie this association remain poorly characterised. In the last 20 years it has become apparent that chronic, low-grade inflammation in obese adipose tissue may contribute to the risk of developing insulin resistance and type 2 diabetes. Furthermore, increased vascular pro-inflammatory signalling is a key event in the development of cardiovascular diseases. Overnutrition exacerbates pro-inflammatory signalling in vascular and adipose tissues, with several mechanisms proposed to mediate this. In this article, we review the molecular and cellular mechanisms by which nutrients are proposed to regulate pro-inflammatory signalling in adipose and vascular tissues. In addition, we examine the potential therapeutic opportunities that these mechanisms provide for suppression of inappropriate inflammation in obesity and vascular disease.


Snippets from the past: is Flint, Michigan, the birthplace of the case-control study?
In the summer of 1924, an outbreak of scarlet fever occurred in Flint, Michigan. Unable to trace it to the usual causes, particularly fresh milk, the Michigan Department of Health used a novel approach to disentangle the enigma: The 116 cases of scarlet fever were compared with 117 "controls" selected from neighbors of the quarantined cases and from patients at the City Health Center who had been treated for ailments unrelated to scarlet fever. The extraordinary culprit was ice cream, which had a frequent/occasional/none consumption prevalence of 60%, 34%, and 6% among the cases and 24%, 51%, and 25% among the controls, respectively. The 1925 report reads, "Detailed epidemiological investigation, by means of case histories and control histories on well persons, confirmed early suspicions and established the fact that the epidemic was spread by ice cream" (Am J Hyg. 1925;5(5):669-681). This forgotten epidemiologic study is the oldest study using the case-control design to have been resurrected thus far. The case-control study design may have been conceived simultaneously, but independently and for different purposes, in England (Janet Lane-Claypon's 1926 report on the determinants of breast cancer) and the United States.


Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis.
Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement. We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14 weeks by European League Against Rheumatism criteria. The validation set included subjects with good, moderate or no response at 12 weeks. Total serum type I IFN activity, IFN-α and IFN-β activity were measured using a functional reporter cell assay. In the test set, an increased ratio of IFN-β to IFN-α (IFN-β/α activity ratio) in pretreatment serum associated with lack of response to TNF inhibition (p=0.013). Anti-cyclic citrullinated peptide antibody titre and class of TNF inhibitor did not influence this relationship. A receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. In the validation set, subjects with an IFN-β/α activity ratio >1.3 were significantly more likely to have non-response than good response (OR=6.67, p=0.018). The test had 77% specificity and 45% sensitivity for prediction of non-response compared with moderate or good response. Meta-analysis of test and validation sets confirmed strong predictive capacity of IFN-β/α activity ratio (p=0.005). Increased pretreatment serum IFN-β/α ratio strongly associated with non-response to TNF inhibition. This study supports further investigation of serum type I IFN in predicting outcome of TNF inhibition in RA.


The functional neuroanatomy of temporal discrimination.
Two identical stimuli, such as a pair of electrical shocks to the skin, are readily perceived as two separate events in time provided the interval between them is sufficiently long. However, as they are presented progressively closer together, there comes a point when the two separate stimuli are perceived as a single stimulus. Damage to posterior parietal cortex, peri-supplementary motor area (peri-SMA), and basal ganglia can disturb this form of temporal discrimination. Our aim was to establish, in healthy subjects, the brain areas that are involved in this process. During functional magnetic resonance imaging scanning, paired electrical pulses, separated by variable inter-stimulus intervals (5-110 msec), were delivered to different sites on one forearm (8-64 mm from the midline). Subjects were required to simply detect the stimulus (control task) or to identify a stimulus property. For temporal discrimination (TD), subjects reported whether they felt one or two stimuli. For spatial discrimination, they reported whether the stimuli were located on the right or left side of the forearm. Subjects reported their choice by pressing a button with the opposite hand. Our results showed that discrimination, as opposed to simply detection, activated several brain areas. Most were common to both discrimination tasks. These included regions of prefrontal cortex, right postcentral gyrus and inferior parietal lobule, basal ganglia, and cerebellum. However, activation of pre-SMA and anterior cingulate was found to be specific to the TD task. This suggests that these two frontal regions may play a role in the temporal processing of somatosensory events.


Childbearing postponement and child well-being: a complex and varied relationship?
Over the past several decades, U.S. fertility has followed a trend toward the postponement of motherhood. The socioeconomic causes and consequences of this trend have been the focus of attention in the demographic literature. Given the socioeconomic advantages of those who postpone having children, some authors have argued that the disadvantage experienced by certain groups would be reduced if they postponed their births. The weathering hypothesis literature, by integrating a biosocial perspective, complicates this argument and posits that the costs and benefits of postponement may vary systematically across population subgroups. In particular, the literature on the weathering hypothesis argues that, as a consequence of their unique experiences of racism and disadvantage, African American women may experience a more rapid deterioration of their health which could offset or eventually reverse any socioeconomic benefit of postponement. But because very few African American women postpone motherhood, efforts to find compelling evidence to support the arguments of this perspective rely on a strategy of comparison that is problematic because a potentially selected group of older black mothers are used to represent the costs of postponement. This might explain why the weathering hypothesis has played a rather limited role in the way demographers conceptualize postponement and its consequences for well-being. In order to explore the potential utility of this perspective, we turn our attention to the UK context. Because first-birth fertility schedules are similar for black and white women, we can observe (rather than assume) whether the meaning and consequences of postponement vary across these population subgroups. The results, obtained using linked UK census and birth record data, reveal evidence consistent with the weathering hypothesis in the United Kingdom and lend support to the arguments that the demographic literature would benefit from integrating insights from this biosocial perspective.


Integrated simultaneous analysis of different biomedical data types with exact weighted bi-cluster editing.
The explosion of biological data has largely influenced the focus of today's biology research. Integrating and analysing large quantity of data to provide meaningful insights has become the main challenge to biologists and bioinformaticians. One major problem is the combined data analysis of data from different types, such as phenotypes and genotypes. This data is modelled as bi-partite graphs where nodes correspond to the different data points, mutations and diseases for instance, and weighted edges relate to associations between them. Bi-clustering is a special case of clustering designed for partitioning two different types of data simultaneously. We present a bi-clustering approach that solves the NP-hard weighted bi-cluster editing problem by transforming a given bi-partite graph into a disjoint union of bi-cliques. Here we contribute with an exact algorithm that is based on fixed-parameter tractability. We evaluated its performance on artificial graphs first. Afterwards we exemplarily applied our Java implementation to data of genome-wide association studies (GWAS) data aiming for discovering new, previously unobserved geno-to-pheno associations. We believe that our results will serve as guidelines for further wet lab investigations. Generally our software can be applied to any kind of data that can be modelled as bi-partite graphs. To our knowledge it is the fastest exact method for weighted bi-cluster editing problem.


A 30 kb region of the Epstein-Barr virus genome is colinear with the rearranged human immunoglobulin gene loci: implications for a "ping-pong evolution" model for persisting viruses and their hosts. A review.
The left part of the Epstein-Barr virus (EBV) genome exhibits a strong colinearity of structural and functional elements with the immunoglobulin (Ig) gene loci which is only partially reflected in nucleotide sequence homologies. We propose that this colinearity may be the result of an inter-dependent co-evolution of the immunoglobulin loci together with EBV. Our observation could help elucidating the mechanisms of somatic hypermutation, explaining the ability of EBV to accidentally cause tumors, and shedding more light on the general mechanisms of viral and organismal evolution. We suggest that persisting viruses served as a complement for the organismal germline like in a ping-pong game and outline The Ping-Pong Evolution Hypothesis.


Decisions for others become less impulsive the further away they are on the family tree.
People tend to prefer a smaller immediate reward to a larger but delayed reward. Although this discounting of future rewards is often associated with impulsivity, it is not necessarily irrational. Instead it has been suggested that it reflects the decision maker's greater interest in the 'me now' than the 'me in 10 years', such that the concern for our future self is about the same as for someone else who is close to us. To investigate this we used a delay-discounting task to compare discount functions for choices that people would make for themselves against decisions that they think that other people should make, e.g. to accept $500 now or $1000 next week. The psychological distance of the hypothetical beneficiaries was manipulated in terms of the genetic coefficient of relatedness ranging from zero (e.g. a stranger, or unrelated close friend), .125 (e.g. a cousin), .25 (e.g. a nephew or niece), to .5 (parent or sibling). The observed discount functions were steeper (i.e. more impulsive) for choices in which the decision-maker was the beneficiary than for all other beneficiaries. Impulsiveness of decisions declined systematically with the distance of the beneficiary from the decision-maker. The data are discussed with reference to the implusivity and interpersonal empathy gaps in decision-making.


Cardiac rhythm and conduction in Duchenne's muscular dystrophy: a prospective study of 20 patients.
This study was designed to determine the types and prevalence of rhythm and conduction disturbances in Duchenne's muscular dystrophy, and examine the results in light of known morphologic abnormalities of the myocardium and the small coronary arteries, and in the context of left ventricular function, regional wall motion, mitral valve prolapse and left atrial size. The observed disorders of impulse and conduction extended from the sinus node to the His-Purkinje system. Rhythm disturbances included persistent and labile sinus tachycardia (gradual or abrupt), sinus arrhythmia, sinus pauses, atrial ectopic beats, atrial ectopic rhythm, junctional rhythm, atrial flutter and ventricular premature beats (uniform, multiform, bigeminal and repetitive). Disorders of conduction included abnormal intraatrial or interatrial conduction, Mobitz type I block, nonconducted atrial premature beats, short PR interval, right ventricular conduction delay and rightward axis compatible with left posterior fascicular block. The role of dystrophic involvement of specialized conduction tissues and of the small vessel coronary arteriopathy remains speculative, but mitral valve prolapse, left atrial size and left ventricular size, function and regional wall motion played no discernible part in the genesis of the rhythm and conduction disturbances. Except for end-stage atrial flutter, these disturbances were not clinically deleterious.