How good are patients with panic disorder at perceiving their heartbeats?
Palpitations are among the most common symptoms of panic attacks. The present review addresses the question of whether systematic differences in heartbeat perception exist between patients with panic disorder and control subjects. Paradigms involving the comparison of heartbeat sensations with external signals such as discrimination task have failed to find group differences. Recent improvements in methodology may give clearer results in future studies. The majority of studies using the mental tracking paradigm have shown that panic disorder patients show a better heartbeat perception than controls. Discrepant results are probably related to different instructions and differences in sample characteristics such as the inclusion of patients on medication affecting the cardiovascular system. More accurate heartbeat perception, may, however, be restricted to those patients who show agoraphobic avoidance behavior. It is also conceivable that group differences in the mental tracking paradigm are due to attentional biases or a tendency to interpret weak sensations as heartbeats rather than differences in perceptual sensitivity. More ambulatory studies are needed to test whether the results can be generalized to the patients' natural environment. So far ambulatory studies have established superior heartbeat perception only in the subgroup of panic disorder patients with cardiac neurosis. A 1-year prospective study showed that heartbeat perception as assessed with the mental tracking paradigm predicted maintenance of panic attacks. This supports the clinical significance of the findings. Increased cardiac awareness may increase the probability of anxiety-inducing bodily sensations triggering the vicious cycle of panic. Laboratory and ambulatory monitoring studies showed that panic disorder patients respond with anxiety when they think that their heart rate has accelerated. Increased cardiac awareness may also contribute to the maintenance of the disorder by motivating the patients to avoid situations in which these sensations occur.


Establishment of a bioluminescence model for microenvironmentally induced oral carcinogenesis with implications for screening bioengineered scaffolds.
Microenvironmental cues play a major role in head and neck cancer. Biodegradable scaffolds used for bone regeneration might also act as stimulative cues for head and neck cancer. The purpose of this study was to establish an experimental model for precise and noninvasive evaluation of tumorigenic potential of microenvironmental cues in head and neck cancer. Bioluminescence was chosen to image tumor formation. Early neoplastic oral keratinocyte (DOK) cells were luciferase-transduced (DOK(Luc) ), then tested in nonobese diabetic severe combined immunodeficient IL2rγnull mice either orthotopically (tongue) or subcutaneously for their potential as "screening sensors" for diverse microenvironmental cues. Tumors formed after inoculation of DOK(Luc) were monitored easier by bioluminescence, and bioluminescence was more sensitive in detecting differences between various microenvironmental cues when compared to manual measurements. Development of tumors from DOK(Luc) grown on scaffolds was also successfully monitored noninvasively by bioluminescence. The model presented here is a noninvasive and sensitive model for monitoring the impact of various microenvironmental cues on head and neck cancer in vivo. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E1177-E1187, 2016.


Intersection crossing considered as intercepting a moving traffic gap: effects of task and environmental constraints.
Safely crossing an intersection requires that drivers actively control their approach to the intersection with respect to characteristics of the flow of incoming traffic. To further our understanding of the perceptual-motor processes involved in this demanding manoeuvre, we designed a driving simulator experiment in which 13 participants actively negotiated intersections by passing through a gap in the train of incoming traffic. Task constraints were manipulated by varying the size of the traffic gap and the initial conditions with respect to the time of arrival of the traffic gap at the intersection. Environment constraints were manipulated by varying the intersection geometry through changes in the angle formed by the crossroads. The results revealed that the task constraints systematically gave rise to continuous and gradual adjustments in approach velocity, initiated well before arriving at the intersection. These functionally appropriate adjustments allowed the drivers to safely cross the intersection, generally just slightly ahead of the center of the traffic gap. Notwithstanding the fact that the geometry of the intersection did not affect the spatiotemporal constraints of the crossing task, approach behavior varied systematically over geometries, suggesting that drivers rely on the traffic gap's bearing angle. Overall, the pattern of results is indicative of a continuous coupling between perception and action, analogous to that observed in locomotor interception tasks.


Mechanisms tagging senescent red blood cells for clearance in healthy humans.
This review focuses on the analysis and evaluation of the diverse senescence markers suggested to prime red blood cells (RBC) for clearance in humans. These tags develop in the course of biochemical and structural alterations accompanying RBC aging, as the decrease of activities of multiple enzymes, the gradual accumulation of oxidative damage, the loss of membrane in form of microvesicles, the redistribution of ions and alterations in cell volume, density, and deformability. The actual tags represent the penultimate galactosyl residues, revealed by desialylation of glycophorins, or the aggregates of the anion exchanger (band 3 protein) to which anti-galactose antibodies bind in the first and anti-band 3 naturally occurring antibodies (NAbs) in the second case. While anti-band 3 NAbs bind to the carbohydrate-free portion of band 3 aggregates in healthy humans, induced anti-lactoferrin antibodies bind to the carbohydrate-containing portion of band 3 and along with anti-band 3 NAbs may accelerated clearance of senescent RBC in patients with anti-neutrophil cytoplasmic antibodies (ANCA). Exoplasmically accessible phosphatidylserine (PS) and the alterations in the interplay between CD47 on RBC and its receptor on macrophages, signal regulatory protein alpha (SIRPalpha protein), were also reported to induce erythrocyte clearance. We discuss the relevance of each mechanism and analyze the strength of the data.


Secondary ion mass spectrometric investigation of penetration of coconut and mineral oils into human hair fibers: relevance to hair damage.
An attempt has been made to show the difference in the penetrability of coconut oil and mineral oil in human hair. We have used secondary ion mass spectrometry (SIMS) in combination with a time-of-flight (TOF) mass spectrometer. Characteristic ions formed by the pure components when bombarded with gallium ions have been identified with their m/z values. The distribution of the ion, characteristic of the particular treatment, has been established in the cross sections of hair treated with coconut and mineral oils. The results show that coconut oil penetrates the hair shaft while mineral oil does not. The difference may be due to the polarity of the coconut oil compared to the nonpolar nature of the mineral oil. The affinity of the penetrant to the protein seems to be the cause for this difference in their behavior. This study also indicates that the swelling of hair is limited by the presence oil. Since the process of swelling and deswelling of hair is one of the causes of hair damage by hygral fatigue, coconut oil, which is a better penetrant than mineral oil, may provide better protection from damage by hygral fatigue.


[Epidemiological general profile of complaints treated at the National Medical Arbitration Commission. 1996-2007].
To analyze medical complaints over a period of 11 years, for making recommendations for prevention and improving planning for responding. We studied the medical complaints at the National Medical Arbitration Commission (Conamed, per its acronym in Spanish) between 1996 and 2007 using descriptive statistics to identify their general profile in relation to the variables of time, place and person. We also studied the frequency of evident medical malpractice as well as the severity of the damage it produces. The request for responses to medical complaints increased between 1996 and 2007 and there was less demand between July and December. Two states in the country account for 69.7% of the complaints and 74.0% are from public institutions. Fifty-eight percent come from women and the 25-34 and 65+ age groups have the highest percentage. We found in 27.0% of the complaints there is evidence of medical malpractice and obstetrics and gynecology have the highest percentage of complaints, physical harm and severity of injury. Complaints about treatment are nearly four times more than diagnosis. It is necessary to improve the quality of diagnosis and treatment and identify cost-effective measures to reduce medical malpractice and the severity of physical damage in patients.


Electromagnetic hypersensitivity (EHS) in the media - a qualitative content analysis of Norwegian newspapers.
Electromagnetic hypersensitivity (EHS) is a condition characterized by experiencing symptoms after perceived exposure to weak electromagnetic fields (EMFs). There is substantial debate concerning the aetiology of EHS, but experimental data indicate no association between EHS and actual presence of EMFs. Newspapers play a key role in shaping peoples' understanding of health-related issues. The aim of this study was to describe the content of newspaper articles concerning aetiology and treatment of EHS. Qualitative content analysis of newspaper articles. Norwegian newspaper articles were identified using a comprehensive electronic media archive. Norwegian newspaper articles published between 1 February 2006 and 11 August 2010. Statements coded according to source of information, whether it was pro or con scientific evidence on EHS aetiology, and type of intervention presented as treatment option for EHS. Of the statements concerning EHS aetiology (n = 196), 35% (n = 69) were categorized as pro evidence, 65% (n = 127) as con evidence. Of the statements about EHS interventions assessed, 78% (n = 99) were categorized as 'radiance reduction', 4% (n = 5) as 'complementary medicine', and 18% (n = 23) as 'other'. Cognitive behavioural therapy (CBT) and psychotropic drugs were never presented as possible treatment options for EHS. The newspaper media discourse of EHS aetiology and recommended treatment interventions is much in conflict with the current evidence in the field. The majority of statements concerning aetiology convey that EHS is related to the presence of weak EMFs, and radiance reduction as the most frequently conveyed measure to reduce EHS-related symptoms.


Modulation of protein properties in living cells using nanobodies.
Protein conformation is critically linked to function and often controlled by interactions with regulatory factors. Here we report the selection of camelid-derived single-domain antibodies (nanobodies) that modulate the conformation and spectral properties of the green fluorescent protein (GFP). One nanobody could reversibly reduce GFP fluorescence by a factor of 5, whereas its displacement by a second nanobody caused an increase by a factor of 10. Structural analysis of GFP-nanobody complexes revealed that the two nanobodies induce subtle opposing changes in the chromophore environment, leading to altered absorption properties. Unlike conventional antibodies, the small, stable nanobodies are functional in living cells. Nanobody-induced changes were detected by ratio imaging and used to monitor protein expression and subcellular localization as well as translocation events such as the tamoxifen-induced nuclear localization of estrogen receptor. This work demonstrates that protein conformations can be manipulated and studied with nanobodies in living cells.


Spatial and temporal effects in protein post-translational modification distributions in the developing mouse brain.
Protein post-translational modification (PTM) is a powerful way to modify the behavior of cellular proteins and thereby cellular behavior. Multiple recent studies of evolutionary trends have shown that certain pairs of protein post-translational modifications tend to occur closer to each other than expected at random. This type of observation may form the basis of a proposed "PTM code", whereby protein function is controlled by complex patterns of multiple PTMs. This code could provide an additional, powerful level of regulatory control for protein function and is a plausible explanation for observations of increasingly frequent and diverse protein modification in cell biology. In this study, we use mass spectrometry and proteomic strategies to present biological data showing spatiotemporal PTM co-localization across multiple PTM categories, which display changes over development of the brain. This may be an indication of the existence of a PTM-based functional coding mechanism, which would significantly expand our view of the ways in which cells use protein PTMs in complex signaling networks.


Enhanced response of neurons in rat somatosensory cortex to stimuli containing temporal noise.
Sensory stimuli under natural conditions often consist of a temporally irregular sequence of events, contrasting with the periodic sequences commonly used as stimuli in the laboratory. These experiments compared the responses of neurons in rat barrel cortex with trains of whisker movements with different frequencies; each train possessed either a periodic or an irregular, "noisy" temporal structure. Periodic stimulus trains were composed of a sequence of 21 whisker deflections separated by 20 equal interdeflection intervals (IDIs). Noisy trains were matched for mean IDI but included intervals shorter and longer than the mean IDI. Cortical responses were equivalent for periodic and noisy stimuli for frequencies up to 10 Hz. Above 10 Hz, temporal noise led to a larger response magnitude, and this effect was amplified as deflection frequency increased. Noise also caused a sharpening of the temporal precision of response to the individual deflections of the stimulus train. Cortical neurons thus appear to be "tuned" to respond in a different way to stimuli characterized by temporal unpredictability. As a consequence, perceptual judgments that depend on somatosensory cortical firing rate may be affected by the presence of temporal noise.


Acute Hemodynamic Changes after Single Administration of Udenafil in Pulmonary Arterial Hypertension: a Phase IIa Study.
Udenafil, a new phosphodiesterase-5 inhibitor (PDE5i), has been used to treat erectile dysfunction. Given the proven benefit of PDE5i in pulmonary arterial hypertension (PAH), we evaluated serial hemodynamic changes after single udenafil administration to determine the appropriate therapeutic dose. Eighteen patients were randomly allocated into one of 3 groups: placebo, udenafil 50 mg (U50), and udenafil 100 mg (U100). Diagnosis for inclusion was idiopathic PAH or PAH associated with connective tissue disease. Patients with any contraindication to PDE5i, and/or PDE5i treatment in the past 1 month were excluded. Continuous hemodynamic monitoring was performed by placing a Swan-Ganz catheter. Information on cardiac index (CI), mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mSAP), pulmonary arterial wedge pressure (PAWP), and pulmonary vascular resistance index (PVRI) was obtained for 4 hours after drug administration. The mPAP significantly decreased in both the U50 and U100 (-11 mmHg and -8 mmHg from baseline, respectively, p<0.1). The mSAP also decreased in both U50 and U100; however, the decrease was greater in the U100 (Δ=-8.5 mmHg and Δ=-14.0 mmHg). CI increased in the U50, but decreased in the U100. Although PVRI decreased in both, statistical significance was only achieved in the U50 compared to placebo. PAWP was stable during monitoring. U50 had at least 4 hour-effect after administration. Only 2 patients with U100 experienced mild adverse events. This is the first demonstration of the acute hemodynamic changes induced by udenafil. U50 is considered an optimal dose for treating PAH with more than 4-hour treatment effect. ClinicalTrials.gov Identifier: NCT01553721.


The effects of intentional weight loss as a latent variable problem.
Although obesity is associated with increased mortality rate and short-term weight loss improves risk factors for mortality, it has not been convincingly shown that weight loss among obese people results in reduced mortality rate. When considering the human literature, it has been pointed out that weight loss is often a sign of illness and that investigators therefore need to separate intentional from unintentional weight loss. It has generally been assumed that among people who state that they do not intend to lose weight, weight change subsequently observed is unintentional. Among such people, weight loss has been consistently associated with increased mortality rate. Complementarily, it has generally been assumed that among people who state that they do intend to lose weight, weight change subsequently observed is intentional. In these people who are intending to lose weight, some studies show apparent benefits of weight loss, some are neutral, and some show deleterious effects. The overall conclusion that some reviewers have drawn from this literature is that intentional weight loss (IWL) is at best not beneficial and may even be harmful with respect to mortality rate. We believe that this conclusion is drawn by inappropriately conflating weight loss (or more generally weight change) among people intending to lose weight with IWL (or change). Herein, under certain assumptions, we: (1) show that the association between mortality rate and weight loss among people intending to lose weight and between mortality rate and IWL are two different things; (2) show that the association between IWL and mortality rate is an inherently unobservable entity; (3) derive a method for estimating the plausible range of true effect of IWL on mortality rate if one is willing to make a number of restrictive, but perhaps reasonable assumptions; and (4) illustrate the method by application to a data set involving middle-age onset calorie restriction in mice.


Curvature interpolation method for image zooming.
We introduce a novel image zooming algorithm, called the curvature interpolation method (CIM), which is partial-differential-equation (PDE)-based and easy to implement. In order to minimize artifacts arising in image interpolation such as image blur and the checkerboard effect, the CIM first evaluates the curvature of the low-resolution image. After interpolating the curvature to the high-resolution image domain, the CIM constructs the high-resolution image by solving a linearized curvature equation, incorporating the interpolated curvature as an explicit driving force. It has been numerically verified that the new zooming method can produce clear images of sharp edges which are already denoised and superior to those obtained from linear methods and PDE-based methods of no curvature information. Various results are given to prove effectiveness and reliability of the new method.


The Andean adaptive toolkit to counteract high altitude maladaptation: genome-wide and phenotypic analysis of the Collas.
During their migrations out of Africa, humans successfully colonised and adapted to a wide range of habitats, including extreme high altitude environments, where reduced atmospheric oxygen (hypoxia) imposes a number of physiological challenges. This study evaluates genetic and phenotypic variation in the Colla population living in the Argentinean Andes above 3500 m and compares it to the nearby lowland Wichí group in an attempt to pinpoint evolutionary mechanisms underlying adaptation to high altitude hypoxia. We genotyped 730,525 SNPs in 25 individuals from each population. In genome-wide scans of extended haplotype homozygosity Collas showed the strongest signal around VEGFB, which plays an essential role in the ischemic heart, and ELTD1, another gene crucial for heart development and prevention of cardiac hypertrophy. Moreover, pathway enrichment analysis showed an overrepresentation of pathways associated with cardiac morphology. Taken together, these findings suggest that Colla highlanders may have evolved a toolkit of adaptative mechanisms resulting in cardiac reinforcement, most likely to counteract the adverse effects of the permanently increased haematocrit and associated shear forces that characterise the Andean response to hypoxia. Regulation of cerebral vascular flow also appears to be part of the adaptive response in Collas. These findings are not only relevant to understand the evolution of hypoxia protection in high altitude populations but may also suggest new avenues for medical research into conditions where hypoxia constitutes a detrimental factor.


Brain drain: the cost of neglected responsibilities in evaluating cumulative effects of environmental chemicals.
Developmental disabilities affect millions of people and have a great impact on their lives, their families and the societies where they live. The prevalence of disorders such as autism, attention deficit hyperactivity disorder as well as subclinical decrements in brain function cannot be explained solely as genetic diseases. Exposures to environmental chemicals, especially during prenatal and early postnatal life, are one likely explanation for some of the decrements. The current chemical risk assessment approach is typically based on the toxicity caused by a single chemical on a variety of organs without acknowledging additional exposures to other chemicals also affecting the same organ or system. We identified more than 300 chemicals allowed in food that may have potential harmful effects on the developing brain. Each individual chemical may or may not have a harmful effect if it were the only one present, but we know next to nothing about their cumulative biological effects on the brain. An expanded cumulative risk assessment approach is needed, and it should focus on health outcomes, like developmental disabilities, arising from the accumulation of effects of multiple chemicals on the brain. The laws regulating the safety of additives already require that regulators in Europe and the USA consider cumulative effects; so far, they seem to have neglected the mandate. We must move beyond treating chemical exposures as isolated incidents and look at their cumulative biological effects on organs and their role in the onset of chronic diseases. The time has come to overhaul chemical risk assessment.


Prevalence of hypertension, and related factors among adults in Wolaita, southern Ethiopia: A community-based cross-sectional study.
Hypertension is a global public health challenge. There is a lack of evidence on the prevalence of hypertension, prehypertension, and related factors among adult populations of Wolaita, southern Ethiopia. To assess the prevalence of hypertension, prehypertension, and related factors among adult populations of Wolaita, southern Ethiopia. A community-based cross-sectional study was conducted on 2483 adult residents, selected using a two-stage random sampling technique. The quantitative data collected from structured questionnaires; anthropometric and biochemical measurements were entered into EpiData version 3.1 using double-entry systems. We determined the weighted prevalence of hypertension and pre-hypertension for the two-stage survey. The multivariate logistic regression analysis was used to assess factors associated with hypertension and carried out after declaring the data set as survey data to account for the effect of clustering. An adjusted coefficient with 95% CI was used to ascertain the significance of the association. The weighted prevalence of hypertension and prehypertension in the Wolaita area was 31.3% (27.7%-35.1%) and 46.4% (42.9%-50.0%) respectively. The weighted prevalence of hypertension of those who were not aware of their hypertension until the time of the survey was 29.8%% (26.5%-33.3%). Where the weighted prevalence of self-reported cases of hypertension was 2.2% (1.2%-3.8%). Obesity, sugar-sweetened food consumption, male sex, elevated total cholesterol, raised fasting blood sugar, and advancing age were positively associated with hypertension. The prevalence of hypertension among adults in Wolaita was high. A small proportion of the affected people are aware of their high blood pressure. This study reported a high prevalence of pre-hypertension; which indicates a high percentage of people at risk of hypertension. It is essential to develop periodic screening programs, and primary intervention strategies such as the prevention of obesity, and reduction of sugar-sweetened food consumption.


The generation of hydroxyl and alkoxyl radicals from the interaction of ferrous bipyridyl with peroxides.
Reaction conditions by which the iron-chelate ferrous bipyridyl can be used as a Fenton reagent to generate specifically alkoxyl radical (.OR) from its corresponding alkyl hydroperoxide (ROOH) without producing hydroxyl radical (.OH) as a result of autoxidation are described. In this manner, the relative ability of common .OH-scavenging agents to react with .OH and various .OR species could be assessed. When .OH was generated from H2O2, 4-methylmercapto-2-oxobutyrate, ethanol and benzoate all were oxidized. When .OR (cumoxyl radical, t-butoxyl radical or ethoxyl radical) was generated specifically, each was found to oxidize 4-methylmercapto-2-oxobutyrate and ethanol. In contrast with .OH, however, none of the .OR radicals mediated the decarboxylation of benzoate. Cross-competition studies with the scavengers showed that, in contrast with the .OH-dependent reaction, the .OR-dependent oxidation of 4-methylmercapto-2-oxobutyrate and ethanol was not inhibited by benzoate. Rate constants for ferrous bipyridyl oxidation by ROOH and by H2O2 were found to be essentially the same, and therefore the differential oxidation of the various scavengers was not a reflection of iron-peroxide interaction, but rather an interaction between generated oxy radicals and the scavengers. In contrast with the H2O2 system, catalase did not inhibit the oxidation of 4-methylmercapto-2-oxobutyrate or ethanol by either the cumene hydroperoxide or the t-butyl hydroperoxide system, suggesting that the oxidizing species was not derived from H2O2. These results suggest that benzoate decarboxylation might serve as a more specific probe to detect the presence of .OH than either 4-methylmercapto-2-oxobutyrate or ethanol, which react readily with .OR.


MORTAR: a rich client application for in silico molecule fragmentation.
Developing and implementing computational algorithms for the extraction of specific substructures from molecular graphs (in silico molecule fragmentation) is an iterative process. It involves repeated sequences of implementing a rule set, applying it to relevant structural data, checking the results, and adjusting the rules. This requires a computational workflow with data import, fragmentation algorithm integration, and result visualisation. The described workflow is normally unavailable for a new algorithm and must be set up individually. This work presents an open Java rich client Graphical User Interface (GUI) application to support the development of new in silico molecule fragmentation algorithms and make them readily available upon release. The MORTAR (MOlecule fRagmenTAtion fRamework) application visualises fragmentation results of a set of molecules in various ways and provides basic analysis features. Fragmentation algorithms can be integrated and developed within MORTAR by using a specific wrapper class. In addition, fragmentation pipelines with any combination of the available fragmentation methods can be executed. Upon release, three fragmentation algorithms are already integrated: ErtlFunctionalGroupsFinder, Sugar Removal Utility, and Scaffold Generator. These algorithms, as well as all cheminformatics functionalities in MORTAR, are implemented based on the Chemistry Development Kit (CDK).


Consumption of flavanol-rich cocoa acutely increases microcirculation in human skin.
Long term cocoa ingestion leads to an increased resistance against UV-induced erythema and a lowered transepidermal water loss. To investigate the acute effects of a single dose of cocoa rich in flavanols on dermal microcirculation. In a crossover design study, 10 healthy women ingested a cocoa drink (100 ml) with high (329 mg) or low (27 mg) content of flavanols. The major flavanol monomer in both drinks was epicatechin, 61 mg in the high flavanol, and 6.6 mg in the low flavanol product per 100 ml. Dermal blood flow and oxygen saturation of hemoglobin were examined by laser Doppler flowmetry and spectroscopically at 1 mm skin depth at t = 0, 1, 2, 4, and 6 h. At the same time points, plasma levels of total epicatechin (free compound plus conjugates) were measured by means of HPLC. Subsequent to the intake of high flavanol cocoa, dermal blood flow was significantly increased by 1.7-fold at t = 2 h and oxygen saturation was elevated 1.8-fold. No statistically significant changes were found upon intake of low flavanol cocoa. Maximum plasma levels of total epicatechin were observed 1 h after ingestion of the high flavanol cocoa drink, 11.6 +/- 7.4 nmol/l at baseline, and 62.9 +/- 35.8 nmol/l at 1 h. No change of total epicatechin was found in the low flavanol group. Flavanol-rich cocoa consumption acutely increases dermal blood flow and oxygen saturation.


A novel method of protein secondary structure prediction with high segment overlap measure: support vector machine approach.
We have introduced a new method of protein secondary structure prediction which is based on the theory of support vector machine (SVM). SVM represents a new approach to supervised pattern classification which has been successfully applied to a wide range of pattern recognition problems, including object recognition, speaker identification, gene function prediction with microarray expression profile, etc. In these cases, the performance of SVM either matches or is significantly better than that of traditional machine learning approaches, including neural networks.The first use of the SVM approach to predict protein secondary structure is described here. Unlike the previous studies, we first constructed several binary classifiers, then assembled a tertiary classifier for three secondary structure states (helix, sheet and coil) based on these binary classifiers. The SVM method achieved a good performance of segment overlap accuracy SOV=76.2 % through sevenfold cross validation on a database of 513 non-homologous protein chains with multiple sequence alignments, which out-performs existing methods. Meanwhile three-state overall per-residue accuracy Q(3) achieved 73.5 %, which is at least comparable to existing single prediction methods. Furthermore a useful "reliability index" for the predictions was developed. In addition, SVM has many attractive features, including effective avoidance of overfitting, the ability to handle large feature spaces, information condensing of the given data set, etc. The SVM method is conveniently applied to many other pattern classification tasks in biology.


Detection of risk of cancer to man.
Epidemiology can pick out large-scale determinants of human cancer, such as smoking. Also, epidemiology can pick out carcinogens such as asbestos to which groups of perhaps a few hundred or a few thousand workers have been heavily exposed for decades. However, if highly exposed groups cannot be studied then epidemiology cannot recognize carcinogens which, although perhaps widely distributed, produce only a small percentage increase in particular cancers. Almost all of the environmental pollutants that can affect human cancer incidence will do so only to a very minor extent, at the levels to which we are currently exposed. For this reason, and also because it is often difficult to define an exposed and an unexposed group which do not differ in other ways as well, it will almost always be impossible to do anything epidemiologically except to set a very crude upper limit on their likely hazards. The only way, therefore, to get any direct estimate of these hazards is by laboratory studies of the effects of high doses on various model systems. For this and for other reasons, it would be highly desirable to have good laboratory models for human carcinogenesis. The characteristics required of satisfactory laboratory systems are reviewed, and it is argued that systematic errors may arise unless one studies epithelial cells from large, long-lived species under conditions of chronic, low-dose exposure to noxious test agents in conjunction with standard chronic doses of agents which may be synergistic with the test agents. (Carcinogenic mutagens may be synergistic with carcinogenic non-mutagens.) For reasons of expense and speed, such studies must be done in vitro. If such in-vitro systems can be developed, either by using tissue explants or cell cultures, an important criterion which they will have to satisfy to be trusted will be that under chronic exposure the rate of transformation should be proportional to something like the fourth power of exposure duration. This paper chiefly reviews the reasons for choosing these specifications for a trustworthy in-vitro model for human carcinogenesis.


Cultural Change: The How and the Why.
More than half a century of cross-cultural research has demonstrated group-level differences in psychological and behavioral phenomena, from values to attention to neural responses. However, cultures are not static, with several specific changes documented for cultural products, practices, and values. How and why do societies change? Here we juxtapose theory and insights from cultural evolution and social ecology. Evolutionary approaches enable an understanding of the how of cultural change, suggesting transmission mechanisms by which the contents of culture may change. Ecological approaches provide insights into the why of cultural change: They identify specific environmental pressures, which evoke shifts in psychology and thereby enable greater precision in predictions of specific cultural changes based on changes in ecological conditions. Complementary insights from the ecological and cultural evolutionary approaches can jointly clarify the process by which cultures change. We end by discussing the relevance of cultural change research for the contemporary societal shifts and by highlighting several critical challenges and future directions for the emerging field of cross-temporal research on culture and psychology.


The role of type 1 angiotensin receptors on T lymphocytes in cardiovascular and renal diseases.
The renin-angiotensin system plays a critical role in the pathogenesis of several cardiovascular diseases, largely through activation of type I angiotensin (AT(1)) receptors by angiotensin II. Treatment with AT(1) receptor blockers (ARBs) is a proven successful intervention for hypertension and progressive heart and kidney disease. However, the divergent actions of AT(1) receptors on individual cell lineages in hypertension may present novel opportunities to optimize the therapeutic benefits of ARBs. For example, T lymphocytes make important contributions to the induction and progression of various cardiovascular diseases, but new experiments indicate that activation of AT(1) receptors on T cells paradoxically limits inflammation and target organ damage in hypertension. Future studies should illustrate how these discrepant functions of AT(1) receptors in target organs versus mononuclear cells can be exploited for the benefit of patients with recalcitrant hypertension and other cardiovascular diseases.


An incidence-based richness estimator for quadrats sampled without replacement.
Most richness estimators currently in use are derived from models that consider sampling with replacement or from the assumption of infinite populations. Neither of the assumptions is suitable for sampling sessile organisms such as plants where quadrats are often sampled without replacement and the area of study is always limited. In this paper, we propose an incidence-based parametric richness estimator that considers quadrat sampling without replacement in a fixed area. The estimator is derived from a zero-truncated binomial distribution for the number of quadrats containing a given species (e.g., species i) and a modified beta distribution for the probability of presence-absence of a species in a quadrat. The maximum likelihood estimate of richness is explicitly given and can be easily solved. The variance of the estimate is also obtained. The performance of the estimator is tested against nine other existing incidence-based estimators using two tree data sets where the true numbers of species are known. Results show that the new estimator is insensitive to sample size and outperforms the other methods as judged by the root mean squared errors. The superiority of the new method is particularly noticeable when large quadrat size is used, suggesting that a few large quadrats are preferred over many small ones when sampling diversity.


Lung cancer screening with low-dose computed tomography: costs, national expenditures, and cost-effectiveness.
A recent randomized trial showed that low-dose CT (LDCT) screening reduces lung cancer mortality. Health care providers need an assessment of the national budget impact and cost-effectiveness of LDCT screening before this intervention is adopted in practice. Using data from the 2009 National Health Interview Survey, CMS, and the National Lung Screening Trial (NLST), the authors performed an economic analysis of LDCT screening that includes a budget impact model, an estimate of additional costs per lung cancer death avoided attributed to screening, and a literature search of cost-effectiveness analyses of LDCT screening. They conducted a one-way sensitivity analysis, reporting expenditures in 2011 U.S. dollars, and took the health care payer and patient perspectives. LDCT screening will add $1.3 to $2.0 billion in annual national health care expenditures for screening uptake rates of 50% to 75%, respectively. However, LDCT screening will avoid up to 8100 premature lung cancer deaths at a 75% screening rate. The prevalence of smokers who qualify for screening, screening uptake rates, and cost of LDCT scan were the most influential parameters on health care expenditures. The additional cost of screening to avoid one lung cancer death is $240,000. Previous cost-effectiveness analyses have not conclusively shown that LDCT is cost-effective. LDCT screening may add substantially to the national health care expenditures. Although LDCT screening can avoid more than 8000 lung cancer deaths per year, a cost-effectiveness analysis of the NLST will be critical to determine the value of this intervention and to guide decisions about its adoption.


2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum.
Thyroid disease in pregnancy is a common clinical problem. Since the guidelines for the management of these disorders by the American Thyroid Association (ATA) were first published in 2011, significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid disease in women during pregnancy, preconception, and the postpartum period. The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. The guideline task force had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. The revised guidelines for the management of thyroid disease in pregnancy include recommendations regarding the interpretation of thyroid function tests in pregnancy, iodine nutrition, thyroid autoantibodies and pregnancy complications, thyroid considerations in infertile women, hypothyroidism in pregnancy, thyrotoxicosis in pregnancy, thyroid nodules and cancer in pregnant women, fetal and neonatal considerations, thyroid disease and lactation, screening for thyroid dysfunction in pregnancy, and directions for future research. We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid disease in pregnant and postpartum women. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with these disorders.


Neural Sources and Underlying Mechanisms of Neural Responses to Heartbeats, and their Role in Bodily Self-consciousness: An Intracranial EEG Study.
Recent research has shown that heartbeat-evoked potentials (HEPs), brain activity in response to heartbeats, are a useful neural measure for investigating the functional role of brain-body interactions in cognitive processes including self-consciousness. In 2 experiments, using intracranial electroencephalography (EEG), we investigated (1) the neural sources of HEPs, (2) the underlying mechanisms for HEP generation, and (3) the functional role of HEPs in bodily self-consciousness. In Experiment-1, we found that shortly after the heartbeat onset, phase distributions across single trials were significantly concentrated in 10% of the recording sites, mainly in the insula and the operculum, but also in other regions including the amygdala and fronto-temporal cortex. Such phase concentration was not accompanied by increased spectral power, and did not correlate with spectral power changes, suggesting that a phase resetting, rather than an additive "evoked potential" mechanism, underlies HEP generation. In Experiment-2, we further aimed to anatomically refine previous scalp EEG data that linked HEPs with bodily self-consciousness. We found that HEP modulations in the insula reflected an experimentally induced altered sense of self-identification. Collectively, these results provide novel and solid electrophysiological evidence on the neural sources and underlying mechanisms of HEPs, and their functional role in self-consciousness.


Depressive symptoms and health problems among Chinese immigrant elders in the US and Chinese elders in China.
Researchers speculate that depression tends to be more prevalent among immigrant elders due to their lack of resources, acculturation stress, language problems, and social isolation. However, other characteristics of elderly immigrants, such as the healthy immigrant effect, may counteract these potential risk factors. This study examined whether depressive symptoms differed between Chinese immigrant elders and their counterparts in China and whether health conditions were similarly associated with depressive symptoms in these two samples. Depression and health information was collected from 177 Chinese immigrant elders in Boston, the US in 2000 and from 428 education and gender-matched elders in Shanghai, China in 2003. Chinese immigrants had a significantly lower score on the modified Center for Epidemiologic Studies Depression Scale (CES-D) and its subscales: somatic symptoms and depressive affect. The association remained for the subscale depressive affect in multivariate analyses. Arthritis and back or neck problems were associated with a higher level of depressive symptoms among Chinese immigrants, while problems in walking were associated with depression among their counterparts in China. Pain was an underlying contributor to the association between depression and these health problems in both the groups. This study suggests that Chinese immigrant elders might be more resilient than their counterparts despite many challenges they face after moving abroad. With the growing number of older Chinese immigrants in the US, a better understanding of depressive symptoms is essential to provide culturally competent services to better serve this population.


Users Polarization on Facebook and Youtube.
Users online tend to select information that support and adhere their beliefs, and to form polarized groups sharing the same view-e.g. echo chambers. Algorithms for content promotion may favour this phenomenon, by accounting for users preferences and thus limiting the exposure to unsolicited contents. To shade light on this question, we perform a comparative study on how same contents (videos) are consumed on different online social media-i.e. Facebook and YouTube-over a sample of 12M of users. Our findings show that content drives the emergence of echo chambers on both platforms. Moreover, we show that the users' commenting patterns are accurate predictors for the formation of echo-chambers.


Cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate in the cerebrospinal fluid of man: relation to blood levels and the effects of age.
The relation between blood and cerebrospinal fluid (CSF) concentrations of cortisol, dehydroepiandrosterone (DHEA), and its sulfate (DHEAS) was measured in 62 subjects aged 3-85 yr old, fitted with ventriculo-peritoneal or lumbar-peritoneal shunts for a variety of diagnoses. There were 36 males and 36 females. Forty-eight subjects were not taking exogenous corticosteroids; the other 14 were receiving either systemic or local steroids. A single sample of blood and CSF was taken from each subject within 10 min for measurement of cortisol, DHEA, and DHEAS. The proportional levels of cortisol (5.8%) and DHEA (5.4%) in the CSF compared with those in the blood were similar in subjects not taking steroids. However, CSF DHEAS levels were only 0.15% of those in the blood. Because DHEAS blood levels were so much greater than DHEA, DHEAS in the CSF was still higher than DHEA despite the reduced penetration of the sulfated steroid. The blood/CSF ratios were similar in subjects taking steroids. There were significant correlations in steroid-free subjects between blood and CSF levels for DHEA (r = 0.65) and DHEAS (r = 0.88) but not for cortisol (r = 0.26). Steroid treatment significantly lowered blood cortisol, DHEA and DHEAS, and CSF DHEA, but not CSF cortisol or DHEAS compared with an age- and sex-matched sample of steroid-free subjects. In steroid-free adults (18 yr and over; n = 37), blood cortisol showed no age-related change. However, CSF cortisol was markedly raised in a proportion of steroid-free subjects over the age of 60 yr. Levels of corticoid-binding globulin in plasma did not alter with age. As expected, there were significant age-related decrements in both blood DHEA and DHEAS. CSF DHEA (r = 0.42) and CSF DHEAS (r = 0.39) were significantly negatively correlated with age. In steroid-free juveniles (n = 11) there were no age-related changes in either blood or CSF cortisol, but significant increases with age in DHEA and DHEAS in both blood and CSF. Calculation of the cortisol/DHEA and cortisol/ DHEAS molar ratios in the CSF showed both to be raised in the very young (3-8 yr) and the elderly (60 yr and over) by a factor of 4-5 compared with young adults aged 18-39. There were no sex differences in any of the parameters measured. These findings show that the relation between levels in the blood and CSF differ for each of these three neuroactive steroids. The brain is exposed to relatively high levels of DHEA and DHEAS during later childhood and early adulthood but to relatively or absolutely high levels of cortisol during infancy and older age. In view of the known antiglucocorticoid action of DHEA and DHEAS, and the direct action of these steroids on membrane-bound transmitter events (such as gamma-aminobutyric acidA receptors), these changes may have important implications for age-related alterations in brain function.


Behavioural sensitivity to binaural spatial cues in ferrets: evidence for plasticity in the duplex theory of sound localization.
For over a century, the duplex theory has guided our understanding of human sound localization in the horizontal plane. According to this theory, the auditory system uses interaural time differences (ITDs) and interaural level differences (ILDs) to localize low-frequency and high-frequency sounds, respectively. Whilst this theory successfully accounts for the localization of tones by humans, some species show very different behaviour. Ferrets are widely used for studying both clinical and fundamental aspects of spatial hearing, but it is not known whether the duplex theory applies to this species or, if so, to what extent the frequency range over which each binaural cue is used depends on acoustical or neurophysiological factors. To address these issues, we trained ferrets to lateralize tones presented over earphones and found that the frequency dependence of ITD and ILD sensitivity broadly paralleled that observed in humans. Compared with humans, however, the transition between ITD and ILD sensitivity was shifted toward higher frequencies. We found that the frequency dependence of ITD sensitivity in ferrets can partially be accounted for by acoustical factors, although neurophysiological mechanisms are also likely to be involved. Moreover, we show that binaural cue sensitivity can be shaped by experience, as training ferrets on a 1-kHz ILD task resulted in significant improvements in thresholds that were specific to the trained cue and frequency. Our results provide new insights into the factors limiting the use of different sound localization cues and highlight the importance of sensory experience in shaping the underlying neural mechanisms.


Sensory modulation disorders in childhood epilepsy.
Altered sensory sensitivity is generally linked to seizure-susceptibility in childhood epilepsy but may also be associated to the highly prevalent problems in behavioral adaptation. This association is further suggested by the frequent overlap of childhood epilepsy with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), conditions in which altered behavioral responses to sensory stimuli have been firmly established. A continuum of sensory processing defects due to imbalanced neuronal inhibition and excitation across these disorders has been hypothesizedthat may lead to common symptoms of inadequate modulation of behavioral responses to sensory stimuli. Here, we investigated the prevalence of sensory modulation disorders among children with epilepsy and their relation with symptomatology of neurodevelopmental disorders. We used the Sensory Profile questionnaire to assess behavioral responses to sensory stimuli and categorize sensory modulation disorders in children with active epilepsy (aged 4-17 years). We related these outcomes to epilepsy characteristics and tested their association with comorbid symptoms of ASD (Social Responsiveness Scale) and ADHD (Strengths and Difficulties Questionnaire). Sensory modulation disorders were reported in 49 % of the 158 children. Children with epilepsy reported increased behavioral responses associated with sensory "sensitivity," "sensory avoidance," and "poor registration" but not "sensory seeking." Comorbidity of ASD and ADHD was associated with more severe sensory modulation problems, although 27 % of typically developing children with epilepsy also reported a sensory modulation disorder. Sensory modulation disorders are an under-recognized problem in children with epilepsy. The extent of the modulation difficulties indicates a substantial burden on daily functioning and may explain an important part of the behavioral distress associated with childhood epilepsy.


Early hatching enhances survival despite beneficial phenotypic effects of late-season developmental environments.
Seasonal shifts in environmental conditions provide predictable cues to which organisms can respond in adaptive ways. For example, seasonal changes in temperature can induce phenotypes at different times of the year that have season-specific fitness benefits. Here, we tested the hypothesis that embryo responses to seasonal changes in thermal environments are adaptively matched to the timing of reproduction (environmental-matching hypothesis). We collected eggs of the brown anole lizard (Anolis sagrei) from early and late seasons, and exposed them to early and late thermal regimes that mimic nest temperatures. After measuring offspring morphology and performance, we quantified their survival in the field. Females had higher fecundity, but produced smaller eggs, early in the season compared with late in the season. Late-season eggs exposed to late thermal regimes had relatively high survival, but early-season eggs exposed to early thermal regimes had similar survival rates to those exposed to mismatched conditions. Late-season nest temperatures and late-season eggs produced offspring that were relatively large and fast runners. However, despite phenotypic benefits of late-season conditions, early-season hatchlings had greater survival in the field. Our results do not fully support the environmental-matching hypothesis but suggest that selection favours seasonal shifts in reproductive investment of mothers (high early-season fecundity) over plastic responses of embryos to seasonal environmental changes.


Fertility Preservation for a Teenager with Differences (Disorders) of Sex Development: An Ethics Case Study.
Fertility preservation has become more common for various populations, including oncology patients, transgender individuals, and women who are concerned about age-related infertility. Little attention has been paid to fertility preservation for patients with differences/disorders of sex development (DSD). Our goal in this article is to address specific ethical considerations that are unique to this patient population. To this end, we present a hypothetical DSD case. We then explore ethical considerations related to patient's age, risk of cancer, concern about genetic transmission of a DSD condition to children, co-occurring gender dysphoria, and access to experimental fertility preservation procedures. Given the limitations of current technologies, we recommend offering fertility preservation to individuals living with DSD using an informed decision-making approach that instills realistic expectations and minimizes the potential for false hope. Finally, we conclude with practical recommendations for this case based on the ethical considerations.


Diabetic foot disorders. A clinical practice guideline (2006 revision).
The prevalence of diabetes mellitus is growing at epidemic proportions in the United States and worldwide. Most alarming is the steady increase in type 2 diabetes, especially among young and obese people. An estimated 7% of the US population has diabetes, and because of the increased longevity of this population, diabetes-associated complications are expected to rise in prevalence. Foot ulcerations, infections, Charcot neuroarthropathy, and peripheral arterial disease frequently result in gangrene and lower limb amputation. Consequently, foot disorders are leading causes of hospitalization for persons with diabetes and account for billion-dollar expenditures annually in the US. Although not all foot complications can be prevented, dramatic reductions in frequency have been achieved by taking a multidisciplinary approach to patient management. Using this concept, the authors present a clinical practice guideline for diabetic foot disorders based on currently available evidence, committee consensus, and current clinical practice. The pathophysiology and treatment of diabetic foot ulcers, infections, and the diabetic Charcot foot are reviewed. While these guidelines cannot and should not dictate the care of all affected patients, they provide evidence-based guidance for general patterns of practice. If these concepts are embraced and incorporated into patient management protocols, a major reduction in diabetic limb amputations is certainly an attainable goal.


Phosphodiesterase 2A as a therapeutic target to restore cardiac neurotransmission during sympathetic hyperactivity.
Elevated levels of brain natriuretic peptide (BNP) are regarded as an early compensatory response to cardiac myocyte hypertrophy, although exogenously administered BNP shows poor clinical efficacy in heart failure and hypertension. We tested whether phosphodiesterase 2A (PDE2A), which regulates the action of BNP-activated cyclic guanosine monophosphate (cGMP), was directly involved in modulating Ca2+ handling from stellate ganglia (SG) neurons and cardiac norepinephrine (NE) release in rats and humans with an enhanced sympathetic phenotype. SG were also isolated from patients with sympathetic hyperactivity and healthy donor patients. PDE2A activity of the SG was greater in both spontaneously hypertensive rats (SHRs) and patients compared with their respective controls, whereas PDE2A mRNA was only high in SHR SG. BNP significantly reduced the magnitude of the calcium transients and ICaN in normal Wistar Kyoto (WKY) SG neurons, but not in the SHRs. cGMP levels stimulated by BNP were also attenuated in SHR SG neurons. Overexpression of PDE2A in WKY neurons recapitulated the calcium phenotype seen in SHR neurons. Functionally, BNP significantly reduced [3H]-NE release in the WKY rats, but not in the SHRs. Blockade of overexpressed PDE2A with Bay 60-7550 or overexpression of catalytically inactive PDE2A reestablished the modulatory action of BNP in SHR SG neurons. This suggests that PDE2A may be a key target in modulating the action of BNP to reduce sympathetic hyperactivity.


Trade-Offs Between Harms and Benefits of Different Breast Cancer Screening Intervals Among Low-Risk Women.
A paucity of research addresses breast cancer screening strategies for women at lower-than-average breast cancer risk. The aim of this study was to examine screening harms and benefits among women aged 50-74 years at lower-than-average breast cancer risk by breast density. Three well-established, validated Cancer Intervention and Surveillance Network models were used to estimate the lifetime benefits and harms of different screening scenarios, varying by screening interval (biennial, triennial). Breast cancer deaths averted, life-years and quality-adjusted life-years gained, false-positives, benign biopsies, and overdiagnosis were assessed by relative risk (RR) level (0.6, 0.7, 0.85, 1 [average risk]) and breast density category, for US women born in 1970. Screening benefits decreased proportionally with decreasing risk and with lower breast density. False-positives, unnecessary biopsies, and the percentage overdiagnosis also varied substantially by breast density category; false-positives and unnecessary biopsies were highest in the heterogeneously dense category. For women with fatty or scattered fibroglandular breast density and a relative risk of no more than 0.85, the additional deaths averted and life-years gained were small with biennial vs triennial screening. For these groups, undergoing 4 additional screens (screening biennially [13 screens] vs triennially [9 screens]) averted no more than 1 additional breast cancer death and gained no more than 16 life-years and no more than 10 quality-adjusted life-years per 1000 women but resulted in up to 232 more false-positives per 1000 women. Triennial screening from age 50 to 74 years may be a reasonable screening strategy for women with lower-than-average breast cancer risk and fatty or scattered fibroglandular breast density.


Noise-processing by signaling networks.
Signaling networks mediate environmental information to the cell nucleus. To perform this task effectively they must be able to integrate multiple stimuli and distinguish persistent signals from transient environmental fluctuations. However, the ways in which signaling networks process environmental noise are not well understood. Here we outline a mathematical framework that relates a network's structure to its capacity to process noise, and use this framework to dissect the noise-processing ability of signaling networks. We find that complex networks that are dense in directed paths are poor noise processors, while those that are sparse and strongly directional process noise well. These results suggest that while cross-talk between signaling pathways may increase the ability of signaling networks to integrate multiple stimuli, too much cross-talk may compromise the ability of the network to distinguish signal from noise. To illustrate these general results we consider the structure of the signalling network that maintains pluripotency in mouse embryonic stem cells, and find an incoherent feedforward loop structure involving Stat3, Tfcp2l1, Esrrb, Klf2 and Klf4 is particularly important for noise-processing. Taken together these results suggest that noise-processing is an important function of signaling networks and they may be structured in part to optimize this task.


Screening and treatment of dyslipidemias in children and adolescents.
Cardiovascular disease is the most prominent cause of mortality worldwide. A key risk factor for atherosclerotic cardiovascular disease is the presence of dyslipidemia. Clinical approaches to evaluation and treatment of dyslipidemia in children and adolescents are presented. A review of published guidelines and presentation of illustrative cases. Dyslipidemia is an important risk factor in early-stage atherosclerosis. Children and adolescents at high risk for dyslipidemia can be identified using a positive family history or the presence of other risk factors as a trigger. Once high-risk individuals are identified, primary treatment is lifestyle modification. In cases where low-density lipoprotein-cholesterol is high, pharmacologic intervention may be needed. Screening of appropriate children and adolescents for dyslipidemia and treating those at high risk are important for the long-term prevention of cardiovascular disease.


Rapid scavenging of jellyfish carcasses reveals the importance of gelatinous material to deep-sea food webs.
Jellyfish blooms are common in many oceans, and anthropogenic changes appear to have increased their magnitude in some regions. Although mass falls of jellyfish carcasses have been observed recently at the deep seafloor, the dense necrophage aggregations and rapid consumption rates typical for vertebrate carrion have not been documented. This has led to a paradigm of limited energy transfer to higher trophic levels at jelly falls relative to vertebrate organic falls. We show from baited camera deployments in the Norwegian deep sea that dense aggregations of deep-sea scavengers (more than 1000 animals at peak densities) can rapidly form at jellyfish baits and consume entire jellyfish carcasses in 2.5 h. We also show that scavenging rates on jellyfish are not significantly different from fish carrion of similar mass, and reveal that scavenging communities typical for the NE Atlantic bathyal zone, including the Atlantic hagfish, galatheid crabs, decapod shrimp and lyssianasid amphipods, consume both types of carcasses. These rapid jellyfish carrion consumption rates suggest that the contribution of gelatinous material to organic fluxes may be seriously underestimated in some regions, because jelly falls may disappear much more rapidly than previously thought. Our results also demonstrate that the energy contained in gelatinous carrion can be efficiently incorporated into large numbers of deep-sea scavengers and food webs, lessening the expected impacts (e.g. smothering of the seafloor) of enhanced jellyfish production on deep-sea ecosystems and pelagic-benthic coupling.


Effects of sodium fluoride exposure on some biochemical parameters in mice: evaluation of the ameliorative effect of royal jelly applications on these parameters.
Forty eight male Balb/c mice, each weighing 30-35 g, were used in the present study. The animals were divided into four equal groups. The first group served as the control group, and the second group was administered royal jelly at a dose of 50 mg/kg bw by gavage for a period of 7 days. The third group received 200 ppm fluoride, as sodium fluoride, for a period of 7 days, in drinking water. Lastly, the fourth group was given 200 ppm fluoride in drinking water, in association with royal jelly at a dose of 50 mg/kg bw by gavage, for a period of 7 days. At the end of the seventh day, blood samples were collected from all groups into heparinised and dry tubes, and liver samples were taken concurrently. Erythrocyte and liver tissue malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were evaluated in the blood and tissue samples obtained. Furthermore, serum cholesterol, triglyceride, glucose, total protein and albumin levels, and aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alcaline phosphatase (ALP) activities were evaluated. In conclusion, fluoride was determined to cause adverse effects in mice, and the administration of royal jelly to these animals alleviated the adverse effects of fluoride.


Relating experimentally-induced fear to pre-existing phobic fear in the human brain.
While prior work has demonstrated that fear-conditioning changes the neural representation of previously neutral stimuli, it remains unknown to what extent this new representation abstracts away from specific fears and which brain areas are involved therein. To investigate this question, we sought commonalities between experimentally-induced fear via electric shocks and pre-existing phobia. Using functional MRI, we tested the effect of fear-conditioning pictures of dogs in 21 spider-fearful participants across three phases: baseline, post-conditioning, and extinction. Considering phobic stimuli as a reference point for the state of fear allowed us to examine whether fear-conditioning renders information patterns of previously neutral stimuli more similar to those of phobic stimuli. We trained a classification algorithm to discriminate information patterns of neutral stimuli (rats) and phobic stimuli and then tested the algorithm on information patterns from the conditioned stimuli (dogs). Performing this cross-decoding analysis at each experimental phase revealed brain regions in which dogs were classified as rats during baseline, as spiders following conditioning, and again as rats after extinction. A follow-up analysis showed that changes in visual perception information cannot explain the changing classification performance. These results demonstrate a common neural representation for processing fear-eliciting information, either pre-existing or acquired by classical conditioning.


Apoe, Mbl2, and Psp plasma protein levels correlate with diabetic phenotype in NZO mice--an optimized rapid workflow for SRM-based quantification.
Male New Zealand Obese (NZO) mice progress through pathophysiological stages similar to humans developing obesity-associated type 2 diabetes (T2D). The current challenge is to establish quantitative proteomics from small plasma sample amounts. We established an analytical workflow that facilitates a reproducible depletion of high-abundance proteins, has high throughput applicability, and allows absolute quantification of proteins from mouse plasma samples by LC-SRM-MS. The ProteoMiner equalizing technology was adjusted to the small sample amount, and reproducibility of the identifications was monitored by spike proteins. Based on the label-free relative quantification of proteins in depleted plasma of a test set of NZO mice, assays for potential candidates were designed for the setup of a targeted selected reaction monitoring (SRM) approach and absolute quantification. We could demonstrate that apolipoprotein E (Apoe), mannose-binding lectin 2 (Mbl2), and parotid secretory protein (Psp) are present at significantly different quantities in depleted plasma of diabetic NZO mice compared to non-diabetic controls using AQUA peptides. Quantification was validated for Mbl2 using the ELISA technology on non-depleted plasma. We conclude that the depletion technique is applicable to restricted sample amounts and suitable for the identification of T2D signatures in plasma.


NUPR1, a new target in liver cancer: implication in controlling cell growth, migration, invasion and sorafenib resistance.
Sorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced hepatocellular carcinoma (HCC). However, its benefits are modest, and as its mechanisms of action remain elusive, a better understanding of its anticancer effects is needed. Based on our previous study results, we investigated here the implication of the nuclear protein 1 (NUPR1) in HCC and its role in sorafenib treatment. NUPR1 is a stress-inducible protein that is overexpressed in various malignancies, but its role in HCC is not yet fully understood. We found that NUPR1 expression was significantly higher in primary human HCC samples than in the normal liver. Knockdown of NUPR1 significantly increased cell sensitivity to sorafenib and inhibited the cell growth, migration and invasion of HCC cells, both in vitro and in vivo. Moreover, NUPR1 silencing influenced the expression of RELB and IER3 genes. Unsurprisingly, RELB and IER3 knockdown also inhibited HCC cell viability, growth and migration. Using gene expression profiling of HCC cells following stable NUPR1 knockdown, we found that genes functionally involved in cell death and survival, cellular response to therapies, lipid metabolism, cell growth and proliferation, molecular transport and cellular movement were mostly suppressed. Network analysis of dynamic gene expression identified NF-κB and ERK as downregulated gene nodes, and several HCC-related oncogenes were also suppressed. We identified Runt-related transcription factor 2 (RUNX2) gene as a NUPR1-regulated gene and demonstrated that RUNX2 gene silencing inhibits HCC cell viability, growth, migration and increased cell sensitivity to sorafenib. We propose that the NUPR1/RELB/IER3/RUNX2 pathway has a pivotal role in hepatocarcinogenesis. The identification of the NUPR1/RELB/IER3/RUNX2 pathway as a potential therapeutic target may contribute to the development of new treatment strategies for HCC management.


DNA polymorphism in recombining and non-recombining mating-type-specific loci of the smut fungus Microbotryum.
The population-genetic processes leading to the genetic degeneration of non-recombining regions have mainly been studied in animal and plant sex chromosomes. Here, we report population genetic analysis of the processes in the non-recombining mating-type-specific regions of the smut fungus Microbotryum violaceum. M. violaceum has A1 and A2 mating types, determined by mating-type-specific 'sex chromosomes' that contain 1-2 Mb long non-recombining regions. If genetic degeneration were occurring, then one would expect reduced DNA polymorphism in the non-recombining regions of this fungus. The analysis of DNA diversity among 19 M. violaceum strains, collected across Europe from Silene latifolia flowers, revealed that (i) DNA polymorphism is relatively low in all 20 studied loci (π∼0.15%), (ii) it is not significantly different between the two mating-type-specific chromosomes nor between the non-recombining and recombining regions, (iii) there is substantial population structure in M. violaceum populations, which resembles that of its host species, S. latifolia, and (iv) there is significant linkage disequilibrium, suggesting that widespread selfing in this species results in a reduction of the effective recombination rate across the genome. We hypothesise that selfing-related reduction of recombination across the M. violaceum genome negates the difference in the level of DNA polymorphism between the recombining and non-recombining regions, and may possibly lead to similar levels of genetic degeneration in the mating-type-specific regions of the non-recombining 'sex chromosomes' and elsewhere in the genome.


Nrf2 activation as target to implement therapeutic treatments.
A chronic increase of oxidative stress is typical of serious pathologies such as myocardial infarction, stroke, chronic limb ischemia, chronic obstructive pulmonary disease (COPD), type II-diabetes, age-related macular degeneration leads to an epic increase of morbidity and mortality in all countries of the world. The initial inflammation followed by an excessive release of reactive oxygen species (ROS) implies a diffused cellular injury that needs to be corrected by an inducible expression of the innate detoxifying and antioxidant system. The transcription factor Nrf2, when properly activated, is able to restore a redox homeostasis and possibly improve human health.


Investigating wettability alteration during MEOR process, a micro/macro scale analysis.
Wettability alteration is considered to be one of the important mechanisms that lead to increased oil recovery during microbial enhanced oil recovery (MEOR) processes. Changes in wettability will greatly influence the petrophysical properties of the reservoir rocks and determine the location, flow and distribution of different fluids inside the porous media. Understanding the active mechanisms of surface wettability changes by the bacteria would help to optimize the condition for more oil recovery. As the mechanisms behind wettability alteration are still poorly understood, the objective of this study is to investigate the wettability alteration at pore scale and find the most effective mechanism of wettability changes in different cases. The experiments were performed on different substrates at fresh condition or aged in crude oil to mimic various wetting conditions. Using an Enterobacter cloacae strain, the influence of bacterial metabolites, bacterial adhesion and bacterial solution with two different carbon sources on wettability were determined for different aging periods. Contact angle measurements were used to quantify the wettability alteration of the solid surfaces. Atomic force microscopy (AFM) experiments were also utilized to combine the macroscopic measurements of wettability with the microscopic study of the surface changes. It was found that the surface wettability could vary from neutral- or oil-wet to water-wet state. Bacterial adhesion and biofilm formation seems to be the dominant mechanism of wettability alteration. The aged glass surfaces regained their initial water wetness where the bacteria could remove the polar and asphaltene compounds from them.


Investigating the antimicrobial activity of natural honey and its effects on the pathogenic bacterial infections of surgical wounds and conjunctiva.
Antimicrobial activities of 10-100% (wt/vol) concentrations of new honey, stored honey, heated honey, ultraviolet-exposed honey, and heated stored honey were tested against common human pathogens, including Escherichia coli, Entrobacter cloacae, Pseudomonas aeruginosa, Shigella dysenteriae, Klebsiella sp., Haemophilus influenzae, Proteus sp., Staphylococcus aureus, Streptococcus hemolyticus group B, and Candida albicans. Antimicrobial activity of honey was tested in acidic, neutral, or alkaline media. These were compared with similar concentrations of glucose in nutrient broth. Surgical wounds were made on the dorsum of mice and infected with S. aureus or Klebsiella sp. The wounds were treated with local application of honey four times a day or appropriate antibiotics and compared with control values. Bacterial conjunctivitis due to E. coli, Proteus sp., S. aureus, Klebsiella sp., and P. aeruginosa was induced in rats. Conjunctival application of honey four times a day or appropriate antibiotics was used for treatment and compared with control values. Growth of all the isolates was completely inhibited by 30-100% honey concentrations. The most sensitive microbes were E. coli, P. aeruginosa, and H. influenzae. Glucose showed less antimicrobial activity than honey, and many microbes showed positive culture even in 100% glucose. Heating to 80 degrees C for 1 hour decreased antimicrobial activity of both new and stored honey. Storage of honey for 5 years decreased its antimicrobial activity, while ultraviolet light exposure increased its activity against some of the microorganisms. Antimicrobial activity of honey was stronger in acidic media than in neutral or alkaline media. Single doses of honey used to prepare the 60% concentration in nutrient broth were bacteriocidal for P. aeruginosa and bacteriostatic for S. aureus and Klebsiella sp. during certain periods. Local application of raw honey on infected wounds reduced redness, swelling, time for complete resolution of lesion, and time for eradication of bacterial infection due to S. aureus or Klebsiella sp. Its potency was comparable to that of local antibiotics. Honey application into infective conjunctivitis reduced redness, swelling, pus discharge, and time for eradication of bacterial infections due to all the isolates tested.


Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies.
Many epidemiological studies have reported on associations between serum triglyceride concentrations and the risk of coronary heart disease, but this association has not been reliably quantified. In the present study, we report 2 separate nested case-control comparisons in 2 different prospective, population-based cohorts, plus an updated meta-analysis of 27 additional prospective studies in general Western populations. Measurements were made in a total of 3582 incident cases of fatal and nonfatal coronary heart disease and 6175 controls selected from among the 44,237 men and women screened in the Reykjavik and the European Prospective Investigation of Cancer (EPIC)-Norfolk studies. Repeat measurements were obtained an average of 4 years apart in 1933 participants in the EPIC-Norfolk Study and an average of 12 years apart in 379 participants in the Reykjavik study. The long-term stability of log-triglyceride values (within-person correlation coefficients of 0.64 [95% CI, 0.60 to 0.68] over 4 years and 0.63 [95% CI, 0.57 to 0.70] over 12 years) was similar to those of blood pressure and total serum cholesterol. After adjustment for baseline values of several established risk factors, the strength of the association was substantially attenuated, and the adjusted odds ratio for coronary heart disease was 1.76 (95% CI, 1.39 to 2.21) in the Reykjavik study and 1.57 (95% CI, 1.10 to 2.24) in the EPIC-Norfolk study in a comparison of individuals in the top third with those in the bottom third of usual log-triglyceride values. Similar overall findings (adjusted odds ratio, 1.72; 95% CI, 1.56 to 1.90) were observed in an updated meta-analysis involving a total of 10,158 incident coronary heart disease cases from 262,525 participants in 29 studies. Available prospective studies in Western populations consistently indicate moderate and highly significant associations between triglyceride values and coronary heart disease risk. Because these associations depend considerably on levels of established risk factors, however, further studies are needed to help assess the nature of any independent associations.


Coughing, mucus accumulation, airway obstruction, and airway inflammation in control horses and horses affected with recurrent airway obstruction.
To investigate relationships between cough frequency and mucus accumulation, airway obstruction, and airway inflammation and to determine effects of dexamethasone on coughing and mucus score. 13 horses with recurrent airway obstruction (RAO) and 6 control horses. 6 RAO-affected and 6 control horses were stabled for 3 days. Coughing was counted for 4 hours before and on each day horses were stabled. Before and on day 3 of stabling, tracheal mucus accumulation was scored, airway obstruction was assessed via maximal change in pleural pressure (deltaPpl(max)), and airway inflammation was evaluated by use of cytologic examination of bronchoalveolar lavage fluid (BALF). Effects of dexamethasone (0.1 mg/kg, IV, q 24 h for 7 days) were determined in 12 RAO-affected horses. To assess frequency, coughing had to be counted for 1 hour. In RAO-affected horses, stabling was associated with increases in cough frequency, mucus score, and deltaPpl(max). Control horses coughed transiently when first stabled. In RAO-affected horses, coughing was correlated with deltaPpl(max), mucus score, and airway inflammation and was a sensitive and specific indicator of deltaPpl(max) > 6 cm H2O, mucus score > 1.0, and > 100 neutrophils/microL and > 20% neutrophils in BALF Dexamethasone reduced cough frequency, mucus score, and deltaPpl(max), but BALF neutrophil count remained increased. Because of its sporadic nature, coughing cannot be assessed accurately by counting during brief periods. In RAO-affected horses, coughing is an indicator of airway inflammation and obstruction. Corticosteroid treatment reduces cough frequency concurrently with reductions in deltaPpl(max) and mucus accumulation in RAO-affected horses.


Evolutionary game theory modelling to represent the behavioural dynamics of economic shutdowns and shield immunity in the COVID-19 pandemic.
The unprecedented global spread of COVID-19 has prompted dramatic public-health measures like strict stay-at-home orders and economic shutdowns. Some governments have resisted such measures in the hope that naturally acquired shield immunity could slow the spread of the virus. In the absence of empirical data about the effectiveness of these measures, policymakers must turn to epidemiological modelling to evaluate options for responding to the pandemic. This paper combines compartmental epidemiological models with the concept of behavioural dynamics from evolutionary game theory (EGT). This innovation allows us to model how compliance with an economic lockdown might wane over time, as individuals weigh the risk of infection against the certainty of the economic cost of staying at home. Governments can, however, increase spending on social programmes to mitigate the cost of a shutdown. Numerical analysis of our model suggests that emergency-relief funds spent at the individual level are effective in reducing the duration and overall economic cost of a pandemic. We also find that shield immunity takes hold in a population most easily when a lockdown is enacted with relatively low costs to the individual. Our qualitative analysis of a complex model provides evidence that the effects of shield immunity and economic shutdowns are complementary, such that governments should pursue them in tandem.


Acceleration-Based Running Intensities of Professional Rugby League Match Play.
Rugby league involves frequent periods of high-intensity running including acceleration and deceleration efforts, often occurring at low speeds. To quantify the energetic cost of running and acceleration efforts during rugby league competition to aid in prescription and monitoring of training. Global positioning system (GPS) data were collected from 37 professional rugby league players across 2 seasons. Peak values for relative distance, average acceleration/deceleration, and metabolic power (Pmet) were calculated for 10 different moving-average durations (1-10 min) for each position. A mixed-effects model was used to assess the effect of position for each duration, and individual comparisons were made using a magnitude-based-inference network. There were almost certainly large differences in relative distance and Pmet between the 10-min window and all moving averages <5 min in duration (ES = 1.21-1.88). Fullbacks, halves, and hookers covered greater relative distances than outside backs, edge forwards, and middle forwards for moving averages lasting 2-10 min. Acceleration/deceleration demands were greatest in hookers and halves compared with fullbacks, middle forwards, and outside backs. Pmet was greatest in hookers, halves, and fullbacks compared with middle forwards and outside backs. Competition running intensities varied by both position and moving-average duration. Hookers exhibited the greatest Pmet of all positions, due to high involvement in both attack and defense. Fullbacks also reached high Pmet, possibly due to a greater absolute volume of running. This study provides coaches with match data that can be used for the prescription and monitoring of specific training drills.


Prescribing patterns of glucosamine in an older population: a national cohort study.
Glucosamine is commonly prescribed as a disease modulating agent in osteoarthritis. However, the evidence to date suggests that it has a limited impact on the clinical symptoms of the disease including joint pain, radiological progression, function and quality of life. The aim of this study was to examine the prescribing patterns of glucosamine from 2002-2011 in an elderly Irish national population cohort using data from the Health Service Executive Primary Care Reimbursement (HSE-PCRS) General medical services (GMS) Scheme. Patients aged ≥ 70 years on the HSE-PCRS pharmacy claims database between January 2002 and December 2011 were included. ATC code M01AX05 (glucosamine) was extracted. Prevalence rates per 1000 eligible population with 95% confidence intervals were calculated for all years and age groups (70-74 years, ≥75 years). A negative binomial regression analysis was used to determine longitudinal usage trends and compare prevalence rates across years, sex and age groups. The annual patient rate of glucosamine prescribing increased significantly from 13.0/1000 eligible population (95% CI 12.6-13.4) in 2002 to 68.7/1000 population (95% CI 67.8-69.5) in 2009 before decreasing to 62.4/1000 population (95% CI 61.6-63.2) in 2011. The rate of prescribing of glucosamine varied with sex, with women receiving significantly more prescriptions than men. The cost of glucosamine also increased from 2002-2008. In 2008 total expenditure reached a high of €4.6 million before decreasing to €2.6 million in 2011. The national trend in prescribing of glucosamine increased significantly from 2002 to 2009 before decreasing in 2010 and 2011, in keeping with current international guidelines. There is a need for awareness among healthcare professionals and patients alike of the best available evidence to inform decision making relating to the prescription and consumption of such supplements.


Transcriptome signature of virulent and attenuated pseudorabies virus-infected rodent brain.
Mammalian alphaherpesviruses normally establish latent infections in ganglia of the peripheral nervous system in their natural hosts. Occasionally, however, these viruses spread to the central nervous system (CNS), where they cause damaging, often fatal, infections. Attenuated alphaherpesvirus derivatives have been used extensively as neuronal circuit tracers in a variety of animal models. Their circuit-specific spread provides a unique paradigm to study the local and global CNS response to infection. Thus, we systematically analyzed the host gene expression profile after acute pseudorabies virus (PRV) infection of the CNS using Affymetrix GeneChip technology. Rats were injected intraocularly with one of three selected virulent and attenuated PRV strains. Relative levels of cellular transcripts were quantified from hypothalamic and cerebellar tissues at various times postinfection. The number of cellular genes responding to infection correlated with the extent of virus dissemination and relative virulence of the PRV strains. A total of 245 out of 8,799 probe sets, corresponding to 182 unique cellular genes, displayed increased expression ranging from 2- to more than 100-fold higher than in uninfected tissue. Over 60% thereof were categorized as immune, proinflammatory, and other cellular defense genes. Additionally, a large fraction of infection-induced transcripts represented cellular stress responses, including glucocorticoid- and redox-related pathways. This is the first comprehensive in vivo analysis of the global transcriptional response of the mammalian CNS to acute alphaherpesvirus infection. The differentially regulated genes reported here are likely to include potential diagnostic and therapeutic targets for viral encephalitides and other neurodegenerative or neuroinflammatory diseases.


Novel Insights into Interleukin 6 (IL-6) Cis- and Trans-signaling Pathways by Differentially Manipulating the Assembly of the IL-6 Signaling Complex.
The IL-6 signaling complex is described as a hexamer, formed by the association of two IL-6·IL-6 receptor (IL-6R)·gp130 trimers, with gp130 being the signal transducer inducing cis- and trans-mediated signaling via a membrane-bound or soluble form of the IL-6R, respectively. 25F10 is an anti-mouse IL-6R mAb that binds to both membrane-bound IL-6R and soluble IL-6R with the unique property of specifically inhibiting trans-mediated signaling events. In this study, epitope mapping revealed that 25F10 interacts at site IIb of IL-6R but allows the binding of IL-6 to the IL-6R and the recruitment of gp130, forming a trimer complex. Binding of 25F10 to IL-6R prevented the formation of the hexameric complex obligate for trans-mediated signaling, suggesting that the cis- and trans-modes of IL-6 signaling adopt different mechanisms for receptor complex assembly. To study this phenomenon also in the human system, we developed NI-1201, a mAb that targets, in the human IL-6R sequence, the epitope recognized by 25F10 for mice. Interestingly, NI-1201, however, did not selectively inhibit human IL-6 trans-signaling, although both mAbs produced beneficial outcomes in conditions of exacerbated IL-6 as compared with a site I-directed mAb. These findings shed light on the complexity of IL-6 signaling. First, triggering cis- versus trans-mediated IL-6 signaling occurs via distinctive mechanisms for receptor complex assembly in mice. Second, the formation of the receptor complex leading to cis- and trans-signaling biology in mice and humans is different, and this should be taken into account when developing strategies to inhibit IL-6 clinically.


The feasibility and acceptability of the provision of alcohol screening and brief advice in pharmacies for women accessing emergency contraception: an evaluation study.
It is widely accepted that excessive drinking contributes to both health and social problems. There has been considerable interest in the potential of community pharmacies as a setting for health advice, and evidence suggests that interventions by pharmacists can be effective. Research on interventions relating to alcohol consumption in primary care has focused on general practice, and although some evidence exists about the efficacy of pharmacy interventions, little research to date has taken place in the UK. The aim of this study was to evaluate the acceptability of alcohol screening and brief interventions to women accessing emergency hormonal contraception (EHC) in community pharmacies. An initiative whereby women who accessed community pharmacies for EHC would be asked to complete an AUDIT questionnaire following their EHC consultation was introduced by a Primary Care Trust (PCT) in the North-East of England. The evaluation incorporated three strands: interviewing pharmacists (n = 14) about the implementation and acceptability of the initiative; interviewing clients (n = 22) identified as "low risk" to understand their perceptions of the initiative; conducting online follow-up surveys with clients in the "risky" group (n = 53) to evaluate the impact of the initiative on their alcohol consumption and contraceptive behaviour, as well as their perceptions of the service. Pharmacists' attitudes towards screening were generally positive, although there were organisational obstacles to providing the service. Some felt uncertain about engaging clients in conversation about a sensitive topic. However, clients themselves did not report feeling embarrassed or upset, and most were happy to talk to the pharmacist and be given advice. Most clients felt that the pharmacist was an appropriate person to carry out alcohol screening and advice. It is feasible for pharmacists to carry out screening and brief advice, and most customers find it acceptable. However, pharmacist take-up of the service and participation in the study was low. Pharmacists were enthusiastic about providing screening and other health promotion services; targeting different population groups for alcohol screening may be more successful. Delivery of the AUDIT tool by pharmacists may not obtain reliable responses from some specific client groups.


Accuracy of impressions of multiple implants in the edentulous arch: a systematic review.
Because there is a paucity of clear-cut evidence regarding which materials and techniques are most accurate for complete-arch, multiple-implant impressions, the current study sought to analyze the data and draw useful conclusions based on the evidence for application in clinical practice. Relevant studies published between 1990 and December 2012 were included in the review. The articles were located through PubMed and manually through reviewing references in the literature. Papers examining implant impression accuracy in completely edentulous arches (three or more implants) were included. Clinical case reports, technique articles, abstracts, and review papers were excluded. One of the 34 studies selected for evaluation was clinical; the remaining 33 were in vitro investigations. Ten studies compared polyvinyl siloxane (PVS) and polyether (PE); eight found that these were statistically equal in terms of impression accuracy. The splint effect was examined by 24 studies; 10 failed to observe any differences between splinted and nonsplinted impressions, whereas 7 (> 25%) showed that the splinted technique was better than the nonsplinted technique. Thirteen studies investigated the differences between pickup and transfer impression techniques; six favored pickup over transfer, and five found insignificant differences between the techniques. The effect of nonparallel implants on edentulous multiple-implant impression accuracy was examined by only two studies. Significant differences in accuracy were observed for 15 degrees of angulation. Most of the evidence supports PVS and PE as the most accurate impression materials for edentulous multiple-implant situations, with no clear advantage of either. Conflicting evidence exists regarding the most accurate impression technique (splinted/nonsplinted, pickup/transfer), and no clear recommendation can be made. Inadequate research exists regarding several other factors that might affect edentulous implant impression accuracy. There is a lack of clinical research to support in vitro findings.


Human demography and reserve size predict wildlife extinction in West Africa.
Species-area models have become the primary tool used to predict baseline extinction rates for species in isolated habitats, and have influenced conservation and land-use planning worldwide. In particular, these models have been used to predict extinction rates following the loss or fragmentation of natural habitats in the absence of direct human influence on species persistence. Thus, where direct human influences, such as hunting, put added pressure on species in remnant habitat patches, we should expect to observe extinction rates higher than those predicted by simple species-area models. Here, we show that extinction rates for 41 species of large mammals in six nature reserves in West Africa are 14-307 times higher than those predicted by models based on reserve size alone. Human population and reserve size accounted for 98% of the observed variation in extinction rates between reserves. Extinction occurred at higher rates than predicted by species-area models for carnivores, primates and ungulates, and at the highest rates overall near reserve borders. Our results indicate that, where the harvest of wildlife is common, conservation plans should focus on increasing the size of reserves and reducing the rate of hunting.


Phase shift estimation from variances of fringe pattern differences.
This paper presents a simple algorithm for estimating phase shifts from only three interferograms. In it, the fringe pattern differences are computed first in order to remove the background component, and then the variances and further the standard deviations (SDs) of fringe pattern differences are calculated. The phase shifts are estimated, by using the law of cosines, from a triangle whose lengths of sides are the SDs just calculated. This algorithm offers several advantages over others, e.g., being efficient, easy to implement, accurate, and less sensitive to noise. Numerical simulations and an experiment are performed to demonstrate its validity.


Assessment of an international breaststroke swimmer using a race readiness test.
Competitive swimmers routinely undertake a 7 x 200-m incremental step test to evaluate their fitness and readiness to compete.An exercise protocol more closely replicating competition swimming speeds may provide further insight into the swimmer's physiological and technical readiness for competition. This case study reports data over a 3-year period from 11 Race Readiness Tests, which were completed, in addition to the 7 x 200-m test, as an attempt to provide the swimmer and coach with a fuller assessment. For this individual, data provided objective information from which to assess training status and race readiness following a transition from 200-m to 100-m race training. Data also raised a question as to whether a 100-m maximal effort 10 minutes before another one actually enhances performance owing to a priming effect.