Variation, race, and multiracial identity in linguistic research.
What is the relationship between ethnolinguistic communities and ways of speaking? Who is an authentic speaker of an ethnolinguistic variety? In a time where scholarly and public conceptualizations of race and ethnicity are variable and rapidly changing, potential effects on both self-identification and ways of speaking present an area ripe for study. However, linguistics and allied fields have often overlooked individuals and communities that do not neatly conform to well-defined racial categories. As multiracially identified individuals are one of the fastest growing demographic groups in the United States, researchers will necessarily need to address the way that traditional methodologies have excluded individuals and groups who fall outside of these racial and ethnic categories. This presents a unique challenge for sociolinguistics in particular, since we are interested in how people draw on linguistic variation to perform aspects of their identities, including their races and ethnicities. This study examines the ways in which race and ethnicity have been traditionally conceptualized in linguistics and allied fields, and draws on research from other social sciences to see how they have begun to study individuals who fall outside of traditionally pre-existing social categories. The study also briefly discusses the results of one of the first major sociolinguistic studies on multiracially identified participants, which found substantial effects of self-conceptualization and self-identification on linguistic behavior of these participants. Finally, it will address future questions and directions for research at the intersection of personal identity, race, and language. This article is categorized under: Linguistics > Evolution of Language Linguistics > Linguistic Theory Linguistics > Computational Models of Language Linguistics > Language Acquisition.


A functional role for transposases in a large eukaryotic genome.
Despite comprising much of the eukaryotic genome, few transposons are active, and they usually confer no benefit to the host. Through an exaggerated process of genome rearrangement, Oxytricha trifallax destroys 95% of its germline genome during development. This includes the elimination of all transposon DNA. We show that germline-limited transposase genes play key roles in this process of genome-wide DNA excision, which suggests that transposases function in large eukaryotic genomes containing thousands of active transposons. We show that transposase gene expression occurs during germline-soma differentiation and that silencing of transposase by RNA interference leads to abnormal DNA rearrangement in the offspring. This study suggests a new important role in Oxytricha for this large portion of genomic DNA that was previously thought of as junk.


Determining c-Myb protein levels can isolate functional hematopoietic stem cell subtypes.
The transcription factor c-Myb was originally identified as a transforming oncoprotein encoded by two avian leukemia viruses. Subsequently, through the generation of mouse models that affect its expression, c-Myb has been shown to be a key regulator of hematopoiesis, including having critical roles in hematopoietic stem cells (HSCs). The precise function of c-Myb in HSCs although remains unclear. We have generated a novel c-myb allele in mice that allows direct observation of c-Myb protein levels in single cells. Using this reporter line we demonstrate that subtypes of HSCs can be isolated based upon their respective c-Myb protein expression levels. HSCs expressing low levels of c-Myb protein (c-Myb(low) HSC) appear to represent the most immature, dormant HSCs and they are a predominant component of HSCs that retain bromodeoxyuridine labeling. Hematopoietic stress, induced by 5-fluorouracil ablation, revealed that in this circumstance c-Myb-expressing cells become critical for multilineage repopulation. The discrimination of HSC subpopulations based on c-Myb protein levels is not reflected in the levels of c-myb mRNA, there being no more than a 1.3-fold difference comparing c-Myb(low) and c-Myb(high) HSCs. This illustrates how essential it is to include protein studies when aiming to understand the regulatory networks that control stem cell behavior.


Dynamic changes in diffusion measures improve sensitivity in identifying patients with mild traumatic brain injury.
The goal of this study was to investigate patterns of axonal injury in the first week after mild traumatic brain injury (mTBI). We performed a prospective cohort study of 20 patients presenting to the emergency department with mTBI, using 3.0T diffusion tensor MRI immediately after injury and again at 1 week post-injury. Corresponding data were acquired from 16 controls over a similar time interval. Fractional anisotropy (FA) and other diffusion measures were calculated from 11 a priori selected axon tracts at each time-point, and the change across time in each region was quantified for each subject. Clinical outcomes were determined by standardized neurocognitive assessment. We found that mTBI subjects were significantly more likely to have changes in FA in those 11 regions of interest across the one week time period, compared to control subjects whose FA measurements were stable across time. Longitudinal imaging was more sensitive to these subtle changes in white matter integrity than cross-sectional assessments at either of two time points, alone. Analyzing the sources of variance in our control population, we show that this increased sensitivity is likely due to the smaller within-subject variability obtained by longitudinal analysis with each subject as their own control. This is in contrast to the larger between-subject variability obtained by cross-sectional analysis of each individual subject to normalized data from a control group. We also demonstrated that inclusion of all a priori ROIs in an analytic model as opposed to measuring individual ROIs improves detection of white matter changes by overcoming issues of injury heterogeneity. Finally, we employed genetic programming (a bio-inspired computational method for model estimation) to demonstrate that longitudinal changes in FA have utility in predicting the symptomatology of patients with mTBI. We conclude concussive brain injury caused acute, measurable changes in the FA of white matter tracts consistent with evolving axonal injury and/or edema, which may contribute to post-concussive symptoms.


The Relationship of Self-efficacy and Explicit and Implicit Associations on the Intention-Behavior Gap.
Recent physical activity research is limited by intention-behavior discordance and is beginning to recognize the importance of automatic processes in exercise. The purpose of the current study was to examine the role of multidimensional exercise self-efficacy (SE), explicit-implicit evaluative discrepancies (EIEDs) for health, and appearance on the intention-behavior gap in exercise. A total of 141 middle-aged inactive participants (mean age = 46.12 [8.17] y) completed measures of intentions, SE, and explicit and implicit evaluations of exercise outcomes. The participants were classified as inclined actors (n = 107) if they successfully started the exercise program and inclined abstainers (n = 35) if they were not successful. The inclined actors and abstainers did not differ on intentions to exercise; however, the inclined actors had higher coping SE and lower EIEDs for health. In addition, the coping SE (Exp [β] = 1.03) and EIEDs for health (Exp [β] = -0.405) were significant predictors of being an inclined actor. The interaction between explicit and implicit processes in regard to health motives for exercise appears to influence the successful enactment of exercise from positive intentions. As most physical activity promotion strategies focus on health as a reason to be active, the role of implicit and explicit evaluations on behavioral decisions to exercise may inform future interventions.


Machine learning for real-time prediction of complications in critical care: a retrospective study.
The large amount of clinical signals in intensive care units can easily overwhelm health-care personnel and can lead to treatment delays, suboptimal care, or clinical errors. The aim of this study was to apply deep machine learning methods to predict severe complications during critical care in real time after cardiothoracic surgery. We used deep learning methods (recurrent neural networks) to predict several severe complications (mortality, renal failure with a need for renal replacement therapy, and postoperative bleeding leading to operative revision) in post cardiosurgical care in real time. Adult patients who underwent major open heart surgery from Jan 1, 2000, to Dec 31, 2016, in a German tertiary care centre for cardiovascular diseases formed the main derivation dataset. We measured the accuracy and timeliness of the deep learning model's forecasts and compared predictive quality to that of established standard-of-care clinical reference tools (clinical rule for postoperative bleeding, Simplified Acute Physiology Score II for mortality, and the Kidney Disease: Improving Global Outcomes staging criteria for acute renal failure) using positive predictive value (PPV), negative predictive value, sensitivity, specificity, area under the curve (AUC), and the F1 measure (which computes a harmonic mean of sensitivity and PPV). Results were externally retrospectively validated with 5898 cases from the published MIMIC-III dataset. Of 47 559 intensive care admissions (corresponding to 42 007 patients), we included 11 492 (corresponding to 9269 patients). The deep learning models yielded accurate predictions with the following PPV and sensitivity scores: PPV 0·90 and sensitivity 0·85 for mortality, 0·87 and 0·94 for renal failure, and 0·84 and 0·74 for bleeding. The predictions significantly outperformed the standard clinical reference tools, improving the absolute complication prediction AUC by 0·29 (95% CI 0·23-0·35) for bleeding, by 0·24 (0·19-0·29) for mortality, and by 0·24 (0·13-0·35) for renal failure (p<0·0001 for all three analyses). The deep learning methods showed accurate predictions immediately after patient admission to the intensive care unit. We also observed an increase in performance in our validation cohort when the machine learning approach was tested against clinical reference tools, with absolute improvements in AUC of 0·09 (95% CI 0·03-0·15; p=0·0026) for bleeding, of 0·18 (0·07-0·29; p=0·0013) for mortality, and of 0·25 (0·18-0·32; p<0·0001) for renal failure. The observed improvements in prediction for all three investigated clinical outcomes have the potential to improve critical care. These findings are noteworthy in that they use routinely collected clinical data exclusively, without the need for any manual processing. The deep machine learning method showed AUC scores that significantly surpass those of clinical reference tools, especially soon after admission. Taken together, these properties are encouraging for prospective deployment in critical care settings to direct the staff's attention towards patients who are most at risk. No specific funding.


Determination of Human Hepatic CYP2C8 and CYP1A2 Age-Dependent Expression to Support Human Health Risk Assessment for Early Ages.
Predicting age-specific metabolism is important for evaluating age-related drug and chemical sensitivity. Multiple cytochrome P450s and carboxylesterase enzymes are responsible for human pyrethroid metabolism. Complete ontogeny data for each enzyme are needed to support in vitro to in vivo extrapolation (IVIVE). This study was designed to determine age-dependent human hepatic CYP2C8 expression, for which only limited ontogeny data are available, and to further define CYP1A2 ontogeny. CYP2C8 and 1A2 protein levels were measured by quantitative Western blotting using liver microsomal samples prepared from 222 subjects with ages ranging from 8 weeks gestation to 18 years after birth. The median CYP2C8 expression was significantly greater among samples from subjects older than 35 postnatal days (n = 122) compared with fetal samples and those from very young infants (fetal to 35 days postnatal, n = 100) (0.00 vs. 13.38 pmol/mg microsomal protein; p < 0.0001). In contrast, the median CYP1A2 expression was significantly greater after 15 months postnatal age (n = 55) than in fetal and younger postnatal samples (fetal to 15 months postnatal, n = 167) (0.0167 vs. 2.354 pmol/mg microsomal protein; p < 0.0001). CYP2C8, but not CYP1A2, protein levels significantly correlated with those of CYP2C9, CYP2C19, and CYP3A4 (p < 0.001), consistent with CYP2C8 and CYP1A2 ontogeny probably being controlled by different mechanisms. This study provides key data for the physiologically based pharmacokinetic model-based prediction of age-dependent pyrethroid metabolism, which will be used for IVIVE to support pyrethroid risk assessment for early life stages.


Predicting fruit consumption: the role of habits, previous behavior and mediation effects.
This study assessed the role of habits and previous behavior in predicting fruit consumption as well as their additional predictive contribution besides socio-demographic and motivational factors. In the literature, habits are proposed as a stable construct that needs to be controlled for in longitudinal analyses that predict behavior. The aim of this study is to provide empirical evidence for the inclusion of either previous behavior or habits. A random sample of 806 Dutch adults (>18 years) was invited by an online survey panel of a private research company to participate in an online study on fruit consumption. A longitudinal design (N = 574) was used with assessments at baseline and after one (T2) and two months (T3). Multivariate linear regression analysis was used to assess the differential value of habit and previous behavior in the prediction of fruit consumption. Eighty percent of habit strength could be explained by habit strength one month earlier, and 64% of fruit consumption could be explained by fruit consumption one month earlier. Regression analyses revealed that the model with motivational constructs explained 41% of the behavioral variance at T2 and 38% at T3. The addition of previous behavior and habit increased the explained variance up to 66% at T2 and to 59% at T3. Inclusion of these factors resulted in non-significant contributions of the motivational constructs. Furthermore, our findings showed that the effect of habit strength on future behavior was to a large extent mediated by previous behavior. Both habit and previous behavior are important as predictors of future behavior, and as educational objectives for behavior change programs. Our results revealed less stability for the constructs over time than expected. Habit strength was to a large extent mediated by previous behavior and our results do not strongly suggest a need for the inclusion of both constructs. Future research needs to assess the conditions that determine direct influences of both previous behavior and habit, since these influences may differ per type of health behavior, per context stability in which the behavior is performed, and per time frame used for predicting future behavior.


Evaluation of the effectiveness and safety of peppermint peel (PMP) soft peeling for skin ageing.
Turning to peeling in a dermatological sphere is extensively common and has been used for a long time. From the use of single acids moving on to the so-called compound peelings (associations of more than one substance in the same product) and the combined peelings which take advantage of the action of different substances in a synergistic manner (different products are applied sequentially) in order to best guarantee a greater effectiveness of the treatment for the recommended target. Superficial peelings, combined and not, have led to a drastic reduction in the percentage of incidence of adverse events typical of medium and deep peels. Nevertheless, it has been demonstrated that superficial peels bring about a rejuvenating effect through the mechanical stimulation of the Skin Stress Response System (SSRS), system designated to repairing the damaged tissue and restoring of the normal homeostasis. Clinical trials aims to evaluate the effectiveness and safety of the peppermint peel (PMP) medical device in subjects with different ageing expressions both in qualitative terms (different blemishes such as discolouration, fine wrinkles, elastosis, atony and skin inelasticity, laxity, scarce superficial hydration) and in quantitative terms (degree, extension and number of lesions). A non-controlled multi-centric clinical trial was done in 121 subjects. The use protocol calls for a session every 2 weeks for a total of 4 sessions. Subjects were evaluated before each subsequent session at the first and at 2-4-8 weeks of the fourth and last treatment. During the study there were no adverse events. Only a minimal scurfy flaking and a very slight redness were reported. From an effectiveness point of view, the percentage of therapeutic failure, judged with a score equal to or greater than 4 or 5 in Global Aesthetic Improvement Scale (GAIS) scale was 0%. Best score was obtained in subjects ranging in ages between 38 and 57 (2.02) and in women (2.02) years, while the less satisfactory one was obtained in males (2.14). The study has demonstrated that PMP and the proposed protocol are effective and safe to treat subject with skin signs of chrono and photo ageing, thanks to its capabilities of carrying out a mechanic action indicated as a coadjuvant in the treatment of the dermoepidermic revitalisation through chemical exfoliation and hydration.


Virulence, serotype, and molecular characteristics of environmental strains of Cryptococcus neoformans var. gattii.
Four strains of Cryptococcus neoformans var. gattii originating from Eucalyptus camaldulensis, three from Australia and one from San Francisco, were tested for their serotype, virulence for mice, and a number of genetic and molecular characteristics. All were found to be serotype B and showed significantly higher virulence for mice than did the type strains of C. neoformans var. gattii and Filobasidiella neoformans var. bacillispora, which were obtained from human cryptococcosis cases. Electrophoretic karyotypes of the strains from Australia were identical, although they were collected from sites at least 15 to 500 km apart. The electrophoretic karyotype of the strain from San Francisco was the same as that of the Australian isolates except for the mobility of one chromosome. On the contrary, no two isolates of serotype B (of a total of 11) from clinical sources were the same, regardless of their geographic origin. Furthermore, none of the clinical isolates showed a chromosomal banding pattern identical to that of Eucalyptus-originated strains. The Eucalyptus-originated strains failed to form dikaryons when crossed with the tester strains of the two varieties of F. neoformans. Hybridization analysis with a nucleic acid probe (AccuProbe C. neoformans Culture Confirmation Test; Gen-Probe Inc., San Diego, Calif.), however, showed signals of equal intensity for clinical strains and the Eucalyptus-originated strains. Various fungi phylogenetically related to C. neoformans, including a phenol oxidase-positive strain of Cryptococcus laurentii obtained from E. camaldulensis, were negative in the nucleic acid hybridization test. These observations confirm that, in spite of karyotypic differences and the lack of dikaryon formation with the tester strains of F. neoformans, Eucalyptus-originated C. neoformans var. gattii is the same organism as those isolated from cases of human infection. Furthermore, the C. neoformans culture confirmation test using a commercial nucleic acid probe is specific for C. neoformans.


Assessment of neuromuscular response characteristics at the knee following a functional perturbation.
Previous research indicates that both the extent and timing of muscular activation at the knee can be influenced by muscle activity state, joint angle, weight-bearing status and trunk position. However, little research to date has evaluated protective neuromuscular response times and activation patterns to an imposed perturbation with the knee joint in a functional, weight-bearing stance. Hence, we designed a lower extremity perturbation device to produce a sudden, forward and either internal or external rotation moment of the trunk and femur relative to the weight-bearing tibia. Surface electromyography (EMG) recorded long latency reflex times of the medial and lateral quadriceps, hamstring and gastrocnemius muscles in 64 intercollegiate lacrosse and soccer players in response to both internal and external rotation perturbation. We found the gastrocnemius fired significantly faster that the hamstring, which in turn fired significantly faster than the quadriceps. There was also a significant difference in activation times of the medial and lateral hamstring not found for the quadriceps or gastrocnemius muscles. Our findings confirmed that reactive neuromuscular responses following this functional perturbation differ markedly from those previously reported using seated, partial weight-bearing and/or uni-planar models under relaxed conditions.


Sitting Time, Physical Activity, and Risk of Mortality in Adults.
It is unclear what level of moderate to vigorous intensity physical activity (MVPA) offsets the health risks of sitting. The purpose of this study was to examine the joint and stratified associations of sitting and MVPA with all-cause and cardiovascular disease (CVD) mortality, and to estimate the theoretical effect of replacing sitting time with physical activity, standing, and sleep. A longitudinal analysis of the 45 and Up Study calculated the multivariable-adjusted hazard ratios (HRs) of sitting for each sitting-MVPA combination group and within MVPA strata. Isotemporal substitution modeling estimated the per-hour HR effects of replacing sitting. A total of 8,689 deaths (1,644 due to CVD) occurred among 149,077 participants over an 8.9-year (median) follow-up. There was a statistically significant interaction between sitting and MVPA only for all-cause mortality. Sitting time was associated with both mortality outcomes in a nearly dose-response manner in the least active groups reporting <150 MVPA min/week. For example, among those reporting no MVPA, the all-cause mortality HR comparing the most sedentary (>8 h/day) to the least sedentary (<4 h/day) groups was 1.52 (95% confidence interval: 1.13 to 2.03). There was inconsistent and weak evidence for elevated CVD and all-cause mortality risks with more sitting among those meeting the lower (150 to 299 MVPA min/week) or upper (≥300 MVPA min/week) limits of the MVPA recommendation. Replacing sitting with walking and MVPA showed stronger associations among high sitters (>6 sitting h/day) where, for example, the per-hour CVD mortality HR for sitting replaced with vigorous activity was 0.36 (95% confidence interval: 0.17 to 0.74). Sitting is associated with all-cause and CVD mortality risk among the least physically active adults; moderate-to-vigorous physical activity doses equivalent to meeting the current recommendations attenuate or effectively eliminate such associations.


Fractional flow reserve to guide surgical coronary revascularization.
Coronary angiography has traditionally been used as the final diagnostic tool in the evaluation of coronary artery disease (CAD). However, conventional angiography identifies anatomically obstructive coronary disease, but it is limited in its ability to identify hemodynamically significant lesions. The emergence of fractional flow reserve (FFR) technology, in conjunction with angiography, offers a functional, as well as anatomic, assessment of epicardial coronary obstructions. Several pivotal studies have demonstrated that FFR-guided coronary revascularization is a safe and effective in patients with single and multivessel CAD. There are emerging data to suggest that FFR may also play an integral role in planning surgical revascularization and in the evaluation of post-coronary artery bypass patients and their graft patency. This review will explore the physiologic underpinnings of FFR methodology, its clinical value and limitations, and its applications in coronary artery bypass grafting (CABG) surgery.


Insights into the life history and ecology of a large shortfin mako shark Isurus oxyrinchus captured in southern California.
In June 2013, a record-breaking female Isurus oxyrinchus (total length 373 cm, mass 600 kg) was captured by rod and reel off Huntington Beach, California, where it was subsequently donated to research and provided a rare opportunity to collect the first data for a female I. oxyrinchus of this size. Counts of vertebral band pairs estimate the shark to have been c. 22 years old, depending upon assumptions of band-pair deposition rates, and the distended uteri and spent ovaries indicated that this shark had recently given birth. The stomach contained a c. 4 year-old female California sea lion Zalophus californianus that confirmed the high trophic position of this large I. oxyrinchus, which was corroborated with the high levels of measured contaminants and tissue isotope analyses.


Gonadotropin-releasing hormone receptor microaggregation. Rate monitored by fluorescence resonance energy transfer.
Gonadotropin-releasing hormone (GnRH) regulates pituitary gonadotropin release and is a therapeutic target for human and animal reproductive diseases. In the present study we have utilized the technique of fluorescence resonance energy transfer to monitor the rate of GnRH receptor-receptor interactions. This technique relies on the observation that the degree of physical intimacy of molecules can be assessed by the tendency of proximal fluorophores to exchange energy. Our data indicate that GnRH agonist, but not antagonist, occupancy of the GnRH receptor promotes physical intimacy (microaggregation) between receptors. The time course indicates that this occurs promptly (<1 min) after occupancy and persists for at least 80 min and within the physiologically relevant range of the releasing hormone. The process measured is not inhibited by 0.1 mm vinblastin, 2 microm cytochalasin D, or 3 mm EGTA, an observation that distinguishes it from macroaggregation (patching, capping, and internalization). These observations, along with reports from other laboratories, are consonant with a growing body of evidence that indicates that microaggregation is an early event following agonist occupancy of the receptor and part of the mechanism by which effector regulation occurs.


Probability density estimation using isocontours and isosurfaces: applications to information-theoretic image registration.
We present a new, geometric approach for determining the probability density of the intensity values in an image. We drop the notion of an image as a set of discrete pixels, and assume a piecewise-continuous representation. The probability density can then be regarded as being proportional to the area between two nearby isocontours of the image surface. Our paper extends this idea to joint densities of image pairs. We demonstrate the application of our method to affine registration between two or more images using information theoretic measures such as mutual information. We show cases where our method outperforms existing methods such as simple histograms, histograms with partial volume interpolation, Parzen windows, etc. under fine intensity quantization for affine image registration under significant image noise. Furthermore, we demonstrate results on simultaneous registration of multiple images, as well as for pairs of volume datasets, and show some theoretical properties of our density estimator. Our approach requires the selection of only an image interpolant. The method neither requires any kind of kernel functions (as in Parzen windows) which are unrelated to the structure of the image in itself, nor does it rely on any form of sampling for density estimation.


SseL is a salmonella-specific translocated effector integrated into the SsrB-controlled salmonella pathogenicity island 2 type III secretion system.
Bacterial pathogens use horizontal gene transfer to acquire virulence factors that influence host colonization, alter virulence traits, and ultimately shape the outcome of disease following infection. One hallmark of the host-pathogen interaction is the prokaryotic type III secretion system that translocates virulence factors into host cells during infection. Salmonella enterica possesses two type III secretion systems that are utilized during host colonization and intracellular replication. Salmonella pathogenicity island 2 (SPI2) is a genomic island containing approximately 30 contiguous genes required to assemble a functional secretion system including the two-component regulatory system called SsrA-SsrB that positively regulates transcription of the secretion apparatus. We used transcriptional profiling with DNA microarrays to search for genes that coregulate with the SPI2 type III secretion machinery in an SsrB-dependent manner. Here we report the identification of a Salmonella-specific translocated effector called SseL that is required for full virulence during murine typhoid-like disease. Analysis of infected macrophages using fluorescence-activated cell sorting revealed that sseL is induced inside cells and requires SsrB for expression. SseL is retained predominantly in the cytoplasm of infected cells following translocation by the type III system encoded in SPI2. Animal infection experiments with sseL mutant bacteria indicate that integration of SseL into the SsrB response regulatory system contributes to systemic virulence of this pathogen.


Crystal Structure of Bicc1 SAM Polymer and Mapping of Interactions between the Ciliopathy-Associated Proteins Bicc1, ANKS3, and ANKS6.
Head-to-tail polymers of sterile alpha motifs (SAM) can scaffold large macromolecular complexes. Several SAM-domain proteins that bind each other are mutated in patients with cystic kidneys or laterality defects, including the Ankyrin (ANK) and SAM domain-containing proteins ANKS6 and ANKS3, and the RNA-binding protein Bicc1. To address how their interactions are regulated, we first determined a high-resolution crystal structure of a Bicc1-SAM polymer, revealing a canonical SAM polymer with a high degree of flexibility in the subunit interface orientations. We further mapped interactions between full-length and distinct domains of Bicc1, ANKS3, and ANKS6. Neither ANKS3 nor ANKS6 alone formed macroscopic homopolymers in vivo. However, ANKS3 recruited ANKS6 to Bicc1, and the three proteins together cooperatively generated giant macromolecular complexes. Thus, the giant assemblies are shaped by SAM domains, their flanking sequences, and SAM-independent protein-protein and protein-mRNA interactions.


Prognostic Role of Cardiopulmonary Exercise Testing in Clinical Practice.
Risk stratification is a mainstay in the care of cardiac and pulmonary disorders, as the identification of adverse outcomes helps provide measures to improve survival and quality of life. The cardiopulmonary exercise test is a useful prognostic tool in the clinical evaluation of several pathological conditions, such as heart diseases, respiratory disorders, and pulmonary hypertension. If not contraindicated, a cardiopulmonary exercise test should always be performed and integrated with clinical, laboratory, and hemodynamic parameters to better stratify patient risk. In heart failure, the cardiopulmonary exercise test is important in all the stages of patient management, from diagnosis to risk assessment. Different exercise variables have been advocated as prognostic indicators in this condition, including peak oxygen uptake, ventilatory efficiency, respiratory patterns, and identification of the anaerobic threshold. The prognostic role of the cardiopulmonary exercise test in heart failure is amplified when included in multiparametric risk stratification methodology, currently considered the best method to assess patient outcome. In respiratory disorders and in pulmonary hypertension, cardiopulmonary exercise test parameters, focusing on ventilatory performance during exercise, may help evaluate the risk of adverse events. Finally, the cardiopulmonary exercise test may help define the presence of coexisting cardiac and respiratory disorders, a combination that leads to increased rates of disability and mortality.


Experimental validation of LIFT for estimation of low-order modes in low-flux wavefront sensing.
Laser Tomographic and Multi-Conjugate Adaptive Optics systems rely on natural guide stars to sense low order aberrations (tip/tilt and focus). LIFT is a novel focal plane wavefront sensor (WFS), performing a maximum likelihood phase retrieval on a single image, with better sensitivity than a 2 × 2 Hartmann-Shack WFS. Its performance for the estimation of tip/tilt and focus is similar to a pyramid WFS without modulation, but with a simpler set-up. We present here the LIFT concept and associated data processing, as well as experimental results. We validate the estimation of tip/tilt and focus, with monochromatic and large bandwidth light, and verify the low noise sensitivity predicted by theory.


Preventable risk factors for noncommunicable diseases in rural Indonesia: prevalence study using WHO STEPS approach.
To gain a better understanding of the health transition in Indonesia, we sought to describe the prevalence and distribution of risk factors for noncommunicable diseases and to identify the risk-factor burden among a rural population and an urban population. Using the protocol of the WHO STEPwise approach to Surveillance (STEPS), risk factors for noncommunicable diseases were determined for 1502 men and 1461 women aged 15-74 years at the Purworejo Demographic Surveillance Site in 2001. Smoking prevalence was high among men (913/1539; weighted percentage=53.9.%) in both rural and urban populations; it was almost non-existent among women. A higher proportion of the urban population and the richest quintile of the rural population had high blood pressure and were classified as being overweight or obese when compared with the poorest quintile of the rural population. Those classified as being in the richest quintile who lived in the rural area were 1.5 times more likely to have raised blood pressure and 8 times more likely to be overweight than those classified as being in the poorest quintile and living in the rural area. Clustering of risk factors was higher among those classified as being in the richest quintile of those living in the rural area compared with those classified as being in the poorest quintile; and the risks of clustering were just 20-30% lower compared with the urban population. Both the rural and urban populations in Purworejo face an unequally distributed burden of risk factors for noncommunicable diseases. The burden among the most well-off group in the rural area has already reached a level similar to that found in the urban area. The implementation of the WHO STEPS approach was feasible, and it provides a comprehensive picture of the burden of risk factors, allowing appropriate health interventions to be implemented to address health inequities.


Rubella susceptibility in pregnant women and results of a postpartum immunization strategy in Catalonia, Spain.
Elimination of congenital rubella syndrome depends not only on effective childhood immunization but also on the identification and immunization of rubella susceptible women. We assessed rubella susceptibility among pregnant women and evaluated the adherence and response to postpartum immunization with measles, mumps and rubella (MMR) vaccine. Cross-sectional study of women who gave birth at the Hospital Clinic de Barcelona (Spain) between January 2008 and December 2013. Antenatal serological screening for rubella was performed in all women during pregnancy. In rubella-susceptible women, two doses of MMR vaccine were recommended following birth. We evaluated rubella serological response to MMR vaccination in mothers who complied with the recommendations. A total of 22,681 pregnant women were included in the study. The mean age was 32.3 years (SD 5.6), and 73.6% were primipara. The proportion of immigrants ranged from 43.4% in 2010 to 38.5% in 2012. The proportion of women susceptible to rubella was 5.9% (1328). Susceptibility to rubella declined with increasing maternal age. Immigrant pregnant women were more susceptible to rubella (7.6%) than women born in Spain (4.6%). Multivariate analyses showed that younger age (≤19 years) aOR 1.7 (95% CI 1.1-2.5), primiparas aOR 1.3 (95% CI 1.1-1.5) and immigrant women aOR 1.6 (95% CI 1.4-1.8) were more likely to be susceptible. The second dose of MMR vaccine was received by 57.2% (718/1256) of rubella-susceptible women, with the highest proportion being immigrant women compared with women born in Spain. After vaccination, all women showed rubella immunity. The higher rubella susceptibility found in the three youngest age groups and in immigrant women highlights the relevance of antenatal screening, in order to ensure identification and postpartum immunization. The postpartum immunization strategy is an opportunity to protect women of childbearing age and consequently prevent occurrence of CRS, and to increase vaccination coverage against rubella and other vaccine-preventable diseases.


Induction of the plasminogen activator inhibitor-2 in cells expressing the ZNF198/FGFR1 fusion kinase that is involved in atypical myeloproliferative disease.
The ZNF198/FGFR1 fusion kinase associated with an atypical myeloproliferative disease is constitutively activated and regulates several STAT transcription factors. We used oligonucleotide microarrays to compare the gene-expression profiles between HEK-293 cells that stably express either the ZNF198/FGFR1 chimeric protein or the wild-type ZNF198 gene. Expression of the plasminogen activator inhibitor-2 (PAI-2/SERPINB2) was highly increased in cells expressing the fusion gene. Western blot analysis demonstrated that HEK-293 cells do not express PAI-2 endogenously, but in ZNF198/FGFR1-expressing cells 2 molecular forms of PAI-2, which were 47 kDa and 32 kDa, were expressed intracellularly, and a 60-kDa form was secreted. Similarly, expression of ZNF198/FGFR1 in BaF/3 mouse hematopoietic cells also induced the expression of the PAI-2 protein. Immunoprecipitation analysis revealed that both intracellular forms of PAI-2 bind to the ZNF198/FGFR1 kinase. Treatment of HEK-293 and BaF/3 cells with TNF-alpha in the presence of cycloheximide, induced apoptosis in both cases. In contrast, HEK-293 and BaF/3 cells expressing ZNF198/FGFR1 were resistant to TNF-alpha-induced apoptosis. These observations suggest that expression of the ZNF198/FGFR1 fusion gene is associated with specific PAI-2-mediated resistance to apoptosis which may contribute to the highly malignant nature of leukemic cells carrying this fusion kinase gene.


Regulation of progesterone receptor-mediated transcription by phosphorylation.
The progesterone receptor (PR) in the chicken oviduct is a phosphoprotein that regulates gene transcription in the presence of progesterone. Treatment with progesterone in vivo stimulates phosphorylation of the progesterone receptor. With transient transfection assays, the present work has tested whether phosphorylation participates in the regulation of PR-mediated transcription. Treatment with 8-bromo-cyclic adenosine monophosphate (8-Br cAMP), a stimulator of cAMP-dependent protein kinase [protein kinase A (PKA)], mimicked progesterone-dependent, receptor-mediated transcription in the absence of progesterone. Inhibition of PKA blocked hormone action. Treatment with okadaic acid, an inhibitor of protein phosphatases 1 and 2A, stimulated transcription in a manner similar to that of progesterone. These observations suggest that phosphorylation of the PR or other proteins in the transcription complex can modulate PR-mediated transcription in vivo.


Risk prediction models for mortality in patients with cardiovascular disease: The BioBank Japan project.
Cardiovascular disease (CVD) is a leading cause of death in Japan. The present study aimed to develop new risk prediction models for long-term risks of all-cause and cardiovascular death in patients with chronic phase CVD. Among the subjects registered in the BioBank Japan database, 15,058 patients aged ≥40 years with chronic ischemic CVD (ischemic stroke or myocardial infarction) were divided randomly into a derivation cohort (n = 10,039) and validation cohort (n = 5019). These subjects were followed up for 8.55 years in median. Risk prediction models for all-cause and cardiovascular death were developed using the derivation cohort by Cox proportional hazards regression. Their prediction performances for 5-year risk of mortality were evaluated in the validation cohort. During the follow-up, all-cause and cardiovascular death events were observed in 2962 and 962 patients from the derivation cohort and 1536 and 481 from the validation cohort, respectively. Risk prediction models for all-cause and cardiovascular death were developed from the derivation cohort using ten traditional cardiovascular risk factors, namely, age, sex, CVD subtype, hypertension, diabetes, total cholesterol, body mass index, current smoking, current drinking, and physical activity. These models demonstrated modest discrimination (c-statistics, 0.703 for all-cause death; 0.685 for cardiovascular death) and good calibration (Hosmer-Lemeshow χ2-test, P = 0.17 and 0.15, respectively) in the validation cohort. We developed and validated risk prediction models of all-cause and cardiovascular death for patients with chronic ischemic CVD. These models would be useful for estimating the long-term risk of mortality in chronic phase CVD.


Cortical and subcortical changes following sphenopalatine ganglion blocks in chronic migraine with medication overuse headache: a preliminary longitudinal study.
The purpose of this pilot study was to investigate potential changes in brain morphology (cortical thickness and cortical/subcortical volume) accompanying a series of sphenopalatine ganglion (SPG) blockade treatments in chronic migraine with medication overuse headaches (CMw/MOH). Local anesthetization of the SPG via intranasal application is used for the treatment for multiple types of headache disorders, including CM. Our previous longitudinal fMRI study revealed improved network connectivity after such treatment. However, the impact of SPG blocks on cortical, subcortical gray matter volume and cortical thickness has yet to be assessed. Using magnetic resonance imaging (MRI), cortical/subcortical volume were measured in 12 chronic migraine patients before and after a series of 12 SPG blocks administered over a 6-week period (2 per week). The average time between MRI assessments was 6 weeks. Targeted, within-subjects t-tests comparing pre-treatment and post-treatment values in specific apriori brain regions of interest, including the hippocampus, amygdala, basal ganglia, somatosensory cortex, temporal cortex and occipital cortex, were used to estimate the impact of repetitive SPG blocks treatment on brain morphology in CMw/MOH. Compared to baseline values, the number of moderate/severe headache days per month, HIT-6, PHQ-9 scores and allodynia scores were all significantly improved at the end of treatment. Analysis of MRI data revealed that the volume of the right hippocampus and the right palladium significantly decreased following SPG block treatment, while the volume of the left nucleus accumbens significantly increased following treatment. Cortical thickness in the left temporal pole and left lateral occipito-temporal gyrus significantly decreased following SPG block treatment. Our results suggest SPG block treatment is associated with significant symptom improvement as well as significant structural brain changes in regions known to be associated with migraine and chronic pain processing in CMw/MOH.


The HIV-1 protein Vpr targets the endoribonuclease Dicer for proteasomal degradation to boost macrophage infection.
The HIV-1 protein Vpr enhances macrophage infection, triggers G2 cell cycle arrest, and targets cells for NK-cell killing. Vpr acts through the CRL4(DCAF1) ubiquitin ligase complex to cause G2 arrest and trigger expression of NK ligands. Corresponding ubiquitination targets have not been identified. UNG2 and SMUG1 are the only known substrates for Vpr-directed depletion through CRL4(DCAF1). Here we identify the endoribonuclease Dicer as a target of HIV-1 Vpr-directed proteasomal degradation through CRL4(DCAF1). We show that HIV-1 Vpr inhibits short hairpin RNA function as expected upon reduction of Dicer levels. Dicer inhibits HIV-1 replication in T cells. We demonstrate that Dicer also restricts HIV-1 replication in human monocyte-derived macrophages (MDM) and that reducing Dicer expression in MDMs enhances HIV-1 infection in a Vpr-dependent manner. Our results support a model in which Vpr complexes with human Dicer to boost its interaction with the CRL4(DCAF1) ubiquitin ligase complex and its subsequent degradation.


Blueberries and cardiovascular disease prevention.
Blueberries are a rich source of (poly)phenols, particularly anthocyanins. Epidemiological studies indicate that anthocyanin-rich foods including blueberries are associated with a reduction in the risk of cardiovascular disease. These observational findings are supported by a number of randomized-controlled trials showing improvements in biomarkers of cardiovascular disease risk. The beneficial effects of blueberry (poly)phenols are particularly clear when measuring flow-mediated dilation over various timeframes and study populations. However, other outcomes are less clear, such as effects on blood pressure, arterial stiffness and blood lipid profile. This may be due to the heterogeneity existing in study designs, such as duration of the intervention, and the health status of participants. Longer-term RCTs using gold standard methods in relevant populations which can be translated to the general public are needed to clarify and strengthen the evidence available. While circulating phenolic blueberry metabolites have been linked with improvements in vascular function, the biological activities and mechanisms of action of individual metabolites and their interaction in vivo are still unknown. Evaluating the bioactivities of metabolites alone and together, and analysing their structure-activity relationship in well-designed and physiologically relevant experimental and human studies are needed to understand the mechanisms of how these metabolites affect vascular function.


Mirodenafil prevents bladder dysfunction induced by chronic bladder ischemia in rats.
To investigate the protective effect of mirodenafil on bladder function in a rat model of chronic bladder ischemia (CBI). Twenty-four Sprague-Dawley rats were randomized to three groups: untreated, sham-operated rats (control group); untreated, CBI model rats (CBI group); and CBI rats treated daily with 4 mg/kg mirodenafil (CBI+mirodenafil group). The CBI and CBI+mirodenafil groups underwent endothelial injury to the iliac arteries and were fed a 2% cholesterol diet after injury. Four weeks after surgery, the CBI+mirodenafil group started daily treatment with mirodenafil for four weeks. Eight weeks after surgery, continuous in vivo cystometry and in vivo organ bath studies of detrusor muscle strips were performed. in vivo cystometry revealed that the rats in the CBI group had a significantly higher micturition frequency, lower bladder capacity, and lower compliance than the rats in the control and CBI+mirodenafil groups. The detrusor muscle strip study showed that the magnitude of the carbachol-induced contractile response was significantly lower in the CBI group compared to either the control or CBI+mirodenafil group. Addition of daily mirodenafil after induction of CBI decreased the contractile response, compared to untreated CBI rats. CBI induced submucosal fibrosis and degenerative changes in bladder walls, which was reversed by the addition of mirodenafil. Daily treatment with mirodenafil showed protective effects against bladder dysfunction resulting from CBI in rats.


Neuroplus biofeedback improves attention, resilience, and injury prevention in elite soccer players.
Performance and injury prevention in elite soccer players are typically investigated from physical-tactical, biomechanical, and metabolic perspectives. However, executive functions, visuospatial abilities, and psychophysiological adaptability or resilience are also fundamental for efficiency and well-being in sports. Based on previous research associating autonomic flexibility with prefrontal cortical control, we designed a novel integrated autonomic biofeedback training method called Neuroplus to improve resilience, visual attention, and injury prevention. Herein, we introduce the method and provide an evaluation of 20 elite soccer players from the Italian Soccer High Division (Serie-A): 10 players trained with Neuroplus and 10 trained with a control treatment. The assessments included psychophysiological stress profiles, a visual search task, and indexes of injury prevention, which were measured pre- and posttreatment. The analysis showed a significant enhancement of physiological adaptability, recovery following stress, visual selective attention, and injury prevention that were specific to the Neuroplus group. Enhancing the interplay between autonomic and cognitive functions through biofeedback may become a key principle for obtaining excellence and well-being in sports. To our knowledge, this is the first evidence that shows improvement in visual selective attention following intense autonomic biofeedback.


Ultrasmall titania nanocrystals and their direct assembly into mesoporous structures showing fast lithium insertion.
Ultrasmall and highly soluble anatase nanoparticles were synthesized from TiCl(4) using tert-butyl alcohol as a new reaction medium. This synthetic protocol widens the scope of nonaqueous sol-gel methods to TiO(2) nanoparticles of around 3 nm with excellent dispersibility in ethanol and tert-butanol. Microwave heating was found to enhance the crystallinity of the nanoparticles and to drastically shorten the reaction time to less than 1 h at temperatures as low as 50 degrees C. The extremely small size of the nanoparticles and their dispersibility make it possible to use commercial Pluronic surfactants for evaporation-induced self-assembly of the nanoparticulate building blocks into periodic mesoporous structures. A solution of particles after synthesis can be directly used for preparation of mesoporous films without the need for particle separation. The mesoporous titania coatings fabricated using this one-pot procedure are crystalline and exhibit high surface areas of up to 300 m(2)/g. The advantages of the retention of the mesoporous order with extremely thin nanocrystalline walls were shown by electrochemical lithium insertion. The films made using microwave-treated nanoparticles showed supercapacitive behavior with high maximum capacitance due to quantitative lithiation with a 10-fold increase of charging rates compared to a standard reference electrode made from 20 nm anatase particles.


Mogamulizumab Treatment Elicits Autoantibodies Attacking the Skin in Patients with Adult T-Cell Leukemia-Lymphoma.
The anti-CCR4 mAb, mogamulizumab, offers therapeutic benefit to patients with adult T-cell leukemia-lymphoma (ATL), but skin-related adverse events (AE) such as erythema multiforme occur frequently. The purpose of this study was to determine the mechanisms by which mogamulizumab causes skin-related AEs in patients with ATL. We investigated whether autoantibodies were present in patients' sera using flow cytometry to determine binding to keratinocytes and melanocytes (n = 17), and immunofluorescence analysis of tissue sections. We analyzed the IgM heavy chain repertoire in peripheral blood mononuclear cells before and after mogamulizumab or other chemotherapy by next-generation sequencing (NGS; n = 16). Autoantibodies recognizing human keratinocytes or melanocytes were found in the sera of 6 of 8 patients suffering from mogamulizumab-induced erythema multiforme. In one patient, complement-dependent cytotoxicity (CDC) mediated by autoantibodies against keratinocytes or melanocytes was proportionally related to the severity of the erythema multiforme. The presence of autoantibodies in the epidermis was confirmed in all biopsy specimens of mogamulizumab-induced erythema multiforme (n = 12). Furthermore, colocalization of autoantibodies and C1q, suggesting the activation of CDC, was observed in 67% (8/12). In contrast, no autoantibody or C1q was found in ATL tumor skin lesions (n = 13). Consistent with these findings, NGS demonstrated that IgM germline genes had newly emerged and expanded, resulting in IgM repertoire skewing at the time of erythema multiforme. Mogamulizumab elicits autoantibodies playing an important role in skin-related AEs, possibly associated with regulatory T-cell depletion. This is the first report demonstrating the presence of skin-directed autoantibodies after mogamulizumab treatment.


pH-sensitive self-associations of the N-terminal domain of NBCe1-A suggest a compact conformation under acidic intracellular conditions.
NBCe1-A is an integral membrane protein that cotransports Na+ and HCO3 - ions across the basolateral membrane of the proximal tubule. It is essential for maintaining a homeostatic balance of cellular and blood pH. In X-ray diffraction studies, we reported that the cytoplasmic, N-terminal domain of NBCe1-A (NtNBCe1-A) is a dimer. Here, biophysical measurements show that the dimer is in a concentration-dependent dynamic equilibrium among three additional states in solution that are characterized by its hydrodynamic properties, molar masses, emission spectra, binding properties, and stabilities as a function of pH. Under physiological conditions, dimers are in equilibrium with monomers that are pronounced at low concentration and clusters of molecular masses up to 3-5 times that of a dimer that are pronounced at high concentration. The equilibrium can be influenced so that individual dimers predominate in a taut conformation by lowering the pH. Conversely, dimers begin to relax and disassociate into an increasing population of monomers by elevating the pH. A mechanistic diagram for the inter-conversion of these states is given. The self-associations are further supported by surface plasmon resonance (SPR-Biacore) techniques that illustrate NtNBCe1-A molecules transiently bind with one another. Bicarbonate and bicarbonate-analog bisulfite appear to enhance dimerization and induce a small amount of tetramers. A model is proposed, where the Nt responds to pH or bicarbonate fluctuations inside the cell and plays a role in self-association of entire NBCe1-A molecules in the membrane.


Supplementation with pumpkin seed oil improves plasma lipid profile and cardiovascular outcomes of female non-ovariectomized and ovariectomized Sprague-Dawley rats.
Pumpkin (Cucurbita species) seed oil (PSO) is a rich source of phytoestrogens and the aim of this study was to examine the effect of PSO supplementation on the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides, high density lipoprotein cholesterol (HDL-C), systolic and diastolic blood pressure in non-ovariectomized and ovariectomized Sprague-Dawley rats. Female rats weighing 220-300 g were divided into non-ovariectomized rats for supplementation with corn oil (control CO; n = 6) or PSO (control PSO; n = 5) and ovariectomized rats for supplementation with corn oil (OVX/CO; n = 6) or PSO (OVX/PSO; n = 5) for 5 days per week for 12 weeks (corn oil 40 mg/kg or PSO 40 mg/kg given orally). Systolic and diastolic blood pressures were measured weekly. Blood was collected at the end of the period for plasma lipid assays. Control PSO had lower TC, LDL-C, triglycerides and higher HDL-C than the control CO. The OVX/CO had higher TC, LDL-C, triglycerides and lower HDL-C than the control CO and these changes were prevented in the OVX/PSO rats. PSO supplementation also resulted in lower systolic and diastolic blood pressures in both non-ovariectomized and ovariectomized rats. It is concluded that PSO supplementation can prevent changes in plasma lipids and blood pressure associated with inadequate oestrogen availability.


Analyzing primary cilia by multiphoton microscopy.
In this chapter, a technique is outlined for the use of immunohistochemistry (IHC) followed by multiphoton microscopy (MPM) for the analysis of incidence, length, and 3D orientation of the axoneme of the primary cilium. Although the application presented specifically emphasizes localizations in tenocytes and chondrocytes, the technique is applicable to cells in a wide range of connective tissues. The primary advantages of utilizing MPM as opposed to TEM for these kinds of ciliary analyses are the rapidity of the technique for preparation of the samples and the ability to collect data from multiple cells simultaneously. Using MPM, the axoneme, basal body, and associated centriole can be visualized by specific IHC with localizing antibodies. However, the resolution achieved through TEM analyses allows the complex morphology of the primary cilium to be visualized, and this remains the primary advantage of TEM versus MPM. SHG, which occurs only with MPM, allows visualization of collagen fibrils and is particularly advantageous for localizing primary cilia associated with cells in connective tissues. This, and the deep penetration with less photobleaching, are the primary advantages of MPM compared to confocal microscopy. As with any microscopical technique, the protocol needs to be optimized for any given tissue. In particular, additional antigen retrieval techniques to enhance the unmasking of specific epitopes for antibody binding may be required for adaptation of this approach to other dense connective tissues with complex spatial organizations such as intervertebral disc or meniscus.


Bayesian Exploratory Factor Analysis.
This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates from a high dimensional set of psychological measurements.


Iliopsoas and gluteal muscles are asymmetric in tennis players but not in soccer players.
To determine the volume and degree of asymmetry of iliopsoas (IL) and gluteal muscles (GL) in tennis and soccer players. IL and GL volumes were determined using magnetic resonance imaging (MRI) in male professional tennis (TP) and soccer players (SP), and in non-active control subjects (CG) (n = 8, 15 and 6, respectively). The dominant and non-dominant IL were hypertrophied in TP (24 and 36%, respectively, P<0.05) and SP (32 and 35%, respectively, P<0.05). In TP the asymmetric hypertrophy of IL (13% greater volume in the non-dominant than in the dominant IL, P<0.01) reversed the side-to-side relationship observed in CG (4% greater volume in the dominant than in the contralateral IL, P<0.01), whilst soccer players had similar volumes in both sides (P = 0.87). The degree of side-to-side asymmetry decreased linearly from the first lumbar disc to the pubic symphysis in TP (r = -0.97, P<0.001), SP (r = -0.85, P<0.01) and CG (r = -0.76, P<0.05). The slope of the relationship was lower in SP due to a greater hypertrophy of the proximal segments of the dominant IL. Soccer and CG had similar GL volumes in both sides (P = 0.11 and P = 0.19, for the dominant and contralateral GL, respectively). GL was asymmetrically hypertrophied in TP. The non-dominant GL volume was 20% greater in TP than in CG (P<0.05), whilst TP and CG had similar dominant GL volumes (P = 0.14). Tennis elicits an asymmetric hypertrophy of IL and reverses the normal dominant-to-non-dominant balance observed in non-active controls, while soccer is associated to a symmetric hypertrophy of IL. Gluteal muscles are asymmetrically hypertrophied in TP, while SP display a similar size to that observed in controls. It remains to be determined whether the different patterns of IL and GL hypertrophy may influence the risk of injury.


Unusual Imaging Findings Associated with Germ Cell Tumors.
Germ cell tumors, because they contain immature and mature elements, can differentiate into different tissue types. They can exhibit unusual imaging features or manifest in a syndromic fashion. The authors describe these features and assign them to one of the following categories: (a) unusual manifestations of metastatic disease (growing teratoma syndrome, choriocarcinoma syndrome, ossified metastases, and gliomatosis peritonei); (b) autoimmune manifestations (sarcoidlike reaction and paraneoplastic syndromes); (c) endocrine syndromes (sex hormone production, struma ovarii, and struma carcinoid); or (d) miscellaneous conditions (ruptured dermoid cyst, squamous cell carcinoma arising from a mature teratoma, Currarino triad, fetus in fetu, pseudo-Meigs syndrome, and pancreatitis). Rare conditions associated with germ cell tumors demonstrate characteristic imaging findings that can help lead to the appropriate diagnosis and management recommendations. When evaluating for potential metastatic disease, alternative benign diagnoses should be considered (eg, growing teratoma syndrome, ossified metastases, ruptured dermoid cyst, gliomatosis peritonei, and sarcoidlike reaction), which may impact management. Germ cell tumors may also lead to life-threatening complications such as extensive hemorrhage from choriocarcinoma metastases or the rupture of mature teratomas, cases in which timely diagnosis is crucial. Autoimmune and endocrine manifestations such as paraneoplastic encephalitis, autoimmune hemolytic anemia, and hyperthyroidism may occur owing to the presence of germ cell tumors and can create a diagnostic dilemma for clinicians. Knowledge of the syndromic and unusual imaging findings associated with germ cell tumors helps guide appropriate management. ©RSNA, 2019.


Protecting the world against meningitis: new recommendations from the CDC's advisory committee on immunization practices.
Meningococcal meningitis is a rare but often fatal disease. Throughout adolescence, the incidence of meningococcal meningitis increases, reaching a peak among individuals between the ages of 16 and 21 years. Vaccines are available to combat this deadly disease. Recently, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices updated its recommendations on meningitis vaccination to improve outcomes and to prevent this disease in adolescents and other vulnerable populations, such as adults traveling internationally to epidemic areas. Improved meningitis vaccines and revised vaccination recommendations will help to create a healthier world.


Endonasal endoscopic skull base multilayer reconstruction surgery with nasal pedicled mucosal flap to manage high flow CSF leakage.
Multilayer reconstruction of skull base using nasal pedicled mucosal flap has been widely accepted as a standard method for repairing high flow cerebrospinal fluid [CSF] leakage. In this study, we analyzed our outcome and summarized several valuable operation experiences from this technique. This study included 20 consecutive patients who underwent endoscopic endonasal multilayer reconstruction using a nasal pedicled mucosal flap to repair high flow CSF leakage and were available for follow-up. In this series, all cases encountered intraoperative high-flow CSF leakage, including 11 (55%) patients with opening of third ventricles (TV) and 9 (45%) patients with wide opening of cistern (CS). After endoscopic endonasal multilayer reconstruction with nasal pedicled mucosal flap, 3 patients (15.0%) encountered CSF leakage in the early postoperative period but were successfully repaired; 2 patients (10.0%) encountered late postoperative CSF leakage. In the TV group, the ratio of CSF leakage was 18.2% (2/11); while the incidence of CSF leakage was 11.1% (1/9) in the CS group. One patient developed meningitis due to CSF leakage four month after surgery, then gave up treatment and died. Multilayer reconstruction with nasal pedicled flap seems to be useful and reliable for the treatment of ventral skull base defects using endoscopic endonasal approach.


Sun protecting and sun exposing behaviors: testing their relationship simultaneously with indicators of ultraviolet exposure among adolescents.
The aim of this study was to build on existing understanding of adolescent sun-related behavior by combining sun protecting and sun exposing behaviors and testing their relationship simultaneously with indicators of ultraviolet (UV) exposure. Data were collected for 692 adolescents aged between 12 and 18 years. General linear modeling was undertaken to test the relationship of sun-related behaviors with indicators of UV exposure. Overall, the combined sun protection and sun exposing behaviors accounted for 13.8% of the variance in the number of sunburns, 28.1% of the variance in current tan and 57.5% of the variance in desired tan, respectively. Results indicated that having a strong desire for a tan was significantly associated with spending time tanning, delaying the use of sun protection, wearing brief clothing and using no sun protection; whereas the number of sunburns was significantly associated with sunscreen use, avoiding peak hours and delaying sun protection. Current tan was significantly associated with wearing sunglasses, shade use and time spent tanning. In examining sun-related behaviors among adolescents, consideration needs to be given to both sun exposing and sun protecting behaviors. This research has important implications for conceptualizing outcomes in programs designed to reduce UV exposure.


Predicted effects of climate warming on the distribution of 50 stream fishes in Wisconsin, USA.
Summer air and stream water temperatures are expected to rise in the state of Wisconsin, U.S.A., over the next 50 years. To assess potential climate warming effects on stream fishes, predictive models were developed for 50 common fish species using classification-tree analysis of 69 environmental variables in a geographic information system. Model accuracy was 56·0-93·5% in validation tests. Models were applied to all 86 898 km of stream in the state under four different climate scenarios: current conditions, limited climate warming (summer air temperatures increase 1° C and water 0·8° C), moderate warming (air 3° C and water 2·4° C) and major warming (air 5° C and water 4° C). With climate warming, 23 fishes were predicted to decline in distribution (three to extirpation under the major warming scenario), 23 to increase and four to have no change. Overall, declining species lost substantially more stream length than increasing species gained. All three cold-water and 16 cool-water fishes and four of 31 warm-water fishes were predicted to decline, four warm-water fishes to remain the same and 23 warm-water fishes to increase in distribution. Species changes were predicted to be most dramatic in small streams in northern Wisconsin that currently have cold to cool summer water temperatures and are dominated by cold-water and cool-water fishes, and least in larger and warmer streams and rivers in southern Wisconsin that are currently dominated by warm-water fishes. Results of this study suggest that even small increases in summer air and water temperatures owing to climate warming will have major effects on the distribution of stream fishes in Wisconsin.


Gold nanoparticles conjugated with DNA aptamer for photoacoustic detection of human matrix metalloproteinase-9.
Matrix metalloproteinase-9 (MMP-9) plays major roles in extracellular matrix (ECM) remodeling and membrane protein cleavage, suggesting a high correlation with cancer cell invasion and tumor metastasis. Here, we present a contrast agent based on a DNA aptamer that can selectively target human MMP-9 in the tumor microenvironment (TME) with high affinity and sensitivity. Surface modification of plasmonic gold nanospheres with the MMP-9 aptamer and its complementary sequences allows the nanospheres to aggregate in the presence of human MMP-9 through DNA displacement and hybridization. Aggregation of gold nanospheres enhances the optical absorption in the first near-infrared window (NIR-I) due to the plasmon coupling effect, thereby allowing us to detect the aggregated gold nanospheres within the TME via ultrasound-guided photoacoustic (US/PA) imaging. Selective and sensitive detection of human MMP-9 via US/PA imaging is demonstrated in solution of nanosensors with the pre-treatment of human MMP-9, in vitro in cell culture, and in vivo in a xenograft murine model of human breast cancer.


Switch to Dolutegravir plus Rilpivirine Dual Therapy in cART-Experienced Subjects: An Observational Cohort.
Little information is available on the efficacy and safety of the dual combination of ripivirine plus dolutegravir. This work aims at beginning to fill this gap. All HIV-1 infected subjects treated with ripivirine plus dolutegravir between October 2014 and September 2015 in eight Italian centres were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48. One hundred and thirty-two subjects were followed for a median of 24 months, mean 33 months. One subject discontinued the study drug at week 24 for headache, one for drug interaction and one died after week 24 of illicit drug abuse. The mean age was 51.8, females 31.7% and non-caucasians 10%. Fifty-seven (43.2%) had at least one failure in their treatment history. Reasons for switching were simplification (53.0%), toxicity (34.8%), drug interactions (n = 7), persistent low-level viremia (n = 4), non-adherence (n = 3) and viral failure (n = 2). Sixty patients (45.5%) had reverse transcriptase (RT) mutations and 69 (44,7%) had protease (PR) mutations. Sixteen had baseline viral replication, 27 had < 50 HIV-1 RNA copies/mL and in 89 (67.4%) no virus was detected (NVD, 0 copies/mL). At w4, 114 (86.4%) had NVD, 15 had 1 to 49 HIV-1 RNA copies/mL and 3 had 50 to 57 copies/mL. At week 24 one subject had viral rebound without mutations due to missed drug refill, 19 had 1 to 49 copies/mL, and 112 had NVD. All 132 subjects were tested at weeks 4 and 24. Of the 50 subjects who had a 48-week follow-up, one had a treatment interruption, four had 1 to 49 copies/mL and 45 had NVD. Among the entire population, one subject had low-level, one intermediate and 4 high-level resistance to rilpivirine: none failed by week 48. Mean serum creatinine increased by +0.1 mg/dL. During the follow-up one patient reported headache and insomnia. Ripivirine plus dolutegravir proved safe and effective in this cohort of non-naïve HIV-1 infected subjects.


Pathological neovascularization is reduced by inactivation of ADAM17 in endothelial cells but not in pericytes.
Pathological neovascularization is a critical component of diseases such as proliferative retinopathies, cancer and rheumatoid arthritis, yet much remains to be learned about the underlying causes. Previous studies showed that vascular endothelial growth factor (VEGF)-A activates the membrane-anchored metalloproteinase ADAM17 (a disintegrin and metalloproteinase 17) in endothelial cells, thereby stimulating crosstalk between VEGF receptor 2 and extracellular signal-regulated kinase. These findings raised interesting questions about the role of ADAM17 in angiogenesis and neovascularization in vivo. The objective of this study was to inactivate ADAM17 in endothelial cells or in pericytes to determine how this affects developmental angiogenesis, pathological retinal neovascularization and heterotopic tumor growth. We generated animals in which floxed ADAM17 was removed by Tie2-Cre in endothelial cells, or by smooth muscle (sm) Cre in smooth muscle cells and pericytes. There were no evident developmental defects in either conditional knockout strain, but pathological retinal neovascularization and growth of heterotopically injected tumor cells was reduced in Adam17flox/flox/Tie2-Cre mice, although not in Adam17flox/flox/sm-Cre mice. Moreover, lack of ADAM17 in endothelial cells decreased ex vivo chord formation, and this could be largely restored by addition of the ADAM17 substrate HB-EGF (heparin-binding epidermal growth factor-like growth factor). Finally we found that ADAM17 is important for the VEGF receptor 2 stimulated processing of several receptors with known functions in endothelial cell biology. These results provide the first evidence for a role for ADAM17 in pathological neovascularization in vivo. Because ADAM17 does not appear to be required for normal developmental angiogenesis or vascular homeostasis, it could emerge as a good target for treatment of pathological neovascularization.


Conceptual biology, hypothesis discovery, and text mining: Swanson's legacy.
Innovative biomedical librarians and information specialists who want to expand their roles as expert searchers need to know about profound changes in biology and parallel trends in text mining. In recent years, conceptual biology has emerged as a complement to empirical biology. This is partly in response to the availability of massive digital resources such as the network of databases for molecular biologists at the National Center for Biotechnology Information. Developments in text mining and hypothesis discovery systems based on the early work of Swanson, a mathematician and information scientist, are coincident with the emergence of conceptual biology. Very little has been written to introduce biomedical digital librarians to these new trends. In this paper, background for data and text mining, as well as for knowledge discovery in databases (KDD) and in text (KDT) is presented, then a brief review of Swanson's ideas, followed by a discussion of recent approaches to hypothesis discovery and testing. 'Testing' in the context of text mining involves partially automated methods for finding evidence in the literature to support hypothetical relationships. Concluding remarks follow regarding (a) the limits of current strategies for evaluation of hypothesis discovery systems and (b) the role of literature-based discovery in concert with empirical research. Report of an informatics-driven literature review for biomarkers of systemic lupus erythematosus is mentioned. Swanson's vision of the hidden value in the literature of science and, by extension, in biomedical digital databases, is still remarkably generative for information scientists, biologists, and physicians.


The 3'-Jα Region of the TCRα Locus Bears Gene Regulatory Activity in Thymic and Peripheral T Cells.
Much progress has been made in understanding the important cis-mediated controls on mouse TCRα gene function, including identification of the Eα enhancer and TCRα locus control region (LCR). Nevertheless, previous data have suggested that other cis-regulatory elements may reside in the locus outside of the Eα/LCR. Based on prior findings, we hypothesized the existence of gene regulatory elements in a 3.9-kb region 5' of the Cα exons. Using DNase hypersensitivity assays and TCRα BAC reporter transgenes in mice, we detected gene regulatory activity within this 3.9-kb region. This region is active in both thymic and peripheral T cells, and selectively affects upstream, but not downstream, gene expression. Together, these data indicate the existence of a novel cis-acting regulatory complex that contributes to TCRα transgene expression in vivo. The active chromatin sites we discovered within this region would remain in the locus after TCRα gene rearrangement, and thus may contribute to endogenous TCRα gene activity, particularly in peripheral T cells, where the Eα element has been found to be inactive.


Ultrasonically Activated Irrigation to Remove Calcium Hydroxide from Apical Third of Human Root Canal System: A Systematic Review of In Vitro Studies.
The aim of this systematic review was to summarize the outcomes of in vitro studies comparing ultrasonically activated irrigation versus other irrigation techniques for removing calcium hydroxide (Ca[OH]2) from the apical third of root canals. The research question was developed according to the PICO strategy. A comprehensive literature search was performed. The Medline, Embase, and TRIP electronic databases were searched. A hand search of the reference lists of identified articles was performed to isolate relevant articles. Two reviewers critically assessed the studies against our inclusion and exclusion criteria. Evaluation of the risk of bias of the studies was performed independently by the 2 reviewers. After study selection, 62 were assessed for eligibility. Of these, 9 met the inclusion criteria and were included in the systematic review. Because considerable heterogeneity was found in the methodologies, it was not possible to combine the results of studies in a meta-analysis. Ultrasonically activated irrigation was found to be superior to syringe irrigation and apical negative pressure irrigation, but insufficient evidence was found to indicate its superiority over the other irrigation techniques such as sonically activated irrigation, the Self-Adjusting File, (ReDent-Nova, Ra'anana, Israel) and the RinsEndo, (Dürr Dental, Bietigheim, Germany). On the basis of available evidence, we determined the effectiveness of ultrasonically activated irrigation compared with syringe and apical negative pressure irrigation. Because of the small sample sizes, low number of included studies, and limitations, further research is needed to confirm our results.


Malignant mesothelioma of tunica vaginalis: an extremely rare case presenting without risk factors.
Testicular tumours have many different manifestations, including hydrocele formation. Herein, we present an extremely rare case of testicular mesothelioma presenting with left hydrocele, but without risk factors. Left radical inguinal orchidectomy was performed, and pathological examination revealed a malignant mesothelioma of the tunica vaginalis of the testis. No infiltration of the spermatic cord was evident, and upon advanced radiological evaluation, no sign of metastasis was detected. Follow-up was still ongoing in our urology outpatient clinic at the time of this report. Although hydrocele is a simple and common condition that is easy to diagnose, a detailed investigation should be performed. Thus, when encountering a patient with hydrocele, the clinician should evaluate the possibility of the presence of an underlying testicular/paratesticular tumour, including a rare one such as mesothelioma of the tunica vaginalis.


NTP Toxicology and Carcinogenesis Studies of Tremolite (CAS No. 14567-73-8) in F344/N Rats (Feed Studies).
A carcinogenesis bioassay of blocky (nonfibrous) tremolite was conducted with male and female F344/N rats. Tremolite was administered at a concentration of 1% in pelleted diet for the entire lifetime of the rats, starting with the dams of the study animals. The studies were started in 1978 and ended in 1981. Group sizes were 118 male and female controls and 250 male and female tremolite-exposed rats. Litter size was not effected by the administration of tremolite to the dams. The offspring from mothers exposed to tremolite were the same size at birth as the controls but were slightly smaller at weaning and remained so throughout their life. Survival was similar in the exposed and control groups. No toxicity or increase in incidence of neoplasia was observed in the tremolite-exposed animals compared with the concurrent controls. Conclusions: Under the conditions of these feed studies, nonfibrous tremolite was not overly toxic or carcinogenic for male or female F344/N rats, following lifetime ingestion of a diet containing 1% tremolite. Target Organs & Incidences from 2-year Studies


Plant community responses to resource availability and heterogeneity during restoration.
Availability and heterogeneity of resources have a strong influence on plant community structure in undisturbed systems, as well as those recovering from disturbance. Less is known about the role of resource availability and heterogeneity in restored communities, although restoration provides a valuable opportunity to test our understanding of factors that influence plant community assembly. We altered soil nitrogen (N) availability and soil depth during a prairie restoration to determine if the availability and/or heterogeneity of soil resources influenced plant community composition in restored grassland communities. Plant community responses to three levels of N availability (ambient, enriched by fertilization, and reduced by carbon amendment) and two levels of soil depth (deep and shallow) were evaluated. In addition, we evaluated plant community responses to four whole plot heterogeneity treatments created from the six possible combinations of soil N availability and soil depth. The soil depth treatment had little influence on community structure during the first 3 years of restoration. Total diversity and richness declined over time under annual N enrichment, whereas diversity was maintained and richness increased over time in soil with reduced N availability. Non-native species establishment was lowest in reduced-N soil in the initial year, but their presence was negligible in all of the soil N treatments by the second year of restoration. Panicum virgatum, a native perennial C(4) grass, was the dominant species in all soil N treatments by year three, but the magnitude of its dominance was lowest in the reduced-N soil and highest in enriched-N soil. Consequently, the relative cover of P. virgatum was strongly correlated with community dominance and inversely related to diversity. The differential growth response of P. virgatum to soil N availability led to a higher degree of community similarity to native prairie in the reduced-N treatment than in the enriched-N treatment. There were no differences in plant community structure among the four whole plot-level heterogeneity treatments, which all exhibited the same degree of similarity to native prairie. Diversity and community heterogeneity in the whole-plot treatments appeared to be regulated by the dominant species' effect on light availability, rather than soil N heterogeneity per se. Our results indicate that a strong differential response of a dominant species to resource availability in a restored community can regulate community structure, diversity, and similarity to the native (or target) community, but the importance of resource heterogeneity in restoring diversity may be dampened in systems where a dominant species can successfully establish across a range of resource availability.


Theory of mind and relational complexity.
Cognitive complexity and control theory and relational complexity theory attribute developmental changes in theory of mind (TOM) to complexity. In 3 studies, 3-, 4-, and 5-year-olds performed TOM tasks (false belief, appearance-reality), less complex connections (Level 1 perspective-taking) tasks, and transformations tasks (understanding the effects of location changes and colored filters) with content similar to TOM. There were also predictor tasks at binary-relational and ternary-relational complexity levels, with different content. Consistent with complexity theories: (a) connections and transformations were easier and mastered earlier than TOM; (b) predictor tasks accounted for more than 80% of age-related variance in TOM; and (c) ternary-relational items accounted for TOM variance, before and after controlling for age and binary-relational items. Prediction did not require hierarchically structured predictor tasks.


Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage.
A group of patients with damage to the ventral part of the frontal lobes was severely impaired relative to a group of patients without damage in this area (the non-ventral group) in the reversal and in the extinction of simple visual discrimination tests. In these tests they continued to make responses to a previously rewarded stimulus. Patients often reported verbally that the contingencies had changed, but were unable to alter their behaviour appropriately. These impairments occurred independently of IQ or verbal memory impairments. The perseverative touching of a previously rewarded stimulus is consistent with work with non-human primates showing impaired reversal and extinction after orbitofrontal lesions. Performance on these reversal and extinction tests was highly correlated with scores obtained on a behaviour questionnaire, which reflected the degree of disinhibited and socially inappropriate behaviour exhibited by patients. It is suggested that a difficulty in modifying responses, especially when followed by negative consequences, as manifested in these simple laboratory tests, may contribute to the inappropriate behaviour shown in daily life by patients with frontal lobe damage.


Long-term macrolide treatment for chronic respiratory disease.
Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been demonstrated to exert anti-inflammatory and immunomodulatory activity in addition to being antimicrobial. Indeed, their spectrum of action extends to the regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation and modulation of host defence mechanisms. As such, the potential benefit of macrolide antibiotics has been evaluated in a variety of chronic respiratory diseases. The best studied condition is cystic fibrosis, of which there have been six randomised controlled trials showing evidence of benefit. However, most of the studies were limited by small numbers of patients and short follow-up. More recently, landmark studies have demonstrated the efficacy of azithromycin in reducing the risk of acute exacerbations in patients with chronic obstructive pulmonary disease, but the optimal duration and dosing of macrolide treatment remain uncertain. With the exception of patients with DPB and cystic fibrosis, until clear evidence of efficacy is available, the long-term use of macrolides should be limited to highly selected patients after careful evaluation of benefit and harm, or in the context of randomised controlled clinical trials.


The incidence and management of secondary abdominoplasty and secondary abdominal contour surgery.
Limited data exist in the literature regarding the general incidence of secondary abdominal contour procedures and secondary abdominoplasty (excluding revisions) or specific recommendations for surgical management of these patients. The authors performed a retrospective chart review of 562 patients who underwent abdominal contouring procedures (liposuction and/or modified or full abdominoplasty) performed by a single surgeon (A.M.) from January of 2004 until October of 2012. Nonsurgical primary cases, secondary surgery that was revisional in nature, and massive weight loss patients were excluded. Seventy-three patients (13.0 percent) underwent secondary abdominal contouring procedures. Forty-six of 73 patients had charts available to be examined in greater detail. Thirty-four of these patients underwent secondary liposuction, whereas 12 of these patients had secondary full abdominoplasty procedures. Secondary operations occurred an average of 4.98 years after the primary procedure (range, 6 months to 15 years). Patients underwent secondary liposuction (n = 34) on average 3.16 years after their initial procedure, significantly sooner than patients who underwent secondary abdominoplasty (n = 12) 8.35 years after their initial procedure (p = 0.002). Patients with a body mass index less than 25 kg/m2 (n = 26) had both secondary liposuction (n = 16) and secondary abdominoplasty (n = 10), whereas all patients who had a body mass index of 25 kg/m2 or greater (n = 20) underwent only secondary liposuction. True secondary abdominal contouring procedures represented 13.0 percent of all abdominal contouring procedures. The most common indication for a secondary procedure was an umbilical-site closure scar. Specific recommendations for surgical management of five common scenarios for secondary abdominal procedures are discussed.


Solution structure of the disulfide-linked dimer of human intestinal trefoil factor (TFF3): the intermolecular orientation and interactions are markedly different from those of other dimeric trefoil proteins.
The trefoil protein TFF3 forms a homodimer (via a disulfide linkage) that is thought to have increased biological activity over the monomer. The solution structure of the TFF3 dimer has been determined by NMR and compared with the structure of the TFF3 monomer and with other trefoil dimer structures (TFF1 and TFF2). The most significant structural differences between the trefoil domain in the monomer and dimer TFF3 are in the orientations of the N-terminal 3(10)-helix (residues 10-12) and in the presence in the dimer of an additional 3(10)-helix (residues 53-55) outside of the core region. The TFF3 dimer forms a more compact structure as compared with the TFF1 dimer where the two trefoil domains are connected by a flexible region with the monomer units being at variable distances from each other and in many different orientations. Although TFF2 is also a compact structure, the dispositions of its monomer units are very different from those of TFF3. The structural differences between the dimers result in the two putative receptor/ligand binding sites that remain solvent exposed in the dimeric structures having very different dispositions in the different dimers. Such differences have significant implications for the mechanism of action and functional specificity for the TFF class of proteins.


Assessment of Macro-Level Socioeconomic Factors That Impact Waterborne Diseases: The Case of Jordan.
The Hashemite Kingdom of Jordan is an example of a country that suffers from high water scarcity. Additionally, due to the economic drivers in the country, such as phosphate and potash extraction and pharmaceutical production, the little fresh water that remains is generally polluted. The infrastructure, often antiquated in urban areas and non-existent in rural areas, also contributes to poor water conditions and to the spread of waterborne diseases. This paper examines the socioeconomic factors that contribute to diarrhea and hepatitis A on a macro level in Jordan and discusses the public-policies that government officials could use to abate those problems. Ordinary least squares time series models are used to understand the macro-level variables that impact the incidence of these diseases in Jordan. Public health expenditure has a significant impact on reducing their incidence. Furthermore, investment in sanitation facilities in rural regions is likely to reduce the number of cases of hepatitis A. Perhaps the most surprising outcome is that importation of goods and services likely results in a decrease in cases of hepatitis A. However, income has little impact on the incidence of diarrhea and hepatitis A.


Integrating what and when across the primate medial temporal lobe.
Episodic memory or memory for the detailed events in our lives is critically dependent on structures of the medial temporal lobe (MTL). A fundamental component of episodic memory is memory for the temporal order of items within an episode. To understand the contribution of individual MTL structures to temporal-order memory, we recorded single-unit activity and local field potential from three MTL areas (hippocampus and entorhinal and perirhinal cortex) and visual area TE as monkeys performed a temporal-order memory task. Hippocampus provided incremental timing signals from one item presentation to the next, whereas perirhinal cortex signaled the conjunction of items and their relative temporal order. Thus, perirhinal cortex appeared to integrate timing information from hippocampus with item information from visual sensory area TE.


Practice patterns, satisfaction, and demographics of reproductive endocrinologists: results of the 2014 Society for Reproductive Endocrinology and Infertility Workforce Survey.
To identify the current and future state of the practice of reproductive medicine. Cross-sectional survey. Not applicable. None. Not applicable. The survey included 57 questions designed to assess practice patterns/metrics and professional satisfaction and morale. A total of 336/1,100 (31%) responded, and they were 38% women, 61% men, and 76% Caucasian, with a mean age of 54. Respondents averaged 2.3 jobs and averaged 53 hours of work per week: 44% work in academia and 50% in private groups. Average practice size was 5.5, with an average of 470 fresh IVF cycles performed per year. Percent effort included 63% infertility, 10% endocrinology, 10% surgery, and 9% research. Respondents performed an average of 13 major surgeries, 69 minor surgeries, and 128 oocyte retrievals per year. A total of 60% were salaried, and 40% were equity partners. Compensation was highly skewed. Greater than 84% had a positive morale and had a positive view of the future, and 92% would again choose REI as a career. The most satisfying areas of employment were patient interactions, intellectual stimulation, interactions with colleagues, and work schedule. The least satisfying areas were work schedule and financial compensation. Training was felt to be too focused on female factor infertility and basic research with insufficient training on embryology, genetics, male factor infertility, and clinical research. In the next 5 years, 57% suggested that the need for specialists would stay the same, while 20% predicted a decrease. A total of 58% felt we are training the correct number of fellows (37% felt we are training a surplus). Compared with academia, those in private practice reported higher compensation, less major surgery, more IVF, less endocrinology, and less research. Men worked more hours, conducted more surgery and IVF cycles, and had higher compensation than women. Morale was similar across age, gender, practice type, and geography. Our subspecialty has an extremely high morale. We are a middle-aged subspecialty with disparate compensation and a focused practice. Some respondents sense a need for a change in our training, and most anticipate only mild growth in our field.


Accept or Decline? An Analytics-Based Decision Tool for Kidney Offer Evaluation.
When a deceased-donor kidney is offered to a waitlisted candidate, the decision to accept or decline the organ relies primarily upon a practitioner's experience and intuition. Such decisions must achieve a delicate balance between estimating the immediate benefit of transplantation and the potential for future higher-quality offers. However, the current experience-based paradigm lacks scientific rigor and is subject to the inaccuracies that plague anecdotal decision-making. A data-driven analytics-based model was developed to predict whether a patient will receive an offer for a deceased-donor kidney at Kidney Donor Profile Index thresholds of 0.2, 0.4, and 0.6, and at timeframes of 3, 6, and 12 months. The model accounted for Organ Procurement Organization, blood group, wait time, DR antigens, and prior offer history to provide accurate and personalized predictions. Performance was evaluated on data sets spanning various lengths of time to understand the adaptability of the method. Using United Network for Organ Sharing match-run data from March 2007 to June 2013, out-of-sample area under the receiver operating characteristic curve was approximately 0.87 for all Kidney Donor Profile Index thresholds and timeframes considered for the 10 most populous Organ Procurement Organizations. As more data becomes available, area under the receiver operating characteristic curve values increase and subsequently level off. The development of a data-driven analytics-based model may assist transplant practitioners and candidates during the complex decision of whether to accept or forgo a current kidney offer in anticipation of a future high-quality offer. The latter holds promise to facilitate timely transplantation and optimize the efficiency of allocation.


Determining brain fitness to fight: Has the time come?
Professional boxing is associated with a risk of chronic neurological injury, with up to 20-50% of former boxers exhibiting symptoms of chronic brain injury. Chronic traumatic brain injury encompasses a spectrum of disorders that are associated with long-term consequences of brain injury and remains the most difficult safety challenge in modern-day boxing. Despite these concerns, traditional guidelines used for return to sport participation after concussion are inconsistently applied in boxing. Furthermore, few athletic commissions require either formal consultation with a neurological specialist (i.e. neurologist, neurosurgeon, or neuropsychologist) or formal neuropsychological testing prior to return to fight. In order to protect the health of boxers and maintain the long-term viability of a sport associated with exposure to repetitive head trauma, we propose a set of specific requirements for brain safety that all state athletic commissions would implement.