Chest Drain Size: the Debate Continues.
Small-bore chest tubes are widely used in the management of common pleural disease. Guidelines suggest that patients with malignant pleural effusions, pneumothorax and pleural infection may be successfully managed with small-bore drains. However, good quality data is often lacking. This article reviews the evidence for the treatment efficacy and potential adverse effects of different chest tube sizes. In a large randomised study, the small difference in pain scores between large and small drains was not clinically significant. However, small-bore chest tubes commonly suffer from blockage or inadvertent removal, and may not be as effective in providing successful pleurodesis for malignant pleural effusions. Although they may be effective in managing pleural infection, and less painful than large drains, small bore drains may be less effective for pleurodesis.


Cross-Modal Correspondence Between Speech Sound and Visual Shape Influencing Perceptual Representation of Shape: the Role of Articulation and Pitch.
Cross-modal correspondence is the tendency to systematically map stimulus features across sensory modalities. The current study explored cross-modal correspondence between speech sound and shape (Experiment 1), and whether such association can influence shape representation (Experiment 2). For the purpose of closely examining the role of the two factors - articulation and pitch - combined in speech acoustics, we generated two sets of 25 vowel stimuli - pitch-varying and pitch-constant sets. Both sets were generated by manipulating articulation - frontness and height of the tongue body's positions - but differed in terms of whether pitch varied among the sounds within the same set. In Experiment 1, participants made a forced choice between a round and a spiky shape to indicate the shape better associated with each sound. Results showed that shape choice was modulated according to both articulation and pitch, and we therefore concluded that both factors play significant roles in sound-shape correspondence. In Experiment 2, participants reported their subjective experience of shape accompanied by vowel sounds by adjusting an ambiguous shape in the response display. We found that sound-shape correspondence exerts an effect on shape representation by modulating audiovisual interaction, but only in the case of pitch-varying sounds. Therefore, pitch information within vowel acoustics plays the leading role in sound-shape correspondence influencing shape representation. Taken together, our results suggest the importance of teasing apart the roles of articulation and pitch for understanding sound-shape correspondence.


Effects of polyamines on NMDA-induced currents in rat hippocampal neurons: a whole-cell and single-channel study.
Actions of the polyamines spermine and spermidine on NMDA-induced currents were examined in cultured hippocampal neurons from embryonic rat. In whole-cell patch experiments using voltage-clamp, spermine (300 microM) produced about a two-fold potentiation of responses to NMDA (at -70 mV in the presence of saturating glycine); half-maximal potentiation was elicited at 207 microM. The potentiation produced by spermine was somewhat greater at positive potentials. The onset of potentiation was fast (t1/2 < 1 s), indicative of an extracellular site of action. Spermidine was of comparable potency but less efficacious than spermine in potentiating NMDA responses. In excised outside-out patches, spermine exhibited two actions on NMDA-induced single-channel responses. In some patches, it increased the channel open probability; both frequency of channel opening and burst length were increased with no significant change in the mean open duration, which accounted for much of the potentiation seen in whole-cell experiments. In all patches, spermine decreased channel conductance at negative voltages, an effect ascribable to fast channel block (with a possible contribution by charge screening). These results are consistent with opposing actions of polyamines mediated at distinct sites on the NMDA receptor.


Studying dyadic structure-function relationships: a review of current modeling approaches and new insights into Ca2+ (mis)handling.
Excitation-contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transient and enabling cardiomyocyte contraction. The spatio-temporal dynamics of calcium release, buffering, and reuptake into the sarcoplasmic reticulum play a central role in excitation-contraction coupling in both normal and diseased cardiac myocytes. However, further quantitative understanding of these cells' calcium machinery and the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease requires accurate knowledge of cardiac ultrastructure, protein distribution and subcellular function. As current imaging techniques are limited in spatial resolution, limiting insight into changes in calcium handling, computational models of excitation-contraction coupling have been increasingly employed to probe these structure-function relationships. This review will focus on the development of structural models of cardiac calcium dynamics at the subcellular level, orienting the reader broadly towards the development of models of subcellular calcium handling in cardiomyocytes. Specific focus will be given to progress in recent years in terms of multi-scale modeling employing resolved spatial models of subcellular calcium machinery. A review of the state-of-the-art will be followed by a review of emergent insights into calcium-dependent etiologies in heart disease and, finally, we will offer a perspective on future directions for related computational modeling and simulation efforts.


Spectroscopic Signatures of the Dynamical Hydrophobic Solvation Shell Formation.
When a hydrophilic solute in water is suddenly turned into a hydrophobic species, for instance, by photoionization, a layer of hydrated water molecules forms around the solute on a time scale of a few picoseconds. We study the dynamic buildup of the hydration shell around a hydrophobic solute on the basis of a time-dependent dielectric continuum model. Information about the solvent is spectroscopically extracted from the relaxation dynamics of a test dipole inside a static Onsager sphere in the nonequilibrium solvent. The growth process is described phenomenologically within two approaches. First, we consider a time-dependent thickness of the hydration layer that grows from zero to a finite value over a finite time. Second, we assume a time-dependent complex permittivity within a finite layer region around the Onsager sphere. The layer is modeled as a continuous dielectric with a much slower fluctuation dynamics. We find a time-dependent frequency shift down to the blue of the resonant absorption of the dipole, together with a dynamically decreasing line width, as compared to bulk water. The blue shift reflects the work performed against the hydrogen-bonded network of the bulk solvent and is a directly measurable quantity. Our results are in agreement with an experiment on the hydrophobic solvation of iodine in water.


Novel benzodioxan derivative, 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl) amino]propoxy]-1,3-benzodioxole HCl (MKC-242), with anxiolytic-like and antidepressant-like effects in animal models.
Behavioral effects of MKC-242 (5-{3-[((2>)-1,4-benzodioxan-2-ylmethyl)amino] propoxy}-1,3-benzodioxole CHl), a novel and selective serotonin 1A receptor agonist, were investigated in rats and mice and compared against those of diazepam, buspirone and tandospirone. MKC-242 (0.0625-0.25 mg/kg, p.o.) significantly increased punished drinking in water-deprived rats. The reference compounds also increased punished drinking at doses of 10 to 40 mg/kg, p.o. The increase by MKC-242 was blocked by N-tert-butyl-3-(4-(2-methoxypenyl)piperazin-1-yl) -2-phenylpropanamide, a serotonin 1A receptor antagonist. MKC-242 (0.1-0.5 mg/kg, p.o.) also increased social interaction under high light and unfamiliar conditions in rats. It had weak benzodiazepine-like side effects in mice. MKC-242 (1, 3 mg/kg, p.o.) attenuated the reduction of locomotion caused by restraint stress in rats, the same effects were observed on both buspirone (100 mg/kg, p.o.) and tandospirone (100 mg/kg, p.o.). In the forced swimming test in rats, MKC-242 (0.3-3 mg/kg, i.p.), 8-hydroxy-2-(di-n-propylamino) tetralin (1, 3 mg/kg, i.p.) and amitriptyline (30 mg/kg, i.p.) reduced immobility, although diazepam, buspirone and tandospirone did not. The reduction by MKC-242 and 8-OH-DPAT was antagonized by N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl) -2-phenylpropanamide. Moreover, the reduction was also blocked by 1-(2--pyrimidinyl)piperazine (1-PP), a common metabolite of buspirone and tandospirone. These findings suggest that MKC-242 possesses potent anxiolytic and antidepressant properties that are mediated via an activation of serotonin 1A receptors.


Markers of B-lymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort.
Little is known about systemic B-cell activation in early rheumatoid arthritis (RA). We therefore evaluated the serum levels of markers of B-cell activation in patients included in the ESPOIR early arthritis cohort. In the ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks but less than 6 months), 710 patients were assessed at 1 year and either met the 1987 American College of Rheumatology criteria for RA (n = 578) or had undifferentiated arthritis (n = 132). Baseline serum samples of patients naïve to corticosteroid and disease-modifying antirheumatic drug treatment were assessed for beta2-microglobulin, IgG, IgA, IgM, immunoglobulin free light chains of immunoglobulins, and B-cell activating factor of the tumor necrosis factor family (BAFF). The BAFF gene 871T>C polymorphism was genotyped in all patients. All markers of B-cell activation except BAFF and IgM were significantly higher in patients with early RA than those with undifferentiated arthritis. Anti-cyclic citrullinated peptide (anti-CCP) and beta2-microglobulin were associated with a diagnosis of early RA in the multivariate analysis. Markers of B-cell activation, except BAFF, were associated with disease activity, rheumatoid factor and anti-CCP secretion. The BAFF gene polymorphism was not associated with early RA. Markers of B-cell activation are elevated in patients with early RA, compared with undifferentiated arthritis, independently of any systemic increase in BAFF secretion, and correlate with disease activity. This study sheds new light on the early pathogenic role of B-lymphocytes in RA and suggests that targeting them might be a useful therapeutic strategy in early RA.


Endoscopic approaches for the diagnosis of autoimmune pancreatitis.
Autoimmune pancreatitis (AIP) is characterized by diffuse pancreatic enlargement and irregular narrowing of the main pancreatic duct (MPD). Immunoglobulin (Ig)G4-related sclerosing cholangitis (IgG4-SC) associated with AIP frequently appears as a bile duct stricture. Therefore, it is important to differentiate AIP and IgG4-SC from pancreatic cancer and cholangiocarcinoma or primary sclerosing cholangitis, respectively. Endoscopy plays a central role in the diagnosis of AIP and IgG4-SC because it provides imaging of the MPD and bile duct strictures as well as the ability to obtain tissue samples for histological evaluations. Diffuse irregular narrowing of MPD on endoscopic retrograde cholangiopancreatography (ERCP) is rather specific to AIP, but localized narrowing of the MPD is often difficult to differentiate from MPD stenosis caused by pancreatic cancer. A long stricture (>1/3 the length of the MPD) and lack of upstream dilatation from the stricture (<5 mm) might be key features of AIP on ERCP. Some cholangiographic features, such as segmental strictures, stric tures of the lower bile duct, and long strictures with prestenotic dilatation, are more common in IgG4-SC than in cholangiocarcinoma. Endoscopic ultrasonography (EUS) reveals diffuse hypoechoic pancreatic enlargement, sometimes with hypoechoic inclusions, in patients with AIP. In addition, EUS-elastography and contrast-enhanced harmonic EUS have been developed with promising results. The usefulness of EUS-guided fine-needle aspiration has been increasingly recognized for obtaining adequate tissue samples for the histological diagnosis of AIP. Further improvement of endoscopic procedures and devices will contribute to more accurate diagnosis of AIP and IgG4-SC.


Health of men, women, and children in post-trafficking services in Cambodia, Thailand, and Vietnam: an observational cross-sectional study.
Trafficking is a crime of global proportions involving extreme forms of exploitation and abuse. Yet little research has been done of the health risks and morbidity patterns for men, women, and children trafficked for various forms of forced labour. We carried out face-to-face interviews with a consecutive sample of individuals entering 15 post-trafficking services in Cambodia, Thailand, and Vietnam. We asked participants about living and working conditions, experience of violence, and health outcomes. We measured symptoms of anxiety and depression with the Hopkins Symptoms Checklist and post-traumatic stress disorder with the Harvard Trauma Questionnaire, and used adjusted logistic regression models to estimate the effect of trafficking on these mental health outcomes, controlling for age, sector of exploitation, and time in trafficking. We interviewed 1102 people, of whom 1015 reached work destinations. Participants worked in various sectors including sex work (329 [32%]), fishing (275 [27%]), and factories (136 [13%]). 481 (48%) of 1015 experienced physical violence, sexual violence, or both, with 198 (35%) of 566 women and girls reporting sexual violence. 478 (47%) of 1015 participants were threatened and 198 (20%) were locked in a room. 685 (70%) of 985 who had data available worked 7 days per week and 296 (30%) of 989 worked at least 11 hours per day. 222 (22%) of 983 had a serious injury at work. 61·2% (95% CI 58·2-64·2) of participants reported symptom of depression, 42·8% (39·8-45·9) reported symptoms of anxiety, and 38·9% (36·0-42·0) reported symptoms of post-traumatic stress disorder. 5·2% (4·0-6·8) had attempted suicide in the past month. Participants who experienced extremely excessive overtime at work, restricted freedom, bad living conditions, threats, or severe violence were more likely to report symptoms of depression, anxiety, and post-traumatic stress disorder. This is the first health study of a large and diverse sample of men, women, and child survivors of trafficking for various forms of exploitation. Violence and unsafe working conditions were common and psychological morbidity was associated with severity of abuse. Survivors of trafficking need access to health care, especially mental health care. Anesvad Foundation and International Organization for Migration International Development Fund.


Reversal of narcotic depression in the neonate by nalozone.
Naloxone 40 mug was administered intravenously one minute after birth to 20 out of 44 neonates whose mother had been given pethidine in labour. These neonates were compared with 20 others whose mothers had had only lumbar epidural block. Alveolar PCO2, alveolar ventilation, and ventilatory rate were measured 10 and 30 minutes after birth. The untreated neonates of mothers who had had pethidine showed significant ventilatory depression compared with infants in the epidural and naloxone-treated groups. The naloxone-treated neonates were comparable with the epidural group, although the effects of naloxone were diminishing at 30 minutes. Naloxone is an effective narcotic antagonist which should be considered to be the drug of choice for treating narcotic depression in the neonate.


Are Male Perpetrators of Intimate Partner Violence Different From Convicted Violent Offenders? Examination of Psychopathic Traits and Life Success in Males From a Community Survey.
We used data from the Cambridge Study in Delinquent Development, a prospective longitudinal survey of more than 400 males in the United Kingdom followed from age 8 to age 48 to investigate intimate partner violence (IPV) and its association with psychopathy. We investigated the differences in psychopathy scores between those men who were convicted of violence, those who were involved in both extra- and intra-familial violence, and those who committed IPV only. We also considered whether these generally violent men had poorer life success overall with regard to their drinking and drug taking, depression, and other mental disorders. Our findings suggest that those men who are violent both within and outside the home (the generally violent men) are distinguished from those who commit violent crimes outside the home and those who are involved in IPV within the home only. The differences appear to be more in degree than in kind. These findings are discussed with a focus on whether specific interventions are required for those who commit IPV or whether early intervention should be focused on violent behavior in general.


Enhanced Radiation Tolerance of Tungsten Nanoparticles to He Ion Irradiation.
Materials exposed to plasmas in magnetic confinement nuclear reactors will accumulate radiation-induced defects and energetically implanted gas atoms (from the plasma and transmutations), of which insoluble helium (He) is likely to be the most problematic. The large surface-area-to-volume ratio exhibited by nanoporous materials provides an unsaturable sink with the potential to continuously remove both point defects and He. This property enhances the possibilities for these materials to be tailored for high radiation-damage resistance. In order to explore the potential effect of this on the individual ligaments of nanoporous materials, we present results on the response of tungsten (W) nanoparticles (NPs) to 15 keV He ion irradiation. Tungsten foils and various sizes of NPs were ion irradiated concurrently and imaged in-situ via transmission electron microscopy at 750 °C. Helium bubbles were not observed in NPs with diameters less than 20 nm but did form in larger NPs and the foils. No dislocation loops or black spot damage were observed in any NPs up to 100 nm in diameter but were found to accumulate in the W foils. These results indicate that a nanoporous material, particularly one made up of ligaments with characteristic dimensions of 30 nm or less, is likely to exhibit significant resistance to He accumulation and structural damage and, therefore, be highly tolerant to radiation.


Minus-lens-stimulated accommodative amplitude decreases sigmoidally with age: a study of objectively measured accommodative amplitudes from age 3.
Guidelines for predicting accommodative amplitude by age are often based on subjective push-up test data that overestimate the accommodative response. Studies in which objective measurements were used have defined expected amplitudes for adults, but expected amplitudes for children remain unknown. In this study, objective methods were used to measure accommodative amplitude in a wide age range of individuals, to define the relationship of amplitude and age from age 3. Accommodative responses were measured in 140 subjects aged 3 to 40 years. Measurements were taken with the Grand Seiko autorefractor (RyuSyo Industrial Co., Ltd., Kagawa, Japan) as the subjects viewed a high-contrast target at 33 cm through minus lenses of increasing power until the responses showed no further increase in accommodation. The maximum accommodative amplitude of each subject was plotted by age, and a curvilinear function fit to the data: y = 7.33 - 0.0035(age - 3)(2) (P < 0.001). Tangent analysis of the fit indicated that the accommodative amplitude remained relatively stable until age 20. Data from this study were then pooled with objective amplitudes from previous studies of adults up to age 70. A sigmoidal function was fit to the data: y = 7.083/(1 + e([0.2031(age-36.2)-0.6109])) (P < 0.001). The sigmoidal function indicated relatively stable amplitudes below age 20 years, a rapid linear decline between 20 and 50 years, and a taper to 0 beyond 50 years. These data indicate that accommodative amplitude decreases in a curvilinear manner from 3 to 40 years. When combined with data from previous studies, a sigmoidal function describes the overall trend throughout life with the biggest decrease occurring between 20 and 50 years.


Differential arrest and adhesion of tumor cells and microbeads in the microvasculature.
To investigate the mechanical mechanisms behind tumor cell arrest in the microvasculature, we injected fluorescently labeled human breast carcinoma cells or similarly sized rigid beads into the systemic circulation of a rat. Their arrest patterns in the microvasculature of mesentery were recorded and quantified. We found that 93% of rigid beads were arrested either at arteriole-capillary intersections or in capillaries. Only 3% were at the capillary-postcapillary venule intersections and in postcapillary venules. In contrast, most of the flexible tumor cells were either entrapped in capillaries or arrested at capillary or postcapillary venule-postcapillary venule intersections and in postcapillary venules. Only 12% of tumor cells were arrested at the arteriole-capillary intersections. The differential arrest and adhesion of tumor cells and microbeads in the microvasculature was confirmed by a χ(2) test (p < 0.001). These results demonstrate that mechanical trapping was responsible for almost all the arrest of beads and half the arrest of tumor cells. Based on the measured geometry and blood flow velocities at the intersections, we also performed a numerical simulation using commercial software (ANSYS CFX 12.01) to depict the detailed distribution profiles of the velocity, shear rate, and vorticity at the intersections where tumor cells preferred to arrest and adhere. Simulation results reveal the presence of localized vorticity and shear rate regions at the turning points of the microvessel intersections, implying that hemodynamic factors play an important role in tumor cell arrest in the microcirculation. Our study helps elucidate long-debated issues related to the dominant factors in early-stage tumor hematogenous metastasis.


Interaction of age with the ischaemic penumbra, leptomeningeal collateral circulation and haemodynamic variables in acute stroke: a pilot study.
Increasing age is the single largest non-modifiable risk factor for ischaemic stroke. Animal models have substantiated the view that age related neuron vulnerability to ischaemia plays a role in stroke and other age related neurological diseases. Given the key role of the ischaemic penumbra in stroke pathophysiology, we hypothesised that age has an impact on penumbral tissue and its acute determinants. We studied a prospective cohort of patients (n=39) at a mean time of 154.7 min from stroke onset, using state of the art whole brain perfusion CT and CT angiography. Penumbral and core were defined using quantitative voxel based thresholds for mean transit time and cerebral blood volume (CBV). Collateral vessel scores were assessed and haemodynamic variables (ie, cerebral blood flow and CBV) were measured in affected and unaffected tissues. While age correlated negatively with normalised penumbral volume (Kendall's τ b=-0.234, p=0.048) and lesion volume (Kendall's τ b=0.238, p=0.045), core volume remained unchanged, accompanied by an incremental collateral response with age (Kendall's τ b=0.496, p<0.0001). Haemodynamic variables remained unaffected by age in our cohort. These findings, described for the first time in a clinical cohort using whole brain CT perfusion and concomitant vascular imaging, suggest that age has a differential effect on acute tissue compartments in the wake of a preserved collateral vascular response and haemodynamic parameters. In agreement with the preclinical literature, the results point to a distinct tissue response to acute ischaemia in the ageing brain and merit validation studies in larger cohorts, particularly in relation to clinical outcomes.


Personal and Financial Risk Typologies Among Women Who Engage in Sex Work in Mongolia: A Latent Class Analysis.
Women engaged in sex work bear a disproportionate burden of HIV infection worldwide, particularly in low- to middle-income countries. Stakeholders interested in promoting prevention and treatment programs are challenged to efficiently and effectively target heterogeneous groups of women. This problem is particularly difficult because it is nearly impossible to know how those groups are composed a priori. Although grouping based on individual variables (e.g., age or place of solicitation) can describe a sample of women engaged in sex work, selecting these variables requires a strong intuitive understanding of the population. Furthermore, this approach is difficult to quantify and has the potential to reinforce preconceived notions, rather than generate new information. We aimed to investigate groupings of women engaged in sex work. The data were collected from a sample of 204 women who were referred to an HIV prevention intervention in Ulaanbaatar, Mongolia. Latent class analysis was used to create subgroups of women engaged in sex work, based on personal and financial risk factors. This analysis found three latent classes, representing unique response pattern profiles of personal and financial risk. The current study approached typology research in a novel, more empirical way and provided a description of different subgroups, which may respond differently to HIV risk interventions.


Complex function and expression of Delta during Drosophila oogenesis.
Delta (Dl) encodes a cell surface protein that mediates cell-cell interactions central to the specification of a variety of cell fates during embryonic and postembryonic development of Drosophila melanogaster. We find that the Delta protein is expressed intermittently in follicle cells and in germ-line cells during stages 1-10 of oogenesis. Furthermore, Delta expression during oogenesis can be correlated with a number of morphogenetic defects associated with sterility observed in Dl mutant females, including failure of stalk formation within the germarium and subsequent fusion of egg chambers, necrosis in germ-line cells, and multiphasic embryonic arrest of fertilized eggs. We have also identified a Dl mutation that leads to context-dependent defects in Dl function during oogenesis. Direct comparison of Delta protein expression with that of the Notch protein in the ovary reveals substantial, but incomplete, coincidence of expression patterns in space and time. We discuss possible roles for the Delta protein in cell-cell interactions required for cell fate specification processes during oogenesis in light of available developmental and histochemical data.


Glucosamine supplementation during late gestation alters placental development and increases litter size.
During late gestation the placental epithelial interface becomes highly folded, which involves changes in stromal hyaluronan. Hyaluronan is composed of glucoronate and N-acetyl-glucosamine. We hypothesized that supplementing gestating dams with glucosamine during this time would support placental folded-epithelial-bilayer development and increase litter size. In Exp. 1, gilts were unilaterally hysterectomized-ovariectomized (UHO). UHO gilts were mated and then supplemented daily with 10 g glucosamine (n = 16) or glucose (control, n = 17) from d 85 of gestation until slaughter (d 105). At slaughter, the number of live fetuses was recorded and each live fetus and its placenta was weighed. Uterine wall samples adjacent to the largest and smallest fetuses within each litter were processed for histology. In Exp. 2, pregnant sows in a commercial sow farm were supplemented with either 10 g glucosamine or glucose daily from d 85 of gestation to farrowing. Total piglets born and born alive were recorded for each litter. In Exp. 3, the same commercial farm and same protocol were used except that the dose of glucosamine and glucose was doubled to 20 g/d. In Exp. 1, the number of live fetuses tended to be greater in glucosamine-treated UHO gilts (P = 0.098). Placental morphometry indicated that the width of the folded bilayer was greater (P = 0.05) in glucosamine-treated gilts. In Exp. 2, litter size did not differ between glucosamine- and glucose-treated sows. However in Exp. 3, the increased dose of glucosamine resulted in a significant treatment by parity interaction (P ≤ 0.01), in which total piglets born and born alive were greater in glucosamine treated sows of later parity (5 and 6). These results indicated that glucosamine supplementation increased the width of the folds of the placental bilayer and increased litter size in later parity, intact pregnant commercial sows.


Equivalence of online and clinician administration of a patellar tendinopathy risk factor and severity questionnaire.
The VISA-P is a questionnaire for assessing the severity of patellar tendinopathy (PT). Our study aim was to evaluate the equivalence of self-administration of the VISA-P online with the addition of risk factor questions to develop a tool suitable for high-volume remote use. A crossover study design with 107 subjects was used to determine equivalence between online and clinician administration. Three population groups were used to ensure construct validity. Online vs clinician administration revealed an intraclass correlation (ICC) of 0.79 [confidence interval (CI): 0.68-0.86] for the VISA-P with a systematic significant difference of 4.99, which is not clinically meaningful. Poor ICCs were seen for questions 7 and 8 of the VISA-P (0.37 and 0.47, respectively) in comparison with earlier questions. There were statistically significant differences between population groups for the VISA-P. The ICC for risk factor questions was excellent at 0.89 (CI: 0.84-0.93) with no mean difference (P = 1.00). The online questionnaire enables equivalent collection of VISA-P data and risk factor information and may well improve further with the suggested modifications to the instructions for questions 7 and 8. There is potential to use this questionnaire electronically to generate large databases in future research.


Epidemiology of tuberculosis in children in Kampala district, Uganda, 2009-2010; a retrospective cross-sectional study.
The global tuberculosis (TB) estimate in 2011 was 500,000 cases among children under 15 years representing 5.7 % of all cases and 64, 000 deaths among HIV negative children representing 6.5 % of the total deaths. In Uganda, the child TB cases reported in 2012 made up less than 3 % of the total cases while recent modelling estimates it at 15-20 % of adult cases. Mapping of these cases in Kampala district most especially for the children under five years would reflect recent transmission in the various communities in the district. We therefore conducted a retrospective study of reported child TB cases in Kampala district Uganda for 2009-2010 to provide an estimate of child TB incidence and map the cases. This was a retrospective cross-sectional study on data collected from the health unit TB registers in the five divisions of Kampala district, Uganda. The data was a starting point in preparation for a TB Vaccine study in children. The extracted data spanned a period from 1st January 2009 to 31st December 2010. The projected population of children below 15 years was 637,922 in 2009 and 744,750 in 2010 for Kampala district. We based our projections on the National Bureau of Statistics most recent census report of 2002 before the study duration while assuming a population growth rate of 3.7 % each year. We captured the data into EPI DATA 3.1 and analysed it using STATA version 12. We accessed 15,499 records and analysed 1167 records that were of children below 15 years old. The child TB cases represented 7.5 % (7.3 in 2009 & 7.6 % in 2010) of all the registered cases in Kampala district. The females were 47 % and the median age was 4 years (IQR 1, 10). The percent of children less than 5 years old was 54 %. The percent of pulmonary TB cases was 89 % (1041/1167) with 15 % smear positive. The proportion of extra-pulmonary TB cases was 11 % (126/1167). Among those that tested for HIV, 60 % (359/620) had test results available with an HIV co-infection rate of 47 % (168/359). Antiretroviral treatment uptake was 24 % among the co-infected. The incidence of child TB in Kampala was 56 (95 % CI 50-62) per 100,000 in 2009 and 44 (95 % CI 40-49) per 100,000 in 2010. Most of the TB cases (60 % (410/685)) in Kampala live in slum areas. There was a higher child TB incidence of 56 per 100,000 in 2009 compared with 44 per 100,000 in 2010. The percentage of child TB cases was much higher at 7.5 % of all the reported TB cases than the WHO reported national average. For the review period, the TB cases clustered in particular slums in Kampala district.


Chitosan-cartilage extracellular matrix hybrid scaffold induces chondrogenic differentiation to adipose-derived stem cells.
Adipose-derived stem cells (ASCs) are potential cell sources for cartilage tissue engineering. Chitosan has been shown to enhance the stemness and differentiation capability of ASCs, and the native extracellular matrix (ECM) derived from articular cartilage has been also reported to induce chondrogenic differentiation of ASCs. Here we tested the hypothesis that a porous three-dimensional (3D) hybrid scaffold composed of chitosan and cartilage ECM can provide a better environment to induce ASC chondrogenesis. Mixed solution composed of chitosan and cartilage ECM was frozen and lyophilized to form a composite construct. The porous 3D scaffolds were further crosslinked by genipin and used for ASC culture. Cultivation of ASCs in the chitosan/cartilage ECM composite 3D scaffolds induced the formation of cell spheroids with profound glycosaminoglycan production after 14 and 28 days culture. Chondrogenesis of ASCs seeded in the 3D scaffolds was also evident by mRNA expressions of cartilage-specific gene COL2A1 and ACAN on day 14. Histology and immunohistochemistry on day 28 also showed abundant cartilage-specific macromolecules, namely collagen type II and proteoglycan, deposited in a surface layer of the composite scaffold with tangential layer, transitional layer, and lacunae-like structures. Otherwise, hypertrophic markers collagen type I and X were concentrated in the area beneath the surface. Our findings demonstrated spatial chondrogenic differentiation of ASCs in the chitosan-cartilage ECM composite scaffolds. This 3D hybrid scaffold exhibits great potentials for ASC-based cartilage tissue engineering.


Morphological study of nanoparticle-polymer solar cells using high-angle annular dark-field electron tomography.
Electron tomography in high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) mode is used to image networks of nanoparticles within polymer-nanoparticle blend photovoltaic devices. Blends of CdSe nanoparticles (∼6.5 nm diameter spheres and ∼33 nm long nanorods) with poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-1,4-phenylene vinylene] (OC(1)C(10)-PPV) are investigated. Blends using spherical particles are found to contain aggregated regions in which well-connected networks of nanoparticles exist, surrounded by lower-density regions with poorer connectivity. As the ratio of nanoparticles to polymer is increased the aggregated regions increase in size, and the connectivity of the particles in the lower-density regions also increases. This has the effect of increasing the overall percentage of the charge-generating interface connected to the electron-collecting electrode, consistent with the trends observed in device performance. Using nanorods instead of spherical particles results in a highly connected network of particles distributed homogeneously through the film. The nanorods are oriented close to parallel to the plane of the film.


Efficacy of sucralfate in the prevention of recurrence of duodenal ulcers.
Eighty-four patients who were endoscopically confirmed to have healed duodenal ulcers were entered into this 1-year, double-blind, placebo-controlled trial of sucralfate, 1g twice daily, in the prevention of duodenal ulcer recurrence. Patients remained in the study until recurrence of ulceration was endoscopically confirmed. Sixty-one patients could be evaluated for efficacy of treatment. Within 6 months, 23 of 31 placebo patients (74%) and 6 of 30 sucralfate patients (20%) had ulcer recurrence. At 12 months, 25 of 31 placebo patients (80%) and 8 of 30 receiving sucralfate (27%) had ulcer recurrence. The lower rate of ulcer recurrence in patients receiving sucralfate was significant (p = 0.0001). Survival curves also showed that sucralfate was significantly more effective in preventing relapse (p = 0.0001). Three patients were judged as experiencing drug-related side effects, two of which were in the placebo group. The results indicate that sucralfate is significantly more effective than placebo in the prevention of recurrence of duodenal ulcer disease.


The case for strategic international alliances to harness nutritional genomics for public and personal health.
Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.


Habitat fragmentation causes immediate and time-delayed biodiversity loss at different trophic levels.
Intensification or abandonment of agricultural land use has led to a severe decline of semi-natural habitats across Europe. This can cause immediate loss of species but also time-delayed extinctions, known as the extinction debt. In a pan-European study of 147 fragmented grassland remnants, we found differences in the extinction debt of species from different trophic levels. Present-day species richness of long-lived vascular plant specialists was better explained by past than current landscape patterns, indicating an extinction debt. In contrast, short-lived butterfly specialists showed no evidence for an extinction debt at a time scale of c. 40 years. Our results indicate that management strategies maintaining the status quo of fragmented habitats are insufficient, as time-delayed extinctions and associated co-extinctions will lead to further biodiversity loss in the future.


Global oral health inequalities: dental caries task group--research agenda.
The IADR Global Oral Health Inequalities Task Group on Dental Caries has synthesized current evidence and opinion to identify a five-year implementation and research agenda which should lead to improvements in global oral health, with particular reference to the implementation of current best evidence as well as integrated action to reduce caries and health inequalities between and within countries. The Group determined that research should: integrate health and oral health wherever possible, using common risk factors; be able to respond to and influence international developments in health, healthcare, and health payment systems as well as dental prevention and materials; and exploit the potential for novel funding partnerships with industry and foundations. More effective communication between and among the basic science, clinical science, and health promotion/public health research communities is needed. Translation of research into policy and practice should be a priority for all. Both community and individual interventions need tailoring to achieve a more equal and person-centered preventive focus and reduce any social gradient in health. Recommendations are made for both clinical and public health implementation of existing research and for caries-related research agendas in clinical science, health promotion/public health, and basic science.


Prognostic value of magnetic resonance imaging in dogs with paraplegia caused by thoracolumbar intervertebral disk extrusion: 77 cases (2000-2003).
To determine whether magnetic resonance imaging findings in dogs with paraplegia caused by thoracolumbar intervertebral disk extrusion were predictive of clinical outcome. Retrospective case series. 77 dogs. Medical records and magnetic resonance images were reviewed; clinical outcome was classified as successful (regained ability to walk with no more than mild neurologic deficits) or unsuccessful (severe neurologic deficits persisted). The prognostic value of magnetic resonance imaging was compared with prognostic value of deep pain perception, duration of clinical signs, and rate of onset of clinical signs. 33 (43%) dogs had areas of hyperintensity of the spinal cord greater than or equal to the length of the L2 vertebral body on T2-weighted magnetic resonance images. All 44 dogs without areas of hyperintensity on T2-weighted images had a successful outcome, but only 18 of the 33 (55%) dogs with an area of hyperintensity did. Only 5 of 16 dogs with an area of hyperintensity that had also lost deep pain perception had a successful outcome. The odds ratio for an unsuccessful outcome for a dog with an area of hyperintensity (29.87) was higher than the odds ratio for a dog that had lost deep pain perception (5.24). Duration and rate of onset of clinical signs were not associated with clinical outcome. Findings suggest that results of magnetic resonance imaging can be used to predict clinical outcome in dogs with paraplegia caused by intervertebral disk extrusion.


Minimum Required Attention: A Human-Centered Approach to Driver Inattention.
To propose a driver attention theory based on the notion of driving as a satisficing and partially self-paced task and, within this framework, present a definition for driver inattention. Many definitions of driver inattention and distraction have been proposed, but they are difficult to operationalize, and they are either unreasonably strict and inflexible or suffer from hindsight bias. Existing definitions of driver distraction are reviewed and their shortcomings identified. We then present the minimum required attention (MiRA) theory to overcome these shortcomings. Suggestions on how to operationalize MiRA are also presented. MiRA describes which role the attention of the driver plays in the shared "situation awareness of the traffic system." A driver is considered attentive when sampling sufficient information to meet the demands of the system, namely, that he or she fulfills the preconditions to be able to form and maintain a good enough mental representation of the situation. A driver should only be considered inattentive when information sampling is not sufficient, regardless of whether the driver is concurrently executing an additional task or not. The MiRA theory builds on well-established driver attention theories. It goes beyond available driver distraction definitions by first defining what a driver needs to be attentive to, being free from hindsight bias, and allowing the driver to adapt to the current demands of the traffic situation through satisficing and self-pacing. MiRA has the potential to provide the stepping stone for unbiased and operationalizable inattention detection and classification.


Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33°C versus 36°C.
Target temperature management is recommended as a neuroprotective strategy after out-of-hospital cardiac arrest. Potential effects of different target temperatures on cognitive impairment commonly described in survivors have not been investigated sufficiently. The primary aim of this study was to evaluate whether a target temperature of 33°C compared with 36°C was favorable for cognitive function; the secondary aim was to describe cognitive impairment in cardiac arrest survivors in general. Study sites included 652 cardiac arrest survivors originally randomized and stratified for site to temperature control at 33°C or 36°C within the Target Temperature Management trial. Survival until 180 days after the arrest was 52% (33°C, n=178/328; 36°C, n=164/324). Survivors were invited to a face-to-face follow-up, and 287 cardiac arrest survivors (33°C, n=148/36°C, n=139) were assessed with tests for memory (Rivermead Behavioural Memory Test), executive functions (Frontal Assessment Battery), and attention/mental speed (Symbol Digit Modalities Test). A control group of 119 matched patients hospitalized for acute ST-segment-elevation myocardial infarction without cardiac arrest performed the same assessments. Half of the cardiac arrest survivors had cognitive impairment, which was mostly mild. Cognitive outcome did not differ (P>0.30) between the 2 temperature groups (33°C/36°C). Compared with control subjects with ST-segment-elevation myocardial infarction, attention/mental speed was more affected among cardiac arrest patients, but results for memory and executive functioning were similar. Cognitive function was comparable in survivors of out-of-hospital cardiac arrest when a temperature of 33°C and 36°C was targeted. Cognitive impairment detected in cardiac arrest survivors was also common in matched control subjects with ST-segment-elevation myocardial infarction not having had a cardiac arrest. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01946932.


Does preoperative heparin increase the postoperative bleeding risk in women undergoing prosthetic breast implant surgery? A review of the data from a single institution.
In 2008, the authors' institution adopted a policy requiring that all patients, regardless of preoperative risk, receive both sequential compression devices and a single preoperative subcutaneous 5000 unit injection of heparin. A previously published 12-year review at this same institution before this policy demonstrated a 1.5% 30-day postoperative incidence of hematoma in primary augmentation or delayed tissue expander based breast reconstructions. To determine the incidence of postoperative bleeding complications associated with preoperative administration of 5000 units of subcutaneous heparin and compare that incidence with previously published data. Patient data were collected prospectively and maintained in a secure database at a single institution with institutional review board approval. Current procedural terminology and International Classification of Diseases, Ninth Revision, coding was then used to identify all patients who received either primary breast augmentation or delayed tissue expander based breast reconstruction during a five-year period. The primary outcome was the incidence of postoperative bleeding complication. A bleeding complication was defined as any hemorrhagic event that required a return to the operating room. The overall incidence of significant postoperative bleeding was 1.47% (five of 340 [1.16% augmentation, 2.50% expander]). Comparing the current results with the previously published data, demonstrated an OR of 0.98 (95% CI 0.38 to 2.55). In women undergoing primary breast augmentation or delayed tissue expander breast reconstruction, heparin prophylaxis did not increase the risk for significant postoperative bleeding compared with historical controls.


Evaluation of treatment adherence in outpatients with schizophrenia.
Treatment nonadherence is a major obstacle in the successful management of schizophrenia. Finding out factors associated with nonadherence and the reasons for nonadherence are important to improve treatment adherence in patients with schizophrenia. This study was conceived to evaluate treatment adherence in patients with schizophrenia and the factors associated with it. A cross-sectional study was conducted in 50 consecutive patients with schizophrenia with the help of semi-structured pro forma consisting of sociodemographic details, information regarding illness and treatment history, (PANSS), and Morisky Medication Adherence Scale-8 to assess medication adherence. Nonadherent patients were further assessed for their reasons for nonadherence. Among the patients, 52% were low adherers (nonadherers). Factors associated with nonadherence were younger age of patients, male gender, low household income, higher PANSS score (positive, negative, and total score), lower grades of insight, lack of family history of psychiatric illness, responsibility of taking self-medications, first-generation antipsychotics, and number of drugs in prescription. Major reason for nonadherence given by patients were adverse effects of medications, treatment perceived as ineffective, financial problems, shame and stigma about illness and treatment, regarding treatment unnecessary and difficulty to access health-care facility. Our study established high proportion of nonadherence in patients with schizophrenia and also brought out factors associated and reasons for nonadherence. Adequate psychoeducation of patients and their caretakers as well as psychosocial interventions, strengthening mental health infrastructure, and community mental health services will significantly improve treatment adherence.


Mixture toxicity and interactions of copper, nickel, cadmium, and zinc to barley at low effect levels: Something from nothing?
Metal contamination is mostly a mixture of different metals, and these multicomponent mixtures can produce significant mixture effects. The present study was set up to investigate the toxicity of multiple metal mixtures of Cu, Ni, Cd, and Zn to plants at metal doses individually causing low-level phytotoxic effects. Barley (Hordeum vulgare L.) root elongation toxicity tests were performed in resin-buffered nutrient solutions to control metal speciation. Treatments included single-metal concentrations and binary, ternary, and quaternary mixtures. Mixtures of different metals at free ion concentrations, each causing <10% inhibition of root elongation, yielded significant mixture effects, with inhibition reaching up to 50%. The independent action (IA) model predicted mixture toxicity statistically better than the concentration addition (CA) model, but some synergisms relative to the IA model were observed. These synergisms relative to IA were most pronounced in quaternary mixtures and when the dose-response curves had steep slopes. Generally, antagonistic interactions relative to the CA model were observed. Increasing solution Zn concentrations shifted metal interactions (CA based) from additive or slightly synergistic at background Zn concentrations to antagonistic at higher Zn concentrations, suggesting a protective effect of Zn. Overall, the present study shows that the CA model can be used as a conservative model to predict metal mixture toxicity to barley. Environ Toxicol Chem 2016;35:2483-2492. © 2016 SETAC.


Nutritional aspect of nephrolithiasis.
Nephrolithiasis is associated with a variety of abnormalities in urinary composition. These abnormal urinary risk factors are due to dietary indiscretions, physiological-metabolic disturbances or both. Stone disease is morbid and costly, and the recurrence rates may be as high as 30-50% after 5 years. Efforts to prevent stone formation are, therefore, essential. Dietary factors play an important role in kidney stone formation. Tailored dietary recommendations based on metabolic evaluation should be offered to patients for the prevention of recurrence of stone formation. Dietary intervention and subsequent evaluations of therapeutic efficacy should be based on results from multiple 24-h urine collections. Urine flow of >1 ml/kg/h almost eliminates the risk of supersaturation for calcium oxalate, calcium phosphate and uric acid, thus protecting from the formation of corresponding kidney stones. In patients with cystenuria, the required urine flow may even be higher and, in cases such as primary xanthinuria, high fluid intake is required. Milk intake in these patients should be within the RDA of calcium and protein. In children, recommendation of a high fluid intake has only limited success. Nevertheless, each patient should be advised about adequate fluid intake to increase urine volume in accordance with body size. Although children with hypocitraturia may benefit from therapeutic agents that raise the urine citrate concentration, all children bearing residual fragments should be counseled on adequate fluid intake along with potassium citrate treatment to prevent stone regrowth or formation.


Oviduct binding ability of porcine spermatozoa develops in the epididymis and can be advanced by incubation with caudal fluid.
The sperm reservoir is formed when spermatozoa bind to the epithelium of the uterotubal junction and caudal isthmus of the oviduct. It is an important mechanism that helps synchronize the meeting of gametes by regulating untimely capacitation and polyspermic fertilization. This study investigated the influence of epididymal maturation and caudal fluid on the ability of spermatozoa to bind to oviduct epithelium using a model porcine oviduct explant assay. Spermatozoa from the rete testis, middle caput (E2-E3), middle corpus (E6), and cauda (E8) of Large White or Large White × Landrace boars aged 10 to 14 months were diluted in modified Androhep solution and incubated with porcine oviduct explants. Results reported in this study support our hypothesis that testicular spermatozoa need to pass through the regions of the epididymis to acquire the ability to bind to the oviduct. There was a sequential increase in the number of spermatozoa that bound to oviduct explants from the rete testis to caudal epididymis. Binding of caudal spermatozoa to isthmic explants was the highest (15.0 ± 1.2 spermatozoa per 1.25 mm(2), mean ± standard error of the mean; P ≤ 0.05) and lowest by spermatozoa from the rete testis (2.0 ± 0.3 per 1.25 mm(2)), and higher to isthmus from sows compared to gilts (35.8 ± 6.7 per 1.25 mm(2) vs. 14.8 ± 3.0 per 1.25 mm(2); P ≤ 0.05). Binding of ejaculated spermatozoa to porcine isthmus was higher than that for caudal spermatozoa (26.3 ± 1.4 per 1.25 mm(2) vs. 15.0 ± 0.8 per 1.25 mm(2); P ≤ 0.05) and higher to porcine than to bovine isthmus (26.3 ± 2.3 per 1.25 mm(2) vs. 18.8 ± 1.9 per 1.25 mm(2); P ≤ 0.05). Incubation of spermatozoa from the caput and corpus in caudal fluid increased the ability of spermatozoa to bind to the oviduct epithelium (P ≤ 0.05). In conclusion, the capacity of testicular spermatozoa to bind to the oviduct epithelium increases during their maturation in the epididymis and can be advanced by components of the caudal fluid.


Early erythropoiesis-stimulating agents in preterm or low birth weight infants.
Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia and to provide neuro protection and protection against necrotising enterocolitis (NEC). Darbepoetin (Darbe) and EPO are currently available ESAs. To assess the effectiveness and safety of ESAs (erythropoietin (EPO) and/or Darbe) initiated early (before eight days after birth) compared with placebo or no intervention in reducing red blood cell (RBC) transfusions, adverse neurological outcomes, and feeding intolerance including necrotising enterocolitis (NEC) in preterm and/or low birth weight infants. Primary objective for studies that primarily investigate the effectiveness and safety of ESAs administered early in reducing red blood cell transfusions: To assess the effectiveness and safety of ESAs initiated early in reducing red blood cell transfusions in preterm infants. Secondary objectives: Review authors performed subgroup analyses of low (≤ 500 IU/kg/week) and high (> 500 IU/kg/week) doses of EPO and the amount of iron supplementation provided: none, low (≤ 5 mg/kg/d), and high (> 5 mg/kg/d). Primary objective for studies that primarily investigate the neuro protective effectiveness of ESAs: To assess the effectiveness and safety of ESAs initiated early in reducing adverse neurological outcomes in preterm infants. Primary objective for studies that primarily investigate the effectiveness of EPO or Darbe administered early in reducing feeding intolerance: To assess the effectiveness and safety of ESAs administered early in reducing feeding intolerance (and NEC) in preterm infants. Other secondary objectives: To compare the effectiveness of ESAs in reducing the incidence of adverse events and improving long-term neurodevelopmental outcomes. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE via PubMed (1966 to 10 March 2017), Embase (1980 to 10 March 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 10 March 2017). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised and quasi-randomised controlled trials. Randomised and quasi-randomised controlled trials of early initiation of EAS treatment versus placebo or no intervention in preterm or low birth weight infants. We used the methods described in the Cochrane Handbook for Systematic Reviews of Interventions and the GRADE approach to assess the quality of evidence. This updated review includes 34 studies enrolling 3643 infants. All analyses compared ESAs versus a control consisting of placebo or no treatment. Early ESAs reduced the risk of 'use of one or more [red blood cell] RBC transfusions' (typical risk ratio (RR) 0.79, 95% confidence interval (CI) 0.74 to 0.85; typical risk difference (RD) -0.14, 95% CI -0.18 to -0.10; I2 = 69% for RR and 62% for RD (moderate heterogeneity); number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 6 to 10; 19 studies, 1750 infants). The quality of the evidence was low. Necrotising enterocolitis was significantly reduced in the ESA group compared with the placebo group (typical RR 0.69, 95% CI 0.52 to 0.91; typical RD -0.03, 95% CI -0.05 to -0.01; I2 = 0% for RR and 22% for RD (low heterogeneity); NNTB 33, 95% CI 20 to 100; 15 studies, 2639 infants). The quality of the evidence was moderate. Data show a reduction in 'Any neurodevelopmental impairment at 18 to 22 months' corrected age in the ESA group (typical RR 0.62, 95% CI 0.48 to 0.80; typical RD -0.08, 95% CI -0.12 to -0.04; NNTB 13, 95% CI 8 to 25. I2 = 76% for RR (high heterogeneity) and 66% for RD (moderate); 4 studies, 1130 infants). The quality of the evidence was low. Results reveal increased scores on the Bayley-II Mental Development Index (MDI) at 18 to 24 months in the ESA group (weighted mean difference (WMD) 8.22, 95% CI 6.52 to 9.92; I2 = 97% (high heterogeneity); 3 studies, 981 children). The quality of the evidence was low. The total volume of RBCs transfused per infant was reduced by 7 mL/kg. The number of RBC transfusions per infant was minimally reduced, but the number of donors to whom infants who were transfused were exposed was not significantly reduced. Data show no significant difference in risk of stage ≥ 3 retinopathy of prematurity (ROP) with early EPO (typical RR 1.24, 95% CI 0.81 to 1.90; typical RD 0.01, 95% CI -0.02 to 0.04; I2 = 0% (no heterogeneity) for RR; I2 = 34% (low heterogeneity) for RD; 8 studies, 1283 infants). Mortality was not affected, but results show significant reductions in the incidence of intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL). Early administration of ESAs reduces the use of red blood cell (RBC) transfusions, the volume of RBCs transfused, and donor exposure after study entry. Small reductions are likely to be of limited clinical importance. Donor exposure probably is not avoided, given that all but one study included infants who had received RBC transfusions before trial entry. This update found no significant difference in the rate of ROP (stage ≥ 3) for studies that initiated EPO treatment at less than eight days of age, which has been a topic of concern in earlier versions of this review. Early EPO treatment significantly decreased rates of IVH, PVL, and NEC. Neurodevelopmental outcomes at 18 to 22 months and later varied in published studies. Ongoing research should evaluate current clinical practices that will limit donor exposure. Promising but conflicting results related to the neuro protective effect of early EPO require further study. Very different results from the two largest published trials and high heterogeneity in the analyses indicate that we should wait for the results of two ongoing large trials before drawing firm conclusions. Administration of EPO is not currently recommended because limited benefits have been identified to date. Use of darbepoetin requires further study.


Metastatic pulmonary calcification in patients with hypercalcemia: findings on chest radiographs and CT scans.
The objective of this study was to characterize the findings on chest radiographs and CT scans in patients with metastatic pulmonary calcification due to hypercalcemia. The chest radiographs and CT scans of seven patients with biopsy-proved metastatic pulmonary calcification were reviewed by two observers. Metastatic calcification was due to chronic renal failure (n = 4), T-cell leukemia (n = 1), multiple endocrine neoplasia type I syndrome (n = 1), and idiopathic hypercalcemia (n = 1). Numerous nodular opacities measuring 3-10 mm in diameter were seen on the chest radiographs in five cases, and patchy areas of parenchymal opacification were seen in two cases. Calcification of the nodules was evident in two cases. On CT scans, pulmonary nodules were present in all seven cases. These nodules were predominant in the upper lung zone in three cases, were diffuse in three cases, and were predominant in the lower lung zone in one case. Calcification of the nodules was evident on the CT scans in four of the seven cases, and calcification of vessels in the chest wall was evident in six of seven cases. Other findings on CT scans included diffuse areas of ground-glass attenuation (n = 3) and patchy consolidation (n = 2). Numerous small nodules are the most common finding on the chest radiographs of patients with metastatic pulmonary calcification. The calcific nature of the nodules is seldom obvious, however. Pulmonary nodules are also the most common finding on CT scans, where the calcific nature of the nodules is more readily apparent. Additionally, calcification is often seen in the vessels of the chest wall on CT scans. The combination of calcified nodules and calcified vessels in the chest wall on CT scans may be characteristic.


Microcephaly with chorioretinal degeneration.
To describe the ophthalmologic findings and electroretinograms in patients with microcephaly and chorioretinal degeneration. We reviewed the hospital records of 20 patients with microcephaly that was not part of a recognizable syndrome prior to initial referral to the institutional consultative practice of one of the authors (RGW). Twelve patients, all from separate families, were diagnosed as having microcephaly with chorioretinopathy. Ten of these patients had ISCEV-standard electroretinograms (ERG). No family history of microcephaly or retinal degeneration was found in any of our patients. Three patients had another family member with mental retardation. Three of the 12 were compatible with the autosomal dominant form of microcephaly with chorioretinopathy (MIM 156590), possibly as a new mutation. Eight patients, who had fundus findings of retinitis pigmentosa, were similar to the autosomal recessive form of microcephaly with chorioretinal degeneration (MIM 251270). The ERGs were moderately to severely subnormal for responses of both rods and cones. The retinal findings varied from no pigmentary changes, pigment clumping and bone spicules, pigmentary granularity, bull's eye maculopathy, choroidal and retinal atrophy, to lacunar depigmentation. Mental retardation was mild to profound. The abnormal findings from MRI/ CT brain scans (8 patients) were cerebellar atrophy (2), agenesis of cerebellar vermis (1), cortical atrophy (1), and pachygyria (1). Dysmorphic features were present in most patients. Chromosome studies were normal, except for one patient with ring chromosome 14. Although the patients reviewed in this study represent a heterogeneous group of disorders, ocular abnormalities, especially retinal degeneration, are frequent among patients with microcephaly.


Biology is the root of variability: cautionary tales in Caenorhabditis elegans biology.
Reproducibility is critical for the standardization, interpretation, and progression of research. However, many factors increase variability and reduce reproducibility. In Caenorhabditis elegans research, there are many possible causes of variability that may explain why experimental outcomes sometimes differ between laboratories and between experiments. Factors contributing to experimental variability include the genetic background of both C. elegans and its bacterial diet, differences in media composition, intergenerational and transgenerational effects that may be carried over for generations, and the use of chemicals or reagents that may have unexpected consequences. This review summarizes sources of variability in C. elegans research and serves to identify laboratory practices that could influence reproducibility.


Single amino acid mutations in the potato immune receptor R3a expand response to Phytophthora effectors.
Both plants and animals rely on nucleotide-binding domain and leucine-rich repeat-containing (NB-LRR or NLR) proteins to respond to invading pathogens and activate immune responses. How plant NB-LRR proteins respond to pathogens is poorly understood. We undertook a gain-of-function random mutagenesis screen of the potato NB-LRR immune receptor R3a to study how this protein responds to the effector protein AVR3a from the oomycete pathogen Phytophthora infestans. R3a response can be extended to the stealthy AVR3aEM isoform of the effector while retaining recognition of AVR3aKI. Each one of eight single amino acid mutations is sufficient to expand the R3a response to AVR3aEM and other AVR3a variants. These mutations occur across the R3a protein, from the N terminus to different regions of the LRR domain. Further characterization of these R3a mutants revealed that at least one of them was sensitized, exhibiting a stronger response than the wild-type R3a protein to AVR3aKI. Remarkably, the N336Y mutation, near the R3a nucleotide-binding pocket, conferred response to the effector protein PcAVR3a4 from the vegetable pathogen P. capsici. This work contributes to understanding how NB-LRR receptor specificity can be modulated. Together with knowledge of pathogen effector diversity, this strategy can be exploited to develop synthetic immune receptors.


D-penicillamine adsorption on gold: an in situ ATR-IR spectroscopic and QCM study.
The adsorption of penicillamine from ethanol on gold was studied in situ by attenuated total reflection infrared (ATR-IR) and quartz crystal microbalance (QCM) experiments. Both ATR-IR and QCM reveal a fast mass uptake. In ethanol, the molecule adopts a zwitterionic form. Upon adsorption, part of the molecules deprotonate at the amine group, which is a relatively slow process that goes along with a strong shift of the nu(as)(COO(-)) mode. Both ATR-IR and QCM confirm a physisorbed layer. ATR-IR furthermore shows that the latter consists of zwitterionic molecules only, whereas both zwitterionic and anionic species are found in the chemisorbed layer. The infrared spectra of the physisorbed and chemisorbed layers are rather different, and the molecules within both layers seem to be oriented with respect to the surface. The ATR-IR spectra furthermore indicate that all three functional groups of penicillamine (i.e., thiol, carboxylate, and amine) interact with the surface, and density functional theory calculations support this finding. QCM also shows that the molecule uses considerably more space on the surface than molecules of similar size, which supports a three-point interaction. The latter leads to a strong anchoring of the molecule to the metal, which may explain the exceptional capability of penicillamine to bind metals.


Body mass index: a risk factor for unstable angina and myocardial infarction in patients with angiographically confirmed coronary artery disease.
In patients with coronary artery disease (CAD), acute thrombosis frequently occurs in coronary arteries with only mild or moderate stenoses. Obesity increases the risk of atherosclerosis, but it is not known whether it also increases the risk of coronary thrombosis. We hypothesized that body mass index (BMI) might be an independent predictor of an acute coronary syndrome in patients with established coronary atherosclerosis. Of 504 patients undergoing coronary angiography, those with evidence of >10% coronary artery stenoses were divided into 2 groups, with either stable (n=226) or unstable CAD (unstable angina or myocardial infarction; n=156). After adjusting for other risk factors (age, gender, blood pressure, lipid levels, insulin resistance, leptin, fibrinogen, C-reactive protein (CRP), CAD severity on angiography, smoking status, and a history of myocardial infarction or hypertension), BMI had a significant independent association with an acute coronary syndrome, with an odds ratio of 1.49 (P=0.014). This positive relation between BMI and the risk of acute coronary events was evident for even mildly elevated BMI values. Multivariate analysis also showed that CRP and the number of coronary lesions were independent predictors of risk of an acute coronary event. In patients with established coronary atherosclerosis, BMI, as well as CRP and number of coronary lesions, are independently associated with acute coronary syndromes. There is evidence of increased risk even at mildly elevated BMI levels.


Driving electromechanically assisted Gait Trainer for people with stroke.
Electromechanically assisted gait training is a promising task-oriented approach for gait restoration, especially for people with subacute stroke. However, few guidelines are available for selecting the parameter values of the electromechanical Gait Trainer (GT) (Reha-Stim; Berlin, Germany) and none is tailored to a patient's motor capacity. We assessed 342 GT sessions performed by 20 people with stroke who were stratified by Functional Ambulatory Category. In the first GT session of all patients, the body-weight support (BWS) required was higher than that reported in the literature. In further sessions, we noted a slow reduction of BWS and a fast increment of walking speed for the most-affected patients. Inverse trends were observed for the less-affected patients. In all the patients, the heart rate increment was about 20 beats per minute, even for sessions in which the number of strides performed was up to 500. In addition, the effective BWS measured during GT sessions was different from that initially selected by the physiotherapist. This difference depended mainly on the position of the GT platforms during selection. Finally, harness acceleration in the anteroposterior direction proved to be higher in patients with stroke than in nondisabled subjects. Our findings are an initial step toward scientifically selecting parameters in electromechanically assisted gait training.


Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps.
We have recently demonstrated using functional magnetic resonance imaging the presence of synchronous low-frequency fluctuations of signal intensities from the resting human brain that have a high degree of temporal correlation (p < 0.0001) both within and across the sensorimotor cortex. A statistically significant overlap between the resting-state functional connectivity map and the task-activation map due to bilateral finger tapping was obtained. Similar results have been obtained in the auditory and visual cortex. Because the pulse sequence used for collecting data was sensitive to blood flow and blood oxygenation, these low-frequency fluctuations of signal intensity may have arisen from variations of both. The objective of this study was simultaneously to determine the contribution of the blood oxygenation level signal and the flow signal to physiological fluctuations in the resting brain using the flow-sensitive alternating inversion recovery pulse sequence. In all subjects, the functional connectivity maps obtained from BOLD had a greater coincidence with task-activation maps than the corresponding functional connectivity maps obtained from blood-flow signals at the same level of statistical significance. Results of this study suggest that while variations in blood flow might contribute to functional connectivity maps, BOLD signals play a dominant role in the mechanism that gives rise to functional connectivity in the resting human brain.


Challenges and opportunities of solvent-based additive extraction methods for plastic recycling.
Additives are ubiquitously used in plastics to improve their functionality. However, they are not always desirable in their 'second life' and are a major bottleneck for chemical recycling. Although research on extraction techniques for efficient removal of additives is increasing, it resembles much like uncharted territory due to the broad variety of additives, plastics and removal techniques. Today solvent-based additive extraction techniques, solid-liquid extraction and dissolution-precipitation, are considered to be the most promising techniques to remove additives. This review focuses on the assessment of these techniques by making a link between literature and physicochemical principles such as diffusion and Hansen solubility theory. From a technical point of view, dissolution-precipitation is preferred to remove a broad spectrum of additives because diffusion limitations affect the solid-liquid extraction recoveries. Novel techniques such as accelerated solvent extraction (ASE) are promising for finding the balance between these two processes. Because of limited studies on the economic and environmental feasibility of extraction methods, this review also includes a basic economic and environmental assessment of two extreme cases for the extraction of additives. According to this assessment, the feasibility of additives removal depends strongly on the type of additive and plastic and also on the extraction conditions. In the best-case scenario at least 70% of solvent recovery is required to extract plasticizers from polyvinyl chloride (PVC) via dissolution-precipitation with tetrahydrofuran (THF), while solid-liquid extraction of phenolic antioxidants and a fatty acid amide slip agents from polypropylene (PP) with dichloromethane (DCM) can be economically viable even without intensive solvent recovery.


Dissecting Resistance to Phytophthora cinnamomi in Interspecific Hybrid Chestnut Crosses Using Sequence-Based Genotyping and QTL Mapping.
The soilborne oomycete Phytophthora cinnamomi-which causes root rot, trunk cankers, and stem lesions on an estimated 5,000 plant species worldwide-is a lethal pathogen of American chestnut (Castanea dentata) as well as many other woody plant species. P. cinnamomi is particularly damaging to chestnut and chinquapin trees (Castanea spp.) in the southern portion of its native range in the United States due to relatively mild climatic conditions that are conductive to disease development. Introduction of resistant genotypes is the most practical solution for disease management in forests because treatment with fungicides and eradication of the pathogen are neither practical nor economically feasible in natural ecosystems. Using backcross families derived from crosses of American chestnuts with two resistant Chinese chestnut cultivars Mahogany and Nanking, we constructed linkage maps and identified quantitative trait loci (QTLs) for resistance to P. cinnamomi that had been introgressed from these Chinese chestnut cultivars. In total, 957 plants representing five cohorts of three hybrid crosses were genotyped by sequencing and phenotyped by standardized inoculation and visual examination over a 6-year period from 2011 to 2016. Eight parental linkage maps comprising 7,715 markers were constructed, and 17 QTLs were identified on four linkage groups (LGs): LG_A, LG_C, LG_E, and LG_K. The most consistent QTLs were detected on LG_E in seedlings from crosses with both 'Mahogany' and 'Nanking' and LG_K in seedlings from 'Mahogany' crosses. Two consistent large and medium effect QTLs located ∼10 cM apart were present in the middle and at the lower end of LG_E; other QTLs were considered to have small effects. These results imply that the genetic architecture of resistance to P. cinnamomi in Chinese chestnut × American chestnut hybrid progeny may resemble the P. sojae-soybean pathosystem, with a few dominant QTLs along with quantitatively inherited partial resistance conferred by multiple small-effect QTLs.


Comparison of three risk of malignancy indices in evaluation of pelvic masses.
The aims of this study were to validate the risk of malignancy index (RMI) incorporating menopausal status, serum CA 125 levels, and ultrasound features for discriminating benign from malignant pelvic masses and to evaluate the performance of the three different risk of malignancy indices (RMI 1, RMI 2, and RMI 3). This is a retrospective study of 152 women admitted at Kasturba Hospital, Manipal, between January 1997 and August 1999 for surgical exploration of pelvic masses. The sensitivity, specificity, and positive predictive value of serum CA 125 levels, ultrasound findings, and menopausal status were taken separately and combined into the RMI 1, RMI 2, and RMI 3 to diagnose ovarian cancer. The risk of malignancy index is the product of menopausal score, ultrasound score, and serum CA 125 levels. The study confirms that the malignancy risk index is more accurate than the menopausal status, serum CA 125 levels, and ultrasound features separately in diagnosing malignancy. There was no statistically significant difference in the performance of these three different malignancy risk indices in identifying malignancy. The risk of malignancy index is able to identify malignant and benign pelvic masses efficiently to optimize therapy. The risk of malignancy index is a simple scoring system which can be used in less specialized gynecology centers. We recommend the use of any of these risk of malignancy indices to facilitate the selection of cases for referral to an oncological unit for adequate staging and optimal debulking.


Cocreative Development of the QoL-ME: A Visual and Personalized Quality of Life Assessment App for People With Severe Mental Health Problems.
Quality of life (QoL) is a prominent outcome measure in mental health. However, conventional methods for QoL assessment rely heavily on language-based communication and therefore may not be optimal for all individuals with severe mental health problems. In addition, QoL assessment is usually based on a fixed number of life domains. This approach conflicts with the notion that QoL is influenced by individual values and preferences. A digital assessment app facilitates both the accessibility and personalization of QoL assessment and may, therefore, help to further advance QoL assessment among individuals with severe mental health problems. This study focused on the development of an innovative, visual, and personalized QoL assessment app for people with severe mental health problems: the QoL-ME. This study targeted 3 groups of individuals with severe mental health problems: (1) people with psychiatric problems, (2) people treated in forensic psychiatry, and (3) people who are homeless. A group of 59 participants contributed to the 6 iterations of the cocreative development of the QoL-ME. In the brainstorming stage, consisting of the first iteration, participants' previous experiences with questionnaires and mobile apps were explored. Participants gave their feedback on initial designs and wireframes in the second to fourth iterations that made up the design stage. In the usability stage that comprised the final 2 iterations, the usability of the QoL-ME was evaluated. In the brainstorming stage, participants stressed the importance of privacy and data security and of receiving feedback when answering questionnaires. Participants in the design stage indicated a preference for paging over scrolling, linear navigation, a clean and minimalist layout, the use of touchscreen functionality in various modes of interaction, and the use of visual analog scales. The usability evaluation in the usability stage revealed good to excellent usability. The cocreative development of the QoL-ME resulted in an app that corresponds to the preferences of participants and has strong usability. Further research is needed to evaluate the psychometric quality of the QoL-ME and to investigate its usefulness in practice.


Admission international normalized ratio levels, early treatment strategies, and major bleeding risk among non-ST-segment-elevation myocardial infarction patients on home warfarin therapy: insights from the National Cardiovascular Data Registry.
Non-ST-segment-elevation myocardial infarction patients on home warfarin pose treatment concerns because of their potential increased risk of bleeding. Expert opinion from the American College of Cardiology/American Heart Association guidelines suggest holding anticoagulants and initiating antiplatelet therapy among therapeutically anticoagulated non-ST-segment-elevation myocardial infarction patients. Yet, little is known about contemporary treatment patterns and bleeding risks in this population. We stratified 5787 non-ST-segment-elevation myocardial infarction patients on home warfarin therapy using data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines by admission international normalized ratio (INR) levels: subtherapeutic (INR <2), therapeutic (INR, 2-3), and supratherapeutic (INR >3). Multivariable logistic generalized estimating equations models were constructed to examine the associations between admission INR level, early antithrombotic treatment and invasive therapy, and risk of in-hospital major bleeding. Among these patients, 46%, 35%, and 19% had subtherapeutic, therapeutic, and supratherapeutic admission INR levels, respectively. Risk of major bleeding was higher among patients with therapeutic (15%; adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.03-1.50) and supratherapeutic (22%; odds ratio, 1.60; 95% CI, 1.30-1.97) anticoagulation compared with the subtherapeutic group (12%). Among patients with admission INR ≥2, 45% were treated with early (within 24 hours) heparin, 35% with early clopidogrel, 14% with early glycoprotein IIb/IIIa inhibitor, and 36% with early invasive strategy. Early antithrombotic treatment was associated with increased bleeding risk (odds ratio, 1.40 [95% CI, 1.14-1.72] for heparin; 1.50 [95% CI, 1.22-1.84] for clopidogrel; and 1.82 [95% CI, 1.43-2.32] for glycoprotein IIb/IIIa inhibitor); however, an early invasive strategy was not (odds ratio, 1.09; 95% CI, 0.86-1.37). No significant interactions were observed between INR level and use of each early treatment in its association with bleeding. National patterns of early antithrombotic treatment for non-ST-segment-elevation myocardial infarction patients on home warfarin diverge from expert opinion provided by current practice guidelines. Early antithrombotic treatment was associated with increased bleeding risk regardless of admission INR level.


Monodisperse magnetic nanoparticles for biodetection, imaging, and drug delivery: a versatile and evolving technology.
Advances in nanotechnology have pushed forward the synthesis of a variety of functional nanoparticles (NPs) such as semiconductor quantum dots (QDs), magnetic and metallic NPs. The unique electronic, magnetic, and optical properties exhibited by these nanometer-sized materials have enabled a broad spectrum of biomedical applications. In particular, iron-oxide-based magnetic NPs have proved to be highly versatile deep-tissue imaging agents, having been incorporated into clinical applications due to their biocompatibility. This Interdisciplinary Review will focus on the recent advances in strategies for the synthesis and surface modification of highly monodisperse magnetic NPs and their use in imaging, drug delivery, and innovative ultrasensitive bioassays.


Species-dependent alteration of electron transfer in the early stages of charge stabilization in Photosystem I.
Electron transfer (ET) in Photosystem I (PS I) is bidirectional, occurring in two pseudosymmetric branches of cofactors. The relative use of two branches in the green alga Chlamydomonas reinhardtii and the cyanobacterium Synechocystis sp. PCC 6803 has been studied by changing the Met axial ligands of the chlorophyll a acceptor molecules, A0A and A0B, to His. The nature of the effect on the ET is found to be species dependent. In C. reinhardtii, transient absorption and transient EPR data show that in the M688HPsaA variant, forward ET from A0A to the quinone, A1A, is blocked in 100% of the PS I complexes. In contrast, in Synechocystis sp. PCC 6803, forward ET from A0A to A1A is blocked in only 50% of the PS I complexes, but in those PS I complexes in which electrons reach A1A, further transfer to the iron-sulfur cluster FX is blocked. Similar species differences are found for the corresponding B-branch variants. One possible explanation of this behavior is that it is the result of two conformers in which an H-bond between the His side chain and the O1 carbonyl group of A1 is either present or absent. The spectroscopic data suggest that the two conformers are present in nearly equal amounts in the Synechocystis sp. PCC 6803 variants, while only the conformer without the H-bond is present in the same variants of C. reinhardtii.


A "humanized" green fluorescent protein cDNA adapted for high-level expression in mammalian cells.
We constructed gfph, a synthetic version of the jellyfish Aequorea victoria green fluorescent protein (gfp) cDNA that is adapted for high-level expression in mammalian cells, especially those of human origin. A total of 92 base substitutions were made in 88 codons in order to change the codon usage within the gfp10 coding sequence so that it was more appropriate for expression in mammalian cells. We also describe a series of versatile recombinant adeno-associated virus and adenovirus vectors for delivery and expression of genes into mammalian cells and, using these vectors, demonstrate the efficient transduction and expression of the gfph gene in the human cell line 293 and also in vivo, within neurosensory cells of guinea pig eye. Cells infected with recombinant adeno-associated virus-GFPH can be readily sorted by fluorescence-activated cell sorting, suggesting that the newly designed gfph gene could be widely used as a reporter in many gene delivery technologies, including human gene therapy.


Reciprocal signaling by Wnt and Notch specifies a muscle precursor in the C. elegans embryo.
The MS blastomere produces one-third of the body wall muscles (BWMs) in the C. elegans embryo. MS-derived BWMs require two distinct cell-cell interactions, the first inhibitory and the second, two cell cycles later, required to overcome this inhibition. The inductive interaction is not required if the inhibitory signal is absent. Although the Notch receptor GLP-1 was implicated in both interactions, the molecular nature of the two signals was unknown. We now show that zygotically expressed MOM-2 (Wnt) is responsible for both interactions. Both the inhibitory and the activating interactions require precise spatiotemporal expression of zygotic MOM-2, which is dependent upon two distinct Notch signals. In a Notch mutant defective only in the inductive interaction, MS-derived BWMs can be restored by preventing zygotic MOM-2 expression, which removes the inhibitory signal. Our results suggest that the inhibitory interaction ensures the differential lineage specification of MS and its sister blastomere, whereas the inductive interaction promotes the expression of muscle-specifying genes by modulating TCF and β-catenin levels. These results highlight the complexity of cell fate specification by cell-cell interactions in a rapidly dividing embryo.


Tumor prevalence and biomarkers of exposure in brown bullhead (Ameiurus nebulosus) from Back River, Furnace Creek, and Tuckahoe River, Maryland.
Brown bullheads (Ameiurus nebulosus) were collected from 2 locations near Baltimore, Maryland, Back River and Furnace Creek, and 1 (reference) location, Tuckahoe River, to compare the prevalence of tumors (liver and skin) and visible skin lesions (fin erosion and abnormal barbels). Cytochrome P450 activity measured as ethoxyresorufin-O-deethylase, biliary PAH-like fluorescent metabolites, and fillet contaminant concentrations were determined as indicators of exposure in a randomly selected subset of the fish. There were no significant differences in liver tumor prevalence: Back River = 8% (4/50), Furnace Creek = 0% (0/50), and Tuckahoe River = 2.6% (1/39; p = 0.20, extension of Fisher's exact test). Skin tumor prevalence was as follows: Furnace Creek = 12% (6/50), Back River = 8% (4/50), and Tuckahoe River = 0% (0/39; p = 0.063). In the Back River fish, there was a 40% (20/50) prevalence of fin erosion and a 28% (14/50) prevalence of abnormal (shortened, clubbed, or missing) barbels. Fin erosion was not observed in the other collections, and only 10% (5/50) of the Furnace Creek fish had abnormal barbels (p < 0.001 for both lesions). There were statistically significant differences in mean EROD activity, with levels in Furnace Creek and Back River fish approximately twice that found in Tuckahoe River fish. There were also significant differences in mean benzo(a)pyrene-like bile metabolite concentrations: the lowest mean was in the Tuckahoe River fish, 8 times higher in Furnace Creek fish, and 13 times higher in Back River fish. Of the 3 groups, the Back River bullheads appear to be most adversely affected by contaminant exposure because they had the highest prevalence of liver tumors, fin erosion, and abnormal barbels.


Towns with extremely low mortality due to ischemic heart disease in Spain.
The cause of coronary disease inframortality in Spain is unknown. The aim of this study is to identify Spanish towns with very low ischemic heart disease mortality, describe their health and social characteristics, and analyze the relationship with a series of contextual factors. We obtained the number of deaths registered for each of 8,122 Spanish towns in the periods 1989-1998 and 1999-2003. Expected deaths, standardized mortality ratio (SMR), smoothed Relative Risk (RR), and Posterior Probability (PP) of RR > 1 were calculated using Bayesian hierarchical models. Inframortality was defined as any town that displayed an RR below the 10th percentile, an SMR of under 1 for both sexes, and a PP of RR > 1 less than or equal to 0.002 for male and 0.005 for female mortality, during the two periods covered. All the remaining towns, except for those with high mortality classified as "tourist towns", were selected as controls. The association among socioeconomic, health, dietary, lifestyle and vascular risk factors was analyzed using sequential mixed logistic regression models, with province as the random-effects variable. We identified 32 towns in which ischemic heart disease mortality was half the national rate and four times lower than the European Union rate, situated in lightly populated provinces spread across the northern half of Spain, and revealed a surprising pattern of geographic aggegation for 23 of the 32 towns. Variables related with inframortality were: a less aged population (OR 0.93, 95% CI 0.89-0.99); a contextual dietary pattern marked by a high fish content (OR 2.13, 95% CI 1.38-3.28) and wine consumption (OR 1.50, 95% CI 1.08-2.07); and a low prevalence of obesity (OR 0.47, 95% CI 0.22-1.01); and, in the case of towns of over 1000 inhabitants, a higher physician-population ratio (OR 3.80, 95% CI 1.17-12.3). Results indicate that dietary and health care factors have an influence on inframortality. The geographical aggregation suggests that other factors with a spatial pattern, e.g., genetic or environmental might also be implicated. These results will have to be confirmed by studies in situ, with objective measurements at an individual level.


Head impacts sustained by male collegiate water polo athletes.
Water polo is a contact sport that is gaining popularity in the United States and carries a risk of repeated head impacts and concussion. The frequency and magnitude of sport-related head impacts have not been described for water polo. We aimed to compare patterns of empirically measured head impact exposure of male collegiate water polo players to patterns previously reported by a survey of current and former water polo athletes. Participants wore water polo caps instrumented with head impact sensors during three seasons of collegiate water polo. Peak linear acceleration (PLA) and peak rotational acceleration (PRA) were recorded for head impacts. Athlete positions were recorded by research staff at the occurrence of each head impact. Head impacts were sustained by athletes in offensive positions more frequently than in defensive and transition positions (246, 59.9% vs. 93, 22.6% vs. 72, 17.5%). 37% of all head impacts during gameplay were sustained by athletes playing the offensive center position. Impact magnitude (means ± SD: PLA = 36.1±12.3g, PRA = 5.0±2.9 krads/sec2) did not differ between position or game scenario. Among goalies, impact frequency and magnitude were similar between games (means ± SD: 0.54±.51 hits/game, PLA = 36.9±14.2g, PRA = 4.3±4.2 krads/sec2) and practices (means ± SD: 0.96±1.11 hits/practice, PLA = 43.7±14.5g, PRA = 3.9±2.5 krads/sec2). We report that collegiate water polo athletes are at risk for sport-related head impacts and impact frequency is dependent on game scenario and player position. In contrast, magnitude does not differ between scenarios or across positions.


Testicular tumors: what radiologists need to know--differential diagnosis, staging, and management.
Cryptorchidism, family history, and infertility are risk factors for testicular cancer. Most testicular cancers occur in young men aged 18-35 years, and seminoma is the most common cell type. Testicular tumors are usually diagnosed at ultrasonography (US) and are staged at computed tomography (CT) or magnetic resonance (MR) imaging. At US, testicular tumors usually appear as a solid intratesticular mass. Because the differential diagnosis includes infarct and infection, correlation with patient history and symptoms is important. At staging CT or MR imaging, retroperitoneal lymph nodes are considered regional lymph nodes, and the greatest nodal diameter is used to distinguish among N1-N3 disease. The right testicular vein drains into the inferior vena cava, and the left testicular vein drains into the left renal vein. Because of venous and lymphatic drainage pathways, retroperitoneal lymph nodes are the initial landing station for testicular cancers. Enlarged lymph nodes in the supraclavicular region, chest, and pelvis are considered distant metastases. Testicular cancer is initially treated with orchiectomy. The patient may then undergo active surveillance, chemotherapy, radiation therapy, or retroperitoneal lymph node resection, depending primarily on the clinical stage. Radiologists play an important role in initial diagnosis, staging, and imaging surveillance of testicular malignancies.


Otx1 and Otx2 activities are required for the normal development of the mouse inner ear.
The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle (Otd) gene in Drosophila. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear. Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads. In this study, we examined, at different developmental stages, the inner ears of mice lacking both Otx1 and Otx2 genes. In wild-type inner ears, Otx1, but not Otx2, was expressed in the lateral canal and ampulla, as well as part of the utricle. Ventral to the mid-level of the presumptive utricle, Otx1 and Otx2 were co-expressed, in regions such as the saccule and cochlea. Paint-filled membranous labyrinths of Otx1-/- mutants showed an absence of the lateral semicircular canal, lateral ampulla, utriculosaccular duct and cochleosaccular duct, and a poorly defined hook (the proximal part) of the cochlea. Defects in the shape of the saccule and cochlea were variable in Otx1-/- mice and were much more severe in an Otx1-/-;Otx2(+/)- background. Histological and in situ hybridization experiments of both Otx1-/- and Otx1-/-;Otx2(+/)- mutants revealed that the lateral crista was absent. In addition, the maculae of the utricle and saccule were partially fused. In mutant mice in which both copies of the Otx1 gene were replaced with a human Otx2 cDNA (hOtx2(1)/ hOtx2(1)), most of the defects associated with Otx1-/- mutants were rescued. However, within the inner ear, hOtx2 expression failed to rescue the lateral canal and ampulla phenotypes, and only variable rescues were observed in regions where both Otx1 and Otx2 are normally expressed. These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs.