The Listeria monocytogenes virulence factor InlJ is specifically expressed in vivo and behaves as an adhesin.
The food-borne pathogen Listeria monocytogenes is adapted to a diversity of environments, such as soil, food, body fluids, and the cytosol of eukaryotic cells. The transition between saprophytic and pathogenic life is mediated through complex regulatory pathways that modulate the expression of virulence factors. Here we examined the expression of inlJ, a recently identified gene encoding a protein of the LPXTG-internalin family and involved in pathogenesis. We show that inlJ expression is controlled neither by the major listerial regulator of virulence genes, PrfA, nor by AxyR, a putative AraC regulator encoded by a gene adjacent to inlJ and divergently transcribed. The InlJ protein is not produced by bacteria grown in vitro in brain heart infusion medium or replicating in the cytosol of tissue-cultured cells. In contrast, it is efficiently produced and localized at the surface of bacteria present in the liver and blood of infected animals. Strikingly, the expression of inlJ by a heterologous promoter in L. monocytogenes or L. innocua promotes bacterial adherence to human cells in vitro. Taken together, these results strongly suggest that InlJ acts as a novel L. monocytogenes sortase-anchored adhesin specifically expressed during infection in vivo.


Nickel oxide nanotubes: synthesis and electrochemical performance for use in lithium ion batteries.
Uniform and aligned Nickel Oxide (NiO) nanotube bundles have been synthesized by a template process. Individual nanotubes are 60 microm long with a 200 nm outer diameter and wall thickness of 20-30 nm. The synthesis involved forming Ni(OH)2 nanotubes that were subsequently heated to 350 degrees C in order to fully convert the product to NiO nanotubes. NiO nanotube powder was used in lithium-ion cells for assessment of lithium storage ability and electrochemical performance. Discharge capacity of the NiO nanotube electrode was in excess of 30% higher than that of the standard NiO nanocrystalline powder electrode after 20 cycles. Impedance data suggests the NiO nanotube electrode provides more controlled and sustainable Li diffusion when compared to the NiO reference powder electrode system.


Assessing the association of oxytocin augmentation with obstetric anal sphincter injury in nulliparous women: a population-based, case-control study.
To assess the association of oxytocin augmentation with obstetric anal sphincter injury among nulliparous women. Population-based, case-control study. Primary and secondary teaching hospital serving a Norwegian region. 15 476 nulliparous women with spontaneous start of labour, single cephalic presentation and gestation ≥37 weeks delivering vaginally between 1999 and 2012. Based on the presence or absence of oxytocin augmentation, episiotomy, operative vaginal delivery and birth weight (<4000 vs ≥4000 g), we modelled in logistic regression the best fit for prediction of anal sphincter injury. Within the modified model of main exposures, we tested for possible confounding, and interactions between maternal age, ethnicity, occiput posterior position and epidural analgaesia. Obstetric anal sphincter injury. Oxytocin augmentation was associated with a higher OR of obstetric anal sphincter injuries in women giving spontaneous birth to infants weighing <4000 g (OR 1.8; 95% CI 1.5 to 2.2). Episiotomy was not associated with sphincter injuries in spontaneous births, but with a lower OR in operative vaginal deliveries. Spontaneous delivery of infants weighing ≥4000 g was associated with a threefold higher OR, and epidural analgaesia was associated with a 30% lower OR in comparison to no epidural analgaesia. Oxytocin augmentation was associated with a higher OR of obstetric anal sphincter injuries during spontaneous deliveries of normal-size infants. We observed a considerable effect modification between the most important factors predicting anal sphincter injuries in the active second stage of labour.


Associations Between Brain Structure and Connectivity in Infants and Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy.
Selective serotonin reuptake inhibitor (SSRI) use among pregnant women is increasing, yet the association between prenatal SSRI exposure and fetal neurodevelopment is poorly understood. Animal studies show that perinatal SSRI exposure alters limbic circuitry and produces anxiety and depressive-like behaviors after adolescence, but literature on prenatal SSRI exposure in humans is limited and mixed. To examine associations between prenatal SSRI exposure and brain development using structural and diffusion magnetic resonance imaging (MRI). A cohort study conducted at Columbia University Medical Center and New York State Psychiatric Institute included 98 infants: 16 with in utero SSRI exposure, 21 with in utero untreated maternal depression exposure, and 61 healthy controls. Data were collected between January 6, 2011, and October 25, 2016. Selective serotonin reuptake inhibitors and untreated maternal depression. Gray matter volume estimates using structural MRI with voxel-based morphometry and white matter structural connectivity (connectome) using diffusion MRI with probabilistic tractography. The sample included 98 mother (31 [32%] white, 26 [27%] Hispanic/Latina, 26 [27%] black/African American, 15 [15%] other) and infant (46 [47%] boys, 52 [53%] girls) dyads. Mean (SD) age of the infants at the time of the scan was 3.43 (1.50) weeks. Voxel-based morphometry showed significant gray matter volume expansion in the right amygdala (Cohen d = 0.65; 95% CI, 0.06-1.23) and right insula (Cohen d = 0.86; 95% CI, 0.26-1.14) in SSRI-exposed infants compared with both healthy controls and infants exposed to untreated maternal depression (P < .05; whole-brain correction). In connectome-level analysis of white matter structural connectivity, the SSRI group showed a significant increase in connectivity between the right amygdala and the right insula with a large effect size (Cohen d = 0.99; 95% CI, 0.40-1.57) compared with healthy controls and untreated depression (P < .05; whole connectome correction). Our findings suggest that prenatal SSRI exposure has an association with fetal brain development, particularly in brain regions critical to emotional processing. The study highlights the need for further research on the potential long-term behavioral and psychological outcomes of these neurodevelopmental changes.


Using multilevel modeling in caregiving research.
Recently, caregiving research has moved towards a greater emphasis on the interactive and dynamic processes of the care situation. As a result, many of the questions are multilevel in nature, involving more than one unit of analysis and placing greater focus on the context of the care dyad. Nevertheless, most caregiving studies use methods that fail to address the hierarchical nature of the care dyad and consequently fail to illuminate variation both within and between dyad processes. The focus of this paper is to promote a dyad approach to the analysis of caregiving data and to highlight the advantages and appropriateness of multilevel modeling when dealing with clustered or hierarchical data. In particular, we discuss how multilevel modeling can be adapted to study change in the care dyad over time, improve the way we evaluate interventions, and enhance our understanding of dyad congruence.


Low prevalence of transmitted HIV type 1 drug resistance among antiretroviral-naive adults in a rural HIV clinic in Kenya.
Low levels of HIV-1 transmitted drug resistance (TDR) have previously been reported from many parts of sub-Saharan Africa (sSA). However, recent data, mostly from urban settings, suggest an increase in the prevalence of HIV-1 TDR. Our objective was to determine the prevalence of TDR mutations among HIV-1-infected, antiretroviral (ARV)-naive adults enrolling for care in a rural HIV clinic in Kenya. Two cross-sectional studies were carried out between July 2008 and June 2010. Plasma samples from ARV-naive adults (>15 years old) at the time of registering for care after HIV diagnosis and before starting ARVs were used. A portion of the pol subgenomic region of the virus containing the protease and part of the reverse transcriptase genes was amplified and sequenced. TDR mutations were identified and interpreted using the Stanford HIV drug resistance database and the WHO list for surveillance of drug resistance strains. Overall, samples from 182 ARV-naive adults [mean age (95% CI): 34.9 (33.3-36.4) years] were successfully amplified and sequenced. Two TDR mutations to nucleoside reverse transcriptase inhibitors [n=1 (T215D)] and protease inhibitors [n=1 (M46L)] were identified, giving an overall TDR prevalence of 1.1% (95% CI: 0.1-3.9). Despite reports of an increase in the prevalence of HIV-1 TDR in some urban settings in sSA, we report a prevalence of HIV-1 TDR of less than 5% at a rural HIV clinic in coastal Kenya. Continued broader surveillance is needed to monitor the extent of TDR in sSA.


Discrimination of speech and non-speech sounds following theta-burst stimulation of the motor cortex.
Perceiving speech engages parts of the motor system involved in speech production. The role of the motor cortex in speech perception has been demonstrated using low-frequency repetitive transcranial magnetic stimulation (rTMS) to suppress motor excitability in the lip representation and disrupt discrimination of lip-articulated speech sounds (Möttönen and Watkins, 2009). Another form of rTMS, continuous theta-burst stimulation (cTBS), can produce longer-lasting disruptive effects following a brief train of stimulation. We investigated the effects of cTBS on motor excitability and discrimination of speech and non-speech sounds. cTBS was applied for 40 s over either the hand or the lip representation of motor cortex. Motor-evoked potentials recorded from the lip and hand muscles in response to single pulses of TMS revealed no measurable change in motor excitability due to cTBS. This failure to replicate previous findings may reflect the unreliability of measurements of motor excitability related to inter-individual variability. We also measured the effects of cTBS on a listener's ability to discriminate: (1) lip-articulated speech sounds from sounds not articulated by the lips ("ba" vs. "da"); (2) two speech sounds not articulated by the lips ("ga" vs. "da"); and (3) non-speech sounds produced by the hands ("claps" vs. "clicks"). Discrimination of lip-articulated speech sounds was impaired between 20 and 35 min after cTBS over the lip motor representation. Specifically, discrimination of across-category ba-da sounds presented with an 800-ms inter-stimulus interval was reduced to chance level performance. This effect was absent for speech sounds that do not require the lips for articulation and non-speech sounds. Stimulation over the hand motor representation did not affect discrimination of speech or non-speech sounds. These findings show that stimulation of the lip motor representation disrupts discrimination of speech sounds in an articulatory feature-specific way.


Mice lacking a Myc enhancer that includes human SNP rs6983267 are resistant to intestinal tumors.
Multiple cancer-associated single-nucleotide polymorphisms (SNPs) have been mapped to conserved sequences within a 500-kilobase region upstream of the MYC oncogene on human chromosome 8q24. These SNPs may affect cancer development through altered regulation of MYC expression, but this hypothesis has been difficult to confirm. We generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer-related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype but were markedly resistant to intestinal tumorigenesis induced by the APCmin mutation. These results establish that a cancer-associated SNP identified in human genome-wide association studies has a functional effect in vivo.


Serological and virological characterization of clinically diagnosed cases of measles in suburban Khartoum.
Measles continues to be a major childhood disease in terms of global morbidity and mortality. In the main areas of its endemicity the only available means of diagnosis are based on clinical criteria: the presence of a maculopapular rash and fever accompanied by cough, coryza, and/or conjunctivitis. We have studied 38 clinically diagnosed cases of measles in Khartoum, Sudan, by means of serology, reverse transcriptase PCR (RT-PCR) on throat swabs and virus isolation from lymphocytes. On the basis of serology, 28 patients were diagnosed as having an acute measles virus (MV) infection, while in 10 cases the clinical symptoms proved to have other causes. It was shown that in cases with low serum immunoglobulin M (IgM) levels, an additional measurement of IgG or virus-neutralizing antibodies was necessary to discriminate between patients with an acute MV infection sampled during an early stage of the disease and patients who had experienced an MV infection in the more distant past. The serological laboratory diagnosis was validated by an MV-specific RT-PCR: for all confirmed measles cases tested a fragment of the correct size which hybridized with a third MV-specific primer could be amplified, while all serologically negative cases were also RT-PCR negative. MV could be isolated from 17 out of 23 of the serologically confirmed cases, demonstrating that virus isolation is less reliable as a diagnostic tool than serology or RT-PCR. This study stresses the urgent need for a rapid diagnostic field test for measles.


Optimizing outcomes of multifocal intraocular lenses.
To update the readers on recent research for further optimizing outcomes and improving the patient satisfaction with multifocal intraocular lenses (IOLs). Recent studies provide few novel approaches on surgical interventions to improve the postoperative outcomes. The use of capsular tension rings can improve preoperative predictability, whereas femtosecond laser cataract surgery was not shown to provide significant benefit to postoperative visual acuity. Other studies broaden and reinforce the previously reported results, such as patient education with blurred vision and dysphotopsia, utilizing an add power of +3.00 to improve intermediate visual acuity, and minimizing the lens decentration and tilt. Multifocal IOLs are currently a popular lens choice for motivated patients who would like to achieve spectacle independence. However, recent research has not provided significant improvements in optimizing outcomes. Newer lens technologies may be required to resolve the current problems of blurred vision and dysphotopsias.


Iterative Augmentation of Visual Evidence for Weakly-Supervised Lesion Localization in Deep Interpretability Frameworks: Application to Color Fundus Images.
Interpretability of deep learning (DL) systems is gaining attention in medical imaging to increase experts' trust in the obtained predictions and facilitate their integration in clinical settings. We propose a deep visualization method to generate interpretability of DL classification tasks in medical imaging by means of visual evidence augmentation. The proposed method iteratively unveils abnormalities based on the prediction of a classifier trained only with image-level labels. For each image, initial visual evidence of the prediction is extracted with a given visual attribution technique. This provides localization of abnormalities that are then removed through selective inpainting. We iteratively apply this procedure until the system considers the image as normal. This yields augmented visual evidence, including less discriminative lesions which were not detected at first but should be considered for final diagnosis. We apply the method to grading of two retinal diseases in color fundus images: diabetic retinopathy (DR) and age-related macular degeneration (AMD). We evaluate the generated visual evidence and the performance of weakly-supervised localization of different types of DR and AMD abnormalities, both qualitatively and quantitatively. We show that the augmented visual evidence of the predictions highlights the biomarkers considered by experts for diagnosis and improves the final localization performance. It results in a relative increase of 11.2± 2.0% per image regarding sensitivity averaged at 10 false positives/image on average, when applied to different classification tasks, visual attribution techniques and network architectures. This makes the proposed method a useful tool for exhaustive visual support of DL classifiers in medical imaging.


Highly Anisotropic Organometal Halide Perovskite Nanowalls Grown by Glancing-Angle Deposition.
Polarizers are ubiquitous components in current optoelectronic devices as displays or photographic cameras. Yet, control over light polarization is an unsolved challenge, since the main drawback of the existing display technologies is the significant optical losses. In such a context, organometal halide perovskites (OMHP) can play a decisive role given their flexible synthesis with tunable optical properties such as bandgap and photoluminescence, and excellent light emission with a low non-radiative recombination rate. Therefore, along with their outstanding electrical properties have elevated hybrid perovskites as the material of choice in photovoltaics and optoelectronics. Among the different OMHP nanostructures, nanowires and nanorods have lately arisen as key players in the control of light polarization for lighting or detector applications. Herein, the fabrication of highly aligned and anisotropic methylammonium lead iodide perovskite nanowalls by glancing-angle deposition, which is compatible with most substrates, is presented. Their high alignment degree provides the samples with anisotropic optical properties such as light absorption and photoluminescence. Furthermore, their implementation in photovoltaic devices provides them with a polarization-sensitive response. This facile vacuum-based approach embodies a milestone in the development of last-generation polarization-sensitive perovskite-based optoelectronic devices such as lighting appliances or self-powered photodetectors.


Endothelial function and stress response after simulated dives to 18 msw breathing air or oxygen.
Decompression sickness is caused by gas bubbles released upon decompression. These bubbles have the potential to occlude blood vessels and damage the vascular endothelium. The aim of this study was to quantify damage to the vascular endothelium resulting from decompression by measuring endothelial microparticles (MP) and endothelial function. Five healthy male volunteers undertook a simulated (hyperbaric chamber) air dive and 1 wk later a second dive breathing 100% oxygen at 283 kPa (18 msw) for 60 min bottom time, decompressed with 5-min stops at 161 kPa (6 msw) and 131 kPa (3 msw). Endothelial function was tested pre- and postdive by reactive hyperemia peripheral artery tonometry (RH-PAT) and CD105 (Endoglin) positive MP were quantified by flow cytometry. Plasma E- and P-selectin, interleukin-6, and serum cortisol were also quantified. RH-PAT showed a significantly decreased endothelial function post-decompression after breathing air when compared to oxygen (-0.33 +/- 0.27 vs. +0.18 +/- 0.14). CD105 MP pre- and postdive showed no change on the oxygen dive (460 +/- 370 to 360 +/- 163), however, they increased after breathing air (440 +/- 70 to 1306 +/- 359). There was no change in expression of CD105 on MP. Furthermore no changes were observed in plasma E- or P-selectin, IL-6, or serum cortisol. From the data, at least in the time frame involved, there appears to be no detectable physiological/stress response to decompression, rather decompression from breathing air probably caused mechanical damage to the endothelium, resulting in both MP release and a reduction in endothelial function.


Loss of lower limb motor evoked potentials and spinal cord injury during the initial exposure in scoliosis surgery.
To report a case of motor evoked potential changes and spinal cord injury during the initial dissection in scoliosis surgery. Motor evoked potentials to transcranial electrical stimulation were recorded from multiple muscles. Somatosensory evoked potentials to limb nerve stimulation were recorded from the scalp. Clear motor evoked potentials were initially present in all monitored muscles. The patient was then pharmacologically paralyzed for the initial dissection. More than usual bleeding was encountered during that dissection, prompting transfusion. As the neuromuscular blockade subsided, motor evoked potentials persisted in the hand muscles but disappeared and remained absent in all monitored leg muscles. The spine had not been instrumented. A wake-up test demonstrated paraplegia; the surgery was aborted. There were no adverse somatosensory evoked potential changes. MRI showed an anterior spinal cord infarct. Copious soft tissue bleeding during the initial dissection might have lowered pressures in critical segmental arteries enough to cause spinal cord infarction through a steal phenomenon. The lack of somatosensory evoked potential changes reflected sparing of the dorsal columns. When neuromuscular blockade is used during the initial soft tissue dissection, motor evoked potentials should be assessed after this, but before spinal instrumentation, to determine whether there had been any spinal cord compromise during the initial dissection.


Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke.
The National Institutes of Health (NIH) estimates that stroke costs now exceed 45 billion dollars per year. Stroke is the third leading cause of death and one of the leading causes of adult disability in North America, Europe, and Asia. A number of well-designed randomized stroke trials and case series have now been reported in the literature to evaluate the safety and efficacy of thrombolytic therapy for the treatment of acute ischemic stroke. These stroke trials have included intravenous studies, intra-arterial studies, and combinations of both, as well as use of mechanical devices for removal of thromboemboli and of neuroprotectant drugs, alone or in combination with thrombolytic therapy. At this time, the only therapy demonstrated to improve outcomes from an acute stroke is thrombolysis of the clot responsible for the ischemic event. There is room for improvement in stroke lysis studies. Divergent criteria, with disparate reporting standards and definitions, have made direct comparisons between stroke trials difficult to compare and contrast in terms of overall patient outcomes and efficacy of treatment. There is a need for more uniform definitions of multiple variables such as collateral flow, degree of recanalization, assessment of perfusion, and infarct size. In addition, there are multiple unanswered questions that require further investigation, in particular, questions as to which patients are best treated with thrombolysis. One of the most important predictors of clinical success is time to treatment, with early treatment of <3 hours for intravenous tissue plasminogen activator and <6 hours for intra-arterial thrombolysis demonstrating significant improvement in terms of 90-day clinical outcome and reduced cerebral hemorrhage. It is possible that improved imaging that identifies the ischemic penumbra and distinguishes it from irreversibly infarcted tissue will more accurately select patients for therapy than duration of symptoms. There are additional problems in the assessment of patients eligible for thrombolysis. These include being able to predict whether a particular site of occlusion can be successfully revascularized, predict an individual patient's prognosis and outcome after revascularization, and in particular, to predict the development of intracerebral hemorrhage, with and without clinical deterioration. It is not clear to assume that achieving immediate flow restoration due to thrombolytic therapy implies clinical success and improved outcome. There is no simple correlation between recanalization and observed clinical benefit in all ischemic stroke patients, because other interactive variables, such as collateral circulation, the ischemic penumbra, lesion location and extent, time to treatment, and hemorrhagic conversion, are all interrelated to outcome. This article was written under the auspices of the Technology Assessment Committees for both the American Society of Interventional and Therapeutic Neuroradiology and the Society of Interventional Radiology. The purpose of this document is to provide guidance for the ongoing study design of trials of intra-arterial cerebral thrombolysis in acute ischemic stroke. It serves as a background for the intra-arterial thrombolytic trials in North America and Europe, discusses limitations of thrombolytic therapy, defines predictors for success, and offers the rationale for the different considerations that might be important during the design of a clinical trial for intra-arterial thrombolysis in acute stroke. Included in this guidance document are suggestions for uniform reporting standards for such trials. These definitions and standards are mainly intended for research trials; however, they should also be helpful in clinical practice and applicable to all publications. This article serves to standardize reporting terminology and includes pretreatment assessment, neurologic evaluation with the NIH Stroke Scale score, imaging evaluation, occlusion sites, perfusion grades, follow-up imaging studies, and neurologic assessments. Moreover, previously used and established definitions for patient selection, outcome assessment, and data analysis are provided, with some possible variations on specific end points. This document is therefore targeted to help an investigator to critically review the scales and scores used previously in stroke trials. This article also seeks to standardize patient selection for treatment based on neurologic condition at presentation, baseline imaging studies, and utilization of standardized inclusion/exclusion criteria. It defines outcomes from therapy in phase I, II, and III studies. Statistical approaches are presented for analyzing outcomes from prospective, randomized trials with both primary and secondary variable analysis. A discussion on techniques for angiography, intra-arterial thrombolysis, anticoagulation, adjuvant therapy, and patient management after therapy is given, as well as recommendations for posttreatment evaluation, duration of follow-up, and reporting of disability outcomes. Imaging assessment before and after treatment is given. In the past, noncontrast CT brain scans were used as the initial screening examination of choice to exclude cerebral hemorrhage. However, it is now possible to quantify the volume of early infarct by using contiguous, discrete (nonhelical) images of 5 mm. In addition, CT angiography by helical scanning and 100 mL of intravenous contrast agent can be used expeditiously to obtain excellent vascular anatomy, define the occlusion site, obtain 2D and 3D reformatted vascular images, grade collateral blood flow, and perform tissue-perfusion studies to define transit times of a contrast bolus through specific tissue beds and regions of interest in the brain. Dynamic CT perfusion scans to assess the whole dynamics of a contrast agent transit curve can now be routinely obtained at many hospitals involved in these studies. The rationale, current status of this technology, and potential use in future clinical trials are given. Many hospitals are also performing MR brain studies at baseline in addition to, or instead of, CT scans. MRI has a high sensitivity and specificity for the diagnosis of ischemic stroke in the first several hours from symptom onset, identifies arterial occlusions, and characterizes ischemic pathology noninvasively. Case series have demonstrated and characterized the early detection of intraparenchymal hemorrhage and subarachnoid hemorrhage by MRI. Echo planar images, used for diffusion MRI and, in particular, perfusion MRI are inherently sensitive for the susceptibility changes caused by intraparenchymal blood products. Consequently, MRI has replaced CT to rule out acute hemorrhage in some centers. The rationale and the potential uses of MR scanning are provided. In addition to established criteria, technology is continuously evolving, and imaging techniques have been introduced that offer new insights into the pathophysiology of acute ischemic stroke. For example, a better patient stratification might be possible if CT and/or MRI brain scans are used not only as exclusion criteria but also to provide individual inclusion and exclusion criteria based on tissue physiology. Imaging techniques might also be used as a surrogate outcome measure in future thrombolytic trials. The context of a controlled study is the best environment to validate emerging imaging and treatment techniques. The final section details reporting standards for complications and adverse outcomes; defines serious adverse events, adverse events, and unanticipated adverse events; and describes severity of complications and their relation to treatment groups. Recommendations are made regarding comparing treatment groups, randomization and blinding, intention-to-treat analysis, quality-of-life analysis, and efficacy analysis. This document concludes with an analysis of general costs associated with therapy, a discussion regarding entry criteria, outcome measures, and the variability of assessment of the different stroke scales currently used in the literature is also featured. In summary, this article serves to provide a more uniform set of criteria for clinical trials and reporting outcomes used in designing stroke trials involving intra-arterial thrombolytic agents, either alone or in combination with other therapies. It is anticipated that by having a more uniform set of reporting standards, more meaningful analysis of the data and the literature will be able to be achieved.


Text Message Feedback to Support Mindfulness Practice in People With Depressive Symptoms: A Pilot Randomized Controlled Trial.
It has been shown that mindfulness practice can be helpful in preventing relapse from depression. However, practicing mindfulness regularly at home is often a challenge for people with depression. Mobile phone text messaging (short message service, SMS) may be a feasible approach to assist regular mindfulness home practice. The aim of this study was to evaluate the feasibility of text message-based feedback to support mindfulness practice in people with depressive symptoms after inpatient psychiatric treatment. Participants received a manualized group introduction to three mindfulness exercises during inpatient treatment and were randomized at hospital discharge. All participants were asked to practice the exercises daily during the 4-month follow-up period. Only participants allocated to the intervention group received reinforcing feedback via mobile phone text messages after reporting their mindfulness practice via text message. Participation rates and satisfaction with the interventions were evaluated, and effects on relevant outcomes were explored. Of the 176 eligible inpatients invited to participate, 65.9% (116/176) attended the introductory mindfulness group at least once, 33.0% (58/176) were willing to participate in the study, and 41 were randomized. The majority 85% (35/41) of these participants completed the study. Among the participants allocated to the intervention group (n=21), 81% (17/21) used the text message support at least once. The average number of text messages sent during the intervention period was 14 (SD 21, range 0-91). Satisfaction rates were high. Preliminary analyses of the effects of the intervention yielded mixed results. Findings indicate that text messaging following inpatient treatment is feasible for some, but not for all people with depressive symptoms. Modest use of the text messaging intervention and its mixed effects imply that dose and ingredients of the intervention should be increased for this group of patients in a future full-size RCT. Such a larger study should also include a process evaluation to investigate moderators of the effect of mindfulness practice and text message feedback on clinical outcome. International Standard Randomized Controlled Trial Number (ISRCTN): 58808893; http://www.controlled-trials.com/ISRCTN58808893 (Archived by Webcite at http://www.webcitation.org/6pmrDRnGt).


Tissue Factor-Negative Cell-Derived Microparticles Play a Distinctive Role in Hemostasis: A Viewpoint Review.
Circulating cell-derived microparticles (MPs) exhibit procoagulant activity and have been investigated for a possible role in some human pathologies. However, their potential role in hemostasis has been neglected and often denied. This review brings to attention a specific body of direct clinical evidence supporting an important but distinctive role of MPs in hemostasis. Evidence for a role of MPs in hemostasis includes: (1) two congenital bleeding disorders attributed to impaired release of MPs; (2) two recent studies of trauma patients relating naturally elevated endogenous MPs at admission to reduced transfusion requirements and better outcomes; (3) a study of coronary surgery patients showing that elevated MP before surgery reduces transfusion requirements during surgery; and (4) a clinical study of patients with immune thrombocytopenia demonstrating that those with high circulating MP have reduced bleeding compared to patients with similar platelet counts but lower MP levels. Mechanisms involving potentiating the contact factor pathway are thought to play a key role and are probably synergistic with polyphosphate released from activated platelets at sites of endothelial injury. Hemostatic defect of patients with deficient MP-mediated coagulation resembles deficiency of FXI (hemophilia C), distinct from hemophilia A or B, so can be termed type C hemostasis. A better understanding of this proposed hemostatic pathway may lead to improved methods for controlling excessive bleeding in surgery, trauma, and other clinical settings.


Novel homozygous PCK1 mutation causing cytosolic phosphoenolpyruvate carboxykinase deficiency presenting as childhood hypoglycemia, an abnormal pattern of urine metabolites and liver dysfunction.
Clinical and laboratory data were collected from three Finnish patients including a sibling pair and another unrelated child with unexplained childhood hypoglycemia. Transient elevation of alanine transaminase, lactate and tricarboxylic acid cycle intermediates, especially fumarate, were noticed in urine organic acid analysis. Exome sequencing was performed for the patients and their parents. A novel homozygous PCK1 c.925G>A (p.G309R) mutation was detected in all affected individuals. COS-1 cells transfected with mutant PCK1 transcripts were used to study the pathogenic nature of the detected variant. The COS-1 transfected cells showed the mutant gene to be incapable of producing a normally functioning cytosolic phosphoenolpyruvate carboxykinase (PEPCK) enzyme. This report further delineates the clinical phenotype of isolated cytosolic PEPCK deficiency and offers a metabolic pattern helping to recognize these patients. Cytosolic PEPCK deficiency should be considered in the differential diagnosis of children presenting with hypoglycemia, hepatic dysfunction and elevated tricarboxylic acid intermediates in urinary organic acid analysis.


NR3A modulates the outer vestibule of the "NMDA" receptor channel.
Classical NMDA receptors (NMDARs), activated by glycine and glutamate, are heteromultimers comprised of NR1 and NR2 subunits. Coexpression of the novel NR3 family of NMDAR subunits decreases the magnitude of NR1/NR2 receptor-mediated currents or forms glycine-activated channels with the NR1 subunit alone. The second (M2) and third (M3) membrane segments of NR1 and NR2 subunits of classical NMDARs form the core of the channel permeation pathway. Structural information regarding NR1/NR3 channels remains unknown. Using the Xenopus oocyte expression system and the SCAM (substituted cysteine accessibility method), we found that M3 segments of both NR1 and NR3A form a narrow constriction in the outer vestibule of the channel, which prevents passage of externally applied sulfhydryl-specific agents. The most internal reactive residue in each M3 segment is the threonine in the conserved SYTANLAAF motif. These threonines appear to be symmetrically aligned. Several NR3A M3 mutations change the behavior of NR1/NR3A channels. Unlike NR1, however, the M3 segment of NR3A does not undergo extensive molecular rearrangement during channel gating by added glycine. Additionally, in the M2 segment, our data suggest that the amino acid at the asparagine (N) site of NR1, but not NR3A, contributes to the selectivity filter of NR1/3A channels. We therefore conclude that NR3A modulates the NR1/NR3A permeation pathway via a novel mechanism of forming a narrow constriction at the outer channel vestibule. This modified channel vestibule may also explain the dominant-negative effect of the NR3 subunit on channel behavior when coexpressed with NR1 and NR2 subunits.


Mycobacterial cervical lymphadenitis in childhood.
A study of 190 children of chronic cervical lymphadenitis showed tuberculous etiology on histopathological examination in 92 (48.4%) and bacteriological evidence of mycobacterial infection (smear and/or culture) in 42 (22.1%). Of these 42, twelve (28.6%) showed histopathological diagnosis of non-specific lymphadenitis. Positive culture for mycobacteria was obtained in 40, of which 30 (75%) were typical M. tuberculosis and 10 (25%) were atypical mycobacteria. The most predominant species of typical mycobacteria was M. scrofulaceum (60%) followed by M. avium intracellulare (40%). There was no remarkable difference in the histopathological pattern of those in which M. tuberculosis was grown and those in which bacterial growth was that of atypical mycobacteria. The diagnosis of chronic cervical lymphadenitis should therefore be taken a step beyond histopathology, up to complete bacteriological examination, especially to confirm the cases of mycobacterial lymphadenitis caused by atypical mycobacteria.


NPHP4 is necessary for normal photoreceptor ribbon synapse maintenance and outer segment formation, and for sperm development.
Nephronophthisis (NPHP) is an autosomal recessive kidney disease that is often associated with vision and/or brain defects. To date, 11 genes are known to cause NPHP. The gene products, while structurally unrelated, all localize to cilia or centrosomes. Although mouse models of NPHP are available for 9 of the 11 genes, none has been described for nephronophthisis 4 (Nphp4). Here we report a novel, chemically induced mutant, nmf192, that bears a nonsense mutation in exon 4 of Nphp4. Homozygous mutant Nphp4(nmf192/nmf192) mice do not exhibit renal defects, phenotypes observed in human patients bearing mutations in NPHP4, but they do develop severe photoreceptor degeneration and extinguished rod and cone ERG responses by 9 weeks of age. Photoreceptor outer segments (OS) fail to develop properly, and some OS markers mislocalize to the inner segments and outer nuclear layer in the Nphp4(nmf192/nmf192) mutant retina. Despite NPHP4 localization to the transition zone in the connecting cilia (CC), the CC appear to be normal in structure and ciliary transport function is partially retained. Likewise, synaptic ribbons develop normally but then rapidly degenerate by P14. Finally, Nphp4(nmf192/nmf192) male mutants are sterile and show reduced sperm motility and epididymal sperm counts. Although Nphp4(nmf192/nmf192) mice fail to recapitulate the kidney phenotype of NPHP, they will provide a valuable tool to further elucidate how NPHP4 functions in the retina and male reproductive organs.


Pharmacological conversion of recent atrial fibrillation: a randomized, placebo-controlled study of three antiarrhythmic drugs.
In this study, we randomly compared single oral doses of flecainide, amiodarone and propafenone versus placebo for the conversion of recent atrial fibrillation (AF) (within 48 hours). This is a randomized prospective, placebo-controlled single-blind study that included 160 consecutive patients with recent AF who were randomly assigned to single oral doses of flecainide (3 mg/kg of weight, n=40), amiodarone (30 mg/kg weight, n=40), propafenone (8.5 mg/kg of weight, n=40) or placebo (n=40). The primary end-point was conversion rate at 24 hours after the drug intake. The association between antiarrhythmic use and conversion rate was tested with multiple logistic regressions. The primary end-point was achieved in 87.5% of patients with flecainide, 85% of patients with amiodarone, 85% of patients with propafenone and 17.5% of patients with placebo (p<0.001 compared with placebo for all 3 drugs). Conversion rate within 3 hours after drug intake was greater with propafenone (57.5%) or flecainide (45%) compared with amiodarone (0%) or placebo (10%). Between 6 and 24 hours, significantly more patients were converted to sinus rhythm with amiodarone than with flecainide or propafenone. The use of antiarrhythmic drugs was a significant predictor of conversion to sinus rhythm compared to placebo (adjusted OR=19.53, 95% CI 3.14-121.55, p<0.001). No serious side effect occurred. In patients with recent-onset AF, oral flecainide, amiodarone or propafenone are superior to placebo in restoring sinus rhythm within the 24-hour period following the drug intake.


Cell oxidation-reduction imbalance after modulated radiofrequency radiation.
Aim of this study was to evaluate an influence of modulated radiofrequency field (RF) of 1800 MHz, strength of 30 V/m on oxidation-reduction processes within the cell. The assigned RF field was generated within Gigahertz Transversal Electromagnetic Mode cell equipped by signal generator, modulator, and amplifier. Cell line V79, was irradiated for 10, 30, and 60 min, specific absorption rate was calculated to be 1.6 W/kg. Cell metabolic activity and viability was determined by MTT assay. In order to define total protein content, colorimetric method was used. Concentration of oxidised proteins was evaluated by enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) marked with fluorescent probe 2',7'-dichlorofluorescin diacetate were measured by means of plate reader device. In comparison with control cell samples, metabolic activity and total protein content in exposed cells did not differ significantly. Concentrations of carbonyl derivates, a product of protein oxidation, insignificantly but continuously increase with duration of exposure. In exposed samples, ROS level significantly (p < 0.05) increased after 10 min of exposure. Decrease in ROS level was observed after 30-min treatment indicating antioxidant defence mechanism activation. In conclusion, under the given laboratory conditions, modulated RF radiation might cause impairment in cell oxidation-reduction equilibrium within the growing cells.


Prevalence estimates of combat-related post-traumatic stress disorder: critical review.
The aim of the present study was to provide a critical review of prevalence estimates of combat-related post-traumatic stress disorder (PTSD) among military personnel and veterans, and of the relevant factors that may account for the variability of estimates within and across cohorts, including methodological and conceptual factors accounting for differences in prevalence rates across nations, conflicts/wars, and studies. MEDLINE and PsycINFO databases were examined for literature on combat-related PTSD. The following terms were used independently and in combinations in this search: PTSD, combat, veterans, military, epidemiology, prevalence. The point prevalence of combat-related PTSD in US military veterans since the Vietnam War ranged from approximately 2% to 17%. Studies of recent conflicts suggest that combat-related PTSD afflicts between 4% and 17% of US Iraq War veterans, but only 3-6% of returning UK Iraq War veterans. Thus, the prevalence range is narrower and tends to have a lower ceiling among combat veterans of non-US Western nations. Variability in prevalence is likely due to differences in sampling strategies; measurement strategies; inclusion and measurement of the DSM-IV clinically significant impairment criterion; timing and latency of assessment and potential for recall bias; and combat experiences. Prevalence rates are also likely affected by issues related to PTSD course, chronicity, and comorbidity; symptom overlap with other psychiatric disorders; and sociopolitical and cultural factors that may vary over time and by nation. The disorder represents a significant and costly illness to veterans, their families, and society as a whole. Further carefully conceptualized research, however, is needed to advance our understanding of disorder prevalence, as well as associated information on course, phenomenology, protective factors, treatment, and economic costs.


Food, home and health: the meanings of food amongst Bengali Women in London.
This paper explores the nature of food and plants and their meanings in a British Bengali urban context. It focuses on the nature of plants and food in terms of their role in home making, transnational connections, generational change and concepts of health. An ethnographic approach to the research was taken, specific methods included participant observation, focus group discussions and semi-structured interviews. Thirty women of Bengali origin were mostly composed of "mother" and "daughter" pairs. The mothers were over 45 years old and had migrated from Bangladesh as adults and their grown-up daughters grew up in the UK. Food and plants play an important role in the construction of home "here" (London) while continuing to connect people to home "there" (Sylhet). This role, however, changes and is re-defined across generations. Looking at perceptions of "healthy" and "unhealthy" food, particularly in the context of Bengali food, multiple views of what constitutes "healthy" food exist. However, there appeared to be little two-way dialogue about this concept between the research participants and health professionals. This seems to be based on "cultural" and power differences that need to be addressed for a meaningful dialogue to occur. In summary, this paper argues that while food is critical to the familial spaces of home (both locally and globally), it is defined by a complex interplay of actors and wider meanings as illustrated by concepts of health and what constitutes Bengali food. Therefore, we call for greater dialogue between health professionals and those they interact with, to allow for an enhanced appreciation of the dynamic nature of food and plants and the diverse perceptions of the role that they play in promoting health.


Sex-dependent vulnerability of fetal nonhuman primate cardiac mitochondria to moderate maternal nutrient reduction.
Poor maternal nutrition in pregnancy affects fetal development, predisposing offspring to cardiometabolic diseases. The role of mitochondria during fetal development on later-life cardiac dysfunction caused by maternal nutrient reduction (MNR) remains unexplored. We hypothesized that MNR during gestation causes fetal cardiac bioenergetic deficits, compromising cardiac mitochondrial metabolism and reserve capacity. To enable human translation, we developed a primate baboon model (Papio spp.) of moderate MNR in which mothers receive 70% of control nutrition during pregnancy, resulting in intrauterine growth restriction (IUGR) offspring and later exhibiting myocardial remodeling and heart failure at human equivalent ∼25 years. Term control and MNR baboon offspring were necropsied following cesarean-section, and left ventricle (LV) samples were collected. MNR adversely impacted fetal cardiac LV mitochondria in a sex-dependent fashion. Increased maternal plasma aspartate aminotransferase, creatine phosphokinase (CPK), and elevated cortisol levels in MNR concomitant with decreased blood insulin in male fetal MNR were measured. MNR resulted in a two-fold increase in fetal LV mitochondrial DNA (mtDNA). MNR resulted in increased transcripts for several respiratory chain (NDUFB8, UQCRC1, and cytochrome c) and adenosine triphosphate (ATP) synthase proteins. However, MNR fetal LV mitochondrial complex I and complex II/III activities were significantly decreased, possibly contributing to the 73% decreased ATP content and increased lipid peroxidation. MNR fetal LV showed mitochondria with sparse and disarranged cristae dysmorphology. Conclusion: MNR disruption of fetal cardiac mitochondrial fitness likely contributes to the documented developmental programming of adult cardiac dysfunction, indicating a programmed mitochondrial inability to deliver sufficient energy to cardiac tissues as a chronic mechanism for later-life heart failure.


Concurrent use of comedications reduces adherence to antiretroviral therapy among HIV-infected patients.
The use of highly active antiretroviral therapy has significantly reduced morbidity and mortality, thus increasing life expectancy of human immunodeficiency virus (HIV)-infected individuals, transforming HIV into a chronic disease. Accordingly, there has been an increase in the number of comorbidities concomitantly present in these individuals and also an increased use of comedications, which may negatively impact antiretroviral therapy adherence. These factors can affect adherence to antiretroviral therapy. The role of the HIV clinical pharmacist is essential to achieve therapeutic objectives and enhance adherence. To determine the influence of the comorbidities and comedications on antiretroviral therapy adherence among HIV-infected patients receiving services from a clinical pharmacist. We conducted a prospective observational study that included HIV-infected outpatients who attended the pharmaceutical care office of a hospital pharmacy service, which initiated antiretroviral treatment between January 2002, and December 2011. The variables analyzed in the study were demographics (sex and age), HIV transmission mode, and the following variables at the time of comedication collection: hepatitis C virus or hepatitis B virus coinfection, HIV plasma viral load (copies/mL) and CD4+ T-cell count (cells/µL), Centers for Disease Control and Prevention HIV classification, number of hospital admissions and emergency room visits, and antiretroviral therapy-related features (type at baseline, treatment-naïve status, and number of changes since starting antiretroviral therapy). For follow-up at 12 months, antiretroviral therapy adherence was measured through pharmacy dispensing records and the Morisky Medication Adherence Scale (MMAS). Patients were considered adherent if antiretroviral therapy adherence through dispensing records was greater than 90%, and the MMAS score was 4. Other variables were number of comorbidities and number of comedications for other chronic diseases (non-HIV drugs). According to the number of comorbidities, patients were categorized as having multiple chronic conditions (polypathology) if they had 2 or more chronic diseases. Polypharmacy was defined specifically as the use of 5 or more prescription medications in a medication regimen. In addition, a complexity therapeutic index of antiretroviral therapy was calculated for each patient. We determined the risk of drug-related problems using the tool Predictor Index. To identify independent predictors of adherence to antiretroviral therapy, we performed a univariate logistic regression. Afterward, those variables that showed statistical significance in the univariate analysis and those with P less than 0.25 were included in a multivariate model. The sample size was estimated by the Freeman equation. We included 594 patients in the study (80.1% men, median age 47 years). In the univariate analysis, the variables that showed statistically significant relationships with antiretroviral therapy adherence were HIV transmission mode, detectable viral load, CD4+ T-cell count, AIDS-defining condition, hospital admission, antiretroviral therapy-naïve treatment, type of antiretroviral therapy, high risk of drug-related problems, polypathology, and polypharmacy. Multivariate analysis showed that independent predictors of nonadherence to antiretroviral therapy were HIV transmission by intravenous drug use (OR = 0.56, 95% CI = 0.35-0.90), previous treatment with antiretroviral therapy (OR = 0.09, CI = 0.04-0.24), nontreatment changes (OR = 0.12, CI = 0.05-0.31), high risk of drug-related problems (OR = 0.38, CI = 0.23-0.63), and polypharmacy (OR = 0.36, CI = 0.21-0.61). The value of the Hosmer and Lemeshow test confirmed the validity of this model (P = 0.378). Recently, the number of HIV-infected patients with polypharmacy has been higher, increasing the risk of nonadherence. Furthermore, previous treatment with antiretroviral therapy, HIV transmission by intravenous drug use, and high risk of drug-related problems are also associated with lower adherence.


Colloquium paper: microbes on mountainsides: contrasting elevational patterns of bacterial and plant diversity.
The study of elevational diversity gradients dates back to the foundation of biogeography. Although elevational patterns of plant and animal diversity have been studied for centuries, such patterns have not been reported for microorganisms and remain poorly understood. Here, in an effort to assess the generality of elevational diversity patterns, we examined soil bacterial and plant diversity along an elevation gradient. To gain insight into the forces that structure these patterns, we adopted a multifaceted approach to incorporate information about the structure, diversity, and spatial turnover of montane communities in a phylogenetic context. We found that observed patterns of plant and bacterial diversity were fundamentally different. While bacterial taxon richness and phylogenetic diversity decreased monotonically from the lowest to highest elevations, plants followed a unimodal pattern, with a peak in richness and phylogenetic diversity at mid-elevations. At all elevations bacterial communities had a tendency to be phylogenetically clustered, containing closely related taxa. In contrast, plant communities did not exhibit a uniform phylogenetic structure across the gradient: they became more overdispersed with increasing elevation, containing distantly related taxa. Finally, a metric of phylogenetic beta-diversity showed that bacterial lineages were not randomly distributed, but rather exhibited significant spatial structure across the gradient, whereas plant lineages did not exhibit a significant phylogenetic signal. Quantifying the influence of sample scale in intertaxonomic comparisons remains a challenge. Nevertheless, our findings suggest that the forces structuring microorganism and macroorganism communities along elevational gradients differ.


[3H]Mianserin: differential labeling of serotonin and histamine receptors in rat brain.
Mianserin, a tetracyclic antidepressant, is a potent serotonin (5-HT) and histamine H1 antagonist in peripheral smooth muscle systems. Mianserin was found to possess high affinity for 5-HT2 and histamine H1 receptor binding sites in brain membranes. By using [3H]mianserin, both 5-HT2 and histamine H1 receptors can be specifically labeled in rat cerebral cortex membranes. Simultaneous incubation of brain membranes with 300 nM triprolidine or 30 nM spiroperidol enables the selective labeling of 5-HT2 or histamine H1 receptors, respectively. In the guinea-pig cerebellum, [3H]mianserin exclusively labels histamine H1 receptors, since 5-HT2 sites are virtually absent in this area.


Cholinergic inhibition of slow delayed-rectifier K+ current in guinea pig sino-atrial node is not mediated by muscarinic receptors.
We studied the effects of cholinergic agonists on slow delayed-rectifier K+ current (IKs) in isolated cells from the sino-atrial node (SAN) region of guinea pig heart, using patch-clamp procedures. Carbachol (5 nM to 10 microM) inhibited IKs in guinea pig SAN cells in the absence of previous beta-adrenergic stimulation and in cells pretreated with 8-(4-chlorophenylthio)-cAMP. Neither the muscarinic antagonist atropine nor the nicotinic antagonist hexamethonium antagonized carbachol inhibition of the current. Similar results were obtained with other cholinergic agonists. Cholinergic stimulation of the muscarinic K+ current was successfully antagonized by atropine in SAN cells where inhibition of IKs persisted. Therefore, the lack of antagonist effects on inhibition of IKs cannot be attributed to either an absence of muscarinic cholinoceptors on SAN cells or a loss of antagonist activity under our experimental conditions. These data demonstrate that cholinergic agonists, including the endogenous neurotransmitter acetylcholine, decrease the amplitude of IKs in guinea pig SAN cells via a non-muscarinic, non-nicotinic, cAMP-independent mechanism. Although the precise nature of this signal transduction pathway has not been elucidated, it is clearly different from those described for regulation of other nodal currents. Differential regulation of IKs in guinea pig SAN and ventricle cannot be attributed to higher basal adenylate cyclase activity in SAN cells. The inhibitory effect of carbachol on IKs was not additive with that of verapamil, a drug that is both an allosteric muscarinic antagonist and a potassium channel-blocking agent. Cholinergic agonists may inhibit IKs in SAN cells via a direct interaction with the SAN IKs channel.


Induction of cardiac fibrosis and transforming growth factor-β1 by motorcycle exhaust in rats.
Motorcycle exhaust (ME) is a major source of air pollution and a potential health hazard in urban areas where motorcycles are a popular means of transportation. The main objectives of this study were to determine the ability of ME to cause cardiotoxicity in rats and investigate the possible mechanisms of toxicity. Male rats were exposed to 1:10 diluted ME by inhalation 2 h daily and Monday through Friday for 8 weeks. Exposure to ME increased heart weight and decreased cardiac antioxidant enzymes glutathione S-transferase (GST), superoxide dismutase and glutathione peroxidase activities in a concentration- and time-dependent manner. Analysis of echocardiographic parameters indicated that ME increased left ventricle posterior wall thickness, interventricular septum thickness and left ventricle mass. Histopathological examinations of the hearts revealed that ME exposure caused focal cardial degeneration and necrosis, mononuclear cell infiltration, and fibrosis. The results of reverse transcriptase-polymerase chain reaction studies showed that ME decreased GST-M1 and GST-P1 mRNA expression and increased the expression of proinflammatory cytokine interleukin-1β, hypertrophy marker atrial natriuretic peptide, fibrosis markers type I and III collagen, profibrotic cytokine connective tissue growth factor, and hypertrophy and fibrosis mediator transforming growth factor (TGF)-β1 in the heart. The data of Western blot analysis showed that cardiac TGF-β1 protein was induced by ME. These findings demonstrate that subchronic ME exposure caused hypertrophy and fibrosis, and modulated GST and TGF-β1 expression in rat heart possibly by mechanisms involving oxidative stress and inflammation.


The analysis of animal bioelectric brain activity influenced by microwaves or by the introduction of strychnine.
The widespread impact made by technology has raised concerns about the safety of human exposure to electromagnetic radiation in the environment. The brain is especially sensitive to the influence of microwaves. The most effective method for estimation of the organism's functional states is an analysis of electroencephalograms. The statistical and spectral methods are usually used for analysis of animal electrocorticograms. The information obtained in such way is the integrated character and it is sometimes insufficient for identification of the brain state charging caused by various factors, especially microwaves altering the ecological situation. The nonlinear dynamics method is used in our work concurrent with the spectral correlation method for animal electrocorticogram processing. The correlation dimensionality represents a numerical criterion allowing for comparative investigation of various dynamic states of the system. In the process of investigation, it has been found that the nonlinear dynamics method may be used to analyze the electrocorticograms of experimental animal in different functional states being confirmed by increasing parameter of the correlation dimensionality in electrocorticograms of animal irradiated by microwaves or subjected to the introduction of strychnine.


On the origin of the stereoselectivity in organocatalysed reactions with trimethylsilyl-protected diarylprolinol.
The origin of the enantioselectivity in the TMS-protected (TMS=trimethylsilyl) prolinol-catalysed alpha-heteroatom functionalisation of aldehydes has been investigated by using density functional theory calculations. Eight different reaction paths have been considered which are based on four different conformers of the TMS-protected prolinol-enamine intermediate. Optimisation of the enamine structures gave two intermediates with nearly the same energy. These intermediates both have an E configuration at the C==C bond and the double bond is positioned anti or syn, relative to the 2-substituent in the pyrrolidine ring. For the four intermediates, the chiral TMS-protected-diaryl substituent effectively shields one of the faces of the reacting C==C bond in the enamine intermediate. A number of transition states have been calculated for the enantioselective fluorination by N-fluorobenzenesulfonimide (NFSI) and based on the transition-state energies it has been found that the enantioselectivity depends on the orientation of the C==C bond, being anti or syn, relative to the 2-substituent on the pyrrolidine ring, rather than the approach of the electrophilic fluorine to the face of the reacting carbon atom in the enamine which is less shielded relative to the face with the highest shielding. The calculated enantiomeric excess of 96 % ee (ee=enantiomeric excess) for the fluorination reaction corresponds well with the experimentally found enantiomeric excess-97 % ee. The transition state for the alpha-amination reaction with the same type of intermediate has also been calculated by using diethyl azodicarboxylate as the amination reagent. The implication of the intermediate structures on the stereoselection of alpha-functionalisation of aldehydes is discussed.


The genetic structure of Arabidopsis thaliana in the south-western Mediterranean range reveals a shared history between North Africa and southern Europe.
Deciphering the genetic structure of Arabidopsis thaliana diversity across its geographic range provides the bases for elucidating the demographic history of this model plant. Despite the unique A. thaliana genomic resources currently available, its history in North Africa, the extreme southern limit in the biodiversity hotspot of the Mediterranean Basin, remains virtually unknown. To approach A. thaliana evolutionary history in North Africa, we have analysed the genetic diversity and structure of 151 individuals collected from 20 populations distributed across Morocco. Genotyping of 249 genome-wide SNPs indicated that Morocco contains substantially lower diversity than most analyzed world regions. However, IBD, STRUCTURE and PCA clustering analyses showed that genetic variation is strongly geographically structured. We also determined the genetic relationships between Morocco and the closest European region, the Iberian Peninsula, by analyses of 201 populations from both regions genotyped with the same SNPs. These analyses detected four genetic groups, but all Moroccan accessions belonged to a common Iberian/Moroccan cluster that appeared highly differentiated from the remaining groups. Thus, we identified a genetic lineage with an isolated demographic history in the south-western Mediterranean region. The existence of this lineage was further supported by the study of several flowering genes and traits, which also found Moroccan accessions similar to the same Iberian group. Nevertheless, genetic diversity for neutral SNPs and flowering genes was higher in Moroccan than in Iberian populations of this lineage. Furthermore, we analyzed the genetic relationships between Morocco and other world regions by joint analyses of a worldwide collection of 337 accessions, which detected an additional weak relationship between North Africa and Asia. The patterns of genetic diversity and structure of A. thaliana in Morocco show that North Africa is part of the species native range and support the occurrence of a glacial refugium in the Atlas Mountains. In addition, the identification of a genetic lineage specific of Morocco and the Iberian Peninsula indicates that the Strait of Gibraltar has been an A. thaliana migration route between Europe and Africa. Finally, the genetic relationship between Morocco and Asia suggests another migration route connecting north-western Africa and Asia.


Endothelial cells mitigate DNA damage and promote the regeneration of hematopoietic stem cells after radiation injury.
Endothelial cells (ECs) are an essential component of the hematopoietic microenvironment, which maintains and regulates hematopoietic stem cells (HSCs). Although ECs can support the regeneration of otherwise lethally-irradiated HSCs, the mechanisms are not well understood. To further understand this phenomenon, we studied HSC regeneration from irradiated bone marrow using co-culture with human aortic ECs (HAECs). Co-culture with HAECs induced a 24-fold expansion of long-term HSCs (CD150(+), lineage(lo), Sca-1(+), c-Kit(+); CD150(+)LSK cells) in vitro. These cells gave rise to functional hematopoietic stem and progenitor cells (HSPCs) with colony-forming activity, multilineage reconstitution and serial transplantation potential. Furthermore, HAECs significantly reduced DNA damage in irradiated LSK cells within 24h. Remarkably, we were able to delay the exposure of irradiated bone marrow to the regenerative, HAEC-derived signals for up to 48h and still rescue functional HSCs. G-CSF is the gold standard for promoting hematopoietic regeneration in vivo. However, when compared to HAECs, in vitro G-CSF treatment promoted lineage differentiation and regenerated 5-fold fewer CD150(+)LSK cells. Together, our results show that HAECs are powerful, direct mitigators of HSC injury and DNA damage. Identification of the HAEC-derived factors that rescue HSCs may lead to improved therapies for hematopoietic regeneration after radiation injury.


Body composition in patients with stable chronic obstructive pulmonary disease: comparison with malnutrition in healthy smokers.
Although malnutrition (body mass index (BMI)<18.5kg/ m(2)) has been associated with impaired health status in patients with chronic obstructive pulmonary disease (COPD), the effects of body composition (body fat and protein percentage) in patients with COPD have not been clearly demonstrated. A total of 180 stable patients with COPD at the stages of moderate, severe, very severe, and 50 healthy subjects were included in this prospective study. All subjects underwent a clinical evaluation, spirometry tests, anthropometric measurements and blood analysis. Frequency of underweight was higher in COPD (11.7%) patients than the control group (8%). The frequency of underweight increased as the severity of COPD worsens. There was body decomposition (protein or fat depletion) in not only all underweight patients but also some normal/overweight COPD patients, as well as in the healthy subjects. Deterioration in FEV1 (L), and FEV1/FVC was more evident in underweight patients with protein and fat depletion compared to normal/overweight patients (p=0.004, and p=0.005). Inspiratory and expiratory respiratory muscle power was lower in under-weight patients with depletion than in normal/overweight patients (p=0.02, and p=0.01). DLCO and DLCO/VA were significantly lower in underweight patients than in normal/overweight patients (p=0.003, and p=0.004), they were also lower in normal/overweight patients with depletion than in normal/overweight patients with no depletion (p=0.01, and p=0.07). Normal/overweight patients with protein depletion had the most frequent number of exacerbations than others (p=0.04). These results show that the body decomposition is important in patients with COPD. Assessment of body composition should be a part of nutritional assessment besides BMI in patients with COPD.


Reducing accident death rates in children and young adults: the contribution of hospital care. Steering Committee of the Major Trauma Outcome Study Group.
To assess the contribution of trauma care to the recent decline in accident death rates among children and young people. Logistic regression modelling of temporal trends in the probability of death in patients admitted to hospital for the treatment of severe injury. Hospitals participating the United Kingdom major trauma outcome study. 3230 patients with an injury severity score of 16 or more, who were admitted for more than three days, transferred or admitted to intensive care, or died from their injuries. Death or survival in hospital within three months of injury. Over the seven year period 1989-95 there was a substantial decline in the probability of death among children and young adults admitted to hospital after severe injury. The overall estimate of the reduction in the odds of death was 16% per year (odds ratio for the yearly trend 0.84; 95% confidence interval 0.79 to 0.89). This decline did not differ significantly between age groups. (0-4 years 0.79; 5-14 years 0.87; 15-24 years 0.83). Reductions in hospital case fatality have made an important contribution to reaching the Health of the Nation targets. The contribution of hospital care in the reduction of accident mortality should be taken into account in decisions about the allocation of resources to preventive and curative services.


A comparison of stochastic programming methods for portfolio level decision-making.
Several methods have been presented in the literature for the management of a pharmaceutical portfolio, i.e. selecting which clinical studies should be conducted. We compare two existing approaches that use stochastic programming techniques and formulate the problem as a mixed integer linear programme (MILP). The first approach will be referred to as the ROV (real option valuation) approach since values are assigned to drug development programmes using methods for real option valuation. The second approach will be referred to as the PS (project scheduling) approach as this approach focusses on the scheduling of clinical studies and is formulated similarly to the resource constrained project scheduling problem. The ROV approach treats the value of a drug development programme as stochastic whereas the PS approach treats the trial outcomes as the stochastic component of the programme. As a consequence, the two approaches may select different portfolios. An advantage of the PS approach is that a schedule for when trials are to be conducted is provided as part of the optimal solution. This advantage comes at a much increased computational burden, however.


Acceptance of nicotine dependence treatment among currently depressed smokers.
This study reports on baseline characteristics associated with acceptance and refusal of available smoking treatment among currently depressed smokers in a psychiatric outpatient clinic who were enrolled in a larger clinical trial. The sample (N=154) was 68% female and 72% White, with a mean age of 41.4 years and average smoking rate of 17 cigarettes/day. All participants were assigned to a repeated contact experimental condition; received a stage-based expert system program to facilitate treatment acceptance; and were then offered smoking treatment, consisting of behavioral counseling, nicotine patch, and bupropion. Acceptors (n=53) were defined as those accepting behavioral counseling and pharmacological treatment at some point during the 18-month study, whereas refusers (n=101) received only the expert system. The number of days to treatment acceptance was significantly predicted by stage of change, with those in preparation entering treatment more quickly than contemplators or precontemplators. In a logistic regression, the variables most strongly associated with accepting treatment were current use of psychiatric medication and perceived success for quitting. Severity of depressive symptoms, duration of depression history, and history of recurrent depression were not related to treatment acceptance. Findings have implications for the psychiatric assessment and treatment of smokers in clinical settings. Psychiatric medication may play a significant role in smoking cessation treatment acceptance by currently depressed smokers.


Cost of atrial fibrillation in United States managed care organizations.
Atrial fibrillation (AF) has been shown to be associated with high healthcare costs; however, limited data are available from large-scale studies quantifying the overall cost burden of AF in the USA. We therefore aimed to provide an up to date estimate of the overall per-patient costs of AF in managed care organizations across the USA. This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from January 2005 to December 2006. Patients included in the analysis were aged > or =20 years and had at least two outpatient AF-related claims without hospitalization, or a hospitalization with a primary or secondary discharge diagnosis of AF in 2005. AF-related inpatient and outpatient costs over 12 months from the initial outpatient claim or first hospitalization were examined. For secondary AF hospitalizations, incremental costs associated with AF were measured by comparing costs for patients with AF with a group of matched controls hospitalized without AF. In total, 35,255 patients diagnosed as having AF (5008 with a primary AF diagnosis, 10,776 with a secondary AF diagnosis, 19,471 with outpatient-managed AF), and 20,571 controls without AF, were included in the analysis. Over 12 months, for primary AF hospitalization patients, inpatient costs were $11,306.53 and outpatient costs were $2826.78 (total $14,133.30) per patient. For hospitalized patients with secondary AF, incremental AF-related inpatient costs were $5181.19 and outpatient costs were $1376.33 (total $6557.52). For AF patients with outpatient management in 2005, 12-month AF-related costs were $2177.30 ($175.47 for AF hospitalizations in 2006 and $2001.85 for outpatient costs). Overall costs of AF in the US managed care organizations are high. Costs are primarily due to inpatient expenses. Improved disease management strategies to reduce AF-related hospitalizations and decrease the overall cost burden of AF are needed.


Reduced dosage of a single fission yeast MCM protein causes genetic instability and S phase delay.
MCM proteins are a conserved family of eukaryotic replication factors implicated in the initiation of DNA replication and in the discrimination between replicated and unreplicated chromatin. However, most mcm mutants in yeast arrest the cell cycle after bulk DNA synthesis has occurred. We investigated the basis for this late S phase arrest by analyzing the effects of a temperature-sensitive mutation in fission yeast cdc19(+ )(mcm2(+)). cdc19-P1 cells show a dramatic loss of viability at the restrictive temperature, which is not typical of all S phase mutants. The cdc19-P1 cell cycle arrest requires an intact damage-response checkpoint and is accompanied by increased rates of chromosome loss and mitotic recombination. Chromosomes from cdc19-P1 cells migrate aberrantly in pulsed-field gels, typical of strains arrested with unresolved replication intermediates. The cdc19-P1 mutation reduces the level of the Cdc19 protein at all temperatures. We compared the effects of disruptions of cdc19(+ )(mcm2(+)), cdc21(+ )(mcm4(+)), nda4(+ )(mcm5(+)) and mis5(+ )(mcm6(+)); in all cases, the null mutants underwent delayed S phase but were unable to proceed through the cell cycle. Examination of protein levels suggests that this delayed S phase reflects limiting, but not absent, MCM proteins. Thus, reduced dosage of MCM proteins allows replication initiation, but is insufficient for completion of S phase and cell cycle progression.


Prevalence and incidence of systemic sclerosis in southern Sweden: population-based data with case ascertainment using the 1980 ARA criteria and the proposed ACR-EULAR classification criteria.
To estimate the prevalence and incidence of systemic sclerosis (SSc) in southern Sweden. In Skåne, the southernmost region of Sweden (total population 1.2 million), healthcare provided is registered in the Skåne Healthcare Register. We identified all Skåne residents who had received an International Classification of Diseases 10 diagnosis of SSc (M34) or Raynaud's phenomenon (I73.0) between 1998 and 2010. Every single case was ascertained by review of medical records in reference to the 1980 American Rheumatism Association preliminary classification criteria for SSc and the proposed American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) classification criteria presented at the ACR/Association of Rheumatology Health Professionals Annual Meeting 2012. We calculated the point prevalence by the end of 2010 by linkage with the population register to exclude deceased persons and we also estimated the mean annual cumulative incidence for 2006-2010. Using the 1980 ARA criteria, the adult prevalence and annual incidence of SSc in the Skåne region were 235 and 14 per 1 million inhabitants respectively. Applying the proposed ACR-EULAR criteria, the corresponding figures were 305 and 19 per 1 million inhabitants. A majority (82%) of the prevalent cases had the limited cutaneous SSc subtype. The prevalence and incidence of SSc in southern Sweden, based on the 1980 ARA criteria, are higher than previously reported in northern Europe and do not support the concept of a north-south gradient of SSc occurrence in Europe. Application of the proposed ACR-EULAR classification criteria in this population results in about 30-40% higher estimates of SSc prevalence and incidence compared to the 1980 ARA criteria.


Extracellular proteolysis in glioblastoma progression and therapeutics.
Gliomas encompass highly invasive primary central nervous system (CNS) tumours of glial cell origin with an often-poor clinical prognosis. Of all gliomas, glioblastoma is the most aggressive form of primary brain cancer. Current treatments in glioblastoma are insufficient due to the invasive nature of brain tumour cells, which typically results in local tumour recurrence following treatment. The latter represents the most important cause of mortality in glioblastoma and underscores the necessity for an in-depth understanding of the underlying mechanisms. Interestingly, increased synthesis and secretion of several proteolytic enzymes within the tumour microenvironment, such as matrix metalloproteinases, lysosomal proteases, cathepsins and kallikreins for extracellular-matrix component degradation may play a major role in the aforementioned glioblastoma invasion mechanisms. These proteolytic networks are key players in establishing and maintaining a tumour microenvironment that promotes tumour cell survival, proliferation, and migration. Indeed, the targeted inhibition of these proteolytic enzymes has been a promisingly useful therapeutic strategy for glioblastoma management in both preclinical and clinical development. We hereby summarize current advances on the biology of the glioblastoma tumour microenvironment, with a particular emphasis on the role of proteolytic enzyme families in glioblastoma invasion and progression, as well as on their subsequent prognostic value as biomarkers and their therapeutic targeting in the era of precision medicine.


Ventilatory strategies in obstructive lung disease.
Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation (EFL) due to progressive airflow obstruction. The various mechanisms that cause EFL are central to understanding the physiopathology of COPD. At the end of expiration, dynamic inflation may occur due to incomplete emptying the lungs. This "extra" volume increases the alveolar pressure at the end of the expiration, resulting in auto-positive end-expiratory pressure (PEEP) or PEEPi. Acute exacerbations of COPD may result in increased airway resistance and inspiratory effort, further leading to dynamic hyperinflation. COPD exacerbations may be triggered by environmental exposures, infections (viral and bacterial), or bronchial inflammation, and may result in worsening respiratory failure requiring mechanical ventilation (MV). Acute exacerbations of COPD need to be distinguished from other events such as cardiac failure or pulmonary emboli. Strategies to treat acute respiratory failure (ARF) in COPD patients include noninvasive ventilation (NIV), pressure support ventilation, and tracheal intubation with MV. In this review, we discuss invasive and noninvasive techniques to address ARF in this patient population. When invasive MV is used, settings should be adjusted in a way that minimizes hyperinflation, while providing reasonable gas exchange, respiratory muscle rest, and proper patient-ventilator interaction. Further, weaning from MV may be difficult in these patients, and factors amenable to pharmacological correction (such as increased bronchial resistance, tracheobronchial infections, and heart failure) are to be systematically searched and treated. In selected patients, early use of NIV may hasten the process of weaning from MV and improve outcomes.


EHR Text Categorization for Enhanced Patient-Based Document Navigation.
Patients with multiple disorders usually have long diagnosis lists, constitute by ICD-10 codes together with individual free-text descriptions. These text snippets are produced by overwriting standardized ICD-Code topics by the physicians at the point of care. They provide highly compact expert descriptions within a 50-character long text field frequently not assigned to a specific ICD-10 code. The high redundancy of these lists would benefit from content-based categorization within different hospital-based application scenarios. This work demonstrates how to accurately group diagnosis lists via a combination of natural language processing and hierarchical clustering with an overall F-measure value of 0.87. In addition, it compresses the initial diagnosis list up to 89%. The manuscript discusses pitfall and challenges as well as the potential of a large-scale approach for tackling this problem.


Angelman syndrome associated with oculocutaneous albinism due to an intragenic deletion of the P gene.
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation, speech impairment, ataxia, and happy disposition with frequent smiling. AS results from the loss of expression of a maternal imprinted gene, UBE3A, mapped within 15q11-q13 region, due to different mechanisms: maternal deletion, paternal UPD, imprinting center mutation, and UBE3A mutation. Deletion AS patients may exhibit hypopigmentation of skin, eye, and hair correlating with deletion of P gene localized in the distal part of Prader-Willi (PWS)/AS region. Our patient presented developmental delay, severe mental retardation, absence of speech, outbursts of laughter, microcephaly, ataxia, hyperactivity, seizures, white skin, no retinal pigmentation, and gold yellow hair. His parents were of African ancestry. The SNURF-SNRPN methylation analysis confirmed AS diagnosis and microsatellite studies disclosed deletion with breakpoints in BP2 and BP3. All of the 25 exons and flanking introns of the P gene of the patient, his father, and mother were investigated. The patient is hemizygous for the deleted exon 7 of the P gene derived from his father who is a carrier of the deleted allele. Our patient manifests OCA2 associated with AS due to the loss of the maternal chromosome 15 with the normal P allele, and the paternal deletion in the P gene. As various degrees of hypopigmentation are associated with PWS and AS patients, the study of the P gene in a hemizygous state could contribute to the understanding of its effect on human pigmentation during development and to disclose the presence of modifier pigmentation gene(s) in the PWS/AS region.


The budding yeast rRNA and ribosome biosynthesis (RRB) regulon contains over 200 genes.
The ribosome biogenesis pathway constitutes one of the major metabolic obligations for a dividing yeast cell and it depends upon the activity of hundreds of gene products to produce the necessary rRNA and ribosomal protein components. Previously, we reported that a set of 65 S. cerevisiae genes that function in the rRNA biosynthesis pathway are transcriptionally co-regulated as cells pass through a variety of physiological transitions. By analysing multiple microarray-based transcriptional datasets, we have extended that study and now suggest that the ribosomal and rRNA biosynthesis regulon contains over 200 genes. This regulon is distinct from the set of ribosomal protein genes, and the promoters of the expanded RRB gene set are highly enriched for the PAC and RRPE motifs. Since a similar pattern of organization and gene regulation can be recognized in C. albicans, the RRB regulon appears to be a conserved, extensive, and metabolically important group of genes.


Unravelling biodiversity, evolution and threats to conservation in the Sahara-Sahel.
Deserts and arid regions are generally perceived as bare and rather homogeneous areas of low diversity. The Sahara is the largest warm desert in the world and together with the arid Sahel displays high topographical and climatic heterogeneity, and has experienced recent and strong climatic oscillations that have greatly shifted biodiversity distribution and community composition. The large size, remoteness and long-term political instability of the Sahara-Sahel, have limited knowledge on its biodiversity. However, over the last decade, there have been an increasing number of published scientific studies based on modern geomatic and molecular tools, and broad sampling of taxa of these regions. This review tracks trends in knowledge about biodiversity patterns, processes and threats across the Sahara-Sahel, and anticipates needs for biodiversity research and conservation. Recent studies are changing completely the perception of regional biodiversity patterns. Instead of relatively low species diversity with distribution covering most of the region, studies now suggest a high rate of endemism and larger number of species, with much narrower and fragmented ranges, frequently limited to micro-hotspots of biodiversity. Molecular-based studies are also unravelling cryptic diversity associated with mountains, which together with recent distribution atlases, allows identifying integrative biogeographic patterns in biodiversity distribution. Mapping of multivariate environmental variation (at 1 km × 1 km resolution) of the region illustrates main biogeographical features of the Sahara-Sahel and supports recently hypothesised dispersal corridors and refugia. Micro-scale water-features present mostly in mountains have been associated with local biodiversity hotspots. However, the distribution of available data on vertebrates highlights current knowledge gaps that still apply to a large proportion of the Sahara-Sahel. Current research is providing insights into key evolutionary and ecological processes, including causes and timing of radiation and divergence for multiple taxa, and associating the onset of the Sahara with diversification processes for low-mobility vertebrates. Examples of phylogeographic patterns are showing the importance of allopatric speciation in the Sahara-Sahel, and this review presents a synthetic overview of the most commonly hypothesised diversification mechanisms. Studies are also stressing that biodiversity is threatened by increasing human activities in the region, including overhunting and natural resources prospection, and in the future by predicted global warming. A representation of areas of conflict, landmines, and natural resources extraction illustrates how human activities and regional insecurity are hampering biodiversity research and conservation. Although there are still numerous knowledge gaps for the optimised conservation of biodiversity in the region, a set of research priorities is provided to identify the framework data needed to support regional conservation planning.


Tissue Resources for the Functional Annotation of Animal Genomes.
In order to generate an atlas of the functional elements driving genome expression in domestic animals, the Functional Annotation of Animal Genome (FAANG) strategy was to sample many tissues from a few animals of different species, sexes, ages, and production stages. This article presents the collection of tissue samples for four species produced by two pilot projects, at INRAE (National Research Institute for Agriculture, Food and Environment) and the University of California, Davis. There were three mammals (cattle, goat, and pig) and one bird (chicken). It describes the metadata characterizing these reference sets (1) for animals with origin and selection history, physiological status, and environmental conditions; (2) for samples with collection site and tissue/cell processing; (3) for quality control; and (4) for storage and further distribution. Three sets are identified: set 1 comprises tissues for which collection can be standardized and for which representative aliquots can be easily distributed (liver, spleen, lung, heart, fat depot, skin, muscle, and peripheral blood mononuclear cells); set 2 comprises tissues requiring special protocols because of their cellular heterogeneity (brain, digestive tract, secretory organs, gonads and gametes, reproductive tract, immune tissues, cartilage); set 3 comprises specific cell preparations (immune cells, tracheal epithelial cells). Dedicated sampling protocols were established and uploaded in https://data.faang.org/protocol/samples. Specificities between mammals and chicken are described when relevant. A total of 73 different tissues or tissue sections were collected, and 21 are common to the four species. Having a common set of tissues will facilitate the transfer of knowledge within and between species and will contribute to decrease animal experimentation. Combining data on the same samples will facilitate data integration. Quality control was performed on some tissues with RNA extraction and RNA quality control. More than 5,000 samples have been stored with unique identifiers, and more than 4,000 were uploaded onto the Biosamples database, provided that standard ontologies were available to describe the sample. Many tissues have already been used to implement FAANG assays, with published results. All samples are available without restriction for further assays. The requesting procedure is described. Members of FAANG are encouraged to apply a range of molecular assays to characterize the functional status of collected samples and share their results, in line with the FAIR (Findable, Accessible, Interoperable, and Reusable) data principles.


Financial and social circumstances and the incidence and course of PTSD in Mississippi during the first two years after Hurricane Katrina.
Hurricane Katrina was the most devastating natural disaster to hit the United States in the past 75 years. The authors conducted interviews of 810 persons who were representative of adult residents living in the 23 southernmost counties of Mississippi before Hurricane Katrina. The prevalence of posttraumatic stress disorder (PTSD) since Hurricane Katrina was 22.5%. The determinants of PTSD were female gender, experience of hurricane-related financial loss, postdisaster stressors, low social support, and postdisaster traumatic events. Kaplan-Meier survival curves suggest that exposure to both hurricane-related traumatic events and to financial and social stressors influenced the duration of PTSD symptoms. Postdisaster interventions that aim to improve manipulable stressors after these events may influence the onset and course of PTSD.


Biophysical modelling of phytoplankton communities from first principles using two-layered spheres: Equivalent Algal Populations (EAP) model.
There is a pressing need for improved bio-optical models of high biomass waters as eutrophication of coastal and inland waters becomes an increasing problem. Seasonal boom conditions in the Southern Benguela and persistent harmful algal production in various inland waters in Southern Africa present valuable opportunities for the development of such modelling capabilities. The phytoplankton-dominated signal of these waters additionally addresses an increased interest in Phytoplankton Functional Type (PFT) analysis. To these ends, an initial validation of a new model of Equivalent Algal Populations (EAP) is presented here. This paper makes a first order comparison of two prominent phytoplankton Inherent Optical Property (IOP) models with the EAP model, which places emphasis on explicit bio-physical modelling of the phytoplankton population as a holistic determinant of inherent optical properties. This emphasis is shown to have an impact on the ability to retrieve the detailed phytoplankton spectral scattering information necessary for PFT applications and to successfully simulate reflectance across wide ranges of physical environments, biomass, and assemblage characteristics.


Inflammatory bowel disease in young patients: challenges faced by black and minority ethnic communities in the UK.
There is strong evidence indicating that inflammatory bowel disease (IBD) is increasing among black and minority ethnic (BME) communities. Despite this rise in prevalence, there is a paucity of research relating to ethnicity and IBD outside the USA. Furthermore, the symptoms of IBD are reported to start during childhood or adolescence in 20-25% of people with the condition. It is therefore important that young people's experiences of diagnosis, treatment and living with IBD are fully understood to ensure effective services and information provision. The study reported on in this paper was commissioned by a UK charity (Crohn's and Colitis UK) with the aim of increasing understanding of the specific issues and service needs of young people with IBD from BME communities. Empirical research entailed in-depth semi-structured interviews with 20 young people from BME groups accessed through gastroenterology departments at three collaborating NHS hospitals in England serving ethnically diverse populations. Interviews were carried out from June to December 2010 and sought to capture young people's views with IBD. A thematic analysis of their experiences identified many commonalities with other young people with IBD, such as the problematic route to formal diagnosis and the impact of IBD on education. The young people also experienced tensions between effective self-management strategies and cultural norms and practices relating to food. Moreover, the ability of parents to provide support was hampered for some young people by the absence of culturally competent services that were responsive to the families' communication needs. The findings highlight the need for more culturally appropriate information concerning IBD, and improved responsiveness to young people with IBD within primary care and the education system, as well as culturally competent messaging relating to the specific nature of the condition among the wider South Asian and black communities.


Error and bias in size estimates of whale sharks: implications for understanding demography.
Body size and age at maturity are indicative of the vulnerability of a species to extinction. However, they are both difficult to estimate for large animals that cannot be restrained for measurement. For very large species such as whale sharks, body size is commonly estimated visually, potentially resulting in the addition of errors and bias. Here, we investigate the errors and bias associated with total lengths of whale sharks estimated visually by comparing them with measurements collected using a stereo-video camera system at Ningaloo Reef, Western Australia. Using linear mixed-effects models, we found that visual lengths were biased towards underestimation with increasing size of the shark. When using the stereo-video camera, the number of larger individuals that were possibly mature (or close to maturity) that were detected increased by approximately 10%. Mean lengths calculated by each method were, however, comparable (5.002 ± 1.194 and 6.128 ± 1.609 m, s.d.), confirming that the population at Ningaloo is mostly composed of immature sharks based on published lengths at maturity. We then collated data sets of total lengths sampled from aggregations of whale sharks worldwide between 1995 and 2013. Except for locations in the East Pacific where large females have been reported, these aggregations also largely consisted of juveniles (mean lengths less than 7 m). Sightings of the largest individuals were limited and occurred mostly prior to 2006. This result highlights the urgent need to locate and quantify the numbers of mature male and female whale sharks in order to ascertain the conservation status and ensure persistence of the species.