Acute Care Diagnostic Collaboration: Bayesian modeling comparative diagnostic assessment of lactate, procalcitonin and CRP in risk stratified population by Mortality in ED (MEDS) score.
To assess and compare the diagnostic value of lactate, procalcitonin (PCT) and C-reactive protein (CRP) in low, moderate, and high-risk stratified population applying Mortality in Emergency Department (MEDS) risk score using Bayesian statistical modeling. MEDS criteria was used to risk stratify into low, moderate and high risk. Each population was attributed a percentage risk, and used as pre-test probability in the Bayesian nomogram. Sensitivity and specificity lactate, PCT and CRP were attained from pooled meta-analysis data. Absolute and relative diagnostic gains were calculated. Pooled diagnostic quality data obtained from a meta-analysis reflected sensitivity for PCT of 77% and specificity of 79%, for lactate sensitivity 49.1% and specificity 74.3% and CRP yielded a sensitivity of 75% and specificity 67%. likelihood ratios (LR) calculations for PCT were LR+ 3.67 and LR- 0.29; for lactate LR+ 1.88 and LR- 0.69; CRP LR+ 2.27 and LR- 0.37. When computed in Bayesian nomogram post-test probabilities for LR+ were as follows: for PCT low risk absolute gain of 11.7% and relative gain of 220%; moderate absolute gain 25.7% relative gain 148.5%; for high risk absolute gain 25.1% and relative gain 42.6%. Lactate LR+ results for low risk absolute gain of 4.7% and relative gain of 88.6%; moderate absolute gain 10.7% and relative gain 61.8%; high risk relative gain 14.1% and relative gain 23.9%. CRP results for low population and LR+ absolute gain 5.7% and relative gain 107.5%; moderate risk 14.7% absolute gain and 84.9% relative gain; high risk 77% post-test 18.1% absolute gain and 30.7% relative gain. Bayesian statistical model demonstrated the superior diagnostic quality of PCT. For ruling out severe disease, lactate yielded a higher benefit with increased relative gain with negative LR.


Autoradiographic localization of radioactivity in rat brain after injection of tritiated sex hormones.
Radioactivity was found in cell bodies of neurons and glial cells throughout brains of male and female rats that had been injected with either testosterone-H(3) or estradiol-H(3). Uptake by limbic and hypothalamic structures was higher and longer lasting than that in nonlimbic structures. In all brains, the preoptic area, prepiriform cortex, olfactory tubercle, and septum had particularly high, long-lasting uptake of both hormones.


Developmental determinants in non-communicable chronic diseases and ageing.
Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.


The social determinants of health: why should we care?
A growing body of empirical research examines the effects of the so-called "social determinants of health" (SDH) on health and health inequalities. Several high-profile publications have issued policy recommendations to reduce health inequalities based on a specific interpretation of this empirical research as well as a set of normative assumptions. This article questions the framework defined by these assumptions by focusing on two issues: first, the normative judgments about the (un)fairness of particular health inequalities; and second, the policy recommendations issued on this basis. We argue that the normative underpinnings of the approach are insufficiently supported and that the policy recommendations do not necessarily follow from the arguments provided. Furthermore, while many of the policies recommended-such as improving people's living conditions and reducing inequalities in wealth and power-are justified in their own right, the way these recommendations are tied to health is problematic.


Accessibility and Applicability of Currently Available e-Mental Health Programs for Depression for People With Poststroke Aphasia: Scoping Review.
Depression affects approximately 60% of people with aphasia 1 year post stroke and is associated with disability, lower quality of life, and mortality. Web-delivered mental health (e-mental health) programs are effective, convenient, and cost-effective for the general population and thus are increasingly used in the management of depression. However, it is unknown if such services are applicable and communicatively accessible to people with poststroke aphasia. The aim of this study was to identify freely available e-mental health programs for depression and determine their applicability and accessibility for people with poststroke aphasia. A Web-based search was conducted to identify and review freely available e-mental health programs for depression. These programs were then evaluated in terms of their (1) general features via a general evaluation tool, (2) communicative accessibility for people with aphasia via an aphasia-specific communicative accessibility evaluation tool, and (3) empirical evidence for the general population and stroke survivors with and without aphasia. The program that met the most general evaluation criteria and aphasia-specific communicative accessibility evaluation criteria was then trialed by a small subgroup of people with poststroke aphasia. A total of 8 programs were identified. Of these, 4 had published evidence in support of their efficacy for use within the general population. However, no empirical evidence was identified that specifically supported any programs' use for stroke survivors with or without aphasia. One evidence-based program scored at least 80% (16/19 and 16/20, respectively) on both the general and aphasia-specific communicative accessibility evaluation tools and was subject to a preliminary trial by 3 people with poststroke aphasia. During this trial, participants were either unable to independently use the program or gave it low usability scores on a post-trial satisfaction survey. On this basis, further evaluation was considered unwarranted. Despite fulfilling majority of the general evaluation and aphasia-specific evaluation criteria, the highest rated program was still found to be unsuitable for people with poststroke aphasia. Thus, e-mental health programs require substantial redevelopment if they are likely to be useful to people with poststroke aphasia.


Visualization of the immunological synapse by dual color time-gated stimulated emission depletion (STED) nanoscopy.
Natural killer cells form tightly regulated, finely tuned immunological synapses (IS) in order to lyse virally infected or tumorigenic cells. Dynamic actin reorganization is critical to the function of NK cells and the formation of the IS. Imaging of F-actin at the synapse has traditionally utilized confocal microscopy, however the diffraction limit of light restricts resolution of fluorescence microscopy, including confocal, to approximately 200 nm. Recent advances in imaging technology have enabled the development of subdiffraction limited super-resolution imaging. In order to visualize F-actin architecture at the IS we recapitulate the NK cell cytotoxic synapse by adhering NK cells to activating receptor on glass. We then image proteins of interest using two-color stimulated emission depletion microscopy (STED). This results in <80 nm resolution at the synapse. Herein we describe the steps of sample preparation and the acquisition of images using dual color STED nanoscopy to visualize F-actin at the NK IS. We also illustrate optimization of sample acquisition using Leica SP8 software and time-gated STED. Finally, we utilize Huygens software for post-processing deconvolution of images.


Valsartan lowers brain beta-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease.
Recent epidemiological evidence suggests that some antihypertensive medications may reduce the risk for Alzheimer disease (AD). We screened 55 clinically prescribed antihypertensive medications for AD-modifying activity using primary cortico-hippocampal neuron cultures generated from the Tg2576 AD mouse model. These agents represent all drug classes used for hypertension pharmacotherapy. We identified 7 candidate antihypertensive agents that significantly reduced AD-type beta-amyloid protein (Abeta) accumulation. Through in vitro studies, we found that only 1 of the candidate drugs, valsartan, was capable of attenuating oligomerization of Abeta peptides into high-molecular-weight (HMW) oligomeric peptides, known to be involved in cognitive deterioration. We found that preventive treatment of Tg2576 mice with valsartan significantly reduced AD-type neuropathology and the content of soluble HMW extracellular oligomeric Abeta peptides in the brain. Most importantly, valsartan administration also attenuated the development of Abeta-mediated cognitive deterioration, even when delivered at a dose about 2-fold lower than that used for hypertension treatment in humans. These preclinical studies suggest that certain antihypertensive drugs may have AD-modifying activity and may protect against progressive Abeta-related memory deficits in subjects with AD or in those at high risk of developing AD.


Ability of new heart rate monitors to measure normal and abnormal heart rate.
The extended use of heart rate monitors to non sportive people, and older ones increases the risk to be facing heart rate troubles. Questions exist upon the ability of this devices to detect such abnormalities. The purpose of the investigation was to evaluate the accuracy of two third generation heart rate monitors, Accurex Plus and Vantage NV and to compared these data with those of an older one, PE 4000. Then we investigate responses of this monitors to abnormal heart rate. The three heart rate monitors were tested in the laboratory, wired in parallel to an ECG simulator under two modes: a normal heart rate program (7 stable heart rate stages with two marked transitions) and an automatic arrhythmia one. 1st program: Values generated by the ECG simulator were compared to the values produced by the three devices. Particular attention was paid to the transition phases (heart rate drop and heart rate fall). Results of heart rate monitors accuracy were expressed at the exact value (devices value=simulator value) and at approximated value of +/-3 beats x min(-1) (devices value=simulator value +/-3 beats x min(-1)); 2nd program: Abnormal rhythms were analysed using an ambulatory ECG recorder (Synésis) as control data, and compared to the data from the three devices. Correlation between simulator generated true values and HRMs read values were calculated. In the 1st normal heart rate program, with an accuracy of exact value, Accurex Plus and Vantage NV, were more accurate than the PE 4000 (94% and 89% of values respectively versus 33% for the PE4000). At +/-3 beats x min(-1), the three devices gave good results: over 98% of total values. In transition phases: the three devices showed a smoothing effect, which was stronger in decelerating heart rate than in accelerating heart rate. In the 2nd program: isolated heart rhythm troubles (missing beat, pause <4 sec, supra-ventricular ectopic activity, and ventricular ectopic activity) were either not detected or were rejected. Signal changes such as changes in QRS (ventricular bigeminy) may cause detection losses, and so modify calculated heart rate. The HR signal rising/dropping slopes caused by sudden heart rhythm disorders, were notably attenuated, with a consequent loss of HR accuracy. In laboratory stable heart rate conditions, third generation HRMs are more accurate than earlier ones. Heart rate monitors are less accurate in transient phases and have not been improved in that domain. The three HRMs ignore isolated heart rate troubles. As expected, the usefulness of HRMs in detecting HR disorders is limited. Nevertheless, these devices have some value with serious troubles, like pause, bradycardia or tachycardia, lasting longer than 4 sec, and especially if they coincide with functional symptoms. The use of such even more accurate devices may consequently be recommended to healthy public for which they were built.


The Value of Pre- and Intraoperative Adjuncts on the Extent of Resection of Hemispheric Low-Grade Gliomas: A Retrospective Analysis.
To achieve maximal resection with minimal risk of postoperative neurologic morbidity, different neurosurgical adjuncts are being used during low-grade glioma (LGG) surgery. To investigate the effect of pre- and intraoperative adjuncts on the extent of resection (EOR) of hemispheric LGGs. Medical records were reviewed to identify patients of any sex, ≥ 18 years of age, who underwent LGG surgery at X Hospital between January 2005 and July 2013. Patients were divided into eight subgroups based on the use of various combinations of a neuronavigation system alone (NN), functional MRI-diffusion tensor imaging (fMRI-DTI) guided neuronavigation (FD), intraoperative MRI (MR), and direct electrical stimulation (DES). Initial and residual tumors were measured, and mean EOR was compared between groups. Of all 128 patients, gross total resection was achieved in 23.4%. Overall mean EOR was 81.3% ± 20.5%. Using DES in combination with fMRI-DTI (mean EOR: 86.7% ± 12.4%) on eloquent tumors improved mean EOR significantly after adjustment for potential confounders when compared with NN alone (mean EOR: 76.4% ± 25.5%; p = 0.001). Using DES in combination with fMRI and DTI significantly improves EOR when LGGs are located in eloquent areas compared with craniotomies in which only NN was used.


Heartsink encounters: a qualitative study of end-of-life care in out-of-hours general practice.
We aimed to establish how prepared GPs who work regular out-of-hours shifts feel when dealing with end-of-life issues in palliative care patients, what they thought about seeing such patients and whether they considered themselves emotionally equipped to do so. Semi-structured interviews were conducted with GPs who worked regular out-of-hours shifts. A detailed analysis of transcripts using Interpretative Phenomenological Analysis was undertaken. South Wales. GPs employed by the local health board's out-of-hours service were contacted. All interview data were analysed systematically and statements that reflected emotional impact and strain were highlighted, coded and interpreted within their context. GPs expressed unease and used terms such as 'heartsink', when having to deal with palliative care issues out-of-hours. Heartsink in this context referred to the subjective experience of the clinician. Emotional 'housekeeping', i.e. looking after oneself after emotionally-charged encounters, was felt to be a very important process and GPs used a range of coping mechanisms, including reflective time, sharing with peers, compartmentalisation and personal empathy to deal with stress. The emotional effects of palliative care encounters on out-of-hours GPs should not be underestimated. Our interpretation distinguished the term 'heartsink' from its usual context, the 'heartsink patient', to a different meaning, that of the imminent palliative care encounter triggering a sensation of heartsink for some out-of-hours doctors. Therefore, the term 'heartsink encounter', rather than heartsink patient, seemed more fitting. Pressed services may encourage a culture where discussion or debrief with a colleague after a palliative care encounter is not perceived as a practical option. This may contribute to work-related burnout in this group of doctors and out-of-hours collaboratives need to be aware of this issue, when planning their services.


Necessary conditions for sustainable water and sanitation service delivery in schools: A systematic review.
Access to water, sanitation, and hygiene (WASH) services confers significant health and economic benefits, especially for children, but only if those services can be delivered on a consistent basis. The challenge of sustainable, school-based WASH service delivery has been widely documented, particularly in resource-constrained contexts. We conducted a systematic review of published research that identifies drivers of, or tests solutions to, this challenge within low- and middle-income countries (PROSPERO 2020 CRD42020199163). Authors in the first group employ cross-sectional research designs and interrogate previously implemented school WASH interventions. Most conclude that dysfunctional accountability and information sharing mechanisms drive school WASH service delivery failures. By contrast, most of the interventions developed and tested experimentally by authors in the second group focus on increasing the financial and material resources available to schools for WASH service delivery. Overall, these authors find negligible impact of such infusions of cash, infrastructure, and supplies across a variety of sustainability outcome metrics. Taken together, the evidence suggests that sustainable service delivery depends on three simultaneously necessary components: resources, information, and accountability. Drawing upon theory and evidence from social psychology, public management, and political science, we identify priority knowledge gaps that can meaningfully improve the design of effective interventions. We also highlight the importance of both interdisciplinary collaboration and local expertise in designing WASH programming that aligns with sociocultural and institutional norms, and is thus more likely to generate sustainable impact.


The anti-lymphoma activity of APO866, an inhibitor of nicotinamide adenine dinucleotide biosynthesis, is potentialized when used in combination with anti-CD20 antibody.
APO866 is an inhibitor of nicotinamide adenine dinucleotide (NAD) biosynthesis that exhibits potent anti-lymphoma activity. Rituximab (RTX), an anti-CD20 antibody, kills lymphoma cells by direct apoptosis and antibody- and complement-dependent cell-mediated cytotoxicities, and has clinical efficacy in non-Hodgkin cell lymphomas. In the present study, we evaluated whether RTX could potentiate APO866-induced human B-lymphoma cell death and shed light on death-mediated mechanisms associated with this drug combination. We found that RTX significantly increases APO866-induced death in lymphoma cells from patients and lines. Mechanisms include enhancement of autophagy-mediated cell death, activation of caspase 3 and exacerbation of mitochondrial depolarization, but not increase of reactive oxygen species (ROS) production, when compared with those induced by each drug alone. In vivo, combined administration of APO866 with RTX in a laboratory model of human aggressive lymphoma significantly decreased tumor burden and prolonged survival over single-agent treatment. Our study demonstrates that the combination of RTX and APO866 optimizes B-cell lymphoma apoptosis and therapeutic efficacy over both compounds administered separately.


Assessing regulatory violations of disinfection by-products in water distribution networks using a non-compliance potential index.
Inactivating pathogens is essential to eradicate waterborne diseases. However, disinfection forms undesirable disinfection by-products (DBPs) in the presence of natural organic matter. Many regulations and guidelines exist to limit DBP exposure for eliminating possible health impacts such as bladder cancer, reproductive effects, and child development effects. In this paper, an index named non-compliance potential (NCP) index is proposed to evaluate regulatory violations by DBPs. The index can serve to evaluate water quality in distribution networks using the Bayesian Belief Network (BBN). BBN is a graphical model to represent contributing variables and their probabilistic relationships. Total trihalomethanes (TTHM), haloacetic acids (HAA5), and free residual chlorine (FRC) are selected as the variables to predict the NCP index. A methodology has been proposed to implement the index using either monitored data, empirical model results (e.g., multiple linear regression), and disinfectant kinetics through EPANET simulations. The index's usefulness is demonstrated through two case studies on municipal distribution systems using both full-scale monitoring and modeled data. The proposed approach can be implemented for data-sparse conditions, making it especially useful for smaller municipal drinking water systems.


Different Muscle-Recruitment Strategies Among Elite Breaststrokers.
To investigate electromyographical (EMG) profiles characterizing the lower-limb flexion-extension in an aquatic environment in high-level breaststrokers. The 2-dimensional breaststroke kick of 1 international- and 2 national-level female swimmers was analyzed during 2 maximal 25-m swims. The activities of biceps femoris, rectus femoris, gastrocnemius, and tibialis anterior were recorded. The breaststroke kick was divided in 3 phases, according to the movements performed in the sagittal plane: push phase (PP) covering 27% of the total kick duration, glide phase (GP) 41%, and recovery phase (RP) 32%. Intrasubject reproducibility of the EMG and kinematics was observed from 1 stroke cycle to another. In addition, important intersubject kinematic reproducibility was noted, whereas muscle activities discriminated the subjects: The explosive PP was characterized by important muscle-activation peaks. During the recovery, muscles were likewise solicited for swimmers 1 (S1) and 2 (S2), while the lowest activities were observed during GP for S2 and swimmer 3 (S3), but not for S1, who maintained major muscle solicitations. The main muscle activities were observed during PP to perform powerful lower-limb extension. The most-skilled swimmer (S1) was the only 1 to solicit her muscles during GP to actively reach better streamlining. Important activation peaks during RP correspond to the limbs acting against water drag. Such differences in EMG strategies among an elite group highlight the importance of considering the muscle parameters used to effectively control the intensity of activation among the phases for a more efficient breaststroke kick.


Successes and failures of compulsory risk mitigation: re-evaluating the Turkish Catastrophe Insurance Pool.
The Turkish Catastrophe Insurance Pool (TCIP) is one of the best practices of public-private partnerships in an emerging market designed to reduce economic losses from disasters. This paper reviews the application of this compulsory mechanism along with data relating to the performance of the scheme following recent earthquakes in Turkey. We also consider the current perceptions of Turkish society towards the TCIP and how they can be enhanced. Our conclusions aim to assist stakeholders in government, homeowners, insurance companies, media, banks and civil society to appreciate the value of the system and key actions necessary to improve it.


The risk of overweight/obesity in mid-life and late life for the development of dementia: a systematic review and meta-analysis of longitudinal studies.
it has been suggested that overweight/obesity as a risk factor for incident dementia differs between mid-life and later life. We performed a systematic review and meta-analysis of the up-to-date current literature to assess this. inclusion criteria included epidemiological longitudinal studies published up to September 2014, in participants without cognitive impairment based on evidence of cognitive assessment and aged 30 or over at baseline assessment with at least 2 years of follow-up. Pubmed, Medline, EMBASE, PsychInfo and the Cochrane Library were searched using combinations of the search terms: Dementia, Alzheimer disease, Vascular Dementia, Multi-Infarct Dementia, Cognitive decline, Cognitive impairment, Mild Cognitive Impairment/Obesity, Overweight, Adiposity, Waist circumference (limits: humans, English language). Handsearching of all papers meeting the inclusion criteria was performed. A random-effects model was used for the meta-analysis. of the 1,612 abstracts identified and reviewed, 21 completely met the inclusion criteria. Being obese below the age of 65 years had a positive association on incident dementia with a risk ratio (RR) 1.41 (95% confidence interval, CI: 1.20-1.66), but the opposite was seen in those aged 65 and over, RR 0.83 (95% CI: 0.74-0.94). this systematic review and meta-analysis suggests a positive association between obesity in mid-life and later dementia but the opposite in late life. Whether weight reduction in mid-life reduces risk is worthy of further study.


Ultrasound for routine lumbar puncture.
The objective was to determine if use of ultrasound (US) by emergency physicians (EPs) to localize spinal landmarks improves the performance of lumbar puncture (LP). This was a prospective, randomized, controlled study conducted in a county teaching hospital. Subjects, adults 18 years of age or older who were to receive LPs for routine clinical care in the emergency department (ED), were randomized either to undergo US localization of the puncture site or to have the puncture site determined by palpation of spinal landmarks. Primary outcomes were the number of needle insertion attempts and success of the procedure. Secondary outcomes were pain associated with the procedure, time to perform the procedure, number of traumatic taps, and patient satisfaction with the procedure. One-hundred patients were enrolled in the study, with 50 in each study group. There were no significant differences between the two groups in terms of age, sex, body mass index (BMI), indication for LP, or ease of palpation of landmarks. For both primary outcomes and secondary outcomes there were no significant differences between those undergoing US localization and those with palpation alone. These data do not suggest any advantage to the routine use of US localization for LP insertion, although further study may be warranted to look for benefit in the difficult to palpate or obese patient subgroups.


Lysosomal delivery of the major myelin glycoprotein in the absence of myelin assembly: posttranslational regulation of the level of expression by Schwann cells.
The major myelin protein, P0, has been shown to have decreased levels of expression and altered oligosaccharide processing after the disruption of Schwann cell-axon interaction. We show here that lysosomal degradation of the glycoprotein shortly after its synthesis accounts for much of its decreased expression in the permanently transected adult rat sciatic nerve, a denervated preparation where there is no axonal regeneration or myelin assembly. If [3H]mannose incorporation into sciatic nerve endoneurial slices is examined in the presence of the lysosomotropic agent, NH4Cl, a marked increase in the level of newly synthesized P0 is seen. Pulse-chase analysis of [3H]mannose-labeled P0 in the presence of NH4Cl indicates that this increase is a consequence of inhibition of P0 degradation that normally occurs 1-2 h after biosynthesis in the transected nerve. P0 degradation can also be inhibited if lysosomal function is disturbed by dilation of secondary lysosomes with L-methionine methyl ester. The addition of deoxymannonojirimycin or swainsonine (SW), inhibitors of oligosaccharide-processing mannosidases I and II, respectively, also results in a decrease in P0 degradation. This inhibition is presumably caused by a blockage of transport to the lysosomes due to altered processing of the glycoprotein, although the direct inhibition of lysosomal mannosidases cannot be excluded. In contrast to the transected nerve, addition of NH4Cl or SW has no effect on P0 levels in the crushed nerve, where myelin assembly occurs. The delivery of P0 to the lysosomes of the transected nerve Schwann cells does not appear to be triggered by the mannose-6-phosphate transport system involved in acid hydrolase routing. The accumulation of a fucosylated species of P0 in the presence of SW indicates that the glycoprotein has progressed at least as far as the site of GlcNAc transferase I without lysosomal delivery, and thus differs from the typical mannose-6-phosphate-containing glycoproteins. Furthermore, there is no evidence of P0 phosphorylation either in the absence or presence of NH4Cl or SW. These findings indicate that the amount of P0 in the transected nerve is regulated at the posttranslational level as well as at the level of transcription.


Consensus strategies for the nonoperative management of patients with blunt splenic injury: a Delphi study.
Nonoperative management is the standard of care in hemodynamically stable patients with blunt splenic injury. However, a number of issues regarding the management of these patients are still unresolved. The aim of this study was to reach consensus among experts concerning optimal treatment and follow-up strategies. The Delphi method was used to reach consensus among 30 expert trauma surgeons and interventional radiologists from around the world. An online survey was used in the two study rounds. Consensus was defined as an agreement of 80% or greater. Response rates of the first and second rounds were 90% and 80%, respectively. Consensus was reached for 43% of the (sub)questions. The American Association for the Surgery of Trauma organ injury scale for grading splenic injury is used by 93% of the experts. In hemodynamically stable patients, observation or splenic artery embolization (SAE) can be applied in the presence of a small or no hemoperitoneum combined with an intraparenchymal contrast extravasation or no contrast extravasation, regardless of the presence of an arteriovenous (AV) fistula/pseudoaneurysm. Hemodynamic instability is an indication for operative management, irrespective of computed tomographic characteristics and grade of splenic injury (≥82% of the experts). Operative management is also indicated in the presence of associated intra-abdominal injuries and/or the need for five or more packed red blood cell transfusions (22 of 27 experts, 82%). Recommended time span to start SAE in a stable patient with an intraparenchymal contrast extravasation is 60 minutes (19 of 24 experts). Patients should be admitted 1 to 3 days to a monitored setting (27 of 27 experts, 100%). Serial hemoglobin checks are performed by all experts, every 4 to 6 hours in the first 24 hours and once or twice a day after that (21 of 24 experts, 88%), in nonoperative management as well as after SAE. Routine postdischarge imaging is not indicated (21 of 24 experts, 88%). Although treatment should always be adjusted to the specific patient, the results of this study may serve as general guidelines.


Association between fat-mass-and-obesity-associated (FTO) gene and hip fracture susceptibility.
Common variants in the fat-mass-and-obesity-associated (FTO) gene are related to body mass index (BMI), which is a predictor of hip fracture risk. This study sought to examine the association between variants in the FTO gene and hip fracture risk. This is a prospective study including 934 postmenopausal women aged 60 years and above living in Dubbo, Australia (Dubbo Osteoporosis Epidemiology Study), followed up between 1989 and 2007. Six single nucleotide polymorphisms (SNPs) (rs1421085, rs1558902, rs1121980, rs17817449, rs9939609 and rs9930506) of the FTO gene were genotyped using Taqman assay. Bone mineral density at the lumbar spine and femoral neck was measured by DXA (GE-Lunar) at baseline. Incidence of hip fractures during the follow-up was ascertained by reviewing X-ray reports. We used Cox's models to estimate the association between the genetic variants and hip fracture risk. We also utilized Bayes factor to evaluate the association. One hundred and two women (11%) had sustained a hip fracture. The incidence of hip fracture was greater in women homozygous for the minor allele of all SNPs. Women homozygous for the minor allele (AA) of rs1121980 had significantly higher risk of hip fracture (hazard ratio, 2.06; 95% CI 1.17-3.62) than women homozygous for the major allele (TT). The observed data favoured the hypothesis of FTO gene and fracture association over the hypothesis of nonassociation by a factor of nine. Common variations in the FTO gene are associated with hip fracture risk in women and that FTO gene may help improve the predictive value of hip fracture risk.


Neuropsychological factors related to college ice hockey concussions.
We analyzed data from 74 male collegiate hockey players. Each athlete's season began with a baseline administration of the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) neuropsychology test battery. Fourteen athletes sustained a sport-related head injury and were readministered the test to assess the impact of the injury. A significant decrease in performance (compared to baseline) on immediate and delayed word recall and designs followed the first concussion. Following a second sport-related concussion, the 4 affected athletes showed significant decrease in visual motor speed. Performance improved on 2 response speed measures (Ps < .01). More errors occurred during a visual processing/discrimination task and immediate recall of designs declined (Ps < .05). We discuss the results in light of recent work related to the impact of early-life concussions and head injury on late-life consequences, such as chronic traumatic encephalopathy, and more immediate issues such as return-to-play decisions for athletes.


Deep characterization of the anti-drug antibodies developed in Fabry disease patients, a prospective analysis from the French multicenter cohort FFABRY.
Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement therapies (ERT) have been available. We aimed to determine the epidemiology and the functional characteristics of anti-drug antibodies. Patients from the French multicenter cohort FFABRY (n = 103 patients, 53 males) were prospectively screened for total anti-agalsidase IgG and IgG subclasses with a home-made enzyme-linked immunosorbent assay (ELISA), enzyme-inhibition assessed with neutralization assays and lysoGb3 plasma levels, and compared for clinical outcomes. Among the patients exposed to agalsidase, 40% of men (n = 18/45) and 8% of women (n = 2/25) had antibodies with a complete cross-reactivity towards both ERTs. Antibodies developed preferentially in men with non-missense GLA mutations (relative risk 2.88, p = 0.006) and classic phenotype (58.6% (17/29) vs 6.7% (1/16), p = 0.0005). Specific anti-agalsidase IgG1 were the most frequently observed (16/18 men), but the highest concentrations were observed for IgG4 (median 1.89 μg/ml, interquartile range (IQR) [0.41-12.24]). In the men exposed to agalsidase, inhibition was correlated with the total IgG titer (r = 0.67, p < 0.0001), especially IgG4 (r = 0.75, p = 0.0005) and IgG2 (r = 0.72, p = 0.001). Inhibition was confirmed intracellularly in Fabry patient leucocytes cultured with IgG-positive versus negative serum (median: 42.0 vs 75.6%, p = 0.04), which was correlated with IgG2 (r = 0.67, p = 0.017, n = 12) and IgG4 levels (r = 0.59, p = 0.041, n = 12). Plasma LysoGb3 levels were correlated with total IgG (r = 0.66, p = 0.001), IgG2 (r = 0.72, p = 0.004), IgG4 (r = 0.58, p = 0.03) and IgG1 (r = 0.55, p = 0.04) titers. Within the classic group, no clinical difference was observed but lysoGb3 levels were higher in antibody-positive patients (median 33.2 ng/ml [IQR 20.6-55.6] vs 12.5 [10.1-24.0], p = 0.005). Anti-agalsidase antibodies preferentially develop in the severe classic Fabry phenotype. They are frequently associated with enzyme inhibition and higher lysoGb3 levels. As such, they could be considered as a hallmark of severity associated with the classic phenotype. The distinction of the clinical phenotypes should now be mandatory in studies dealing with Fabry disease and its current and future therapies.


The facts about sexual (Dys)function in schizophrenia: an overview of clinically relevant findings.
A limited number of studies have evaluated sexual functioning in patients with schizophrenia. Most patients show an interest in sex that differs little from the general population. By contrast, psychiatric symptoms, institutionalization, and psychotropic medication contribute to frequently occurring impairments in sexual functioning. Women with schizophrenia have a better social outcome, longer lasting (sexual) relationships, and more offspring than men with schizophrenia. Still, in both sexes social and interpersonal impairments limit the development of stable sexual relationships. Although patients consider sexual problems to be highly relevant, patients and clinicians not easily discuss these spontaneously, leading to an underestimation of their prevalence and contributing to decreased adherence to treatment. Studies using structured interviews or questionnaires result in many more patients reporting sexual dysfunctions. Although sexual functioning can be impaired by different factors, the use of antipsychotic medication seems to be an important factor. A comparison of different antipsychotics showed high frequencies of sexual dysfunction for risperidone and classical antipsychotics, and lower frequencies for clozapine, olanzapine, quetiapine, and aripiprazole. Postsynaptic dopamine antagonism, prolactin elevation, and α1-receptor blockade may be the most relevant factors in the pathogenesis of antipsychotic-induced sexual dysfunction. Psychosocial strategies to treat antipsychotic-induced sexual dysfunction include psychoeducation and relationship counseling. Pharmacological strategies include lowering the dose or switching to a prolactin sparing antipsychotic. Also, the addition of a dopamine agonist, aripiprazole, or a phosphodiesterase-5 inhibitor has shown some promising results, but evidence is currently scarce.


Evaluation and outcome of antenatal hydronephrosis: a prospective study.
Antenatal hydronephrosis (AHN), defined as dilatation of renal pelvis and/or calyces, is the most frequently detected antenatal abnormality. However, postnatal management of AHN is controversial. The purpose of this study was to describe the clinical outcomes of infants with AHN and to contribute to the definition of the postnatal evaluation of these patients. One hundred and thirty-six infants with AHN were prospectively followed up to 18 months. Patients were divided into two groups according to the degree of sonographic hydronephrosis (HN) on days 5-7: group I (n = 87, 64%) included patients who had grades 1 and 2 (64%) and group II (n = 49, 36%) included patients who had grade 3 and above HN. The grade of HN was found to be correlated with the increased risk of urologic pathologies. Frequency of vesicoureteral reflux was found to be significantly lower in patients with mild HN (6%) as compared to patients with severe AHN (29%) (p = 0.005). In addition, the risk of urinary tract infection increases with increasing grades of HN (10% vs. 29%, p = 0.006). The frequency of spontaneous resolution in patients with mild AHN (64%) was also significantly higher than in patients with severe HN (29%) (p < 0.001). The degree of AHN can be used for making decision about further diagnostic imaging and treatment. Our results strongly suggest that low-grade HN is a relatively self-limited condition and needs minimal investigation. In contrast, the outcome of more severe degrees of AHN needs clarification.


Neutral density filters with Risley prisms: analysis and design.
We achieve the analysis and design of optical attenuators with double-prism neutral density filters. A comparative study is performed on three possible device configurations; only two are presented in the literature but without their design calculus. The characteristic parameters of this optical attenuator with Risley translating prisms for each of the three setups are defined and their analytical expressions are derived: adjustment scale (attenuation range) and interval, minimum transmission coefficient and sensitivity. The setups are compared to select the optimal device, and, from this study, the best solution for double-prism neutral density filters, both from a mechanical and an optical point of view, is determined with two identical, symmetrically movable, no mechanical contact prisms. The design calculus of this optimal device is developed in essential steps. The parameters of the prisms, particularly their angles, are studied to improve the design, and we demonstrate the maximum attenuation range that this type of attenuator can provide.


Use of the "NYC Condom" among people who use drugs.
We assessed awareness and use of the "NYC Condom" among persons who use heroin and cocaine in New York City. The NYC Condom distribution program is the largest free condom distribution program in the USA, with over 30 million condoms distributed per year. It includes a condom social marketing program for a specific brand, the NYC Condom with its own packaging and advertising. People who use heroin and cocaine are at relatively high risk for HIV infection and are an important target population for the program. In order to assess awareness of the NYC Condom, structured interviews and blood testing for HIV, HSV-2, and sexually transmitted infections (STI) were conducted among entrants to the Beth Israel Medical Center drug detoxification and methadone treatment programs. Participants were asked about drug use, sexual risk behaviors, and awareness and use of the NYC Condom. Univariate and multivariable regression analyses were conducted to examine the associations between use of NYC Condoms and consistent condom use with primary and casual sexual partners. A total of 970 subjects were recruited between February 2011 and December 2012. Subjects were primarily African-American and Hispanic, with a mean age of 43. Fifty-five percent of subjects reported being sexually active with primary sexual partners, and 25 % reported being sexually active with a casual partner for the 6 months prior to the interview. Sixty-five percent of subjects had heard of the NYC Condom, 48 % of those who had heard of the condom had used it, and 58 % of those who had ever used it were currently using it (in the previous 6 months). In multivariable regression analyses, current use of NYC Condoms was strongly associated with consistent condom use with primary sexual partners (adjusted odds ratio (AOR) = 3.99, 95 % confidence interval (CI) 1.85-8.58) and consistent condom use with casual sexual partners (AOR = 4.48, 95 % CI 1.49-13.42). In terms of market share, 38 % of subjects consistently using condoms with primary partners were using the NYC Condom, and 47 % of those consistently using condoms with casual partners were using the NYC Condom. The NYC Condom is an important tool for reducing sexual transmission of HIV and STI among persons who use drugs in the city. Given the strong relationship between using the NYC Condom and consistent condom use, further efforts to promote the NYC Condom brand would be easily justified.


Phase diagram and superconductivity of compressed zirconium hydrides.
It is known that pressure can be applied to fundamentally alter the bonding patterns between the chemical elements. By employing an unbiased structure search method based on a particle swarm optimization (PSO) methodology, the phase diagram and crystal structures of Zr-H compounds are systematically investigated at a high pressure up to 150 GPa. Interestingly, some unexpectedly stable compounds with unusual chemical and physical properties are predicted to be formed, for example, four stable and metallic species with stoichiometries of ZrH, ZrH2, ZrH3, and ZrH6 are identified for the first time. It is interesting to note that Cmc21-ZrH6 adopts intriguing structures with H2 units. Surprisingly, it is found that Cmcm-ZrH is superconducting with Tc as high as 10.6 K. Our study opens a novel avenue for designing superconducting Zr-H compounds by applying pressure.


Adsorptive removal of trace oxytetracycline from water by acid-modified zeolite: influencing factors.
Because of the wide use of antibiotics in the livestock industry, trace tetracycline antibiotics are frequently detected in swine wastewater and water bodies near pig farms. Based on natural zeolite, modified zeolite was synthesized by treatment with nitric acid. As one kind of typical tetracyclines, oxytetracycline (OTC) was chosen as the target adsorbate. Removal of trace OTC by modified zeolite and the effects of several main water matrices on OTC adsorption were studied in detail. OTC removal efficiency by acid-modified zeolite was about 90%, compared to less than 20% by natural zeolite. In general, in acidic conditions the removal efficiency of OTC by modified zeolite was about 90%, which was much higher than 20-35% in alkaline conditions. An increase in ionic strength from 0.01 to 1.0 M led to a decrease in adsorption efficiency from 90 to 27%. The presence of 10.0 mg L(-1) dissolved humic acid accelerated sorption of OTC on modified zeolite, while 100.0 mg L(-1) humic acid resulted in the opposite effect. An increase in temperature contributed to enhancing the adsorption efficiency.


Access to Formally Ni(I) States in a Heterobimetallic NiZn System.
Heterobimetallic NiZn complexes featuring metal centers in distinct coordination environments have been synthesized using diimine-dioxime ligands as binucleating scaffolds. A tetramethylfuran-containing ligand derivative enables a stable one-electron-reduced S = 1/2 species to be accessed using Cp2Co as a chemical reductant. The resulting pseudo-square planar complex exhibits spectroscopic and crystallographic characteristics of a ligand-centered radical bound to a Ni(II) center. Upon coordination of a π-acidic ligand such as PPh3, however, a five-coordinate Ni(I) metalloradical is formed. The electronic structures of these reduced species provide insight into the subtle effects of ligand structure on the potential and reversibility of the NiII/I couple for complexes of redox-active tetraazamacrocycles.


Emergency department management of acute exacerbations of chronic obstructive pulmonary disease and factors associated with hospitalization.
Currently there is a paucity of information about biomarkers that can predict hospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients presenting to the emergency department (ED). There is limited data on the consistency of ED management of AECOPD with local COPD guidelines. The aim of this study was to identify biomarkers associated with hospitalization in AECOPD patients and to determine if the ED management was concordant with local COPD guidelines. We performed a retrospective audit of consecutive AECOPD patients presenting to the Gold Coast Hospital ED over a 6-month period. During the study period, 122 AECOPD patients (51% male, mean age (SE) 71 (±11) years) presented to the ED. Ninety-eight (80%) patients were hospitalized. Univariate analysis identified certain factors associated with hospitalization: Older age, former smokers, home oxygen therapy, weekday presentation, SpO2 < 92%, and raised inflammatory markers (white cell count (WCC) and C-reactive protein (CRP)). After adjustment for multiple variable, increased age was significantly associated with hospitalization (odds ratio (OR) 1.09; 95% confidence interval (CI): 1.00-1.18; P = 0.05). Radiology assessment and pharmacological management was in accordance with COPD guidelines. However, spirometry was performed in 17% of patients and 28% of patients with hypercapneic respiratory failure received noninvasive ventilation (NIV). We identified several factors on univariate analysis that were associated with hospitalization. Further research is required to determine the utility of these biomarkers in clinical practice. Also, while overall adherence to local COPD guidelines was good, there is scope for improvement in performing spirometry and provision of NIV to eligible patients.


Evolution of correlation structure of industrial indices of U.S. equity markets.
We investigate the dynamics of correlations present between pairs of industry indices of U.S. stocks traded in U.S. markets by studying correlation-based networks and spectral properties of the correlation matrix. The study is performed by using 49 industry index time series computed by K. French and E. Fama during the time period from July 1969 to December 2011, which spans more than 40 years. We show that the correlation between industry indices presents both a fast and a slow dynamics. The slow dynamics has a time scale longer than 5 years, showing that a different degree of diversification of the investment is possible in different periods of time. Moreover, we also detect a fast dynamics associated with exogenous or endogenous events. The fast time scale we use is a monthly time scale and the evaluation time period is a 3-month time period. By investigating the correlation dynamics monthly, we are able to detect two examples of fast variations in the first and second eigenvalue of the correlation matrix. The first occurs during the dot-com bubble (from March 1999 to April 2001) and the second occurs during the period of highest impact of the subprime crisis (from August 2008 to August 2009).


The Role of Interactive Visualization in Fostering Trust in AI.
The increasing use of artificial intelligence (AI) technologies across application domains has prompted our society to pay closer attention to AI's trustworthiness, fairness, interpretability, and accountability. In order to foster trust in AI, it is important to consider the potential of interactive visualization, and how such visualizations help build trust in AI systems. This manifesto discusses the relevance of interactive visualizations and makes the following four claims: i) trust is not a technical problem, ii) trust is dynamic, iii) visualization cannot address all aspects of trust, and iv) visualization is crucial for human agency in AI.


Prevalence of the metabolic syndrome among a racially/ethnically diverse group of U.S. eighth-grade adolescents and associations with fasting insulin and homeostasis model assessment of insulin resistance levels.
The purpose of this study was to report the prevalence of the International Diabetes Federation (IDF)-defined metabolic syndrome and its components among a cross-sectional sample of racially/ethnically diverse eighth grade youths and examine the association between the presence of the syndrome and participant fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels. Data were from a cross-sectional study with 1,453 racially/ethnically diverse eighth grade students from 12 middle schools in three U.S. states (Texas, North Carolina, and California). Height, weight, waist circumference, and blood pressure were recorded. Fasting blood samples were analyzed for triglycerides, HDL cholesterol, glucose, and insulin; HOMA-IR was calculated. Sex, race/ethnicity, and pubertal stage were self-reported. IDF criteria were used to determine the prevalence of the metabolic syndrome. The odds ratio for being classified with the syndrome was calculated by quintiles of fasting insulin and HOMA-IR. Of the sample, 138 students (9.5%) were classified with metabolic syndrome. Hispanics were more likely to have high abdominal adiposity and high triglycerides. Male adolescents were more likely to have high triglycerides, low HDL cholesterol, high blood pressure, and high fasting glucose. Participants in the highest insulin quintile were almost 200 times more likely to be classified with the syndrome than participants in the lowest quintile with comparable associations for HOMA-IR quintiles. In a racially/ethnically diverse sample of U.S. adolescents, 9.5% of participants were identified with the metabolic syndrome using the IDF criteria. The likelihood of metabolic syndrome classification significantly increased with higher insulin and HOMA-IR values.


Flow diversion to treat aneurysms: the free segment of stent.
Flow diverters (FDs) have led to spectacular results in otherwise untreatable aneurysm cases, but complications can occur. There is a pressing need to study factors that might predict their safety and efficacy. The anatomical constraints that may impact on the ability of FDs to redirect blood flow and provide a scaffold for neointima formation across the aneurysm or branch ostia are explored and classified. A nomenclature is needed to identify the key factors that should be taken into account before contemplating the use of FDs in clinical aneurysms, and that should be reproduced in experimental models, if they are to guide safe clinical use. The free stent segment (FSS), the portion of the device that covers an aneurysm or branch origin, dictates whether aneurysms or branches will remain patent. Three levels of increasing complexity must be taken into account to anticipate what will occur at the FSS level. (1) Virtual models can provide basic principles; (2) in vitro studies allow testing FSS deformations that may occur in various anatomical circumstances and impact on efficacy and safety; (3) but only in vivo studies can provide key information on neointimal closure following implantation that will differentiate success from failure. A nomenclature is necessary to determine the optimal or suboptimal conditions for FDs and to design the virtual, in vitro and in vivo studies that will allow a better understanding of the factors involved in the success or failure of this novel treatment.


Tissue clearing of both hard and soft tissue organs with the PEGASOS method.
Tissue clearing technique enables visualization of opaque organs and tissues in 3-dimensions (3-D) by turning tissue transparent. Current tissue clearing methods are restricted by limited types of tissues that can be cleared with each individual protocol, which inevitably led to the presence of blind-spots within whole body or body parts imaging. Hard tissues including bones and teeth are still the most difficult organs to be cleared. In addition, loss of endogenous fluorescence remains a major concern for solvent-based clearing methods. Here, we developed a polyethylene glycol (PEG)-associated solvent system (PEGASOS), which rendered nearly all types of tissues transparent and preserved endogenous fluorescence. Bones and teeth could be turned nearly invisible after clearing. The PEGASOS method turned the whole adult mouse body transparent and we were able to image an adult mouse head composed of bones, teeth, brain, muscles, and other tissues with no blind areas. Hard tissue transparency enabled us to reconstruct intact mandible, teeth, femur, or knee joint in 3-D. In addition, we managed to image intact mouse brain at sub-cellular resolution and to trace individual neurons and axons over a long distance. We also visualized dorsal root ganglions directly through vertebrae. Finally, we revealed the distribution pattern of neural network in 3-D within the marrow space of long bone. These results suggest that the PEGASOS method is a useful tool for general biomedical research.


Design, calibration and validation of a novel 3D printed instrumented spatial linkage that measures changes in the rotational axes of the tibiofemoral joint.
An accurate axis-finding technique is required to measure any changes from normal caused by total knee arthroplasty in the flexion-extension (F-E) and longitudinal rotation (LR) axes of the tibiofemoral joint. In a previous paper, we computationally determined how best to design and use an instrumented spatial linkage (ISL) to locate the F-E and LR axes such that rotational and translational errors were minimized. However, the ISL was not built and consequently was not calibrated; thus the errors in locating these axes were not quantified on an actual ISL. Moreover, previous methods to calibrate an ISL used calibration devices with accuracies that were either undocumented or insufficient for the device to serve as a gold-standard. Accordingly, the objectives were to (1) construct an ISL using the previously established guidelines,(2) calibrate the ISL using an improved method, and (3) quantify the error in measuring changes in the F-E and LR axes. A 3D printed ISL was constructed and calibrated using a coordinate measuring machine, which served as a gold standard. Validation was performed using a fixture that represented the tibiofemoral joint with an adjustable F-E axis and the errors in measuring changes to the positions and orientations of the F-E and LR axes were quantified. The resulting root mean squared errors (RMSEs) of the calibration residuals using the new calibration method were 0.24, 0.33, and 0.15 mm for the anterior-posterior, medial-lateral, and proximal-distal positions, respectively, and 0.11, 0.10, and 0.09 deg for varus-valgus, flexion-extension, and internal-external orientations, respectively. All RMSEs were below 0.29% of the respective full-scale range. When measuring changes to the F-E or LR axes, each orientation error was below 0.5 deg; when measuring changes in the F-E axis, each position error was below 1.0 mm. The largest position RMSE was when measuring a medial-lateral change in the LR axis (1.2 mm). Despite the large size of the ISL, these calibration residuals were better than those for previously published ISLs, particularly when measuring orientations, indicating that using a more accurate gold standard was beneficial in limiting the calibration residuals. The validation method demonstrated that this ISL is capable of accurately measuring clinically important changes (i.e. 1 mm and 1 deg) in the F-E and LR axes.


Comparative histopathology and immunohistochemistry of human and canine mammary tumors.
This study aimed at establishing aspects of comparison between canine and human mammary gland tumors. In order to achieve that, 44 specimens of canine mammary tumors and 70 specimens of human breast tumors were examined in order to state points of similarity in morphology, cells of origin, behavior and existence of tissue markers. We found that the ratio of benign to malignant forms was 4.5% to 95.5% in canine samples and 45.7% to 54.3% in human samples. In both species, malignant tumors composed of infiltrating ductal cells were in the forefront despite dissimilarity in nomenclature. Other kinds of lower rate of existence included, invasive micro-papillary carcinoma, mucinous carcinoma and invasive comedo-carcinoma which have displayed similar morphology and terminology in both species. Chondroid and squamous differentiation were found in human and canine specimens. In human samples, fibro-adenoma mounted up to 30 out of 32 benign tumors (93.8%). Her-2 and Ki-67 were detected in the specimens of both species but ER was detected in human specimens only. Our findings suggest a significant degree of resemblance between certain mammary tumor in canine and human. Such findings are in support of employing dogs in research investigation for human mammary tumors.


The effect of surgical delay on acute infection following 554 open fractures in children.
Traditional recommendations hold that open fractures in both children and adults require urgent surgical debridement for a number of reasons, including the preservation of soft-tissue viability and vascular status as well as the prevention of infection. Following the widespread use of early administration of antibiotics, a number of single-institution studies challenged the belief that urgent surgical debridement decreases the risk of acute infection. We performed a retrospective, multicenter study of open fractures that had been treated at six tertiary pediatric medical centers between 1989 and 2000. The standard protocol at each medical center was for all children to be given intravenous antibiotics upon arrival in the emergency department. The medical records of all children with open fractures were reviewed to identify the location of the fracture, the interval between the injury and the time of surgery, the Gustilo and Anderson classification, and the occurrence of acute infection. The analysis included 554 open fractures in 536 consecutive patients who were eighteen years of age or younger. The overall infection rate was 3% (sixteen of 554). The infection rate was 3% (twelve of 344) for fractures that had been treated within six hours after the injury, compared with 2% (four of 210) for those that had been treated at least seven hours after the injury; this difference was not significant (p = 0.43). When the fractures were separated according to the Gustilo and Anderson classification system, there were no significant differences in the infection rate between those that had been treated within six hours after the injury and those that had been treated at least seven hours after the injury. Specifically, these infection rates were 2% (three of 173) and 2% (two of 129), respectively, for type-I fractures, 3% (three of 110) and 0% (zero of forty-four), respectively, for type-II fractures, and 10% (six of sixty-one) and 2% (two of thirty-seven), respectively, for type-III fractures (p > 0.05 for all three comparisons). In the present retrospective, multicenter study of children with Gustilo and Anderson type-I, II, and III open fractures, the rates of acute infection were similar regardless of whether surgery was performed within six hours after the injury or at least seven hours after the injury. The findings of the present study suggest that, in children who receive early antibiotic therapy following an open fracture, surgical debridement within six hours after the injury offers little benefit over debridement within twenty-four hours after the injury with regard to the prevention of acute infection.


The protective effect of neighborhood social cohesion in child abuse and neglect.
Relations between parents within a neighborhood have the potential to provide a supportive environment for healthy and positive parenting. Neighborhood social cohesion, or the mutual trust and support among neighbors, is one process through which parenting may be improved. The current study investigates the association between neighborhood social cohesion and abuse and neglect, as well as specific types of abuse and neglect. The sample for the study is comprised of 896 parents in one urban Midwestern County in the United States. Participants were recruited from Women, Infants, and Children clinics. Negative binomial regression is used to examine the association between neighborhood social cohesion and child maltreatment behaviors, as measured by the Conflict Tactics Scale, Parent-to-Child Version (Straus et al., 1998). In this sample of families, neighborhood social cohesion is associated with child neglect, but not abuse. In examining the relationship with specific types of abuse and neglect, it was found that neighborhood social cohesion may have a protective role in some acts of neglect, such as meeting a child's basic needs, but not potentially more complex needs like parental substance abuse.


Primary care vs specialist sleep center management of obstructive sleep apnea and daytime sleepiness and quality of life: a randomized trial.
Due to increasing demand for sleep services, there has been growing interest in ambulatory models of care for patients with obstructive sleep apnea. With appropriate training and simplified management tools, primary care physicians are ideally positioned to take on a greater role in diagnosis and treatment. To compare the clinical efficacy and within-trial costs of a simplified model of diagnosis and care in primary care relative to that in specialist sleep centers. A randomized, controlled, noninferiority study involving 155 patients with obstructive sleep apnea that was treated at primary care practices (n=81) in metropolitan Adelaide, 3 rural regions of South Australia or at a university hospital sleep medicine center in Adelaide, Australia (n = 74), between September 2008 and June 2010. Primary care management of obstructive sleep apnea vs usual care in a specialist sleep center; both plans included continuous positive airway pressure, mandibular advancement splints, or conservative measures only. The primary outcome was 6-month change in Epworth Sleepiness Scale (ESS) score, which ranges from 0 (no daytime sleepiness) to 24 points (high level of daytime sleepiness). The noninferiority margin was -2.0. Secondary outcomes included disease-specific and general quality of life measures, obstructive sleep apnea symptoms, adherence to using continuous positive airway pressure, patient satisfaction, and health care costs. There were significant improvements in ESS scores from baseline to 6 months in both groups. In the primary care group, the mean baseline score of 12.8 decreased to 7.0 at 6 months (P < .001), and in the specialist group, the score decreased from a mean of 12.5 to 7.0 (P < .001). Primary care management was noninferior to specialist management with a mean change in ESS score of 5.8 vs 5.4 (adjusted difference, -0.13; lower bound of 1-sided 95% CI, -1.5; P = .43). There were no differences in secondary outcome measures between groups. Seventeen patients (21%) withdrew from the study in the primary care group vs 6 patients (8%) in the specialist group. Among patients with obstructive sleep apnea, treatment under a primary care model compared with a specialist model did not result in worse sleepiness scores, suggesting that the 2 treatment modes may be comparable. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12608000514303.


Noninvasive estimation of cerebral perfusion pressure with transcranial Doppler ultrasonography in traumatic brain injury.
In traumatic brain injury (TBI) patients, to overcome the secondary insults, cerebral perfusion pressure (CPP) oriented therapy is recommended. The study is assigned to estimate CPP values with middle cerebral artery (MCA) flow velocities measured noninvasively using transcranial Doppler ultrasonography (TCD). Forty-seven TBI patients were studied. Intracranial pressure (ICP), mean arterial pressure (MAP) and MCA flow velocities of the patients were monitored. Invasive CPP was calculated as the difference between MAP and ICP. The formula : 'MAP x FVd/FVm +14' was used to estimate CPP noninvasively. Correlation of the noninvasive and invasive values were analysed. The mean values of noninvasive CPP and invasive CPP were 66.10 ± 10.55 mmHg and 65.40 ± 10.03 mmHg respectively. The correlation between noninvasive and invasive CPP measurements was strongly significant (p < 0.001) with a correlation coefficient of r = 0.920. With ICP monitoring systems, CPP is calculated and the therapy is guided according to these values. As it is recognized that brain perfusion can be assessed with TCD waveforms, noninvasive CPP estimation with MCA flow velocities may help to observe the trends in CPP values.


Manufactured volvulus.
Malrotation with a common mesentery is the classical pathology allowing midgut volvulus to occur. There are only a few reports of small bowel volvulus without malrotation or other pathology triggering volvulation. We describe three cases of small bowel volvulus in very premature newborns with a perfectly normal intra-abdominal anatomy and focus on the question, what might have set off volvulation. In 2005 to 2008, three patients developed small bowel volvulus without any underlying pathology. Retrospective patient chart review was performed with special focus on clinical presentation, preoperative management, intraoperative findings, and potential causative explanations. Mean follow-up period was 46 months. All patients were born between 27 and 31 weeks (mean 28 weeks) with a birth weight between 800 and 1,000 g (mean 887 g). They presented with an almost identical pattern of symptoms including sudden abdominal distension, abdominal tenderness, erythema of the abdominal wall, high gastric residuals, and radiographic signs of ileus. All of them were treated with intensive abdominal massage or pelvic rotation to improve bowel movement before becoming symptomatic. Properistaltic maneuvers including abdominal massage and pelvic rotation may cause what we term a "manufactured" volvulus in very premature newborns. Thus, this practice was stopped.


Sustaining sleep: Results from the randomized controlled work, family, and health study.
Although calls for intervention designs are numerous within the organizational literature and increasing efforts are being made to conduct rigorous randomized controlled trials, existing studies have rarely evaluated the long-term sustainability of workplace health intervention outcomes, or mechanisms of this process. This is especially the case with regard to objective and subjective sleep outcomes. We hypothesized that a work-family intervention would increase both self-reported and objective actigraphic measures of sleep quantity and sleep quality at 6 and 18 months post-baseline in a sample of information technology workers from a U.S. Fortune 500 company. Significant intervention effects were found on objective actigraphic total sleep time and self-reported sleep insufficiency at the 6- and 18-month follow-up, with no significant decay occurring over time. However, no significant intervention effects were found for objective actigraphic wake after sleep onset or self-reported insomnia symptoms. A significant indirect effect was found for the effect of the intervention on objective actigraphic total sleep time through the proximal intervention target of 6-month control over work schedule and subsequent more distal 12-month family time adequacy. These results highlight the value of long-term occupational health intervention research, while also highlighting the utility of this work-family intervention with respect to some aspects of sleep. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Memory recall involves a transient break in excitatory-inhibitory balance.
The brain has a remarkable capacity to acquire and store memories that can later be selectively recalled. These processes are supported by the hippocampus which is thought to index memory recall by reinstating information stored across distributed neocortical circuits. However, the mechanism that supports this interaction remains unclear. Here, in humans, we show that recall of a visual cue from a paired associate is accompanied by a transient increase in the ratio between glutamate and GABA in visual cortex. Moreover, these excitatory-inhibitory fluctuations are predicted by activity in the hippocampus. These data suggest the hippocampus gates memory recall by indexing information stored across neocortical circuits using a disinhibitory mechanism.


Substance use among women: associations with pregnancy, parenting, and race/ethnicity.
To examine the association of pregnancy and parenting (0- to 2-year-old child) statuses with past 30-day use of alcohol, cigarettes and marijuana, psychotherapeutics and cocaine among American women aged 18-44, overall and by race/ethnicity. Five years of data (2002-2006) from the National Survey on Drug Use and Health (NSDUH) were pooled. Binary logistic regression analyses stratified by race/ethnicity were performed to examine the relationships adjusting for age, marital status, education and family income. Overall, past 30-day alcohol, cigarette, marijuana, psychotherapeutic or cocaine use was substantially lower among pregnant women, particularly in their second or third trimesters, than among their parenting or non-pregnant counterparts. Logistic regression analysis suggested a strong negative association between pregnancy status and substance use, with no considerable variations in the magnitude of the relationship by race/ethnicity for most measures. The relationship between parenting status and substance use was in the same direction, but relatively weak, and not statistically significant for non-Hispanic (NH) blacks for any measures except for alcohol use. Regardless of pregnancy and parenting statuses, NH white women reported substance use at the highest rates, followed by Hispanics and NH blacks. There is indirect evidence of postpregnancy resumption in substance use. Pregnant and parenting women, regardless of race/ethnicity, could benefit from prevention efforts focusing on cessation rather than temporary abstinence from substance use.


Association of door-in to door-out time with reperfusion delays and outcomes among patients transferred for primary percutaneous coronary intervention.
Patients with ST-elevation myocardial infarction (STEMI) requiring interhospital transfer for primary percutaneous coronary intervention (PCI) often have prolonged overall door-to-balloon (DTB) times from first hospital presentation to second hospital PCI. Door-in to door-out (DIDO) time, defined as the duration of time from arrival to discharge at the first or STEMI referral hospital, is a new clinical performance measure, and a DIDO time of 30 minutes or less is recommended to expedite reperfusion care. To characterize time to reperfusion and patient outcomes associated with a DIDO time of 30 minutes or less. Retrospective cohort of 14,821 patients with STEMI transferred to 298 STEMI receiving centers for primary PCI in the ACTION Registry-Get With the Guidelines between January 2007 and March 2010. Factors associated with a DIDO time greater than 30 minutes, overall DTB times, and risk-adjusted in-hospital mortality. Median DIDO time was 68 minutes (interquartile range, 43-120 minutes), and only 1627 patients (11%) had DIDO times of 30 minutes or less. Significant factors associated with a DIDO time greater than 30 minutes included older age, female sex, off-hours presentation, and non-emergency medical services transport to the first hospital. Patients with a DIDO time of 30 minutes or less were significantly more likely to have an overall DTB time of 90 minutes or less compared with patients with DIDO times greater than 30 minutes (60% [95% confidence interval {CI}, 57%-62%] vs 13% [95% CI, 12%-13%]; P < .001). Among patients with DIDO times greater than 30 minutes, only 0.6% (95% CI, 0.5%-0.8%) had an absolute contraindication to fibrinolysis. Observed in-hospital mortality was significantly higher among patients with DIDO times greater than 30 minutes vs patients with DIDO times of 30 minutes or less (5.9% [95% CI, 5.5%-6.3%] vs 2.7% [95% CI, 1.9%-3.5%]; P < .001; adjusted odds ratio for in-hospital mortality, 1.56 [95% CI, 1.15-2.12]). A DIDO time of 30 minutes or less was observed in only a small proportion of patients transferred for primary PCI but was associated with shorter reperfusion delays and lower in-hospital mortality.


Platelets, inflammation and tissue regeneration.
Blood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from a-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed.


Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial.
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressant, yet it is not known whether one SSRI is more effective than another. To compare the effectiveness of 3 SSRIs (paroxetine, fluoxetine, and sertraline) in depressed primary care patients. Open-label, randomized, intention-to-treat trial, with patient enrollment occurring in April-November 1999. Thirty-seven clinics in 2 US primary care research networks. A total of 573 depressed adult patients for whom their primary care physician thought that antidepressant therapy was warranted and who completed a baseline interview. Patients were randomly assigned to receive paroxetine (n = 189), fluoxetine (n = 193), or sertraline (n = 191) for 9 months. Primary care physicians were allowed to switch patients to a different SSRI or non-SSRI antidepressant if they did not adequately respond to or tolerate the initial SSRI. The primary outcome measure was change in the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) Mental Component Summary score (range, 0-100), compared across treatment groups at 1, 3, 6, and 9 months. Secondary outcomes included other depression and psychological measures, multiple measures of social and work functioning, and other domains of health-related quality of life, such as physical functioning, concentration and memory, vitality, bodily pain, sleep, and sexual functioning. Follow-up interviews were successfully completed in 94% of patients at 1 month, 87% at 3 months, 84% at 6 months, and 79% at 9 months. Responses to the 3 SSRIs were comparable on all measures and at all time points. The mean change in the SF-36 Mental Component Summary score at 9 months was + 15.8 in the paroxetine group, + 15.1 in the fluoxetine group, and + 17.4 in the sertraline group. The drugs were also associated with similar incidences of adverse effects and discontinuation rates. The SSRI antidepressants paroxetine, fluoxetine, and sertraline were similar in effectiveness for depressive symptoms as well as multiple domains of health-related quality of life over the entire 9 months of this trial.


Geographical distribution of salmonid alphavirus subtypes in marine farmed Atlantic salmon, Salmo salar L., in Scotland and Ireland.
Sequence data from salmonid alphavirus (SAV) strains obtained from farmed marine Atlantic salmon, Salmo salar L. , over a 20-year period between 1991 and 2011 was reviewed to examine the geographical distribution of the genetically defined SAV subtypes in twelve regions across Ireland and Scotland. Of 160 different Atlantic salmon SAV strains examined, 62 belonged to subtype 1, 28 to subtype 2, 34 to subtype 4, 35 to subtype 5 and 1 to subtype 6. SAV subtypes 1, 4 and 6 were found in Ireland, while subtypes 1, 2, 4 and 5 were found in Scotland. In the majority of regions, there was a clear clustering of subtypes, with SAV subtype 1 being the dominant subtype in Ireland overall, as well as in Argyll and Bute in Scotland. SAV subtype 2 predominated in the Shetland and Orkney Islands. The emergence in Atlantic salmon of subtype 2 strains typically associated with sleeping disease in rainbow trout in Argyll and Bute, strongly suggesting transmission of infection between these species, was noted for the first time. SAV subtype 4 was the most common subtype found in the southern Western Isles, while SAV subtype 5 predominated in the northern Western Isles and north-west mainland Scotland. No single strain was dominant on sites in the western Highlands, with a number of sites in this region in particular having more than one subtype detected in different submissions. The significance of these results in relation to aspects of the epidemiology of infection, including transmission, biosecurity and wildlife reservoirs are discussed and knowledge gaps identified.


Brief Report: Pediatric Cancer Burden and Treatment Resources Within the Pediatric IeDEA Consortium.
The incidence and treatment of cancer in HIV-infected children from resource-limited settings has not been extensively studied. Develop and implement a cross-sectional survey to evaluate pediatric cancer burden, diagnostic modalities in use, and treatment availability as perceived by HIV clinic staff at regional International Epidemiology Databases to Evaluate AIDS (IeDEA) sites. IeDEA regional investigators developed a cross-sectional clinical site survey which included questions on the numbers and types of pediatric cancers observed, modalities used to treat identified cancers, and treatment options available at individual sites in the Asia-Pacific, Latin America, Central Africa, East Africa, West Africa, and Southern Africa regions. Kaposi sarcoma, non-Hodgkin lymphoma, and Burkitt lymphoma were reported by site personnel to be the most prevalent types of cancer in the pediatric HIV population. Survey results indicate that access to comprehensive cancer treatment modalities is very limited for children in these regions despite HIV care and treatment sites reporting that they diagnose pediatric cancers. Responses also showed that evaluating cancer in the pediatric HIV population is a challenge due to a lack of resources and varying treatment availability within regions. Further study is needed to increase our understanding of the changing epidemiology of cancer in HIV-infected pediatric populations. Increased financial and technical resources are critical to aid in the advancement of health services to support treatment of these children in resource-constrained settings.


Neural sensitivity to phonological characteristics is stable across the lifespan.
Aging is often associated with declines in language production. For example, compared to younger adults, older adults experience more tip-of-the-tongue (TOT) states, show decreased speed and accuracy in naming objects, and have more pauses and fillers in speech, all of which indicate age-related increases in retrieval difficulty. While prior work has suggested that retrieval difficulty may be phonologically based, it is unclear whether there are age-related differences in the organization of phonological information per se or whether age-related difficulties may arise from accessing that information. Here we used fMRI to investigate the neural and behavioral basis of phonological neighborhood denisty (PND) effects on picture naming across the lifespan (N=91, ages 20-75). Consistent with prior work, behavioral results revealed that higher PND led to faster picture naming times and higher accuracies overall, and that older adults were less accurate in their responses. Consistent with the behavioral analyses, fMRI analyses showed that increasing PND was associated with decreased activation in auditory and motor language regions, including bilateral superior temporal gyri and bilateral precentral gyri. Interestingly, although there were age-related increases in functional activation to picture naming, there were no age-related modulations of neural sensitivity to PND. Overall, these results suggest that having a large cohort of phonological neighbors facilitates language production, and although aging is associated with increases in language production difficulty, sensitivity to phonological features during language production is stable across the lifespan.


Impact of body mass index on the incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis.
Pancreatitis is a potential major complication after endoscopic retrograde cholangiopancreatography (post-ERCP pancreatitis; PEP). Obesity has been associated with increased severity of acute pancreatitis. However, the correlation between obesity and PEP is controversial. Therefore, our study aimed to clarify the relationship between body mass index (BMI) and the incidence and severity of PEP. A retrospective cohort study was conducted to elucidate the relationship between BMI and PEP in all patients who underwent ERCP in a tertiary referral center between January 2009 and October 2016. Patient characteristics and procedure details were collected. PEP was defined by consensus criteria. Multivariate logistic regression was used to determine the association between BMI and PEP. The analysis included 2236 patients whose BMI was recorded and had adequate follow up (921 with BMI≥30 kg/m2, 1315 with BMI<30 kg/m2). PEP was diagnosed in 107 (4.8%) patients. PEP was seen in 49 obese patients (5.3%) and 58 non-obese patients (4.4%). In the univariate and multivariate analysis BMI≥30 kg/m2 was not associated with PEP (odds ratio 1.2, 95%CI 0.8-1.8; P=0.32). A subgroup analysis of different BMI subcategories found that BMI was not associated with the incidence or severity of PEP. In the largest study to date, neither obesity nor low body weight increased the incidence or severity of PEP.


Rationale and design of "Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)" study : A randomised trial modulating endogenous fibrinolysis in patients with acute coronary syndrome.
Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.


Multiple health behaviour change primary care intervention for smoking cessation, physical activity and healthy diet in adults 45 to 75 years old (EIRA study): a hybrid effectiveness-implementation cluster randomised trial.
This study aimed to evaluate the effectiveness of a) a Multiple Health Behaviour Change (MHBC) intervention on reducing smoking, increasing physical activity and adherence to a Mediterranean dietary pattern in people aged 45-75 years compared to usual care; and b) an implementation strategy. A cluster randomised effectiveness-implementation hybrid trial-type 2 with two parallel groups was conducted in 25 Spanish Primary Health Care (PHC) centres (3062 participants): 12 centres (1481 participants) were randomised to the intervention and 13 (1581 participants) to the control group (usual care). The intervention was based on the Transtheoretical Model and focused on all target behaviours using individual, group and community approaches. PHC professionals made it during routine care. The implementation strategy was based on the Consolidated Framework for Implementation Research (CFIR). Data were analysed using generalised linear mixed models, accounting for clustering. A mixed-methods data analysis was used to evaluate implementation outcomes (adoption, acceptability, appropriateness, feasibility and fidelity) and determinants of implementation success. 14.5% of participants in the intervention group and 8.9% in the usual care group showed a positive change in two or all the target behaviours. Intervention was more effective in promoting dietary behaviour change (31.9% vs 21.4%). The overall adoption rate by professionals was 48.7%. Early and final appropriateness were perceived by professionals as moderate. Early acceptability was high, whereas final acceptability was only moderate. Initial and final acceptability as perceived by the participants was high, and appropriateness moderate. Consent and recruitment rates were 82.0% and 65.5%, respectively, intervention uptake was 89.5% and completion rate 74.7%. The global value of the percentage of approaches with fidelity ≥50% was 16.7%. Eight CFIR constructs distinguished between high and low implementation, five corresponding to the Inner Setting domain. Compared to usual care, the EIRA intervention was more effective in promoting MHBC and dietary behaviour change. Implementation outcomes were satisfactory except for the fidelity to the planned intervention, which was low. The organisational and structural contexts of the centres proved to be significant determinants of implementation effectiveness. ClinicalTrials.gov , NCT03136211 . Registered 2 May 2017, "retrospectively registered".


Isolation and characterization of a variant porcine epidemic diarrhea virus in China.
An outbreak of diarrhea in pigs started in Guangdong, South China in January 2011. Cases were characterized by watery diarrhea, dehydration and vomiting, with 80-100% morbidity and 50-90% mortality in suckling piglets. The causative agent of the diarrhea was ultimately identified as porcine epidemic diarrhea virus (PEDV). In this study, we isolated a PEDV strain designated CHGD-01 from piglet intestines using Vero cell cultures, and its specific cytopathic effects were confirmed in susceptible cells by direct immunofluorescence testing and electron microscopy. The complete genome of CHGD-01 was shown to be 28,035 nucleotides in length, with a similar structure to that of PEDV reference strains. Phylogenetic analyses based on the whole genome revealed that CHGD-01 shared nucleotide sequence identities of 98.2-98.4% with two other Chinese isolates reported in the same year, thus constituting a new cluster. Amino acid sequence analysis based on individual virus genes indicated a close relationship between the spike protein gene of CHGD-01 and the field strain KNU0802 in Korea. Its ORF3 and nucleoprotein genes, however, were divergent from all other sequenced PEDV isolate clusters and therefore formed a new group, suggesting a new variant PEDV isolate in China. Further studies will be required to determine the immunogenicity and pathogenicity of this new variant.


Dual channel STED nanoscopy of lytic granules on actin filaments in natural killer cells.
Natural killer (NK) cells are innate immune effectors that eliminate diseased and tumorigenic targets through the directed secretion of specialized secretory lysosomes, termed lytic granules. This directed secretion is triggered following the formation of an immunological synapse (IS), which is characterized by actin re-modeling and receptor organization at the interface between the NK cell and its susceptible target. Actin at the IS has been described to be permissive to secretion by forming a large central clearance through which lytic granules are released. However we, and others, have recently shown that the actin network in NK cells at the IS is dynamic yet pervasive. These efforts used multiple high resolution imaging techniques to demonstrate that the actin network does not act as a barrier to secretion, but instead enables the secretion of lytic granules through minimally sized clearances. In our recent publication we visualized actin using continuous wave stimulated emission depletion (CW-STED) and lytic granules using the confocal modality. Here we report for the first time dual channel STED nanoscopy of NK cell lytic granules on actin filaments.


Effects of Genotype and Sleep on Temperament.
Sleep problems are frequent in young children; however, children vary in the degree to which they are affected by poor sleep quality. We investigated whether a polymorphism in the serotonin transporter gene, which is linked to emotional function, is a potential moderator of the influences of sleep duration on infant temperament using longitudinal data. We examined the interactive effects of average sleep duration between 6 and 36 months of age and the 5-HTTLPR genotype on negative emotionality/behavioral dysregulation at 36 months in 209 children recruited into a longitudinal birth cohort study. Triallelic genotyping of 5-HTTLPR was performed by looking at SLC6A4 genotype, focusing on the serotonin transporter-linked polymorphic region (5-HTTLPR) including the SNP polymorphism (rs23351). Child sleep habits were assessed with a maternal self-report questionnaire. After controlling for demographics and both previous and concurrent maternal depression, multiple linear regression analyses revealed a significant interaction effect of average sleep duration for the first 3 years of life and 5-HTTLPR genotype on child negative emotionality/behavioral dysregulation such that the effects were exclusive to those with low-expressing 5-HTTLPR genotypes. The results suggest differential susceptibility to the effect of sleep duration early in life, which reiterates that the short allele of the 5-HTTLPR represents a marker of increased environmental sensitivity regarding emotional development. Differential susceptibility theory posits that certain factors may increase an individual's susceptibility to the environment, in either a positive or negative fashion.


Applications of spatial light modulators in atom optics.
We discuss the application of spatial light modulators (SLMs) to the field of atom optics. We show that SLMs may be used to generate a wide variety of optical potentials that are useful for the guiding and dipole trapping of atoms. This functionality is demonstrated by the production of a number of different light potentials using a single SLM device. These include Mach-Zender interferometer patterns and the generation of a bottle-beam. We also discuss the current limitations in SLM technology with regard to the generation of both static and dynamically deformed potentials and their use in atom optics.


Peritoneal recurrence in serosa-negative gastric adenocarcinoma after curative surgery.
The rate of recurrence increases in proportion to the degree of tumor depth, even after curative resection for gastric adenocarcinoma. Serosal exposure is considered as an important risk factor of peritoneal recurrence. However, some patients with serosa-negative cancer were found to have peritoneal recurrence. There are few reports concerning risk factors of peritoneal recurrence in serosa-negative gastric adenocarcinoma. The aim of this study is to evaluate the incidence and risk factors of peritoneal recurrence in serosa-negative gastric adenocarcinoma after curative resection. Total 1128 serosa-negative gastric cancer patients (574 pT1, 251 pT2, 303 pT3) diagnosed as gastric adenocarcinoma that underwent R0 resection from 1988 to 2005 were enrolled. Peritoneal recurrence was observed in 50 (4.4%) patients, including 3 pT1, 3 pT2 and 44 pT3 patients. The incidence of peritoneal recurrence increased significantly with tumor invading subserosa (pT3). Multivariate analysis showed that the independent risk factor of peritoneal recurrence was tumor depth. The incidence of peritoneal recurrence in serosa-negative cancer is low, and tumor depth is a significant risk factor. We should be aware of peritoneal recurrence during follow-up, especially for patients with subserosal tumor invasion.


Functional expression of single-chain variable fragment antibody against c-Met in the cytoplasm of Escherichia coli.
c-Met, a high affinity receptor for hepatocyte growth factor/scatter factor, shown to be overexpressed in a variety of malignant cells, is a potential biomarker as well as a therapeutic target. Thus, single-chain antibody fragment (scFv) specific for c-Met is expected to be efficiently employed in the clinical treatment or imaging of many cancer cells. Here, we constructed the expression system for anti-c-Met scFv fused with T7 tag at its N-terminus using pET vector and investigated the expression conditions to achieve a functional and soluble expression of the scFv in the cytoplasm of recombinant Escherichia coli. The redox potential of E. coli cytoplasm was the most critical factor for the functional expression of anti-c-Met scFv. The employment of a host with oxidizing cytoplasm, E. coli trxB/gor double mutant, improved the productivity of functional anti-c-Met scFv by approximately 10-fold compared to the production of anti-c-Met scFv in the reducing cytoplasm of wild type E. coli. Productivity of functional anti-c-Met scFv could be further enhanced by co-expressing molecular chaperones such as GroELS, trigger factor, and DsbC with the scFv. Coexpression of DsbC increased the yield of functional anti-c-Met scFv about 2.5-fold in the cytoplasm of E. coli trxB/gor mutant compared to the production of scFv without DsbC coexpression. Lowering the IPTG concentration from 1 to 0.05 mM led to the slight enhancement, approximately 1.6-fold, of productivity of functional scFv. Although the use of low temperature for anti-c-Met scFv expression increased the ratio of soluble scFv fraction to insoluble fraction, productivity of soluble scFv decreased owing to the significant reduction of expression rate. The addition of 0.5 M sucrose in the medium inhibited the formation of intracellular insoluble anti-c-Met scFv. To purify the anti-c-Met scFv simply, we fused hexahistidine at the C-terminus of scFv and purified the scFv showing 98% of purity through the interaction between Ni2+ and histidine.