New aspects on treatment modalities for thromboembolic episodes.
Venous thromboembolism (VTE) has been treated with a glycosaminoglycan, followed by a vitamin K antagonist during the past 60 years. During the past two decades the glycosaminoglycans have undergone refinement, allowing for simplification of care for these patients, but parenteral administration is still required. Therefore, the current completion of phase III trials with selective, predictable and orally available anticoagulants with rapid onset brings promise for a change in paradigm in the treatment of VTE in the next few years. Whereas these efforts will lead to further simplification of the therapy there are also trials conducted to advance the treatment by rapid resolution of the thromboembolism in order to improve long-term outcome. Catheter-directed thrombolysis, perhaps also with thrombus fragmentation and stent insertion, if demonstrated to be successful for the reduction of the postthrombotic syndrome, will only be an alternative for a minority of patients due to the complexity, risks and cost of therapy. This treatment increases the complexity at the same time as new drug regimens offer simplicity. This review focuses on the novel therapies for VTE although the new anticoagulants will also play a major role in the management of arterial disease, which will be briefly presented.


Beneficial effects of l-carnitine supplementation for weight management in overweight and obese adults: An updated systematic review and dose-response meta-analysis of randomized controlled trials.
Despite preclinical studies demonstrating the efficacy of l-carnitine supplementation for weight management, findings in clinical setting are contradictory. Electronic bibliographical databases were systematically searched up to February 2019 with no limitation in language, including Scopus, PubMed, ISI Web of Science and Cochrane Library. Clinical trials registry platform were also searched. All randomized controlled trials (RCTs) which reported an effect of l-carnitine supplementation on obesity-related indices were included. Weighted mean difference (WMD) was estimated using a random-effect model (DerSimonian-Laird method). Eventually 43 eligible RCTs were included for quantitative analysis. Meta-analysis results revealed that l-carnitine supplementation significantly decreased weight (WMD: -1.129 kg, 95 % CI: -1.590, -0.669; I2: 63.4), body mass index (BMI) (WMD: -0.359 kg/m2, 95 % CI: -0.552, -0.167; I2: 85.2) and fat mass (WMD: -1.158 kg, 95 % CI: -1.763, -0.554, I2: 15.5). However, l-carnitine supplementation did not change body fat percentage (WMD: -0.874 %, 95 % CI: -1.890, 0.142, I2: 98.2) or waist circumference (WMD: -0.883 mg/dl, 95 % CI: -1.770, 0.004, I2: 74.8). l-Carnitine supplementation changed weight (r = -0.98) and BMI (r = -0.67) in a non-linear fashion based on carnitine dosage and BMI according to trial duration (r = -0.04). Interestingly subgroup analysis revealed that l-carnitine showed anti-obesity effects only in overweight and obese subjects; l-carnitine decreased weight, and BMI alone when combined with other lifestyle modifications. Anthropometric indexes were not changed following l-carnitine supplementation among patients' undergoing hemodialysis. Our study revealed that l-carnitine supplementation might have a positive effects in achieving an improved body weight and BMI especially in overweight and obese subjects.


Patterns of media use and alcohol brand consumption among underage drinking youth in the United States.
This study investigated whether underage drinkers with varied media use patterns differentially consume popular brands of alcohol. A survey was conducted with a national online panel of 1,032 underage youth 13-20 years of age who had consumed at least 1 drink in the past 30 days. A latent class analysis identified four distinct media use patterns. Further analyses explored whether these media use groups differentially consumed the most frequently used alcohol brands. The results showed that past 30-day consumption of specific alcohol brands differed significantly across the four media use clusters, even after controlling for sex, race/ethnicity, household income, U.S. geographic region, frequency of parent's alcohol overconsumption, cigarette smoking, and seatbelt use. This study shows that youth use media in different ways, and this differential use is significantly associated with the consumption of specific alcohol brands. The media clusters revealed in this analysis may inform future research about the association between specific alcohol media exposures and individual brand consumption.


Examination of bacterial flagellation by dark-field microscopy.
A method is described for visualizing unstained bacterial flagella by dark-field light microscopy. Since individual filaments can be seen, a genus such as Salmonella, which is peritrichously flagellated, can readily be distinguished from a polarly flagellated genus such as Pseudomonas. Polarly flagellated bacteria generally swim much faster than peritrichously flagellated bacteria, and turn by abrupt reversals. The differences in flagellation and motility provide diagnostic criteria that may be useful in clinical microbiology.


Family stature in idiopathic scoliosis.
The standing heights of 40 children with scoliosis and 110 persons from their immediate families were compared with those of a group of 349 contemporary control subjects. Skeletal bone ages and puberty ratings did not differ from normal, but the children with scoliosis were found to be significantly taller than the controls. They were also taller than their unaffected relatives, suggesting that the increased stature is not due to genetic factors alone. Scoliotic children with an affected immediate-family member were of normal height, which suggests that growth is of less etiological importance in children with a strong genetic susceptibility.


The natural evolution of idiophatic epimacular membrane.
Epiretinal membrane (ERM) refers to a semi-translucent tissue layer found on the inner surface of the retina especially in older people. Surgical treatment remains controversial, optimal timing for such treatment is difficult to determine and data on the natural evolution of this disorder are limited. In this study we evaluated the natural course of idiopathic epimacular membrane in 49 patients (53 eyes). Retrospective evaluation of a group of 49 patients (53 eyes) with idiopathic epimacular membrane confirmed by biomicroscopy, photography and optical coherence tomography (OCT). Patient age ranged from 51-85 years (median 72). The average follow-up was 21.3 months (± 14). Between the initial and final best corrected visual acuity (BCVA) there was no statistically significant difference although there was a significant tendency to decrease in BCVA (Spearman P=0.05) during the follow-up. Initial BCVA correlated with initial central retinal thickness (CRT), final CRT, final volume, and age. The final BCVA significantly correlated with all parameters measured. BCVA during follow-up tended to decrease: difference of starting BCVA and final BCVA values depending on the time of monitoring is significant. This we attribute to a slow gradual progression of macular changes. But, initial and final BCVA measurements were not substantially different at the end. Thus, in the absence of any clear signs of ERM progression, we can safely postpone the decision whether to perform PPV.


Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells.
Vascular endothelial cells contain a constitutive nitric oxide (NO) synthase that is Ca2(+)-dependent. In addition, we have found that these cells express, after activation with interferon-gamma and lipopolysaccharide, an inducible Ca2(+)-independent NO synthase that is distinct from the constitutive enzyme. The generation of NO by this enzyme was detectable after a lag period of 2 hr, reached a maximum between 6 and 12 hr, and was maintained for the duration of the experiment (48 hr). The expression of the inducible NO synthase was inhibited by the protein synthesis inhibitor cycloheximide, a compound that had no direct effect on the activity of either of the two enzymes. Furthermore, hydrocortisone and dexamethasone, but not progesterone, inhibited the expression of the inducible enzyme, without directly affecting the activity of either enzyme, without directly affecting the activity of either enzyme. The effect of these steroids was inhibited in a concentration-dependent manner by cortexolone, a partial agonist of glucocorticoid receptors. Thus, the inhibition of the induction of an NO synthase by glucocorticoids is a receptor-mediated event involving the inhibition of the synthesis of mRNA for de novo synthesis of this enzyme. The induction of this NO synthase may contribute to the pathophysiology of immunologically based conditions. Furthermore, the inhibition of this induction by anti-inflammatory steroids may explain some of the therapeutic and adverse effects of these compounds.


Changes in ocular aquaporin-4 (AQP4) expression following retinal injury.
Changes in the expression of water channels or aquaporins (AQP) have been reported in several diseases. However, such changes and mechanisms remain to be evaluated for retinal injury. This study was designed to analyze changes in the expression of AQP4 following elevation of intraocular pressure (IOP) and after intravitreal endothelin-1 injection and the potential involvement of the ubiquitin-dependent proteasome. Retinal injuries were induced by the elevation of intraocular pressure in rat eyes using the Morrison model or following endothelin-1 intravitreal injection. Immunohistochemistry using a combination of glial fibrillary acidic protein (GFAP) and aquaporin-4 antibodies were employed to follow changes in the optic nerve head astrocytes. Real-time quantitative PCR (Q-PCR) was used for measuring changes in AQP4, ubiquitin hydrolase L1 (UCH-L1), and beta-actin messages. Changes in AQP4, caspase-3, thy-1, ubiquitination, and GFAP expression were also followed in total retinal extracts using western blotting. An S5a column was used to purify ubiquitinated proteins. In retinas of both injury models, there was an upregulation of GFAP (a marker of astrogliosis), caspase-3, and downregulation of thy-1, a marker for retinal ganglion cell stress, and decreased retinal AQP4 mRNA and protein levels as determined by Q-PCR, and western blotting, respectively. By contrast, IOP enhanced expression and co-localization of GFAP and AQP4 in optic nerve astrocytes. AQP4 was detected in affinity-purified ubiquitinated proteins using S5a column, suggesting that AQP4 is a target for degradation by the ubiquitin-dependent proteasome. While elevation of IOP induced an increase in ubiquitination in retinal extracts, it decreased ubiquitination in optic nerve extracts as detected by western blotting. Enhanced ubiquitination and decreased ubiquitination appear to correlate with AQP4 expression. IOP decreased UCH-L1 (or protein gene protein [PGP9.5]) in retinal extracts as judged by Q-PCR. The enhanced expression of AQP4 in optic nerve astrocytes following elevation of IOP may explain the astrocytic hypertrophy normally seen in glaucoma patients and may involve alteration in the activity of ubiquitin-dependent proteasomal degradation system. The decreased ubiquitination in the optic nerve may lead to increased levels of proapoptotic proteins known to be degraded by the proteasome, and thus to axonal degeneration in glaucoma.


cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis.
Many hormones or neurotransmitters act at cell surface receptors to increase the intracellular free calcium concentration, triggering a wide range of cellular responses. As the source of this Ca2+ is often internal stores, additional messengers are required to convey the hormonal message from the plasma membrane. Cyclic ADP-ribose (cADPR) has been proposed as the endogenous activator of Ca(2+)-induced Ca2+ release by the ryanodine receptor in sea urchin eggs and in several mammalian cell types. A second messenger role for cADPR requires that its intracellular levels be under the control of extracellular stimuli. Here we demonstrate a novel action of 3',5'-cyclic guanosine monophosphate (cGMP) in stimulating the synthesis of cADPR from beta-NAD+ by activating its synthetic enzyme ADP-ribosyl cyclase in sea urchin eggs and egg homogenates. We suggest that cADPR may transduce signals generated by cell surface receptors or gaseous transmitters linked to cGMP production.


Transfer of learning after updating training mediated by the striatum.
Process-specific training can improve performance on untrained tasks, but the magnitude of gain is variable and often there is no transfer at all. We demonstrate transfer to a 3-back test of working memory after 5 weeks of training in updating. The transfer effect was based on a joint training-related activity increase for the criterion (letter memory) and transfer tasks in a striatal region that also was recruited pretraining. No transfer was observed to a task that did not engage updating and striatal regions, and age-related striatal changes imposed constraints on transfer. These findings indicate that transfer can occur if the criterion and transfer tasks engage specific overlapping processing components and brain regions.


Spontaneous poorly differentiated carcinoma with cells positive for vimentin in a salivary gland of a young rat.
Spontaneous salivary gland tumors in rats are rare. The authors report a poorly differentiated carcinoma of a submandibular gland in a ten-week-old rat that was positive for vimentin. Microscopically, the neoplastic cells showed a diffuse growth pattern in most areas of the tumor mass and a nestlike structure in a part of the peripheral area. Immunohistochemically, the cells were positive for keratin and vimentin but not for alpha-smooth muscle actin. Ultrastructurally, desmosome-like structures were observed. Based on these findings, the tumor was diagnosed as a poorly differentiated carcinoma. The origin of the neoplastic cells would be either acinar or ductal cells. This suggests that acinar or ductal cells have the potential to transform into vimentin-expressing cells.


Effect of a single oral administration of Lactobacillus plantarum DSMZ 8862/8866 before and at the time point of weaning on intestinal microbial communities in piglets.
The aim of this study was to evaluate whether a single administration of two strains of Lactobacillus plantarum (DSMZ 8862 and 8866) either before or at the time point of weaning can influence the intestinal microbiota of piglets. A total of 176 piglets were allocated into five groups: control (LP0), administration of 5 x 10(9) or 5x10(10) cfu at day 25 of life (LP1, LP2) and administration of 5 x 10(9) or 5 x 10(10) cfu at day 28 of life (LP3, LP4). Piglets were weaned on day 28 of life. On day 25 (LP1, LP2), 28 (LP0, LP3, LP4), 33 (all groups) and 39 (all groups) of life, 10-13 animals of each group were killed and genomic DNA was extracted from small and large intestinal contents. Denaturing gradient gel electrophoresis demonstrated that administration of L. plantarum had a significant effect in GIT microbial communities as revealed by the Simpson's index of diversity and cluster analysis based on the Dice similarity index; this effect was more pronounced in groups LP3 and LP4. A treatment dependent presence of Clostridium glycolicum-like, Lactobacillus sobrius-like, Eubacterium rectale-like and Roseburia faecalis-like phylotypes was observed. The results show that the administration of L. plantarum at the point of weaning can influence gastrointestinal microbiota in weaning piglets which may have positive results on gastrointestinal health.


Treatment of previously undiagnosed psychiatric disorders in persons with developmental disabilities decreased or eliminated self-injurious behavior.
Self-injurious behavior (SIB) is one of the most common challenging behaviors in persons with autistic disorder or severe/profound mental retardation. Many psychotropic drugs have been evaluated for their effectiveness in SIB. Results have varied, and no one psychotropic drug has been indicated for SIB. In this prospective, open clinical study, psychotropic drugs were used to treat the previously undiagnosed psychiatric disorder in persons exhibiting SIB. Data were collected from 26 individuals with mental retardation (14 males, 12 females), 7 to 45 years of age (mean = 30.3 years), who exhibited SIB. Psychiatric diagnosis was made according to DSM-III-R and DSM-IV criteria. The Behavior Problem Inventory, Yudofsky's Overt Aggression Scale, repeated direct observation, and information on use of protective devices and Likert scales from log books were used to evaluate degree of SIB. Most of the patients were treated with different psychotropic drugs and behavior modification before they were evaluated for this study, but only 7 of them carried a psychiatric diagnosis. Data were collected between 1987 and 1997. Depressive disorders, impulse-control disorder, and anxiety disorder were the most common final diagnoses. Neuroleptics were discontinued in 5 patients and tapered by 50% to 75% in 14 patients. Antidepressants were added in 12 patients. Treatment of psychiatric disorders produced significant (p < .001) decrease in the severity of SIB in the 26 patients, and SIB was eliminated in 12 patients. The severity of SIB decreased to mild from a moderate, severe, or extreme degree in 11 patients and from an extreme to a severe degree in 3 patients. The most effective treatment for SIB that is resistant to environment changes and behavior modification in persons with developmental disabilities is the treatment of their psychiatric disorders with the appropriate psychotropics.


Oxygen hole doping of nanodiamond.
Surface-graphitized nanodiamonds (NDs) are promising hybrid nanomaterials which appear to combine core properties of diamond with surface properties of graphene-based materials. Here we demonstrate that NDs covered by graphene islands, so-called Fullerene-Like Reconstructions (FLRs), are sensitive to hole doping by molecular oxygen in water. NDs covered by FLRs (NDs-FLRs) are prepared by annealing under vacuum of detonation NDs at 750 °C. We propose that oxygen hole doping is promoted on FLRs due to a unique electronic interaction between the diamond core and the outer graphene layer. As a consequence, NDs-FLRs exhibit positive zeta potential in water, unlike NDs surrounded by several graphitic layers. Surface hole-doped NDs may be promising nanomaterials for new electronic and biomedical applications.


Vascular endothelial growth factor 121 and 165 in the subacromial bursa are involved in shoulder joint contracture in type II diabetics with rotator cuff disease.
Vascular endothelial growth factor (VEGF) is a glycoprotein that plays an important role in neovascularization and increases vascular permeability. We reported that VEGF is involved in motion pain of patients with rotator cuff disease by causing synovial proliferation in the subacromial bursa (SAB). The present study investigates whether VEGF is also involved in the development of shoulder contracture in diabetics with rotator cuff disease. We examined 67 patients with rotator cuff disease, including 36 with complete cuff tears, 20 with incomplete tears, and 11 without apparent tears (subacromial bursitis). The patients were into groups according to the presence or absence of diabetes (14 type II diabetics and 53 non-diabetics). Specimens of the synovium of the SAB were obtained from all patients during surgery. Expression of the VEGF gene in the synovium of the subacromial bursa was evaluated by using the reverse transcriptase polymerase chain reaction. The VEGF protein was localized by immunohistochemistry, and the number of vessels was evaluated based on CD34 immunoreactivity. The results showed that VEGF mRNA was expressed in significantly more diabetics (100%, 14/14) than in non-diabetics (70%, 37/53) (P=0.0159, Fisher's test). Investigation of VEGF isoform expression revealed VEGF121 in all 14 diabetics and in 37 of the 53 non-diabetics, VEGF165 in 12 of the 14 diabetics and in 21 of the 53 non-diabetics, and VEGF189 in 1 of the 14 diabetics and in 2 of the 53 non-diabetics. No VEGF206 was expressed in either group. VEGF protein was localized in both vascular endothelial cells and synovial lining cells. The mean number of VEGF-positive vessels and the vessel area were also significantly greater in the diabetics (p<0.015, Mann-Whitney U test). Synovial proliferation and shoulder joint contracture were more common in the diabetics (P=0.0329 and P=0.073, respectively; Fisher's test). The mean preoperative range of shoulder motion significantly differed in terms of elevation between two groups: 103.8 degrees in diabetics and 124.9 degrees in no diabetics (p=0.0039 Mann-Whitney U test). In contrast, external rotation did not significantly differ: 44 degrees in diabetics and 49 degrees in non-diabetics (p=0.4957, Mann-Whitney U test). These results suggest that VEGF121 and VEGF165 expression in the SAB is responsible for the development of shoulder joint contracture, especially in elevation, among type II diabetic patients with rotator cuff disease.


Ellagic acid protects mice against sleep deprivation-induced memory impairment and anxiety by inhibiting TLR4 and activating Nrf2.
Sleep disorder has become a prevalent issue in current society and is connected with the deterioration of neurobehaviors such as mood, cognition and memory. Ellagic acid (EA) is a phenolic phytoconstituent extracted from grains and fruits that has potent neuroprotective properties. This research aimed to study the alleviative effect and mechanism of EA on memory impairment and anxiety caused by sleep deprivation (SD). EA ameliorated behavioral abnormalities in SD mice, associated with increased dendritic spine density, and reduced shrinkage and loss of hippocampal neurons. EA reduced the inflammatory response and oxidative stress injury caused by SD, which may be related to activation of the Nrf2/HO-1 pathway and mitigation of the TLR4-induced inflammatory response. In addition, EA significantly reduced the mortality and ROS levels in glutamate (Glu)-induced hippocampal neuron injury, and these effects of EA were enhanced in TLR4 siRNA-transfected neurons. However, knockdown of Nrf2 dramatically restrained the protective impact of EA on Glu-induced toxicity. Taken together, EA alleviated memory impairment and anxiety in sleep-deprived mice potentially by inhibiting TLR4 and activating Nrf2. Our findings suggested that EA may be a promising nutraceutical ingredient to prevent cognitive impairment and anxiety caused by sleep loss.


Support the underground: characteristics of beyond-mainstream music listeners.
Music recommender systems have become an integral part of music streaming services such as Spotify and Last.fm to assist users navigating the extensive music collections offered by them. However, while music listeners interested in mainstream music are traditionally served well by music recommender systems, users interested in music beyond the mainstream (i.e., non-popular music) rarely receive relevant recommendations. In this paper, we study the characteristics of beyond-mainstream music and music listeners and analyze to what extent these characteristics impact the quality of music recommendations provided. Therefore, we create a novel dataset consisting of Last.fm listening histories of several thousand beyond-mainstream music listeners, which we enrich with additional metadata describing music tracks and music listeners. Our analysis of this dataset shows four subgroups within the group of beyond-mainstream music listeners that differ not only with respect to their preferred music but also with their demographic characteristics. Furthermore, we evaluate the quality of music recommendations that these subgroups are provided with four different recommendation algorithms where we find significant differences between the groups. Specifically, our results show a positive correlation between a subgroup's openness towards music listened to by members of other subgroups and recommendation accuracy. We believe that our findings provide valuable insights for developing improved user models and recommendation approaches to better serve beyond-mainstream music listeners.


Positive risk management: Staff perspectives in acute mental health inpatient settings.
To explore inpatient staff's understanding and implementation of positive risk management. Risk management is an essential skill for staff working in acute mental health inpatient settings. National policies advocate the use of positive risk management as a form of collaborative, recovery-focused risk management. However, little is known about how staff understand, operationalize, and use positive risk management in practice. Qualitative reflexive thematic analysis study. The authors recruited a purposive sample of healthcare professionals working in acute inpatient settings (N = 16) in 2019 across three National Health Service Trusts in the North-West of England. Participants completed semi-structured interviews which were analysed using reflexive thematic analysis. The analysis generated three themes: (a) within staff barriers; (b) within service user barriers; and (c) delivery in practice. Understanding and implementation of positive risk management was dependant on multiple factors, including staffs' beliefs about mental health, levels of worry and anxiety, and amount of experience and seniority. Staff were more likely to use positive risk management with service users that they perceived as being trustworthy and less risky. Use of positive risk management was reliant on the support practitioners received, how able they were to view situations from multiple perspectives, and the degree to which they felt able to prioritize positive risk management. Although staff expressed the desire and intention to practice positive risk management, the current study highlights challenges around operationalization and implementation. The authors discuss the clinical implications of the findings.


Cytosine methylation alters DNA mechanical properties.
DNA methylation plays an essential role in transcriptional control of organismal development in epigenetics, from turning off a specific gene to inactivation of entire chromosomes. While the biological function of DNA methylation is becoming increasingly clear, the mechanism of methylation-induced gene regulation is still poorly understood. Through single-molecule force experiments and simulation we investigated the effects of methylation on strand separation of DNA, a crucial step in gene expression. Molecular force assay and single-molecule force spectroscopy revealed a strong methylation dependence of strand separation. Methylation is observed to either inhibit or facilitate strand separation, depending on methylation level and sequence context. Molecular dynamics simulations provided a detailed view of methylation effects on strand separation, suggesting the underlying physical mechanism. According to our study, methylation in epigenetics may regulate gene expression not only through mechanisms already known but also through changing mechanical properties of DNA.


Induction of T cell adhesion by antigen stimulation and modulation by the coreceptor CD4.
T cell adhesion induced after physiological stimulation by antigen was investigated using murine T cell hybridomas specific for a tetanus toxin peptide. By employing a novel assay, the T cell hybridomas were shown to strongly adhere to peptide-pulsed APC in a dose-dependent fashion. Adhesion peaked at 30-60 min and declined thereafter. This assay allowed us to study the relationship between T cell adhesion and later activation responses using tetanus toxin peptide and alanine monosubstituted analogs. We show that the degree of peptide-induced T cell adhesion correlated with the magnitude of late functional responses. CD4, LFA-1 (CD11a/CD18), and CD28 were critical in the adhesion response. The enhancing role of CD4 was further demonstrated by reduced levels of T cell adhesion and late responses of CD4- T cell hybridomas. Reexpression of CD4 reversed these defects. Our data suggest a link between antigen-induced T cell adhesion and late responses and also suggest that signals mediated by TCR and CD4 coengagement may induce a greater activation and/or recruitment of molecules involved in T cell adhesion.


Snf1 kinases with different beta-subunit isoforms play distinct roles in regulating haploid invasive growth.
The Snf1 protein kinase of Saccharomyces cerevisiae has been shown to have a role in regulating haploid invasive growth in response to glucose depletion. Cells contain three forms of the Snf1 kinase, each with a different beta-subunit isoform, either Gal83, Sip1, or Sip2. We present evidence that different Snf1 kinases play distinct roles in two aspects of invasive growth, namely, adherence to the agar substrate and filamentation. The Snf1-Gal83 form of the kinase is required for adherence, whereas either Snf1-Gal83 or Snf1-Sip2 is sufficient for filamentation. Genetic evidence indicates that Snf1-Gal83 affects adherence by antagonizing Nrg1- and Nrg2-mediated repression of the FLO11 flocculin and adhesin gene. In contrast, the mechanism(s) by which Snf1-Gal83 and Snf1-Sip2 affect filamentation is independent of FLO11. Thus, the Snf1 kinase regulates invasive growth by at least two distinct mechanisms.


The Added Value of Volume-of-Interest C-Arm CT Imaging during Endovascular Treatment of Intracranial Aneurysms.
Successful endovascular treatment of intracranial aneurysms requires understanding the exact relationship of implanted devices to the aneurysm, parent artery, and other branch vessels during the treatment. Intraprocedural C-arm CT imaging has been shown to provide such information. However, its repeated use is limited due to increasing radiation exposure to the patient. The goal of this study was to evaluate a new volume-of-interest C-arm CT imaging technique, which would provide device-specific information through multiple 3D acquisitions of only the region of interest, thus reducing cumulative radiation exposure to the patient. VOI C-arm CT images were obtained in 28 patients undergoing endovascular treatment of intracranial aneurysms. VOI images were acquired with the x-ray source collimated around the deployed device, both horizontally and vertically. The images were reconstructed by using a novel prototype robust reconstruction algorithm to minimize truncation artifacts from double collimation. The reconstruction accuracy of VOI C-arm CT images was assessed quantitatively by comparing them with the full-head noncollimated images. Quantitative analysis showed that the quality of VOI C-arm CT images is comparable with that of the standard Feldkamp, Davis, and Kress reconstruction of noncollimated C-arm CT images (correlation coefficient = 0.96 and structural similarity index = 0.92). Furthermore, 91.5% reduction in dose-area product was achieved with VOI imaging compared with the full-head acquisition. VOI imaging allows multiple 3D C-arm CT acquisitions and provides information related to device expansion, parent wall apposition, and neck coverage during the procedure, with very low additional radiation exposure to the patient.


Association between prenatal exposure to perfluoroalkyl substances and respiratory tract infections in preschool children.
Prenatal exposure to perfluoroalkyl substances (PFAS) is considered to affect adversely the immune function. However, the effect of prenatal PFAS exposure on respiratory tract infections (RTIs) in children is unclear. Thus, we evaluated whether cord blood PFAS levels were associated with RTI in the first 5 years of life. The Shanghai Prenatal Cohort is an on-going birth cohort, which included all the mothers during pregnancy. Children were followed by paediatricians once a year after birth. The levels of 10 PFAS in cord blood were tested using liquid chromatography-mass spectrometry. RTIs were diagnosed based on face-to-face interviews with the parents and review of medical records. Immunoglobulin G (IgG) and immunoglobulin E (IgE) levels, as biomarkers of humoral immunity, were assessed using enzyme-linked immunosorbent assay at age 5 years. Multivariable logistic and linear regression models were applied to study the association between prenatal PFAS exposure and RTIs. A total of 743 children completed the follow-up, 344 of them had detail information of cord blood PFAS, IgG, and IgE concentrations. Eight PFAS were detected in more than 90% of the cord blood samples, except for perfluoroheptanoic acid (PFHpA) and perfluorooctane sulfonamide (FOSA). During the 5-year follow-up period, the frequency of RTIs increased with age, reaching a peak at age 4. Moreover, 20.6% of the children were diagnosed with recurrent RTIs. Children with recurrent RTIs had higher prenatal perfluorobutane sulfonic acid (PFBS) concentration. Higher prenatal PFBS concentration was positively associated with total RTI frequency (β = 6.05, 95% CI [0.84, 11.26]) in first 5 years of life and negatively associated with IgG level (β = -0.82, 95% CI [-1.67, -0.01]) at age 5. Children with higher prenatal PFBS were more vulnerable to RTIs in early life, which may be attributed to immunosuppression of IgG production. These findings need to be further verified in larger prospective studies.


Airway smooth muscle responsiveness from dogs with airway hyperresponsiveness after O3 inhalation.
Airway hyperresponsiveness occurs after inhalation of O3 in dogs. The purpose of this study was to examine the responsiveness of trachealis smooth muscle in vitro to electrical field stimulation, exogenous acetylcholine, and potassium chloride from dogs with airway hyperresponsiveness after inhaled O3 in vivo and to compare this with the responsiveness of trachealis muscle from control dogs. In addition, excitatory junction potentials were measured with the use of single and double sucrose gap techniques in both groups of dogs to determine whether inhaled O3 affects the release of acetylcholine from parasympathetic nerves in trachealis muscle. Airway hyperresponsiveness developed in all dogs after inhaled O3 (3 ppm for 30 min). The acetylcholine provocative concentration decreased from 4.11 mg/ml before O3 inhalation to 0.66 mg/ml after O3 (P less than 0.0001). The acetylcholine provocative concentration increased slightly after control inhalation of dry room air. Airway smooth muscle showed increased responses to both electrical field stimulation and exogenous acetylcholine but not to potassium chloride in preparations from dogs with airway hyperresponsiveness in vivo. The increased response to electrical field stimulation was not associated with a change in excitatory junctional potentials. These results suggest that a postjunctional alteration in trachealis muscle function occurs after inhaled O3 in dogs, which may account for airway hyperresponsiveness after O3 in vivo.


Rat plasma lipoproteins and apolipoproteins in experimental hypothyroidism.
Hyperlipidemia associated with hypothyroidism is well documented in man and several animal species. The effect of hypothyroidism on apolipoprotein metabolism in the absence of complicating factors such as high cholesterol or fat content in the diet is virtually unknown. Hypothyroidism was therefore induced in male Sprague-Dawley rats by radiothyroidectomy (RTx-treated) or treatment with propylthiouracil (PTU-treated). Both treatments resulted in an over 90% decrease in circulating thyroid hormone concentrations accompanied by a 50-100% increase in plasma cholesterol and a 20-40% reduction in plasma triglyceride concentrations. Plasma apo E and apo B concentrations increased by 100% in the PTU-treated group and 40-50% in the RTx-group. Apo A-I increased 10 and 30% in the RTx- and PTU-treated rats, respectively, while the concentration of apo A-IV was not altered. A large increase in the low-density (LDL) and high-density lipoprotein (HDL) protein was observed and accompanied by a marked reduction of very low density lipoprotein (VLDL) in the hypothyroid rats. The electrophoretic pattern of plasma lipoproteins in the hypothyroid rats was changed by the appearance of a slow pre-beta band shown to be beta-VLDL. A redistribution of apo B occurred within the lipoprotein fractions. Apo B content in the VLDL fraction decreased and a large increase was noted in LDL. The major portion of the apo E and apo A-I increment was recovered in the HDL and to a lesser degree in LDL. An accumulation of apo E-rich larger HDL particles, resembling HDLc in apolipoprotein composition and distinct from the apo A-I-containing species, was observed by column chromatography. The results presented are consistent with the hypothesis that hypothyroidism in the rat may induce an accelerated production of VLDL catabolic remnants, including LDL, but at the same time reduce the rate of removal of these lipoproteins from the circulation.


Real-time estimates in early detection of SARS.
We propose a Bayesian statistical framework for estimating the reproduction number R early in an epidemic. This method allows for the yet-unrecorded secondary cases if the estimate is obtained before the epidemic has ended. We applied our approach to the severe acute respiratory syndrome (SARS) epidemic that started in February 2003 in Hong Kong. Temporal patterns of R estimated after 5, 10, and 20 days were similar. Ninety-five percent credible intervals narrowed when more data were available but stabilized after 10 days. Using simulation studies of SARS-like outbreaks, we have shown that the method may be used for early monitoring of the effect of control measures.


Cystic echinococcosis in slaughtered domestic ruminants from Tunisia.
A total of 10,818 domestic ruminants (3913 cattle, 2722 sheep, 3779 goats, 404 dromedaries) slaughtered in various abattoirs in Tunisia between 2003 and 2010 were examined for the presence of Echinococcus granulosus hydatid cysts. The prevalence of cystic echinococcosis (CE) was 16.42% in sheep, 8.56% in cattle, 5.94% in dromedaries and 2.88% in goats. CE prevalence increased with age according to an asymptotic model and there was evidence of variation in infection pressure depending on the region of Tunisia where the animals were slaughtered. Cattle appeared to have the highest infection pressure of the species examined. The mean intensity of hepatic cysts was higher than that of pulmonary cysts in all species. The highest mean intensity of infection with E. granulosus larvae was observed in cattle (18.14) followed by sheep (9.58), goats (2.31) and dromedaries (2.12). The abundance of infection increased in a linear fashion with age in all animal species. Cyst abundance varied with species of animal and district of Tunisia. Cysts from dromedaries were more fertile (44.44%) than those from sheep (30.25%), goats (30.32%) and cattle (0.95%). The viability of the protoscoleces from fertile cysts from cattle (78.45%) was higher than those from sheep (70.71%) and camels (69.57%). The lowest protoscolex viability was recorded for hydatid cysts from goats (20.21%). This epidemiological study confirms the importance of CE in all domestic ruminant species, particularly in sheep, throughout Tunisia and emphasizes the need to interrupt parasite transmission by preventive integrated approaches in a CE control programme.


The growing trend of cannabidiol in skincare products.
Recently, cannabidiol has garnered considerable attention in the public and media as a trendy and popular ingredient in skincare products. Cannabidiol is a cannabinoid that lacks psychoactive properties. It has been marketed to consumers as being antiinflammatory, analgesic, hydrating, moisturizing, and wrinkle-reducing. Others claim it to be a cure for skin aging, acne, eczema, psoriasis, and pruritus. However, current data is limited regarding its safety and efficacy. Clinicians should be aware of current regulatory concerns and the limited available evidence.


Is the domestic dog (Canis familiaris) a reservoir host of American cutaneous leishmaniasis? A critical review of the current evidence.
Originally associated with forested areas, the transmission cycle of American cutaneous leishmaniasis (ACL) has now adapted to the domestic environment in at least 9 Latin American countries. Several studies have suggested that the domestic dog (Canis familiaris), which is already incriminated as the primary reservoir host of zoonotic visceral leishmaniasis (ZVL), may have a reservoir role in the domestic transmission of human ACL caused by Leishmania braziliensis, L. panamensis, and L. peruviana. This article reviews more than 90 studies reporting ACL infections in dogs, and concludes that as yet there is only circumstantial evidence to support that claim. Almost no data are available on the infectiousness of dogs to sandfly vectors of ACL, and there are few indications that either dog ownership or dog abundance are risk factors for ACL. Nevertheless, it has been proposed that incidence of ACL in humans could be reduced by targeting infected dogs. While this control strategy has been used for many decades against ZVL in Latin America, Europe, and Asia, there is little evidence to demonstrate its effectiveness either in theory or in practice. Particular concerns over the sensitivity and specificity of diagnostic tools, low compliance rates among dog owners, and cost-effectiveness are likely to apply equally to ACL control.


Insulin secretion in hypoglycemia after adrenal vein ligature or splachnicotomy.
During bonito insulin-induced hypoglycemia in dogs, pancreatic venous dog insulin concentration (IRI), radioimmunoassayed differentially from bonito insulin, was progressively diminished in response to local glucose infusion (0.6 mg/kg - min) for 4 min into the superior pancreaticoduodenal artery. Basal arterial plasma glucose was significantly lower after bilateral splanchnicotomy (BSNC) than after bilateral adrenal vein ligature (BAVL). During local glucose infusion in both normoglycemia and hypoglycemia, the increment of pancreatic venous IRI was significantly greater after BAVL or BSNC than in the controls, and the increment of pancreatic venous glucose was also significantly greater after BAVL than in the controls or after BSNC. It is suggested that under the stress of major surgery the splanchnic nerves partially suppress insulin secretion in normoglycemia as well as in hypoglycemia, and epinephrine released from the adrenal medulla may interfere with glucose-mediated insulin secretion in profound hypoglycemia.


Comparison of methods for extraction of nucleic acid from hemolytic serum for PCR amplification of hepatitis B virus DNA sequences.
The sensitivity of PCR for the amplification of target nucleic acid sequences in clinical diagnostics may often be reduced due to the presence of inhibitory factors. Hemolytic serum contains a number of PCR inhibitors, one of which is hemin. In this study we have found that conventional methods of DNA extraction were not sufficient for the removal of PCR-inhibitory compounds in hemolytic serum. We have therefore compared the efficiency of several commercial and noncommercial methods of nucleic acid purification from hemolytic serum samples prior to PCR amplification. Separation with the QIAamp HCV kit, dialysis with Millipore filters, and bovine serum albumin absorption were all found to be suitable extraction methods for eliminating inhibitors from hemolytic serum for PCR amplification. Using these methods we were able to detect very low levels of hepatitis B virus DNA in hemolytic serum.


Phase III trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE): results from a randomised, double-blind, placebo-controlled trial.
Targeted inhibitors of B-cell activating factor (BAFF) have been evaluated in phase III trials in over 4000 patients with systemic lupus erythematosus (SLE). Post hoc analyses of these studies identify greater treatment effect in patients entering with higher disease activity, greater corticosteroid doses, anti double-stranded DNA (dsDNA) and low complement C3 or C4. To evaluate the efficacy and safety of blisibimod, a BAFF inhibitor, in a population of patients with SLE enriched for high disease activity. 442 patients with SLE with antinuclear antibodies or anti-dsDNA and Safety of Estrogen in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥10 on standard-of-care medications were randomised to receive weekly subcutaneous blisibimod (200 mg) or placebo. Corticosteroid taper was encouraged from week 8. The primary end point was the week 52 SLE Responder Index-6 (SRI-6). The SRI-6 primary end point was not met. There was a statistically significant steroid-sparing effect, and significantly more blisibimod-treated subjects achieved corticosteroid taper. Increased blisibimod treatment effect on SRI-6 was observed in subjects who achieved a concomitant decrease in corticosteroid dose from baseline. In subjects with baseline urinary protein:creatinine ratio (UPCR) ≥56.5 mg/mmol, significantly higher proportions of blisibimod subjects achieved >50% reduction in UPCR and/or UPCR <56.5 mg/mmol. Reductions in SLE autoantibodies and B cells, and increases in complement C3 and C4 were observed with blisibimod.Blisibimod was well-tolerated. The most common adverse events were upper respiratory tract infection, urinary tract infection, injection site erythema/reaction and diarrhoea. Although the SRI-6 end point was not met, blisibimod was associated with successful steroid reduction, decreased proteinuria and biomarker responses. NCT01395745.


EPR characterization of Mn(ii) complexes for distance determination with pulsed dipolar spectroscopy.
The four Mn(ii) complexes Mn-DOTA, Mn-TAHA, Mn-PyMTA, and Mn-NO3Py were characterized by electron paramagnetic resonance (EPR), electron-nuclear double resonance (ENDOR), and relaxation measurements, to predict their relative performance in the EPR pulse dipolar spectroscopy (PDS) experiments. High spin density localization on the metal ions was proven by ENDOR on 1H, D, 14N, and 55Mn nuclei. The transverse relaxation of the Mn(ii) complexes appears to be slow enough for PDS-based spin-spin distance determination. Rather advantageous ratios of T1/Tm were measured allowing for good relaxation induced dipolar modulation enhancement (RIDME) performance and, in general, fast shot repetitions in any PDS experiment. Relaxation properties of the Mn(ii) complexes correlate with the strengths of their zero field splitting (ZFS). Further, a comparison of Mn(ii)-DOTA and Gd(iii)-DOTA based spin labels is presented. The RIDME technique to measure nanometer-range Mn(ii)-Mn(ii) distances in biomolecules is discussed as an alternative to the well-known DEER technique that often appears challenging in cases of metal-metal distance measurements. The use of a modified kernel function that includes dipolar harmonic overtones allows model-free computation of the Mn(ii)-Mn(ii) distance distributions. Mn(ii)-Mn(ii) distances are computed from RIDME data of Mn-rulers consisting of two Mn-PyMTA complexes connected by a rodlike spacer of defined length. Level crossing effects seem to have only a weak influence on the distance distributions computed from this set of Mn(ii)-Mn(ii) RIDME data.


Novel Mutations in EPCAM Cause Congenital Tufting Enteropathy.
Congenital tufting enteropathy (CTE) is a rare autosomal recessive form of intractable diarrhea of infancy. Patients develop chronic diarrhea within days after birth, leading to severe malabsorption and significant mortality. CTE is characterized by subtotal villous atrophy with crypt hyperplasia. Typical features include abnormal villi in the intestinal epithelium and disorganization of surface enterocytes with focal crowding, resembling tufts. The pathogenesis of CTE remains poorly understood. CTE has been reported in Western populations, but until now had not been reported in China. The objective of this study was to identify the gene responsible for CTE in a Chinese individual. A 13-year-old girl with suspected CTE, whose parents were both healthy, was evaluated in our clinic. Tissues were obtained by endoscopy and examined by electron microscopy. Genomic DNA, extracted from the peripheral blood of the child and parents, was subjected to whole-exome sequencing. After mutations in the gene encoding epithelial cell adhesion molecule (EPCAM) were identified, expression of EPCAM was examined by immunohistochemistry staining. Whole-exome sequencing revealed compound heterozygous mutations in EPCAM in the patient, with immunohistochemical analysis showing complete loss of EPCAM expression in the intestinal villi and crypts. We identified compound heterozygous mutations in EPCAM, with loss of EPCAM expression in duodenal enterocytes, in a patient with intractable diarrhea since infancy who was subsequently diagnosed with CTE. This is the first case of CTE to be reported in a Chinese patient.


Increased endobiotic fatty acid methyl esters following exposure to methanol.
Human exposure to methanol is likely to increase in the future due to its proposed use as an alternate automobile fuel. Since alcohols are known to esterify the fatty acids in the body and some of those esterified esters are toxic, we studied the formation of fatty acid esters of methanol in Long-Evans male rats given a single oral dose of 3.5 g/kg body weight of methanol in saline. Animals given an equal volume of saline served as control. Three rats were euthanized at 1, 3, 6, 12 and 24 hr following the treatment. Fatty acid methyl esters, extracted from whole blood, liver, pancreas, and brown fat were separated by thin-layer chromatography and quantitated by gas chromatography (GC). Their identity was then confirmed by GC-mass spectrometry. Average levels as high as 596, 5293, 2239, 1106, 9665, 7728, 562, and 2792 micrograms/g (wet weight basis) of 14:0, 16:0, 16:1, 18:0, 18:1, 18:2, 18:3, and 20:4 fatty acid methyl esters, respectively, were found in the pancreas of methanol-treated rats. The average concentration of total fatty acid methyl esters was computed to be 4513, 29594, 22871, 18956, 17014, and 9702 micrograms/g in the pancreas compared to 1.9, 25.4, 36.8, 18.5, 18.9, and 14.2 micrograms/g in the liver at 0, 1, 3, 6, 12, and 24 hr, respectively, following methanol exposure. On dry lipid weight basis, the levels were significantly higher again in pancreas followed by brown fat and liver. In whole blood, only low levels of 16:0, 18:0, and 20:4 fatty acid methyl esters could be detected at all time points. The highest concentration of total fatty acid methyl esters in the pancreas, liver, and brown fat was detected at 1, 3, and 24 hr, respectively. Most of the fatty acid methyl esters found in the liver and pancreas decreased after 6 hr of methanol exposure. The fatty acid methyl esters of higher concentrations were 16:0 in the whole blood, 18:0, 18:1, 18:2, and 20:4 in liver, 18:1, and 18:2 in pancreas and 16:0, 18:1, and 18:2 in brown fat. These fatty acid methyl esters were also detected in the tissues of control rats indicating their endogenous formation. Significant increase in methylation of the fatty acids during methanol exposure, as found in this study, may serve as a defense mechanism for preventing available methanol from oxidative metabolism to render toxicity. However, the biological significance of these fatty acid methyl esters is yet to be understood.


NIOSH national survey of long-haul truck drivers: Injury and safety.
Approximately 1,701,500 people were employed as heavy and tractor-trailer truck drivers in the United States in 2012. The majority of them were long-haul truck drivers (LHTDs). There are limited data on occupational injury and safety in LHTDs, which prompted a targeted national survey. The National Institute of Occupational Safety and Health conducted a nationally representative survey of 1265 LHTDs at 32 truck stops across the contiguous United States in 2010. Data were collected on truck crashes, near misses, moving violations, work-related injuries, work environment, safety climate, driver training, job satisfaction, and driving behaviors. Results suggested that an estimated 2.6% of LHTDs reported a truck crash in 2010, 35% reported at least one crash while working as an LHTD, 24% reported at least one near miss in the previous 7 days, 17% reported at least one moving violation ticket and 4.7% reported a non-crash injury involving days away from work in the previous 12 months. The majority (68%) of non-crash injuries among company drivers were not reported to employers. An estimate of 73% of LHTDs (16% often and 58% sometimes) perceived their delivery schedules unrealistically tight; 24% often continued driving despite fatigue, bad weather, or heavy traffic because they needed to deliver or pick up a load at a given time; 4.5% often drove 10miles per hours or more over the speed limit; 6.0% never wore a seatbelt; 36% were often frustrated by other drivers on the road; 35% often had to wait for access to a loading dock; 37% reported being noncompliant with hours-of-service rules (10% often and 27% sometimes); 38% of LHTDs perceived their entry-level training inadequate; and 15% did not feel that safety of workers was a high priority with their management. This survey brings to light a number of important safety issues for further research and interventions, e.g., high prevalence of truck crashes, injury underreporting, unrealistically tight delivery schedules, noncompliance with hours-of-service rules, and inadequate entry-level training.


Metabolism of platelet-activating factor in human haematopoietic cell lines. Differences between myeloid and lymphoid cells.
The binding and metabolism of platelet-activating factor (PAF) was studied in human cell lines resembling myeloid cells (HL60 and U937) and B and T lymphocytes (Daudi and Jurkat). All of the cell lines were found to bind and catabolize exogenous [3H]PAF in a time- and temperature-dependent manner. PAF binding could also be demonstrated in isolated membrane fractions, which provides further evidence of the existence of true membrane receptors. Myeloid cell lines contained numbers of receptors at least 10-fold higher than in lymphoid cell lines. Biosynthesis of PAF upon challenge by ionophore A23187 could be demonstrated in HL60 and U937 cells. In contrast, lymphoid cell lines were unable to produce PAF. Incubation with [14C]acetate showed incorporation of the label into three main fractions: neutral lipids, phosphatidylcholine and PAF, but the distribution of the label varied depending on the cell line. Significant incorporation into phosphatidylcholine was observed in uninduced myeloid cell lines. A phospholipase A2 acting on 1-O-hexadecyl-2-arachidonoyl-sn-glycero-3-phosphocholine and an acetyl-CoA:lyso-PAF acetyltransferase were expressed in the HL60 cell line and showed variations in specific activity with granulocytic differentiation. In contrast, these enzyme activities were not expressed in Daudi and Jurkat cell lines. These data indicate (1) the occurrence of PAF binding and catabolism in both myeloid and lymphoid cell lines; (2) the restriction of PAF biosynthesis to myeloid cell lines, especially HL60 cells; (3) the occurrence of differentiation-elicited changes in the specific activities of the enzymes involved in PAF biosynthesis by the remodelling pathway; and (4) the central role played by the disposal of lyso-PAF, a product of the phospholipase A2 reaction, in PAF biosynthesis.


Owner Perceptions of Long-Term Systemic Use of Subcutaneous Administration of Polysulfated Glycosaminoglycan.
Polysulfated glycosaminoglycan (PSGAG) is a slow-acting disease-modifying agent used to treat degenerative joint disease. Although labeled for intramuscular use, it is commonly given by owners via a subcutaneous (SC) route. There is little information on adverse events related to SC administration or what other therapies are used concurrently with PSGAG. We hypothesized that SC PSGAG is perceived by owners as having minimal adverse events and that it would most often be given with other therapies. Owners (n = 378) were surveyed about their perceptions regarding SC PSGAG prescribed to dogs at one veterinary rehabilitation clinic. Complete surveys were provided for 69 dogs (two owners had multiple dogs). Overall, 13/69 (18.8%) dogs had an adverse event reported during the use of PSGAG. Most events were considered minor (stomach upset, loose stool, pain at injection site, fear) and did not lead to discontinuation of PSGAG. One dog experienced a moderate adverse event (persistent gastrointestinal symptoms) and one a severe adverse event (thrombocytopenia, bruising), which resolved after discontinuing PSGAG. PSGAG is most commonly administered along with other medications and rehabilitation therapies. The present study demonstrates that SC administration of PSGAG is well tolerated in most of the dogs, with primarily mild, self-resolving adverse events.


Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): study protocol for a randomized phase II trial.
Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control. Survival outcomes for patients with oligometastatic disease treated with SABR appear promising, but conclusions are limited by patient selection, and the lack of adequate controls in most studies. The goal of this multicenter randomized phase II trial is to assess the impact of a comprehensive oligometastatic SABR treatment program on overall survival and quality of life in patients with up to 5 metastatic cancer lesions, compared to patients who receive standard of care treatment alone. After stratification by the number of metastases (1-3 vs. 4-5), patients will be randomized between Arm 1: current standard of care treatment, and Arm 2: standard of care treatment + SABR to all sites of known disease. Patients will be randomized in a 1:2 ratio to Arm 1:Arm 2, respectively. For patients receiving SABR, radiotherapy dose and fractionation depends on the site of metastasis and the proximity to critical normal structures. This study aims to accrue a total of 99 patients within four years. The primary endpoint is overall survival, and secondary endpoints include quality of life, toxicity, progression-free survival, lesion control rate, and number of cycles of further chemotherapy/systemic therapy. This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with oligometastatic disease, and will inform the design of a possible phase III study.


Maternal bisphenol and phthalate urine concentrations and weight gain during pregnancy.
Insufficient or excessive gestational weight gain are associated with increased risks of adverse birth and childhood outcomes. Increasing evidence suggests that exposure to bisphenols and phthalates may disrupt hormonal pathways and thereby influence gestational weight gain. To examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with gestational weight gain. In a population-based prospective cohort study among 1,213 pregnant women, we measured early and mid-pregnancy bisphenol and phthalate urine concentrations. Maternal anthropometrics before pregnancy were obtained by questionnaire and repeatedly measured at our research center during pregnancy. We used linear and logistic regressions to evaluate the associations of bisphenols and phthalates with total and period-specific gestational weight gain. Higher maternal total bisphenols and bisphenol S were associated with a lower total gestational weight gain at nominal level. Stratification by body mass index group showed that higher total bisphenols and bisphenol S were associated with lower total gestational weight gain specifically in normal weight women (respectively -509 g [95% CI -819, -198] and -398 g [95% CI -627, -169]). Each log unit increase in early pregnancy total bisphenol and bisphenol A urine concentrations were associated with lower mid- to late pregnancy gestational weight gain in the whole group (effect estimates -218 g/log unit increase [95% CI -334, -102] and -132 g/log unit increase [95% CI -231, -34], respectively). These associations were independent of mid-pregnancy compounds. Mid-pregnancy bisphenols and phthalates concentrations were not associated with gestational weight gain. Higher maternal bisphenol urine concentrations in early pregnancy may lead to reduced gestational weight in second half of pregnancy. Further research is needed to assess the effects of maternal bisphenols and phthalates urine concentrations on placental and fetal growth and development.


Why is transition between child and adult services a dangerous time for young people with chronic kidney disease? A mixed-method systematic review.
Young people age 14-25 years with chronic kidney disease have been identified as generally having poor health outcomes and are a high-risk group for kidney transplant loss due in part to poor self-management. This raises a key question as to what happens during transition from child to adult services? This paper presents a mixed-method systematic review of health and social care evidence concerning young people with chronic kidney disease transitioning from child to adult health and social care services. Quantitative and qualitative evidence were synthesised in streams followed by an overarching synthesis. Literature searches (2000 to March 2017) were conducted using Pubmed, BioMed Central and Cochrane Library, grey literature sources ZETOC, .gov.uk, third sector organisations, NHS Evidence, SCIE, TRIP, Opengrey. Snowball searching was conducted in the databases Ovid, CINAHL, ISI Web of Science, Scopus and Google Scholar. Of 3,125 records screened, 60 texts were included. We found that while strategies to support transition contained consistent messages, they supported the principle of a health-dominated pathway. Well-being is mainly defined and measured in clinical terms and the transition process is often presented as a linear, one-dimensional conduit. Individual characteristics, along with social, familial and societal relationships are rarely considered. Evidence from young people and their families highlights transition as a zone of conflict between independence and dependency with young people feeling powerless on one hand and overwhelmed on the other. We found few novel interventions and fewer that had been evaluated. Studies were rarely conducted by allied health and social care professionals (e.g. renal social workers and psychologists) as part of multi-disciplinary renal teams. We conclude that there is a lack of good evidence to inform providers of health and social care services about how best to meet the needs of this small but vulnerable cohort.


Efferent projections of neuropeptide Y-expressing neurons of the dorsomedial hypothalamus in chronic hyperphagic models.
The dorsomedial hypothalamus (DMH) has long been implicated in feeding behavior and thermogenesis. The DMH contains orexigenic neuropeptide Y (NPY) neurons, but the role of these neurons in the control of energy homeostasis is not well understood. NPY expression in the DMH is low under normal conditions in adult rodents but is significantly increased during chronic hyperphagic conditions such as lactation and diet-induced obesity (DIO). To understand better the role of DMH-NPY neurons, we characterized the efferent projections of DMH-NPY neurons using the anterograde tracer biotinylated dextran amine (BDA) in lactating rats and DIO mice. In both models, BDA- and NPY-colabeled fibers were limited mainly to the hypothalamus, including the paraventricular nucleus of the hypothalamus (PVH), lateral hypothalamus/perifornical area (LH/PFA), and anteroventral periventricular nucleus (AVPV). Specifically in lactating rats, BDA-and NPY-colabeled axonal swellings were in close apposition to cocaine- and amphetamine-regulated transcript (CART)-expressing neurons in the PVH and AVPV. Although the DMH neurons project to the rostral raphe pallidus (rRPa), these projections did not contain NPY immunoreactivity in either the lactating rat or the DIO mouse. Instead, the majority of BDA-labeled fibers in the rRPa were orexin positive. Furthermore, DMH-NPY projections were not observed within the nucleus of the solitary tract (NTS), another brainstem site critical for the regulation of sympathetic outflow. The present data suggest that NPY expression in the DMH during chronic hyperphagic conditions plays important roles in feeding behavior and thermogenesis by modulating neuronal functions within the hypothalamus, but not in the brainstem.


Public support for air travel restrictions to address COVID-19 or climate change.
An improved understanding of public support is essential to design effective and feasible climate policies for aviation. Our motivation is the contrast between high support for air travel restrictions responding to the COVID-19 pandemic and low support for restrictions to combat climate change. Can the same factors explain individuals' support for restrictive measures across two different problems? Using a survey, we find that largely the same factors explain support. Support increases with expected effectiveness, perceived threat and imminence of the problem, shorter expected duration of the measure, knowledge, and trust, while support decreases with expected negative consequences for self and the poor. When controlling for all perceptions, there is no significant residual difference in support depending on whether the measures address climate change or COVID-19. The level of support differs because COVID-19 is perceived as a more imminent threat, and because measures are expected to be shorter-lasting and more effective.


The effect of health shocks on smoking and obesity.
To investigate whether negative changes in their own health (i.e. health shocks) or in that of a smoking or obese household member, lead smokers to quit smoking and obese individuals to lose weight. The study is informed by economic models ('rational addiction' and 'demand for health' models) which offer hypotheses on the relationship between health shocks and health-related behaviour. Each hypothesis was tested applying a discrete-time hazard model with random effects using up to ten waves of the German Socioeconomic Panel (GSOEP) and statistics on cigarette, food and beverage prices provided by the Federal Statistical Office. Health shocks had a significant positive impact on the probability that smokers quit during the same year in which they experienced the health shock. Health shocks of a smoking household member between year t-2 and t-1 also motivated smoking cessation, although statistical evidence for this was weaker. Health shocks experienced by obese individuals or their household members had, on the other hand, no significant effect on weight loss, as measured by changes in Body Mass Index (BMI). The results of the study suggest that smokers are aware of the risks associated with tobacco consumption, know about effective strategies to quit smoking, and are willing to quit for health-related reasons. In contrast, there was no evidence for changes in health-related behaviour among obese individuals after a health shock.


Reporting of Clinical Trial Interventions Published in Leading Otolaryngology-Head and Neck Surgery Journals.
Randomized controlled trials (RCTs) play a crucial role in advancing patient care within otolaryngology-head and neck surgery (OTL-HNS), yet studies have shown the reporting of these trials needs improvement. Here, we evaluate the completeness of intervention reporting of RCTs in OTL-HNS and evaluate whether the publication of the Template for Intervention Description and Replication (TIDieR) checklist has influenced intervention reporting. Retrospective Cross-Sectional Analysis. We searched PubMed for RCTs published in top OTL-HNS journals in two cohorts, one before the release of the TIDieR and one afterward. A sample of 300 RCTs was randomly selected and screened for inclusion. Once the dataset was finalized, we extracted trial characteristics and assessed each trial's adherence to the TIDieR checklist. We then used descriptive characteristics, a generalized estimated equation, time-series analysis, and a two-sample t test to analyze our data. After screening was completed, 173 RCTs were included in our analysis. Of these RCTs, 103 (59.5%) showed <60% adherence to the TIDieR checklist. We found a slight increase in adherence to TIDieR items after the checklist was released, although this was not statistically significant (P = .91). In addition, we found that trials with a crossover study design or multiple interventions and those that provided a Consolidated Standards for Reporting Trials statement were associated with greater adherence to the TIDieR checklist. The majority of OTL-HNS RCTs included in our analysis showed suboptimal reporting factors related to the TIDieR checklist. Requiring a TIDieR statement and automating the journal requirements process for all OTL-HNS clinical trials would be a worthwhile, efficient approach to improving research quality and ultimately patient care within OTL-HNS. NA Laryngoscope, 130:E507-E514, 2020.


Confocal Raman microscopy for investigating synthesis and characterization of individual optically trapped vinyl-polymerized surfactant particles.
Small polymeric particles are increasingly employed as adsorbent materials, as molecular carriers, as delivery vehicles, and in preconcentration applications. The rational development of these materials requires in situ methods of analysis to characterize their synthesis, structure, and applications. Optical-trapping confocal Raman microscopy is a spectroscopic method capable of acquiring information at several stages of the development of such dispersed particulate materials. In the present study, an example material is developed and tested using confocal Raman microscopy for characterization at each stage of the process. Specifically, the method is used to investigate the synthesis, structure, and applications of individual polymeric surfactant particles produced by the vinyl polymerization of sodium 11-acrylamidoundecanoate (SAAU). The kinetics of polymerization can be monitored over time by measuring the loss of the acrylamide C=C functional groups using confocal Raman microscopy of particles optically trapped by the excitation laser, where, within the limits of detecting the vinyl functional group, the complete polymerization of the SAAU monomer was achieved. The polymerized SAAU particles are spherical, and they exhibit uniform access to water throughout their structure, as tested by the penetration of heavy water (D2O) and collection of spatially resolved Raman spectra from the interior of the particle. These porous particles contain hydrophobic domains that can be used to accumulate molecules for adsorption or carrier applications. This property was tested by using confocal Raman microscopy to measure the accumulation equilibria and kinetics of a model compound, dioxybenzone. The partitioning of this compound into the polymer surfactant could be determined on a quantitative basis using relative scattering cross sections of the SAAU monomer and the adsorbate. The study points out the utility of optical-trapping confocal Raman microscopy for investigating the synthesis, structure, and potential carrier applications of polymeric particle materials.


Detection and Genetic Characterization of Lineage IV Peste Des Petits Ruminant Virus in Kazakhstan.
Peste des petits ruminant (PPR) is endemic in many Asian countries with expansion of the range in recent years including across China during 2013-2014 (OIE, 2014). Till the end of 2014, no cases of PPR virus (PPRV) were officially reported to the Office Internationale des Epizooties (OIE) from Kazakhstan. This study describes for the first time clinicopathological, epidemiological and genetic characterization of PPRV in 3 farm level outbreaks reported for the first time in Zhambyl region (oblast), southern Kazakhstan. Phylogenetic analysis based on partial N gene sequence data confirms the lineage IV PPRV circulation, similar to the virus that recently circulated in China. The isolated viruses are 99.5-99.7% identical to the PPRV isolated in 2014 from Heilongjiang Province in China and therefore providing evidence of transboundary spread of PPRV. There is a risk of further maintenance of virus in young stock despite vaccination of adult sheep and goats, along livestock trade and pastoral routes, threatening both small livestock and endangered susceptible wildlife populations throughout Kazakhstan.


Different approaches for extracting information from the co-occurrence matrix.
In 1979 Haralick famously introduced a method for analyzing the texture of an image: a set of statistics extracted from the co-occurrence matrix. In this paper we investigate novel sets of texture descriptors extracted from the co-occurrence matrix; in addition, we compare and combine different strategies for extending these descriptors. The following approaches are compared: the standard approach proposed by Haralick, two methods that consider the co-occurrence matrix as a three-dimensional shape, a gray-level run-length set of features and the direct use of the co-occurrence matrix projected onto a lower dimensional subspace by principal component analysis. Texture descriptors are extracted from the co-occurrence matrix evaluated at multiple scales. Moreover, the descriptors are extracted not only from the entire co-occurrence matrix but also from subwindows. The resulting texture descriptors are used to train a support vector machine and ensembles. Results show that our novel extraction methods improve the performance of standard methods. We validate our approach across six medical datasets representing different image classification problems using the Wilcoxon signed rank test. The source code used for the approaches tested in this paper will be available at: http://www.dei.unipd.it/wdyn/?IDsezione=3314&IDgruppo_pass=124&preview=.


Office prenatal formula advertising and its effect on breast-feeding patterns.
To compare the effect of formula company-produced materials about infant feeding to breast-feeding promotion materials without formula advertising on breast-feeding initiation and duration. Five hundred forty-seven pregnant women were randomized to receive either formula company (commercial; n = 277) or specially designed (research; n = 270) educational packs about infant feeding at their first prenatal visit. Feeding method was determined at delivery. Breast-feeding duration of the 294 women who chose to breast-feed was ascertained at 2, 6, 12, and 24 weeks. Survival analyses were used to evaluate continuous outcomes, and chi2 and logistic regression analyses were used to evaluate discrete outcomes. Breast-feeding initiation (relative risk [RR] 0.93, 95% confidence interval [CI] 0.61, 1.43) and duration after 2 weeks (hazard ratio 1.19, 95% CI 0.86, 1.64) were not affected. Women in the commercial group were more likely to cease breast-feeding before hospital discharge (RR 5.80, 95% CI 1.25, 54.01) and before 2 weeks (adjusted odds ratio [OR] 1.91, 95% CI 1.02, 3.55). In subgroup analyses, women with uncertain goals for breast-feeding or goals of 12 weeks or less experienced shortened exclusive (hazard ratio 1.53, 95% CI 1.06, 2.21), full (hazard ratio 1.70, 95% CI 1.18, 2.48), and overall (hazard ratio 1.75, 95% CI 1.16, 2.64) breast-feeding duration when exposed to the commercial intervention. Although breast-feeding initiation and long-term duration were not affected, exposure to formula promotion materials increased significantly breast-feeding cessation in the first 2 weeks. Additionally, among women with uncertain goals or breast-feeding goals of 12 weeks or less, exclusive, full, and overall breast-feeding duration were shortened. Educational materials about infant feeding should support unequivocally breast-feeding as optimal nutrition for infants; formula promotion products should be eliminated from prenatal settings.


Causes of Mortality and Lesions Observed Post mortem in European Moles (Talpa europaea) in Cornwall, South-west England.
European moles (Talpa europaea) are a common species in the UK, but there are few published data on the causes of mortality in these animals. An opportunistic post-mortem study was carried out on 44 moles found dead or dying in Cornwall, UK. Assessment of muscle condition and fat reserves, where possible, indicated that most (27 of 37, 73%) were in good nutritive condition. The majority had died of trauma (n = 40, 91%), the principal cause of which was predation (n = 36, 81.8%) by foxes and domestic cats and dogs. The carcases were in a variable state of preservation, but 28 cases were suitable for histopathological examination. This revealed lesions in the lungs of 92.8 % (26 of 28) of the animals. The commonest lesions comprised localized infiltration of the parenchyma by macrophages and eosinophils and in most cases the lesions were unlikely to have been of clinical significance; in two cases they were associated with infection by a parasitic nematode. One mole showed severe pneumonitis and hepatitis caused by infection with Toxoplasma gondii. Adiaspiromycosis was diagnosed in two moles, one by direct microscopical examination of the lung and one by histopathology; the lesions were not considered to be of clinical significance. Severe pleurisy and pericarditis caused by infection with Streptobacillus moniliformis was seen in a mole that had suffered bite wounds to a foot previously. Cholangitis due to infection by a protozoal parasite, provisionally identified as Cyclospora talpae, was a common histopathological finding (11 of 28, 39.3%); infection by the parasite did not appear to affect body condition adversely. Miscellaneous conditions identified were ulcerative dermatitis associated with gram-positive cocci (n = 1), extra medullary haemopoiesis in spleens (six of 12, 50%) and mineralized foci in pulmonary blood vessels (three of 28, 10.7%). No significant pathology was seen in the kidneys. This study suggests that the health status of moles in Cornwall is generally good and predation is a common cause of mortality. Pulmonary disease, associated in some cases with nematode infections, is also prevalent, but probably of little clinical significance. There is a high prevalence of cholangitis due to infection with a protozoan parasite believed to be C. talpae. Other diseases identified include adiaspiromycosis, streptobacillosis and toxoplasmosis.


Cost-effectiveness of total hip arthroplasty versus resurfacing arthroplasty: economic evaluation alongside a clinical trial.
To report on the relative cost-effectiveness of total hip arthroplasty and resurfacing arthroplasty (replacement of articular surface of femoral head only) in patients with severe arthritis suitable for hip joint resurfacing arthroplasty. Cost-effectiveness analysis on an intention-to-treat basis of a single-centre, single-blind randomised controlled trial of 126 adult patients within 12 months of treatment. Missing data were imputed using multiple imputations with differences in baseline quality of life and gender adjusted using regression techniques. A large teaching hospital trust in the UK. A total of 126 adult patients with severe arthritis of the hip joint suitable for a resurfacing arthroplasty of the hip. Data were received for 126 patients, 4 of whom did not provide any resource use data. For the remainder, data were imputed for costs or quality of life in at least one time point (baseline, 3, 6 months and 1 year) for 18 patients. Patients in the resurfacing arm had higher quality of life at 12 months (0.795 vs 0.727) and received 0.032 more QALYs within the first 12 months postoperation. At an additional cost of £564, resurfacing arthroplasty offers benefits at £17 451 per QALY within the first 12 months of treatment. When covariates are considered, the health economic case is stronger in men than in women. Resurfacing arthroplasty appears to offer very short-term efficiency benefits over total hip arthroplasty within a selected patient group. The short-term follow-up in this trial should be noted, particularly in light of the concerns raised regarding adverse reactions to metal debris from metal-on-metal bearing surfaces in the longer term. Longer-term follow-up of resurfacing arthroplasty patients and decision analytic modelling is also advised. Current controlled Trials ISRCTN33354155. UKCRN 4093.


A Hybrid Textile Electrode for Electrocardiogram (ECG) Measurement and Motion Tracking.
Wearable sensors have great potential uses in personal health monitoring systems, in which textile-based electrodes are particularly useful because they are comfortable to wear and are skin and environmentally friendly. In this paper, a hybrid textile electrode for electrocardiogram (ECG) measurement and motion tracking was introduced. The hybrid textile electrode consists of two parts: A textile electrode for ECG monitoring, and a motion sensor for patient activity tracking. In designing the textile electrodes, their performance in ECG measurement was investigated. Two main influencing factors on the skin-electrode impedance of the electrodes were found: Textile material properties, and electrode sizes. The optimum textile electrode was silver plated, made of a high stitch density weft knitted conductive fabric and its size was 20 mm × 40 mm. A flexible motion sensor circuit was designed and integrated within the textile electrode. Systematic measurements were performed, and results have shown that the hybrid textile electrode is capable of recording ECG and motion signals synchronously, and is suitable for ambulatory ECG measurement and motion tracking applications.


Discriminating signal from noise: recognition of a movement-based animal display by artificial neural networks.
In this study, we investigated the feasibility of applying neural networks to understanding movement-based visual signals. Networks based on three different models were constructed, varying in their input format and network architecture: a Static Input model, a Dynamic Input model and a Feedback model. The task for all networks was to distinguish a lizard (Amphibolurus muricatus) tail-flick from background plant movement. Networks based on all models were able to distinguish the two types of visual motion, and generalised successfully to unseen exemplars. We used curves defined by the receiver-operating characteristic (ROC) to select a single network from each model to be used in regression analyses of network response and several motion variables. Collectively, the models predicted that tail-flick efficacy would be enhanced by faster speeds, greater acceleration and longer durations.


Chromatographic preparation of a therapeutic highly purified von Willebrand factor concentrate from human cryoprecipitate.
A therapeutic highly purified von Willebrand factor (vWF) concentrate has been prepared from cryoprecipitate by a three-step chromatographic procedure. After solvent/detergent treatment to inactivate viruses, the cryoprecipitate solution was chromatographed on DEAE-fractogel TSK 650 M to separate vWF from most cryoprecipitate proteins, including factor VIII (FVIII) and fibrinogen. A second DEAE-fractogel TSK 650 M was then performed to further purify vWF and to allow concentrating it to over 100 U ristocetin cofactor activity/ml. The last step on immobilized gelatin removed fibronectin and increased the purity of vWF. vWF was recovered with about 18 and 40% yield in antigen and collagen-binding (CB) activity, respectively, from cryoprecipitate. vWF was obtained in an essentially pure state corresponding to a purification factor of over 10,000-fold from plasma. Immunonephelometric and SDS-PAGE analyses of the concentrate did not reveal any detectable cryoprotein contaminants, especially fibrinogen, fibronectin, immunoglobulins and albumin. The content in intermediate- and high-molecular-weight multimers in the concentrate was similar or higher than that of plasma, as the ion-exchanger selectively favored the binding and concentration of the larger multimeric forms while reducing the amount of the smaller forms with abnormal structure and low activity. Other characteristics of the concentrate included a CB activity to antigen ratio of 1.69 and a high capacity (86%) to correct platelet adhesion in a perfusion system. Clinical use of this standardized vWF concentrate has been shown to be efficacious in the treatment of vWF patients.


Structurally tunable resonant absorption bands in ultrathin broadband plasmonic absorbers.
Light absorption is a fundamental optical process playing significantly important role in wide variety of applications ranging from photovoltaics to photothermal therapy. Semiconductors have well-defined absorption bands with low-energy edge dictated by the band gap energy, therefore it is rather challenging to tune the absorption bandwidth of semiconductors. However, resonant absorbers based on plasmonic nanostructures and optical metamaterials emerged as alternative light absorbers due to spectrally selective absorption bands resulting from optical resonances. Recently, a broadband plasmonic absorber design was introduced by Aydin et al. with a reasonably high broadband absorption. Based on that design, here, structurally tunable, broadband absorbers with improved performance are demonstrated. This broadband absorber has a total thickness of 190 nm with 80% average measured absorption (90% simulated absorption) over the entire visible spectrum (400 - 700 nm). Moreover, the effect of the metal and the oxide thicknesses on the absorption spectra are investigated and results indicate that the shorter and the longer band-edge of broadband absorption can be structurally tuned with the metal and the oxide thicknesses, as well as with the resonator size. Detailed numerical simulations shed light on the type of optical resonances that contribute to the broadband absorption response and provide a design guideline for realizing plasmonic absorbers with structurally tunable bandwidths.


Self and Informant Memory Reports in FINGER: Associations with Two-Year Cognitive Change.
Subjective memory complaints (SMCs) may be the first sign of cognitive decline in aging. To examine whether SMCs reported by oneself and informant predict cognitive change over 2 years among at-risk elderly people, and to determine the relationship of different types of SMCs (prospective and retrospective memory complaints) and change in cognitive function. This investigation is part of the FINGER project, which is a multicenter randomized controlled trial aiming at preventing cognitive decline in cognitively healthy older adults with increased risk of dementia. A subsample of 303 control-group participants (aged 60-80 years) and their informants (n = 261) rated the frequency of SMCs, using the Prospective and Retrospective Memory Questionnaire (PRMQ). Cognitive performance was measured at baseline and at 1- and 2-year follow-up visits using a neuropsychological test battery. Participants who reported more SMCs improved less in global cognition, executive function, and memory during the subsequent 2 years in the fully-adjusted analyses. Self-reported retrospective memory problems predicted less improvement in all cognitive domains, whereas prospective memory problems did not. Informant-reported memory problems were not linked to subsequent change in cognition. Our results indicate that self-reported SMCs, measured with PRMQ, predict future cognitive change in several cognitive domains. By contrast, reports by informants were not linked to changes in cognition. Among cognitively healthy at-risk elderly individuals, the persons themselves observe more easily problems relevant for their future cognitive trajectories than their informants.


Relative contributions of adiposity in childhood and adulthood to vascular health of young adults.
Vascular damage is suggested to have origins in childhood adiposity, but it is not clear whether this is a direct consequence of being obese in childhood. We aimed to estimate the associations of childhood body size or adiposity with adult vascular health, and to investigate whether these associations were independent of adult body size or adiposity. Subjects were 2328 participants aged 7-15 years at baseline in 1985 with follow-up during 2004-2006 when aged 26-36 years. Anthropometric measures were taken at both baseline and follow-up. Carotid intima-media thickness (IMT) and three measures of large artery stiffness (LAS) were measured by ultrasound at follow-up. Childhood body size or adiposity was positively associated with both adult IMT and LAS. Participants who were obese in adulthood had the greatest LAS, particularly those who were normal weight in childhood. Adjustment for adult body size or adiposity eliminated effects of childhood body size or adiposity on LAS. For IMT, adjustment for adult body size or adiposity reduced estimated effects of child height by 44% (male) and 27% (female), of child weight by 46% (male) and 70% (female) and, after adjusting for sex, of child body mass index and body surface area by 60% and 53% respectively. Whereas IMT appeared to be influenced by body size or adiposity during childhood and early adulthood, LAS depended primarily on current adiposity and magnitude of adiposity gain between childhood and adulthood.


Validation and Variation of Upper Layer Thickness in South China Sea from Satellite Altimeter Data.
Satellite altimeter data from 1993 to 2005 has been used to analyze the seasonal variation and the interannual variability of upper layer thickness (ULT) in the South China Sea (SCS). Base on in-situ measurements, the ULT is defined as the thickness from the sea surface to the depth of 16°C isotherm which is used to validate the result derived from satellite altimeter data. In comparison with altimeter and in-situ derived ULTs yields a correlation coefficient of 0.92 with a slope of 0.95 and an intercept of 6 m. The basin averaged ULT derived from altimeter is 160 m in winter and 171 m in summer which is similar to the in-situ measurements of 159 m in winter and 175 m in summer. Both results also show similar spatial patterns. It suggests that the sea surface height data derived from satellite sensors are usable for study the variation of ULT in the semi-closed SCS. Furthermore, we also use satellite derived ULT to detect the development of eddy. Interannual variability of two meso-scale cyclonic eddies and one anticyclonic eddy are strongly influenced by El Niño events. In most cases, there are highly positive correlations between ULT and sea surface temperature except the periods of El Niño. During the onset of El Niño event, ULT is deeper when sea surface temperature is lower.


A Multipurpose, High-Throughput Single-Nucleotide Polymorphism Chip for the Dengue and Yellow Fever Mosquito, Aedes aegypti.
The dengue and yellow fever mosquito, Aedes aegypti, contributes significantly to global disease burden. Genetic study of Aedes aegypti is essential to understanding its evolutionary history, competence as a disease vector, and the effects and efficacy of vector control methods. The prevalence of repeats and transposable elements in the Aedes aegypti genome complicates marker development and makes genome-wide genetic study challenging. To overcome these challenges, we developed a high-throughput genotyping chip, Axiom_aegypti1. This chip screens for 50,000 single-nucleotide polymorphisms present in Aedes aegypti populations from around the world. The array currently used genotypes 96 samples simultaneously. To ensure that these markers satisfy assumptions commonly made in many genetic analyses, we tested for Mendelian inheritance and linkage disequilibrium in laboratory crosses and a wild population, respectively. We have validated more than 25,000 of these markers to date, and expect this number to increase with more sampling. We also present evidence of the chip's efficacy in distinguishing populations throughout the world. The markers on this chip are ideal for applications ranging from population genetics to genome-wide association studies. This tool makes rapid, cost-effective, and comparable genotype data attainable to diverse sets of Aedes aegypti researchers, from those interested in potential range shifts due to climate change to those characterizing the genetic underpinnings of its competence to transmit disease.


Asteroid 1986 DA: Radar Evidence for a Metallic Composition.
Echoes from the near-Earth object 1986 DA show it to be significantly more reflective than other radar-detected asteroids. This result supports the hypothesis that 1986 DA is a piece of NiFe metal derived from the interior of a much larger object that melted, differentiated, cooled, and subsequently was disrupted in a catastrophic collision. This 2-kilometer asteroid, which appears smooth at centimeter to meter scales but extremely irregular at 10- to 100-meter scales, might be (or have been a part of the parent body of some iron meteorites.


IL-10 plays an important role in the control of inflammation but not in the bacterial burden in S. epidermidis CNS catheter infection.
Shunt infection is a frequent and serious complication in the surgical treatment in hydrocephalus. Previous studies have shown an attenuated immune response to these biofilm-mediated infections. We proposed that IL-10 reduces the inflammatory response to Staphylococcus epidermidis (S. epidermidis) CNS catheter infection. In this study, a murine model of catheter-associated S. epidermidis biofilm infection in the CNS was generated based on a well-established similar model for S. aureus. The catheters were pre-coated with a clinically derived biofilm-forming strain of S. epidermidis (strain 1457) which were then stereotactically implanted into the lateral left ventricle of 8-week-old C57BL/6 and IL-10 knockout (IL-10 knockout) mice. Bacterial titers as well as cytokine and chemokine levels were measured at days 3, 5, 7, and 10 in mice implanted with sterile and S. epidermidis-coated catheters. Cultures demonstrated a catheter-associated and parenchymal infection that persisted through 10 days following infection. Cytokine analysis of the tissue surrounding the catheters revealed greater levels of IL-10, an anti-inflammatory cytokine, in the infected group compared to the sterile. In IL-10 KO mice, we noted no change in bacterial burdens, showing that IL-10 is not needed to control the infection in a CNS catheter infection model. However, IL-10 KO mice had increased levels of pro-inflammatory mediators in the tissues immediately adjacent to the infected catheter, as well as an increase in weight loss. Together our results indicate that IL-10 plays a key role in regulating the inflammatory response to CNS catheter infection but not in control of bacterial burdens. Therefore, IL-10 may be a useful therapeutic target for immune modulation in CNS catheter infection but this should be used in conjunction with antibiotic therapy for bacterial eradication.


The biological and ethical basis of the use of human embryonic stem cells for in vitro test systems or cell therapy.
Human embryonic stem cells (hESC) are now routinely cultured in many laboratories, and differentiation protocols are available to generate a large variety of cell types. In an ongoing ethical debate opinions of different groups are based on varying sets of religious, historical, cultural and scientific arguments as well as on widely differing levels of general information. We here give an overview of the biological background for non-specialists, and address all is- sues of the current stem cell debate that are of concern in different cultures and states. Thirty-five chapters address embryo definition, potential killing and the beginning of human life, in addition to matters of human dignity, patenting, commercialisation, and potential alternatives for the future, such as induced pluripotent (reprogrammed) stem cells. All arguments are compiled in a synopsis, and compromise solutions, e.g. for the definition of the beginning of personhood and for assigning dignity to embryos, are suggested. Until recently, the major application of hESC was thought to be transplantation of cells derived from hESC for therapeutic use. We discuss here that the most likely immediate uses will rather be in vitro test systems and disease models. Major and minor pharmaceutical companies have entered this field, and the European Union is sponsoring academic research into hESC-based innovative test systems. This development is supported by new testing strategies in Europe and the USA focussing on human cell-based in vitro systems for safety evaluations, and shifting the focus of toxicology away from classical animal experiments towards a more mechanistic understanding.


Big Data Clinical Research: Validity, Ethics, and Regulation.
Electronic Health Records (EHR) promise improvement for patient care and also offer great value for biomedical research including clinical, public health, and health services research. Unfortunately, the full potential of EHR big data research has remained largely unrealized. The purpose of this study was to identify rate limiting factors, and develop recommendations to better balance unrestricted extramural EHR access with legitimate safeguarding of EHR data in retrospective research. By exploring primary, secondary, and tertiary sources, this review identifies external constraints and provides a comparative analysis of social influencers in retrospective EHR-based research. Results indicate that EHRs have the advantage of reflecting the reality of patient care but also show a frequency of between 4.3-86% of incomplete and inaccurate data in various fields. The rapid spread of alternative analytics for health data challenges traditional interpretations of confidentiality protections. A confusing multiplicity of controls creates barriers to big data EHR research. More research on the use of EHR big data is likely to improve accuracy and validity. Information governance and research approval processes should be simplified. Comprehensive regulatory policies that do not exclusively cover health care entities, are needed. Finally, new computing safeguards are needed to address public concerns, like research access only to aggregate data and not to individually identifiable information.