Reaching out or missing out: approaches to outreach with family carers in social care organisations.
Outreach is advocated as a way of improving the uptake of services among underserved populations and of filling the gaps between mainstream services and the populations they are intended to support. Despite the policy emphasis on providing better help for family carers, research consistently shows that many of those providing unpaid care to a family member or friend report difficulties in finding out about the assistance to which they are entitled. This article presents results from a concurrent mixed-methods study, which aimed to describe different ways of working with family carers in adult social care departments and to collect the views of a range of stakeholders about the advantages and disadvantages of the approaches that were identified. A total of 86 semi-structured face-to-face interviews were undertaken with a purposive sample of funders, carers' workers, representatives of voluntary organisations and family carers based in four contrasting localities. An email survey was sent to all local councils in England with social care responsibilities and resulted in a 53% response rate. Data collection took place in 2012, with a small number of interviews being completed in 2011. Our approach to data analysis combined methodological, data and theoretical triangulation. The findings presented here mainly draw on the interview data to highlight the different models of outreach that we identified. The article highlights important differences between outreach and the provision of information. It concludes that organisations providing support for carers need to consider the advantages and disadvantages of different models of outreach as they develop carers' support and the extent to which different models might be more effective than others in reaching particular types of carer.


EEG-informed fMRI analysis during a hand grip task.
In the last decade, an increasing interest has arisen in investigating the relationship between the electrophysiological and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI. In particular, changes in BOLD have been shown to be associated with changes in the spectral profile of neuronal activity, rather than with absolute neural power. On the other hand, though, recent findings showed that different EEG rhythms are independently related to changes in the BOLD signal: therefore, it would be important to distinguish between the contributions of the different EEG rhythms to BOLD fluctuations when modeling the relationship between EEG and BOLD. Here we proposed a novel method to perform EEG-informed fMRI analysis, so that the EEG regressors take into account both the changes in the spectral profile and the rhythms distinction. We applied it to EEG-fMRI data during a bimanual motor task in healthy subjects, and compared the results with those obtained by regressing fMRI data onto a single regressor covering the entire range of frequencies, ignoring the distinction between different EEG rhythms. Our results showed that the proposed method better captures the correlations between BOLD signal and EEG rhythms modulations, identifying task-related well localized activated volumes.


Absence of duplication of chromosome 21 genes in familial and sporadic Alzheimer's disease.
The possibility that Alzheimer's disease (AD) is caused by overexpression or duplication of one or more genes on chromosome 21 has been raised by the observation of AD-like neuropathologic changes in individuals with Down syndrome and by the mapping of both the defect for familial AD and the amyloid beta protein gene to this autosome. Possible duplication on chromosome 21 was investigated in both familial and sporadic AD by means of restriction fragment length polymorphisms for the amyloid and SODI loci, as well as for DNA markers in the vicinity of the familial AD defect and in the critical Down syndrome region of chromosome 21. No evidence of increased DNA dosage was observed in either brain or leukocytes of patients with inherited or sporadic forms of AD. Duplication of these regions is therefore not a frequent event in either form of AD. Furthermore, no significant allelic association was detected between AD and any of the loci, including the amyloid and SODI genes, providing no support for the hypothesis that defects in these specific genes are the primary cause of AD.


Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells.
The debate about possible adverse effects of bisphenol A (BPA) has been ongoing for decades. Bisphenol F (BPF) and S (BPS) have been suggested as "safer" alternatives. In the present study we used hepatocyte-like cells (HLCs) derived from the human embryonic stem cell lines Man12 and H9 to compare the three bisphenol derivatives. Stem cell-derived progenitors were produced using an established system and were exposed to BPA, BPF and BPS for 8 days during their transition to HLCs. Subsequently, we examined cell viability, inhibition of cytochrome P450 (CYP) activity, and genome-wide RNA profiles. Sub-cytotoxic, inhibitory concentrations (IC50) of CYP3A were 20, 9.5 and 25 µM for BPA, BPF and BPS in Man12 derived HLCs, respectively. The corresponding concentrations for H9-derived HLCs were 19, 29 and 31 µM. These IC50 concentrations were used to study global expression changes in this in vitro study and are higher than unconjugated BPA in serum of the general population. A large overlap of up- as well as downregulated genes induced by the three bisphenol derivatives was seen. This is at least 28-fold higher compared to randomly expected gene expression changes. Moreover, highly significant correlations of expression changes induced by the three bisphenol derivatives were obtained in pairwise comparisons. Dysregulated genes were associated with reduced metabolic function, cellular differentiation, embryonic development, cell survival and apoptosis. In conclusion, no major differences in cytochrome inhibitory activities of BPA, BPF and BPS were observed and gene expression changes showed a high degree of similarity.


MR Findings of Fungus Ball: Significance of High Signal Intensity on T1-Weighted Images.
Central dark-signal intensity with high-signal, hypertrophic mucosal wall of paranasal sinuses on T2-weighted images (T2WI) is a characteristic magnetic resonance imaging (MRI) feature of sinonasal fungus ball. However, this finding is usually interpreted as non-fungal chronic sinusitis with central normal sinus air. In addition, T1-weighted images (T1WI) and T2WI are basic sequences of all magnetic resonance (MR) examinations. Therefore, we evaluated the usefulness of T1WI for detecting fungus balls comparing with computed tomography (CT) findings and T2-weighted MRI findings. This retrospective study was approved by the Institutional Review Board of Korea University Guro Hospital. Two reviewers assessed preoperative CT and MR images of 55 patients with pathologically confirmed fungus balls. Reviewers evaluated the presence and patterns of calcifications on CT. Overall signals and the presence and extent of certain signals of fungus balls on MRI were also assessed. The relationship between calcifications and MRI signals was also evaluated. Of the patients, 89.1% had calcifications on CT. All had dark signal portions with high signal, hypertrophic mucosal walls on T2WI. Most (92.7%) patients showed iso- to hyper-intense overall signals on T1WI and 89.1% had T1-weighted high signal portions on MRI. The presence, patterns, and location of calcifications had no significant correlation with T1-weighted high-signal intensity portion. Fungus ball can be suggested by the presence of the hyper-signal intensity portions in the fungal mass on T1WI in conjunction with dark-signal lesions surrounded by high-signal, hypertrophic mucosal walls in paranasal sinuses on T2WI.


Combination therapy with a second-generation androgen receptor antagonist and a metastasis vaccine improves survival in a spontaneous prostate cancer model.
Enzalutamide, a second-generation androgen antagonist, was approved by the U.S. Food and Drug Administration (FDA) for castration-resistant prostate cancer (CRPC) treatment. Immunotherapy has been shown to be a promising strategy for prostate cancer. This study was performed to provide data to support the combination of enzalutamide and immunotherapy for CRPC treatment. Male C57BL/6 or TRAMP (transgenic adenocarcinoma of the mouse prostate) prostate cancer model mice were exposed to enzalutamide and/or a therapeutic vaccine targeting Twist, an antigen involved in epithelial-to-mesenchymal transition and metastasis. The physiologic and immunologic effects of enzalutamide were characterized. The generation of Twist-specific immunity by Twist-vaccine was assessed. Finally, the combination of enzalutamide and Twist-vaccine to improve TRAMP mice overall survival was evaluated. Enzalutamide mediated immunogenic modulation in TRAMP-C2 cells. In vivo, enzalutamide mediated reduced genitourinary tissue weight, enlargement of the thymus, and increased levels of T-cell excision circles. Because no changes were seen in T-cell function, as determined by CD4(+) T-cell proliferation and regulatory T cell (Treg) functional assays, enzalutamide was determined to be immune inert. Enzalutamide did not diminish the ability of Twist-vaccine to generate Twist-specific immunity. Twist was confirmed as a valid tumor antigen in TRAMP mice by immunohistochemistry. The combination of enzalutamide and Twist-vaccine resulted in significantly increased overall survival of TRAMP mice compared with other treatment groups (27.5 vs. 10.3 weeks). Notably, the effectiveness of the combination therapy increased with disease stage, i.e., the greatest survival benefit was seen in mice with advanced-stage prostate tumors. These data support the combination of enzalutamide and immunotherapy as a promising treatment strategy for CRPC. Clin Cancer Res; 19(22); 6205-18. ©2013 AACR.


Ecological models in support of regulatory risk assessments of pesticides: developing a strategy for the future.
This brief communication reports on the main findings of the LEMTOX workshop, held from 9 to 12 September 2007, at the Helmholtz Centre for Environmental Research (UFZ) in Leipzig, Germany. The workshop brought together a diverse group of stakeholders from academia, regulatory authorities, contract research organizations, and industry, representing Europe, the United States, and Asia, to discuss the role of ecological modeling in risk assessments of pesticides, particularly under the European regulatory framework. The following questions were addressed: What are the potential benefits of using ecological models in pesticide registration and risk assessment? What obstacles prevent ecological modeling from being used routinely in regulatory submissions? What actions are needed to overcome the identified obstacles? What recommendations should be made to ensure good modeling practice in this context? The workshop focused exclusively on population models, and discussion was focused on those categories of population models that link effects on individuals (e.g., survival, growth, reproduction, behavior) to effects on population dynamics. The workshop participants concluded that the overall benefits of ecological modeling are that it could bring more ecology into ecological risk assessment, and it could provide an excellent tool for exploring the importance of, and interactions among, ecological complexities. However, there are a number of challenges that need to be overcome before such models will receive wide acceptance for pesticide risk assessment, despite having been used extensively in other contexts (e.g., conservation biology). The need for guidance on Good Modeling Practice (on model development, analysis, interpretation, evaluation, documentation, and communication), as well as the need for case studies that can be used to explore the added value of ecological models for risk assessment, were identified as top priorities. Assessing recovery potential of exposed nontarget species and clarifying the ecological relevance of standard laboratory test results are two areas for which ecological modeling may be able to provide considerable benefits.


Thymus Regeneration and Future Challenges.
Thymus regenerative therapy implementation is severely obstructed by the limited number and expansion capacity in vitro of tissue-specific thymic epithelial stem cells (TESC). Current solutions are mostly based on growth factors that can drive differentiation of pluripotent stem cells toward tissue-specific TESC. Target-specific small chemical compounds represent an alternative solution that could induce and support the clonal expansion of TESC and reversibly block their differentiation into mature cells. These compounds could be used both in the composition of culture media designed for TESC expansion in vitro, and in drugs development for thymic regeneration in vivo. It should allow reaching the ultimate objective - autologous thymic tissue regeneration in paediatric patients who had their thymus removed in the course of cardiac surgery.


Geophysicists in moscow: signs of easier relations.
Science editor Philip H. Abelson attended the 15th general assembly of the International Union of Geodesy and Geophysics in Moscow on 1 through 14 August. There he served as principal U.S. delegate to the International Association of Volcanology and Chemistry of the Earth's Interior. In preparing the following notes for publication, he checked his own impressions extensively against those of American scientists who participated in other sections of the meeting, and against the impressions of those who visited scientific institutions in the Moscow region.


Nanoelectromagnetic of the N-doped single wall carbon nanotube in the extremely high frequency band.
Materials offering excellent mechanical flexibility, high electrical conductivity and electromagnetic interference (EMI) attenuation with minimal thickness are in high demand, particularly if they can be easily processed into films. Carbon nanotube films deposited on a PDMS substrate combine these requirements. In this work, the potential of single wall carbon nanotubes (SWCNT) deposited on flexible polydimethylsiloxane (PDMS) polymer substrates for EMI attenuation is demonstrated. A 6-micrometer-thick SWCNT film exhibits EMI shielding effectiveness of 24.5 decibels in the extreme high frequency band (EHF), reaching 40 decibels when the SWCNTs are N-doped, which is one of the highest specific EMI attenuation performances optimized with film thickness realized to date. This performance stems from the good electrical conductivity of N-SWCNT films (150 Siemens per centimeter) and possible internal multireflections within the SWCNTs network. The excellent mechanical flexibility and easy coating processing enable them to sheathe complex shaped surfaces while providing high electromagnetic interference attenuation efficiency.


Henneguya cuniculator sp. nov., a parasite of spotted sorubim Pseudoplatystoma corruscans in the São Francisco Basin, Brazil.
Henneguya cuniculator sp. nov. was found infecting spotted sorubim catfish Pseudoplatystoma corruscans from the São Francisco River, Minas Gerais, Brazil. The parasites form elongated plasmodia of up to 1 cm in length in the gill filaments. Mature spores were ellipsoidal from the frontal view, with total length of 29.4 ± 2.4 (mean ± SD, range 23.3-32.4) µm, body length of 12.1 ± 1.0 (10.0-14.7) µm, width of 4.8 ± 0.4 (4.0-5.9) µm, and tail length of 16.7 ± 2.0 (12.3-19.4) µm. From the lateral view, spores were biconvex, with thickness of 4.2 ± 0.7 (3.9-4.9) µm. The polar capsules were elongated and equal in size, 6.2 ± 0.3 (5.2-6.2) µm in length, and 1.8 ± 0.1 (1.4-1.9) µm in width. Ultrastructural analysis showed that the plasmodial wall had delicate projections towards the host tissue and a thin layer that prevented contact between the host cells and the parasite. In the ectoplasm, few mitochondria were observed, while generative cells, early stages of sporogenesis, and advanced spore development occurred in the plasmodial periphery, and more mature spores in internal regions. Histopathological analysis showed that plasmodia developed in the sub-epithelial connective tissue of gill filaments, causing compression of the adjacent tissues, deformation of gill filaments, and lamellar fusion. Phylogenetic analysis, based on 18S rDNA genes and using only Henneguya/Myxobolus species parasites of siluriform fish, showed grouping according to the fish family.


Novel decapeptides that bind avidly and deliver radioisotope to colon cancer cells.
The rapidly growing field of targeted tumor therapy often utilizes an antibody, sometimes tagged with a tumor-ablating material such as radioisotope, directed against a specific molecule. This report describes the discovery of nine novel decapeptides which can be radioactively labeled, bind to, and deliver (32)P to colon cancer cells. The decapeptides vary from one another by one to three amino acids and demonstrate vastly different binding abilities. The most avidly binding decapeptide can permanently deliver very high levels of radioisotope to the adenocarcinoma cancer cell lines at an efficiency 35 to 150 times greater than to a variety of other cell types, including cell lines derived from other types of cancer or from normal tissue. This experimental approach represents a new example of a strategy, termed peptide binding therapy, for the potential treatment of colorectal and other adenocarcinomas.


FixingTIM: interactive exploration of sequence and structural data to identify functional mutations in protein families.
Knowledge of the 3D structure and functionality of proteins can lead to insight into the associated cellular processes, speed up the creation of pharmaceutical products, and develop drugs that are more effective in combating disease. We present the design and implementation of a visual mining and analysis tool to help identify protein mutations across a family of structural models and to help discover the effect of these mutations on protein function. We integrate 3D structure and sequence information in a common visual interface; multiple linked views and a computational backbone allow comparison at the molecular and atomic levels, while a novel trend-image visual abstraction allows for the sorting and mining of large collections of sequences and of their residues. We evaluate our approach on the triosephosphate isomerase (TIM) family structural models and sequence data and show that our tool provides an effective, scalable way to navigate a family of proteins, as well as a means to inspect the structure and sequence of individual proteins. The TIM application shows that our tool can assist in the navigation of families of proteins, as well as in the exploration of individual protein structures. In conjunction with domain expert knowledge, this interactive tool can help provide biophysical insight into why specific mutations affect function and potentially suggest additional modifications to the protein that could be used to rescue functionality.


Intravenous fat emulsion as treatment for ivermectin toxicosis in three dogs homozygous for the ABCB1-1Δ gene mutation.
To describe the outcome of 3 cases of ivermectin toxicosis in dogs homozygous for the ABCB1-1Δ gene mutation treated with intravenous fat emulsion (IFE). One Australian Shepherd and 2 Miniature Australian Shepherds were treated for naturally occurring ivermectin toxicosis with IFE. All 3 dogs were homozygous for the ABCB1-1Δ gene mutation. Serum ivermectin concentrations confirmed ivermectin exposure in each case. All 3 dogs exhibited tremors, ptyalism, and central nervous system depression, which progressed over several hours to stupor in 2 dogs, and to a comatose state requiring mechanical ventilation in the remaining dog. A 20% formulation of IFE(a) was administered as an IV bolus (1.5 mL/kg) followed by a slow IV infusion (7.5-15 mL/kg [0.25-0.5 mL/kg/m], over 30 minutes). No change was observed in the neurologic status of any patient. Lipemia visible upon blood sampling persisted for 36 hours in 1 dog however, no other adverse effects were noted. Flumazenil (0.01 mg/kg IV), followed by a constant rate infusion(CRI) of 0.01 mg/kg/h IV was administered in 1 case, without any apparent clinical benefit or adverse effect. IFE was ineffective in the treatment of ivermectin toxicosis in these ABCB1-1Δ homozygous mutant dogs. Further investigation is necessary to determine why IFE treatment was unsuccessful in these cases and whether its use can be optimized to yield better results.


Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection.
Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. By combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.


Linking allergy to autoimmune disease.
Type I allergy is a classical Th2-driven hypersensitivity disease based on IgE recognition of environmental allergens. Exposure of allergic individuals to exogenous allergens leads to immediate type inflammation caused by degranulation of mast cells via IgE-allergen immune complexes and the release of inflammatory mediators, proteases and pro-inflammatory cytokines. However, allergic inflammation can occur and persist in the absence of exposure to exogenous allergens and might paradoxically resemble a Th1-mediated chronic inflammatory reaction. We summarize evidence supporting the view that autoimmune mechanisms might contribute to these processes. IgE recognition of autoantigens might augment allergic inflammation in the absence of exogenous allergen exposure. Moreover, autoantigens that activate Th1-immune responses could contribute to chronic inflammation in allergy, thus linking allergy to autoimmunity.


Estimating two-stage models for genetic influences on alcohol, tobacco or drug use initiation and dependence vulnerability in twin and family data.
Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions, recovery of simulated genetic and environmental correlations becomes possible. Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.


Laparohysteroscopy in female infertility: A diagnostic cum therapeutic tool in Indian setting.
To evaluate the role of laparohysteroscopy in female infertility andto study the effect of therapeutic procedures in achieving fertility. Patients with female infertility presenting to outpatient Department of Obstetrics and Gynecology were evaluated over a period of 18 months. Fifty consenting subjects excluding male factor infertility with normal hormonal profile and no contraindication to laparoscopy were subject to diagnostic laparoscopy and hysteroscopy. T-test. We studied 50 patients comprising of 24 (48%) cases of primary infertility and 26 (52%) patients of secondary infertility. The average age of active married life for 50 patients was between 8 and 9 years. In our study, the most commonly found pathologies were PCOD, endometroisis and tubal blockage. 11 (28.2) patients conceived after laparohysteroscopy followed by artificial reproductive techniques. This study demonstrates the benefit of laparohysteroscopy for diagnosis and as a therapeutic tool in patients with primary and secondary infertility. We were able to achieve a higher conception rate of 28.2%.


A conserved alpha-herpesvirus protein necessary for axonal localization of viral membrane proteins.
Pseudorabies virus, an alpha-herpesvirus, is capable of infecting the nervous system and spreading between synaptically connected neurons in diverse hosts. At least three viral membrane proteins (gE, gI, and Us9) are necessary for the spread of infection from presynaptic to postsynaptic neurons (anterograde spread) in infected rodents. To understand how these proteins effect anterograde spread between neurons, we analyzed the subcellular localization of viral proteins after infection of cultured rat sympathetic neurons with wild-type or mutant viruses. After Us9-null mutant infections but not gE-null mutant infections, only a subset of the viral structural proteins had entered axons. Surprisingly, capsid and tegument proteins but not viral membrane proteins were detected in axons. The spread of Us9 missense mutants in the rodent nervous system correlated with the amount of viral membrane proteins localized to axons. We conclude that the Us9 membrane protein controls axonal localization of diverse viral membrane proteins but not that of capsid or tegument proteins. The data support a model where virion subassemblies but not complete virions are transported in the axon. Our results provide new insight into the process of virion assembly and exit from neurons that leads to directional spread of herpesviruses in the nervous system.


Characteristics of online treatment seekers interested in a text messaging intervention for problem drinking: adults 51 and older versus middle-aged and younger adults.
According to the Institute of Medicine, the vast older adult population is estimated to have mental health and substance use disorders at unprecedented rates and will place high demand on an unprepared healthcare system. Online and mobile health interventions, such as text messaging, could provide an alternative form of frontline intervention that could alleviate some of the burden on the healthcare system; however, it remains unknown what are characteristics of adults over 50 who might be interested in a mobile health behavioral intervention and how they may differ from their younger counterparts. To explore the characteristics of those interested in a text messaging intervention by age, we examined screening data for a randomized controlled trial testing a text messaging intervention to reduce drinking among 1,128 hazardous and problem drinkers, aged 21-30, 31-50, and 51 and older. Participants were recruited online through website advertising on alcoholscreening.org and moderationmanagement.org. Results demonstrated that over a quarter of individuals pursuing online and/or text messaging treatment were 51 and older. These participants reported heavy drinking, with significantly greater number of days drinking and binge drinking than the younger groups, but with fewer consequences. Across age groups, a vast majority of participants were female. Findings demonstrate that a group of adult heavy drinkers 51 and older already pursue online treatment and are interested in using a text messaging intervention to help them reduce drinking, suggesting an avenue to engage this population using an alternative frontline treatment.


Environmental DNA reflects spatial and temporal jellyfish distribution.
Recent development of environmental DNA (eDNA) analysis allows us to survey underwater macro-organisms easily and cost effectively; however, there have been no reports on eDNA detection or quantification for jellyfish. Here we present the first report on an eDNA analysis of marine jellyfish using Japanese sea nettle (Chrysaora pacifica) as a model species by combining a tank experiment with spatial and temporal distribution surveys. We performed a tank experiment monitoring eDNA concentrations over a range of time intervals after the introduction of jellyfish, and quantified the eDNA concentrations by quantitative real-time PCR. The eDNA concentrations peaked twice, at 1 and 8 h after the beginning of the experiment, and became stable within 48 h. The estimated release rates of the eDNA in jellyfish were higher than the rates previously reported in fishes. A spatial survey was conducted in June 2014 in Maizuru Bay, Kyoto, in which eDNA was collected from surface water and sea floor water samples at 47 sites while jellyfish near surface water were counted on board by eye. The distribution of eDNA in the bay corresponded with the distribution of jellyfish inferred by visual observation, and the eDNA concentration in the bay was ~13 times higher on the sea floor than on the surface. The temporal survey was conducted from March to November 2014, in which jellyfish were counted by eye every morning while eDNA was collected from surface and sea floor water at three sampling points along a pier once a month. The temporal fluctuation pattern of the eDNA concentrations and the numbers of observed individuals were well correlated. We conclude that an eDNA approach is applicable for jellyfish species in the ocean.


Lipoprotein (a) concentrations as risk indicators for atherosclerosis.
The plasma concentration of different lipoproteins were measured in 102 control children, in 42 children with a parent suffering from coronary heart disease (CHD), and in 50 children with a parent with cerebrovascular disease (CVD). Significant differences between controls and children in the other two groups were found for apolipoprotein A I, apolipoprotein B, and high density lipoprotein-cholesterol. Children of parents with CHD differed from controls in total cholesterol and apolipoprotein A II concentrations. A highly significant difference furthermore was found in lipoprotein (a) concentrations from children of parents with CHD in comparison with controls, but not between children of parents with CVD and controls. The difference in lipoprotein (a) concentrations (children of parents with CHD compared with controls) were only noticed in children above the age of 10 years. This could be explained by the observed rise of lipoprotein (a) between age 2 and 13 years, which was much more pronounced in the group with parents who had CHD. Plasma glycosaminoglycan concentrations were also measured in the three groups. They were significantly higher in children of parents with CHD and CVD compared with controls; they also varied with age.


Digital optical cellular image processor (DOCIP): experimental implementation.
We demonstrate experimentally the concept of the digital optical cellular image processor architecture by implementing one processing element of a prototype optical computer that includes a 54-gate processor, an instruction decoder, and electronic input-output interfaces. The processor consists of a twodimensional (2-D) array of 54 optical logic gates implemented by use of a liquid-crystal light valve and a 2-D array of 53 subholograms to provide interconnections between gates. The interconnection hologram is fabricated by a computer-controlled optical system.


Predictors of vitamin D status and its association with parathyroid hormone in young New Zealand children.
Despite increased awareness of the adverse health effects of low vitamin D status, few studies have evaluated 25-hydroxyvitamin D [25(OH)D] status in young children. We aimed to assess vitamin D status on the basis of 25(OH)D and its relation with parathyroid hormone (PTH) and to identify possible predictors of 25(OH)D status in young children living in a country with minimal vitamin D fortification. Serum 25(OH)D and PTH concentrations were measured in a cross-sectional sample of children aged 12-22 mo [n = 193 for 25(OH)D, n = 144 for PTH] living in Dunedin, New Zealand (latitude: 45 degrees S). Anthropometric, dietary, and sociodemographic data were collected. The majority of children sampled in the summer (94%; 47 of 50) had 25(OH)D >50 nmol/L; however, nearly 80% of children sampled in the winter (43 of 55) had serum concentrations < or =50 nmol/L. In season-adjusted multivariate analysis, breastfeeding and higher levels of education were independently associated with lower 25(OH)D concentrations, whereas male sex and cigarette-smoke exposure were positively associated with 25(OH)D (all P < 0.05). Fractional polynomial regression was used to describe the nonlinear relation between serum PTH and 25(OH)D (P < 0.001). When 25(OH)D concentrations were >60-65 nmol/L, a plateau in PTH was evident. Seasonal variation in 25(OH)D concentration implies that postsummer vitamin D stores were insufficient to maintain status >50 nmol/L year-round. Examination of the predictors of 25(OH)D in our model shows few modifiable risk factors, and thus effective dietary strategies may be required if future research determines that children with 25(OH)D concentrations <50 nmol/L are at significant health risk. This trial was registered at www.actr.org.au as ACTRN12605000487617.


Crystallization of synthetic haemozoin (beta-haematin) nucleated at the surface of lipid particles.
The mechanism of formation of haemozoin, a detoxification by-product of several blood-feeding organisms including malaria parasites, has been a subject of debate; however, recent studies suggest that neutral lipids may serve as a catalyst. In this study, a model system consisting of an emulsion of neutral lipid particles was employed to investigate the formation of beta-haematin, the synthetic counterpart of haemozoin, at the lipid-water interface. A solution of monoglyceride, either monostearoylglycerol (MSG) or monopalmitoylglycerol (MPG), dissolved in acetone and methanol was introduced to an aqueous surface. Fluorescence, confocal and transmission electron microscopic (TEM) imaging and dynamic light scattering analysis of samples obtained from beneath the surface confirmed the presence of homogeneous lipid particles existing in two major populations: one in the low micrometre size range and the other in the hundred nanometre range. The introduction of haem (Fe(iii)PPIX) to this lipid particle system under biomimetic conditions (37 degrees C, pH 4.8) produced beta-haematin with apparent first-order kinetics and an average half life of 0.5 min. TEM of monoglycerides (MSG or MPG) extruded through a 200 nm filter with haem produced beta-haematin crystals aligned and parallel to the lipid-water interface. These TEM data, together with a model system replacing the lipid with an aqueous organic solvent interface using either methyl laurate or docosane demonstrated that the OH and C[double bond, length as m-dash]O groups are apparently necessary for efficient nucleation. This suggests that beta-haematin crystallizes via epitaxial nucleation at the lipid-water interface through interaction of Fe(iii)PPIX with the polar head group. Once nucleated, the crystal grows parallel to the interface until growth is terminated by the curvature of the lipid particle. The hydrophobic nature of the mature crystal favours an interior transport resulting in crystals aligned parallel to the lipid-water interface and each other, strikingly similar to that seen in malaria parasites.


Doing masculinity, not doing health? A qualitative study among Dutch male employees about health beliefs and workplace physical activity.
Being female is a strong predictor of health promoting behaviours. Workplaces show great potential for lifestyle interventions, but such interventions do not necessarily take the gendered background of lifestyle behaviours into account. A perspective analyzing how masculine gender norms affect health promoting behaviours is important. This study aims to explore men's health beliefs and attitudes towards health promotion; in particular, it explores workplace physical activity in relation to masculine ideals among male employees. In the Fall of 2008, we interviewed 13 white Dutch male employees aged 23-56 years. The men worked in a wide range of professions and occupational sectors and all interviewees had been offered a workplace physical activity program. Interviews lasted approximately one to one-and-a-half hour and addressed beliefs about health and lifestyle behaviours including workplace physical activity, as well as normative beliefs about masculinity. Thematic analysis was used to analyze the data. Two normative themes were found: first, the ideal man is equated with being a winner and real men are prepared to compete, and second, real men are not whiners and ideally, not vulnerable. Workplace physical activity is associated with a particular type of masculinity - young, occupied with looks, and interested in muscle building. Masculine norms are related to challenging health while taking care of health is feminine and, hence, something to avoid. Workplace physical activity is not framed as a health measure, and not mentioned as of importance to the work role. Competitiveness and nonchalant attitudes towards health shape masculine ideals. In regards to workplace physical activity, some men resist what they perceive to be an emphasis on muscled looks, whereas for others it contributes to looking self-confident. In order to establish a greater reach among vulnerable employees such as ageing men, worksite health promotion programs including workplace physical activity may benefit from greater insight in the tensions between health behaviours and masculinity.


Preoperative multidisciplinary treatment with hyperthermia for soft tissue sarcoma.
We report the results of phase I/II studies of preoperative multidisciplinary treatment of 14 patients with soft tissue sarcoma using hyperthermia from November 1990 to April 1995. The preoperative treatment was conducted with thermo-radio-chemotherapy in 11 cases of stage III, and with thermo-radiotherapy as well as thermo-chemotherapy in three cases of stages I and II. Hyperthermia was carried out twice a week with totals ranging from 4 to 14 times (average: 8.4 times); each session lasted 60 min. Radiotherapy was administered four or five times per week, and the dose was 1.8 2Gy/fraction, with a total of 30-40 Gy in a four week period. Chemotherapy was mainly in the form of MAID regimen (2-mercaptoethanesulphonic acid (mesna), adriamycin, ifosfamide and dacarbazine). The tumors were surgically resected in all patients after completing the preoperative treatment. The efficacy rate, as expressed by the percentage of either tumors in which reduction rate was 50% or more, or tumors for which post-treatment contrast enhanced CT image revealed low density volumes occupying 50% or more of the total mass, was 71% (ten of the 14 tumors). The mean tumor necrosis rate in the resected specimens was 78%. The tumor necrosis rate was significantly high (P < 0.05) in patients whose Time > or = 42 degrees C was of long duration. Postoperative complications were observed in six patients; among these, two patients developed wound infection that required surgical treatment as a complication of surgery performed in the early stage following the preoperative treatment. After a mean postoperative follow-up of 27 months, distant metastasis occurred in four patients resulting in three fatalities. The three-year cumulative survival rate was 64.3%. No local recurrence was observed in any patient during the follow-up, thus confirming our hypothesis that preoperative multidisciplinary treatment has an excellent local efficacy. We think that it would be valuable to conduct, at many facilities, phase III studies on the treatment of soft tissue sarcoma by a combination of surgery and preoperative multidisciplinary treatment using hyperthermia, paying close attention to the interval between these two modalities.


Obesity measures, metabolic profiles, blood pressure and intake of dietary fatty acids in rural women of Asian Indian origin: Santiniketan women study.
The present cross-sectional study was aimed to investigate obesity measures, metabolic profiles, blood pressure, and intake of dietary fatty acids in rural women of Asian Indian origin. A total of 280 healthy rural women aged 25-65 years took part in the study. A random sampling procedure using a local voters' registration list was followed to select the participants. All participants belonged to the Bengalee population and were inhabitants of the Bolpur-Santiniketan area, West Bengal, India. Anthropometric measures, namely, height, weight, circumferences of waist and hip, skinfolds at biceps, triceps, subscapular, and suprailiac regions, etc., were collected using standard techniques. Body mass index (BMI), percentages of body fat (PBFs), basal metabolic rate (BMR), and intra-abdominal visceral fat (IVF) were measured using an Omron body fat analyzer (Omron Corporation, Tokyo, Japan). Fat mass (FM), fat free mass (FFM), waist-hip ratio (WHR), and sum of four skinfolds (SF4) were also taken into consideration. Blood pressure and metabolic and hormonal profiles were measured using standard techniques. The weekly consumption (frequency) of food stuffs was collected using an already validated food frequency schedule. The result showed that the mean age was 41.52 ± 10.95, BMI 23.07 ± 4.34, PBF 31.76 ± 7.06, BMR 1162.34 ± 139.59, WHR 0.83 ± 0.06, systolic blood pressure 118.84 ± 20.35, diastolic blood pressure 77.77 ± 12.12, total cholesterol 185.61 ± 25.19, triglyceride level 135.82 ± 30.39, high-density lipoprotein 48.13 ± 6.13, low-density lipoprotein 109.90 ± 22.53, fasting blood glucose 90.91 ± 7.98, and insulin 11.98 ± 3.42. The result also shows the mean intake of total protein to be 177.01 ± 47.79, total energy 8321.60 ± 1354.86, total fat 210.36 ± 53.57, total PUFA 82.02 ± 49.73, and total MUFA 94.01 ± 16.38. The percentile distribution of the dietary fat intake revealed that the 10th and 95th percentile values of the total protein intake were 125.3 and 261.5, total energy intake were 7491.6 and 10470.2, total fat intake were 178.8 and 273.5, total PUFA intake were 55.5 and 191.7, and of the total MUFA intake were 86.0 and 126.9, respectively. It seems reasonable to argue that dietary management including dietary guidelines across India is essential to retard the growing incidence of cardiovascular diseases in coming years.


Dewetted Gold Nanostructures onto Exfoliated Graphene Paper as High Efficient Glucose Sensor.
Non-enzymatic electrochemical glucose sensing was obtained by gold nanostructures on graphene paper, produced by laser or thermal dewetting of 1.6 and 8 nm-thick Au layers, respectively. Nanosecond laser annealing produces spherical nanoparticles (AuNPs) through the molten-phase dewetting of the gold layer and simultaneous exfoliation of the graphene paper. The resulting composite electrodes were characterized by X-ray photoelectron spectroscopy, cyclic voltammetry, scanning electron microscopy, micro Raman spectroscopy and Rutherford back-scattering spectrometry. Laser dewetted electrode presents graphene nanoplatelets covered by spherical AuNPs. The sizes of AuNPs are in the range of 10-150 nm. A chemical shift in the XPS Au4f core-level of 0.25-0.3 eV suggests the occurrence of AuNPs oxidation, which are characterized by high stability under the electrochemical test. Thermal dewetting leads to electrodes characterized by faceted not oxidized gold structures. Glucose was detected in alkali media at potential of 0.15-0.17 V vs. saturated calomel electrode (SCE), in the concentration range of 2.5μM-30 mM, exploiting the peak corresponding to the oxidation of two electrons. Sensitivity of 1240 µA mM-1 cm-2, detection limit of 2.5 μM and quantifications limit of 20 μM were obtained with 8 nm gold equivalent thickness. The analytical performances are very promising and comparable to the actual state of art concerning gold based electrodes.


Ptk7 promotes non-canonical Wnt/PCP-mediated morphogenesis and inhibits Wnt/β-catenin-dependent cell fate decisions during vertebrate development.
Using zebrafish, we have characterised the function of Protein tyrosine kinase 7 (Ptk7), a transmembrane pseudokinase implicated in Wnt signal transduction during embryonic development and in cancer. Ptk7 is a known regulator of mammalian neural tube closure and Xenopus convergent extension movement. However, conflicting reports have indicated both positive and negative roles for Ptk7 in canonical Wnt/β-catenin signalling. To clarify the function of Ptk7 in vertebrate embryonic patterning and morphogenesis, we generated maternal-zygotic (MZ) ptk7 mutant zebrafish using a zinc-finger nuclease (ZFN) gene targeting approach. Early loss of zebrafish Ptk7 leads to defects in axial convergence and extension, neural tube morphogenesis and loss of planar cell polarity (PCP). Furthermore, during late gastrula and segmentation stages, we observe significant upregulation of β-catenin target gene expression and demonstrate a clear role for Ptk7 in attenuating canonical Wnt/β-catenin activity in vivo. MZptk7 mutants display expanded differentiation of paraxial mesoderm within the tailbud, suggesting an important role for Ptk7 in regulating canonical Wnt-dependent fate specification within posterior stem cell pools post-gastrulation. Furthermore, we demonstrate that a plasma membrane-tethered Ptk7 extracellular fragment is sufficient to rescue both PCP morphogenesis and Wnt/β-catenin patterning defects in MZptk7 mutant embryos. Our results indicate that the extracellular domain of Ptk7 acts as an important regulator of both non-canonical Wnt/PCP and canonical Wnt/β-catenin signalling in multiple vertebrate developmental contexts, with important implications for the upregulated PTK7 expression observed in human cancers.


A Novel Educational Prescription Web-Based Application to Support Education for Caregivers of People Living With Dementia: Development and Usability Study With Clinicians.
It is estimated that 564,000 Canadians are currently living with dementia and there are approximately 486,000 to 1.1 million informal family/friend caregivers. Family/friend caregivers often receive little to no education or training about dementia but are expected to provide ongoing support for a complex condition. Web-based family/friend caregiver interventions may be helpful, but little is known about how best to implement them. The objectives of this study were to 1) design and develop a novel education prescription application to help scale and spread web-based dementia education to family/friend caregivers, 2) conduct user testing, and 3) conduct a larger-scale field trial. A novel education prescription web-based application was designed and developed. Initial user testing used task completion and the "think aloud" technique with a small sample of representative clinicians who work with people living with dementia and family/friend caregivers. Following iterative incorporation of feedback, a larger field trial was conducted with a convenience sample of clinicians. Account invitations were sent to 55 clinicians and, following a 2-month trial period, surveys were administered to participants including the System Usability Scale and the Net Promoter Score. During the initial user testing phase, participants (N=7) from representative disciplines easily completed associated tasks, and had very positive feedback with respect to the usability of the application. The System Usability Scale score during this phase was 91.4. Suggestions from feedback were incorporated into the application. During the larger field trial phase, participants (total N=55; activated account n=17; did not activate account n=38) were given access to the iGeriCare education prescription application. During this period, 2 participants created educational prescriptions; a total of 3 educational prescriptions were sent. Survey completers who did not activate their account (n=5) identified that their lack of use was due to time constraints, competing priorities, or forgetting to use the application. Survey completers who activated their account (n=5) identified their lower use was due to lack of time, lack of eligible family/friend caregivers during trial period, and competing priorities due to the COVID-19 pandemic. The System Usability Scale score during this phase was 78.75, and the Net Promoter Score was 50. Study findings indicate a generally positive response for the usability of a web-based application for clinicians to prescribe dementia education to family/friend caregivers. The dissonance between the promising data and widespread enthusiasm for the design and purpose of the education prescription application found in the initial user testing phase and subsequent lack of significant adoption in the field trial represents both an important lesson for other novel health technologies and a potential area for further investigation. Further research is required to better understand factors associated with implementation of this type of intervention and impact on dissemination of education to family/friend caregivers.


Hanbury Brown Twiss effect for ultracold quantum gases.
We have studied two-body correlations of atoms in an expanding cloud above and below the Bose-Einstein condensation threshold. The observed correlation function for a thermal cloud shows a bunching behavior, whereas the correlation is flat for a coherent sample. These quantum correlations are the atomic analog of the Hanbury Brown Twiss effect. We observed the effect in three dimensions and studied its dependence on cloud size.


A Retrospective Examination of Two Professional Society-Sponsored Fellowships for Predoctoral Microbiology Students.
At the American Society for Microbiology (ASM), fellowships are a key means of providing immersive research opportunities for the student sector. To assess the impact of ASM student activities and inform their planning, the Society commissioned a study of two long-standing initiatives in 2015, namely the ASM Undergraduate Research Fellowship (URF), established in 1993, and the ASM Robert D. Watkins Graduate Research Fellowship (Watkins) Program, established in 1980. A mixed-methods approach was used to collect data about the participants' fellowship experience, track educational and employment status, and determine program impacts from 325 individuals (223 URF and 73 Watkins fellows). Challenges presented by the study include the fact that inherent in fellowships is the provision of financial support that affords participants opportunities that might otherwise be unavailable to them. As a result, participant feelings of indebtedness to the Society may have introduced biased study responses. In addition, some respondents were asked to reflect on experiences from 20 to 30 years ago-a lapse in time that may have challenged their memories. Based on measures such as enrollment in or completion of advanced degree programs, employment in science, and publication and presentation history, project participants show evidence of accomplishment. Participants also reported gains in affective behaviors such as confidence and belonging.


Unfavorable clinical implications for hypermethylation of RUNX3 in patients with salivary gland adenoid cystic carcinoma.
To elucidate the potential etiological role of RUNX3 in the development of salivary gland adenoid cystic carcinoma (ACC), we analyzed the methylation status of RUNX3 in a series of 114 ACC tissues and 3 ACC cell lines. Results showed that the methylated rate of RUNX3 was 50.9 and 3.5% in the 114 ACC samples and the corresponding normal salivary glands, respectively, achieving a significant difference (P<0.001). There was a significant correlation between RUNX3 methylation and various clinicopathological parameters of ACCs, such as perineural invasion, lymph node involvement, T-stage and distant metastasis (P<0.001). RUNX3 methylation was a significant predictor of the 5-year disease-free survival in ACC patients after surgery. Partial methylation was found in all 3 ACC cell lines, and the reactivation and more potent expression of RUNX3 was induced by 5-triazole-2-deoxycytidine. Our findings indicate that RUNX3 methylation may occur as a common event in the development of ACC and that methylation may be a major mechanism for inactivation of RUNX3 in ACC.


Yeast meiosis-specific protein Hop1 binds to G4 DNA and promotes its formation.
DNA molecules containing stretches of contiguous guanine residues can assume a stable configuration in which planar quartets of guanine residues joined by Hoogsteen pairing appear in a stacked array. This conformation, called G4 DNA, has been implicated in several aspects of chromosome behavior including immunoglobulin gene rearrangements, promoter activation, and telomere maintenance. Moreover, the ability of the yeast SEP1 gene product to cleave DNA in a G4-DNA-dependent fashion, as well as that of the SGS1 gene product to unwind G4 DNA, has suggested a crucial role for this structure in meiotic synapsis and recombination. Here, we demonstrate that the HOP1 gene product, which plays a crucial role in the formation of synaptonemal complex in Saccharomyces cerevisiae, binds robustly to G4 DNA. The apparent dissociation constant for interaction with G4 DNA is 2 x 10(-10), indicative of binding that is about 1,000-fold stronger than to normal duplex DNA. Oligonucleotides of appropriate sequence bound Hop1 protein maximally if the DNA was first subjected to conditions favoring the formation of G4 DNA. Furthermore, incubation of unfolded oligonucleotides with Hop1 led to their transformation into G4 DNA. Methylation interference experiments confirmed that modifications blocking G4 DNA formation inhibit Hop1 binding. In contrast, neither bacterial RecA proteins that preferentially interact with GT-rich DNA nor histone H1 bound strongly to G4 DNA or induced its formation. These findings implicate specific interactions of Hop1 protein with G4 DNA in the pathway to chromosomal synapsis and recombination in meiosis.


Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years.
Anthrax is a rare disease in humans but elicits great public fear because of its past use as an agent of bioterrorism. Injectional anthrax has been occurring sporadically for more than ten years in heroin consumers across multiple European countries and this outbreak has been difficult to trace back to a source. We took a molecular epidemiological approach in understanding this disease outbreak, including whole genome sequencing of Bacillus anthracis isolates from the anthrax victims. We also screened two large strain repositories for closely related strains to provide context to the outbreak. Analyzing 60 Bacillus anthracis isolates associated with injectional anthrax cases and closely related reference strains, we identified 1071 Single Nucleotide Polymorphisms (SNPs). The synapomorphic SNPs (350) were used to reconstruct phylogenetic relationships, infer likely epidemiological sources and explore the dynamics of evolving pathogen populations. Injectional anthrax genomes separated into two tight clusters: one group was exclusively associated with the 2009-10 outbreak and located primarily in Scotland, whereas the second comprised more recent (2012-13) cases but also a single Norwegian case from 2000. Genome-based differentiation of injectional anthrax isolates argues for at least two separate disease events spanning > 12 years. The genomic similarity of the two clusters makes it likely that they are caused by separate contamination events originating from the same geographic region and perhaps the same site of drug manufacturing or processing. Pathogen diversity within single patients challenges assumptions concerning population dynamics of infecting B. anthracis and host defensive barriers for injectional anthrax. This work was supported by the United States Department of Homeland Security grant no. HSHQDC-10-C-00,139 and via a binational cooperative agreement between the United States Government and the Government of Germany. This work was supported by funds from the German Ministry of Defense (Sonderforschungsprojekt 25Z1-S-431,214). Support for sequencing was also obtained from Illumina, Inc. These sources had no role in the data generation or interpretation, and had not role in the manuscript preparation. We searched PubMed for any article published before Jun. 17, 2015, with the terms "Bacillus anthracis" and "heroin", or "injectional anthrax". Other than our previously published work (Price et al., 2012), we found no other relevant studies on elucidating the global phylogenetic relationships of B. anthracis strains associated with injectional anthrax caused by recreational heroin consumption of spore-contaminated drug. There were, however, publically available genome sequences of two strains involved (Price et al., 2012, Grunow et al., 2013) and the draft genome sequence of Bacillus anthracis UR-1, isolated from a German heroin user (Ruckert et al., 2012) with only limited information on the genotyping of closely related strains (Price et al., 2012, Grunow et al., 2013). Injectional anthrax has been plaguing heroin drug users across Europe for more than 10 years. In order to better understand this outbreak, we assessed genomic relationships of all available injectional anthrax strains from four countries spanning a > 12 year period. Very few differences were identified using genome-based analysis, but these differentiated the isolates into two distinct clusters. This strongly supports a hypothesis of at least two separate anthrax spore contamination events perhaps during the drug production processes. Identification of two events would not have been possible from standard epidemiological analysis. These comprehensive data will be invaluable for classifying future injectional anthrax isolates and for future geographic attribution.


The Synaptic Vesicle Cycle Revisited: New Insights into the Modes and Mechanisms.
Neurotransmission is sustained by endocytosis and refilling of synaptic vesicles (SVs) locally within the presynapse. Until recently, a consensus formed that after exocytosis, SVs are recovered by either fusion pore closure (kiss-and-run) or clathrin-mediated endocytosis directly from the plasma membrane. However, recent data have revealed that SV formation is more complex than previously envisaged. For example, two additional recycling pathways have been discovered, ultrafast endocytosis and activity-dependent bulk endocytosis, in which SVs are regenerated from the internalized membrane and synaptic endosomes. Furthermore, these diverse modes of endocytosis appear to influence both the molecular composition and subsequent physiological role of individual SVs. In addition, previously unknown complexity in SV refilling and reclustering has been revealed. This review presents a modern view of the SV life cycle and discusses how neuronal subtype, physiological temperature, and individual activity patterns can recruit different endocytic modes to generate new SVs and sculpt subsequent presynaptic performance.


Barriers to ultrasound training in critical care medicine fellowships: a survey of program directors.
Ultrasonography is an effective tool for making quick diagnoses and guiding therapeutic procedures. National organizations have advocated increasing the use of critical care ultrasonography. The purpose of this study was to investigate the prevalence of teaching of critical care ultrasonography in fellowship programs. In addition, we hoped to identify barriers to establishment of ultrasound training programs. All pulmonary/critical care and critical care medicine (CCM) program directors in the United States were invited to participate in an online survey. We asked respondents for demographic information about their programs and perceived barriers to training, as well as current training opportunities for their fellows in five aspects of critical care ultrasonography. A five-point Likert scale was used for survey answers. Web-based survey. Pulmonary/critical care and CCM program directors in the United States. Web-based survey. Ninety (66%) of 136 program directors responded. Ultrasonography training was offered by fellowship programs in the following areas: vascular access (98%), lung and pleural (74%), cardiac (55%), vascular diagnostic (33%), and abdominal (37%). Ninety-two percent of respondents agreed or strongly agreed that ultrasound training is useful, and 80% were interested in getting their fellows trained. Forty-one percent indicated that they lacked sufficient faculty trained in ultrasound use. Eighty-four percent agreed or strongly agreed that fellow turnover was an impediment to training. Forty-eight percent believed that cardiac echocardiography required a long training time. Although ultrasound training in vascular access was nearly universal, training in other aspects of ultrasound was less prevalent. We identified several barriers, including fellow turnover, insufficient faculty training, and perceived length of time required for echocardiography training.


Ascorbic acid effect on intestinal iron absorption in different types of anaemias.
The study deals with investigations on anaemia due to iron or protein calorie deficiency and that associating acute glomerulonephritis, nephrosis and schistosoma haematobium. The rate of intestinal iron absorption using an oral dose of ferrous sulphate equivalent to 4 mg clemental iron/kg body weight was studied. The supplementing action of ascorbic acid in iron absorption in these cases was also investigated. The rate of intestinal iron absorption was enhanced in pure iron deficiency anaemia, acute glomerulonephritis and schistosoma haematobium, retarded in kwashiorkor, marasmus and nephrosis. Ascorbic acid markedly promoted iron absorption in normal subjects but slightly in pure iron deficiency anaemia. It improved iron absorption in acute glomerulonephritis and schistosoma haematobium but not in kwashiorkor, marasmus and nephrotic cases. It is concluded that ascorbic acid supplementation is of certain beneficial effect in alleviating the state of anaemia when intestinal iron absorption is not impaired. Also, it may prove to be of value to be given along with protein rehabilitation in anaemias associating protein deficiency.


Bone morphogenetic proteins, genetics and the pathophysiology of primary pulmonary hypertension.
Several recent papers have shown that both familial primary pulmonary hypertension (FPPH) and sporadic primary pulmonary hypertension (PPH) may have a common etiology that is associated with the inheritance and/or spontaneous development of germline mutations in the bone morphogenetic protein receptor (BMPR) type II gene. Because BMPR-II is a ubiquitously expressed receptor for a family of secreted growth factors known as the bone morphogenetic proteins (BMPs), these findings suggest that BMPs play an important role in the maintenance of normal pulmonary vascular physiology. In the present commentary we discuss the implications of these findings in the context of BMP receptor biology, and relate these data to the genetics and pulmonary pathophysiology of patients with PPH.


Clutch size evolution under sexual conflict enhances the stability of mating systems.
Models of optimal clutch size often implicitly assume a situation with uniparental care. However, the evolutionary conflict between males and females over the division of parental care will have a major influence on the evolution of clutch size. Since clutch size is a female trait, a male has little possibility of directly influencing it. However, the optimal clutch size from a female's perspective will depend on the amount of paternal care her mate is expected to provide. The sexual conflict over parental care will in its turn be affected by clutch size, since a larger clutch makes male care more valuable. Hence, there will be joint evolution of mating system and clutch size. In this paper, we demonstrate that this joint evolution will tend to stabilize the mating system. In a situation with conventional sex roles, this joint evolution might result in either increased clutch size and biparental care or reduced clutch size and uniparental female care. Under some circumstances the initial conditions might determine which will be the outcome. These results demonstrate that it may be difficult to deduce whether biparental care evolved because of few opportunities for breeding males increasing their fitness by attracting additional mates or because of the importance of male care for offspring fitness by studying prevailing mating systems using, for example, male removals or manipulation of males' opportunities for finding additional mates. In general terms, we demonstrate that models of life-history evolution have to consider the social context in which they evolve.


Both interaction surfaces within cohesin's hinge domain are essential for its stable chromosomal association.
The cohesin complex that mediates sister chromatid cohesion contains three core subunits: Smc1, Smc3, and Scc1. Heterotypic interactions between Smc1 and Smc3 dimerization domains create stable V-shaped Smc1/Smc3 heterodimers with a hinge at the center and nucleotide-binding domains (NBDs) at the ends of each arm. Interconnection of each NBD through their association with the N- and C-terminal domains of Scc1 creates a tripartite ring, within which sister DNAs are thought to be entrapped (the ring model). Crystal structures show that the Smc1/Smc3 hinge has a toroidal shape, with independent "north" and "south" interaction surfaces on an axis of pseudosymmetry. The ring model predicts that sister chromatid cohesion would be lost by transient hinge opening. We find that mutations within either interface weaken heterodimerization of isolated half hinges in vitro but do not greatly compromise formation of cohesin rings in vivo. They do, however, reduce the residence time of cohesin on chromosomes and cause lethal defects in sister chromatid cohesion. This demonstrates that mere formation of rings is insufficient for cohesin function. Stable cohesion requires cohesin rings that cannot easily open. Either the north or south hinge interaction surface is sufficient for the assembly of V-shaped Smc1/Smc3 heterodimers in vivo. Any tendency of Smc proteins with weakened hinges to dissociate will be suppressed by interconnection of their NBDs by Scc1. We suggest that transient hinge dissociation caused by the mutations described here is incompatible with stable sister chromatid cohesion because it permits chromatin fibers to escape from cohesin rings.


Genetic incorporation of a herpes simplex virus type 1 thymidine kinase and firefly luciferase fusion into the adenovirus protein IX for functional display on the virion.
An advantage of the adenoviral vector is its molecular flexibility, which allows for vector tropism modifications for the purpose of cell targeting. In addition to targeting ligands, the capacity to incorporate heterologous peptides has allowed capsid incorporation of other functionalities. We have defined the minor capsid protein IX (pIX) as a locus capable of presenting incorporated ligands on the virion surface. Thus, we sought to exploit the possibility of incorporating functional proteins at pIX. In our current study, we sought to expand the potential utility of our capsid labeling strategy by developing simultaneous imaging capacity for dedicated small animal positron emission tomography and bioluminescence imaging on a single adenoviral vector. Therefore, we constructed an adenovirus that incorporates a fusion protein of herpes simplex virus type 1 thymidine kinase and firefly luciferase (Luc) (TK-Luc) into adenovirus capsid pIX. Our study herein clearly demonstrates our ability to rescue viable adenoviral particles that display functional TK-Luc as a component of their capsid surface. Most importantly, Ad-pIX-TK-Luc retained dual enzymatic functions in vitro and in vivo. This dual-modality approach will allow dynamic or real-time imaging analysis of adenovirus-based interventions with maximized analytic flexibility and enhanced resolution potential.


Controlled Measurement and Comparative Analysis of Cellular Components in E. coli Reveals Broad Regulatory Changes in Response to Glucose Starvation.
How do bacteria regulate their cellular physiology in response to starvation? Here, we present a detailed characterization of Escherichia coli growth and starvation over a time-course lasting two weeks. We have measured multiple cellular components, including RNA and proteins at deep genomic coverage, as well as lipid modifications and flux through central metabolism. Our study focuses on the physiological response of E. coli in stationary phase as a result of being starved for glucose, not on the genetic adaptation of E. coli to utilize alternative nutrients. In our analysis, we have taken advantage of the temporal correlations within and among RNA and protein abundances to identify systematic trends in gene regulation. Specifically, we have developed a general computational strategy for classifying expression-profile time courses into distinct categories in an unbiased manner. We have also developed, from dynamic models of gene expression, a framework to characterize protein degradation patterns based on the observed temporal relationships between mRNA and protein abundances. By comparing and contrasting our transcriptomic and proteomic data, we have identified several broad physiological trends in the E. coli starvation response. Strikingly, mRNAs are widely down-regulated in response to glucose starvation, presumably as a strategy for reducing new protein synthesis. By contrast, protein abundances display more varied responses. The abundances of many proteins involved in energy-intensive processes mirror the corresponding mRNA profiles while proteins involved in nutrient metabolism remain abundant even though their corresponding mRNAs are down-regulated.


Limitations in life participation and independence due to secondary conditions.
The effects of secondary conditions across adults with autism, Down syndrome, and cerebral palsy were explored in terms of overall limitation in life participation and independence, changes over time, and the degree and nature of limitation in specific secondary conditions. Information was obtained for 35 adults with autism, 49 with Down syndrome, and 29 with cerebral palsy (N = 113). Caregivers completed a questionnaire exploring secondary conditions on two occasions. Participants with cerebral palsy experienced the greatest overall limitations of the three groups. This finding is due to several secondary conditions. There were no changes in limitation scores over time. Implications related to health care for these groups are discussed.


Quantification of human pharmaceuticals in water samples by high performance liquid chromatography-tandem mass spectrometry.
An improved analytical method for determination of human pharmaceuticals in natural and wastewaters with ng L(-1) sensitivity is presented. The method is applicable to pharmaceuticals from a wide range of therapeutic classes including antibiotics, analgesics, anti-inflammatories and anti-cancer compounds. Pharmaceuticals were extracted from waters using solid-phase extraction, and after concentration, analysed by high performance liquid chromatography with tandem mass spectrometric detection (HPLC-MS/MS). Identification of each compound was secured using retention time and by the selected reaction monitoring of two transitions, one of which was additionally used for quantification. Limits of detection ranged from 0.03 to 0.96 ng L(-1) and were up to two orders of magnitude lower than those of previously published methods. The method was validated using spiked samples prepared from tap, river and sea water as well as wastewater effluents, collected from the North of Scotland. Analysis of wastewater effluents revealed the presence of mefenamic acid, ibuprofen, erythromycin, diclofenac and trimethoprim. None of the selected pharmaceuticals were detected in river, tap or sea water samples.


Predictors of dental care utilization in north-central Appalachia in the USA.
Dental utilization is an important determinant of oral health and well-being. The aim of this study was to evaluate potential associations between a variety of biopsychosocial factors and dental utilization in north-central Appalachia, USA, a region where oral health disparities are profound. This study used household-based data from the Center for Oral Health Research in Appalachia (COHRA1) study in north-central Appalachia, including 449 families with 868 adults. The generalized estimating equation (GEE) approach was used to determine the best-fitting predictor model for dental utilization among adult family members. On average across West Virginia and Pennsylvania, having dental insurance was associated with greater dental utilization over a 3-year time period (OR = 2.20, 95% CI = 1.54, 3.14). When stratified by state, the association held for only West Virginia (OR = 2.41, 95% CI = 1.54, 3.79) and was nonsignificant for Pennsylvania residents (OR = 1.50, 95% CI = 0.80, 2.79). Individuals from Pennsylvania were more likely to utilize dental care and participants from West Virginia less so (2.31, 95% CI = 1.57, 3.40). Females from Pennsylvania were more likely than males to regularly seek dental care (OR = 1.44, 95% CI = 1.00, 2.05), and a higher income was associated with greater frequency of regular dental visits (OR = 1.21, 95% CI = 1.09, 1.34) in West Virginia. Individuals from Pennsylvania who scored higher on the Physiological Arousal subscale of the Dental Fear Survey were more likely to attend routine care visits (OR = 1.18, 95% CI = 1.03, 1.35). Across both states, more fatalistic beliefs related to oral health care also predicted less routine care (OR = 0.87, 95% CI = 0.81, 0.94), and more investment in or more positive attitudes towards one's oral health also was associated with higher utilization (OR = 1.18, 95% CI = 1.13, 1.23). Overall, the findings of this study suggest state residency, sex, insurance, income, fatalistic beliefs, health values, and aspects of dental care-related anxiety and fear predicted dental care utilization in north-central Appalachia. These findings reinforce the need to address insurance and other economic factors affecting utilization and to consider how individual-level fatalistic beliefs and oral health values may affect utilization of routine oral health care.


Making college worth it: a review of the returns to higher education.
Despite a general rise in the return to college, likely due to technological change, the cost-benefit calculus facing prospective students can make the decision to invest in and attend college dauntingly complex. Philip Oreopoulos and Uros Petronijevic review research on the varying costs and benefits of higher education and explore in full the complexity of the decision to invest in and attend college. Optimal college attainment decisions are different for all prospective students, who diverge in terms of what they are likely to get out of higher education and what specific options might be best for them. Earnings of college graduates depend in important measure on the program of study and eventual occupation they choose. Students uninterested in or unable to complete a four-year college degree appear to benefit from completing a two-year degree. Prospective students may also face both financial constraints, which prohibit them from taking advantage of more education, and information problems and behavioral idiosyncrasies, such as reluctance to take on debt, which keep them from making optimal decisions about attending college. In their discussion of how student debt figures in the college investment, the authors note that some students borrow too little and, as a result, underinvest in their education. Carefully calculating the return on the college investment can help determine the "appropriate" amount of debt. Students are more likely to benefit from postsecondary education the more informed they are about the expenses associated with college and the potential options for financial aid, which can be extremely complex. To make the best college investment, Oreopoulos and Petronijevic stress, prospective students must give careful consideration to selecting the institution itself, the major to follow, and the eventual occupation to pursue. For any particular program at a particular school, anticipated future labor market earnings, the likelihood of completion, the costs, and the value of any student debt must all be factored into the assessment.


Endotoxin (LPS) increases mesenteric vascular resistance (MVR) and bacterial translocation (BT).
Endotoxemia is responsible for many of the pathophysiologic alterations that occur with Gram-negative sepsis. We utilized a chronic ovine model to determine the hemodynamic disturbances in the gastrointestinal tract during endotoxemia. Sheep with indwelling arterial, venous, and pulmonary arterial catheters were used. An ultrasonic flow probe was placed on the cephalic mesenteric artery. The animals were subjected to: 1) Ringer's lactate infusion (sham n = 6); or 2) 1.5 mcg/kg E. coli endotoxin (n = 6) over over a period of one half hour and were monitored for 48 hours. They were then sacrificed and specimens of mesenteric lymph node, liver, spleen, kidney, and lung obtained for bacteriologic cultures and histologic analysis. Sheep receiving endotoxin showed more than 50% reduction in the mesenteric blood flow. Mesenteric vascular resistance increased while non-mesenteric systemic vascular resistance decreased. The increase in the total systemic vascular resistance, noted during endotoxemia, was thus likely due to the increase in the mesenteric vascular resistance. At autopsy there were positive cultures for microorganism in the mesenteric lymph nodes in six out of six sheep with endotoxemia as compared to one out of six of control. Thus the vasoconstriction in the mesenteric areas may have resulted in bacterial translocation from the GI tract.


Increased NQO1 but not c-MET and survivin expression in non-small cell lung carcinoma with KRAS mutations.
Cigarette smoking is one of the most significant public health issues and the most common environmental cause of preventable cancer deaths worldwide. EGFR (Epidermal Growth Factor Receptor)-targeted therapy has been used in the treatment of LC (lung cancer), mainly caused by the carcinogens in cigarette smoke, with variable success. Presence of mutations in the KRAS (Kirsten rat sarcoma viral oncogene homolog) driver oncogene may confer worse prognosis and resistance to treatment for reasons not fully understood. NQO1 (NAD(P)H:quinone oxidoreductase), also known as DT-diaphorase, is a major regulator of oxidative stress and activator of mitomycins, compounds that have been targeted in over 600 pre-clinical trials for treatment of LC. We sequenced KRAS and investigated expression of NQO1 and five clinically relevant proteins (DNMT1, DNMT3a, ERK1/2, c-MET, and survivin) in 108 patients with non-small cell lung carcinoma (NSCLC). NQO1, ERK1/2, DNMT1, and DNMT3a but not c-MET and survivin expression was significantly more frequent in patients with KRAS mutations than those without, suggesting the following: (1) oxidative stress may play an important role in the pathogenesis, worse prognosis, and resistance to treatment reported in NSCLC patients with KRAS mutations, (2) selecting patients based on their KRAS mutational status for future clinical trials may increase success rate, and (3) since oxidation of nucleotides also specifically induces transversion mutations, the high rate of KRAS transversions in lung cancer patients may partly be due to the increased oxidative stress in addition to the known carcinogens in cigarette smoke.


Flagellar morphogenesis: protein targeting and assembly in the paraflagellar rod of trypanosomes.
The paraflagellar rod (PFR) of the African trypanosome Trypanosoma brucei represents an excellent model to study flagellum assembly. The PFR is an intraflagellar structure present alongside the axoneme and is composed of two major proteins, PFRA and PFRC. By inducible expression of a functional epitope-tagged PFRA protein, we have been able to monitor PFR assembly in vivo. As T. brucei cells progress through their cell cycle, they possess both an old and a new flagellum. The induction of expression of tagged PFRA in trypanosomes growing a new flagellum provided an excellent marker of newly synthesized subunits. This procedure showed two different sites of addition: a major, polar site at the distal tip of the flagellum and a minor, nonpolar site along the length of the partially assembled PFR. Moreover, we have observed turnover of epitope-tagged PFRA in old flagella that takes place throughout the length of the PFR structure. Expression of truncated PFRA mutant proteins identified a sequence necessary for flagellum localization by import or binding. This sequence was not sufficient to confer full flagellum localization to a green fluorescent protein reporter. A second sequence, necessary for the addition of PFRA protein to the distal tip, was also identified. In the absence of this sequence, the mutant PFRA proteins were localized both in the cytosol and in the flagellum where they could still be added along the length of the PFR. This seven-amino-acid sequence is conserved in all PFRA and PFRC proteins and shows homology to a sequence in the flagellar dynein heavy chain of Chlamydomonas reinhardtii.


Peak alpha frequency is a neural marker of cognitive function across the autism spectrum.
Cognitive function varies substantially and serves as a key predictor of outcome and response to intervention in autism spectrum disorder (ASD), yet we know little about the neurobiological mechanisms that underlie cognitive function in children with ASD. The dynamics of neuronal oscillations in the alpha range (6-12 Hz) are associated with cognition in typical development. Peak alpha frequency is also highly sensitive to developmental changes in neural networks, which underlie cognitive function, and therefore, it holds promise as a developmentally sensitive neural marker of cognitive function in ASD. Here, we measured peak alpha band frequency under a task-free condition in a heterogeneous sample of children with ASD (N = 59) and age-matched typically developing (TD) children (N = 38). At a group level, peak alpha frequency was decreased in ASD compared to TD children. Moreover, within the ASD group, peak alpha frequency correlated strongly with non-verbal cognition. As peak alpha frequency reflects the integrity of neural networks, our results suggest that deviations in network development may underlie cognitive function in individuals with ASD. By shedding light on the neurobiological correlates of cognitive function in ASD, our findings lay the groundwork for considering peak alpha frequency as a useful biomarker of cognitive function within this population which, in turn, will facilitate investigations of early markers of cognitive impairment and predictors of outcome in high risk infants.


Loving-kindness and compassion meditation: potential for psychological interventions.
Mindfulness-based meditation interventions have become increasingly popular in contemporary psychology. Other closely related meditation practices include loving-kindness meditation (LKM) and compassion meditation (CM), exercises oriented toward enhancing unconditional, positive emotional states of kindness and compassion. This article provides a review of the background, the techniques, and the empirical contemporary literature of LKM and CM. The literature suggests that LKM and CM are associated with an increase in positive affect and a decrease in negative affect. Preliminary findings from neuroendocrine studies indicate that CM may reduce stress-induced subjective distress and immune response. Neuroimaging studies suggest that LKM and CM may enhance activation of brain areas that are involved in emotional processing and empathy. Finally, preliminary intervention studies support application of these strategies in clinical populations. It is concluded that, when combined with empirically supported treatments, such as cognitive-behavioral therapy, LKM and CM may provide potentially useful strategies for targeting a variety of different psychological problems that involve interpersonal processes, such as depression, social anxiety, marital conflict, anger, and coping with the strains of long-term caregiving.


Listening to the voices of patients with cancer, their advocates and their nurses: A hermeneutic-phenomenological study of quality nursing care.
This article presents the findings from a hermeneutic-phenomenological study looking at the meanings of "quality nursing care" through the experiences of patients with cancer, their advocates and their nurses. Twenty-five patients were interviewed from which fifteen also participated in two focus groups. Six patients' advocates participated in a focus group and twenty nurses were individually interviewed. The informants came from the three major hospitals in Cyprus which provide in-patient cancer care. Patients' advocates came from the two major cancer associations in Cyprus. Having analysed the data, seven major themes were identified: receiving care in easily accessible cancer care services, being cared for by nurses who effectively communicate with them and their families and provide emotional support, being empowered by nurses through information giving, being cared for by clinically competent nurses, nurses addressing their religious and spiritual needs, being cared for in a nursing environment which promotes shared decision-making, and patients being with and involving the family in the care. These findings stress the need to integrate these aspects in the care of patients with cancer. In doing so, nurses will need support and adequate training in order to acquire the relevant skills towards better caring for the patients.


[Psychosocial aspects of childhood epilepsy].
Epilepsy is without a doubt one of the most ancient and enigmatic conditions in the history of medicine, as it was already described in remote times. From the ancestral obscure understanding of epilepsy to the present, there have been important scientific advances in the knowledge of its diagnosis and treatment. The management of a child with epilepsy requires following a protocol that includes a detailed clinical and laboratory evaluation. All chronic diseases, and also epilepsy, are felt as a double aggression: 1) Internal, related to the changes that the disease causes, and 2) external, related to the tests, medications, excessive protection, and all the rules and prohibitions that are applied. The doctor (pediatrician, pediatric neurologist or epileptologist), when initiating a relationship with the child with epilepsy, is going to propose "a new code", often hard to accept. He is going to intervene far away from the crisis, or soon after it happened, in an environment characterized by significant anguish for the family. There is no question that the disease is difficult for the child, as it is also for the parents, who become responsible for a different type of care, are preoccupied daily about their son taking the medication regularly, and suffer awaiting for another crisis to happen. Epilepsy, more than other conditions, creates a high level of restlessness because of the spectacular, dramatic nature of its presentation and for the ancestral myths still attributed to it. For all these reasons, the diagnosis of epilepsy is frequently accompanied by three relevant reactions in the family: anxiety, guilt and aggressiveness. The intervention of the doctor in the treatment of childhood epilepsy must be "global". With mystic devotion, the doctor must embrace the true Hippocratic concept of patient care.


Xenon as an adjuvant to sevoflurane anesthesia in children younger than 4 years of age, undergoing interventional or diagnostic cardiac catheterization: A randomized controlled clinical trial.
Xenon has repeatedly been demonstrated to have only minimal hemodynamic side effects when compared to other anesthetics. Moreover, in experimental models, xenon was found to be neuroprotective and devoid of developmental neurotoxicity. These properties could render xenon attractive for the anesthesia in neonates and infants with congenital heart disease. However, experience with xenon anesthesia in children is scarce. We hypothesized that in children undergoing cardiac catheterization, general anesthesia with a combination of sevoflurane with xenon results in superior hemodynamic stability, compared to sevoflurane alone. In this prospective, randomized, single-blinded, controlled clinical trial, children with a median age of 12 [IQR 3-36] months undergoing diagnostic/interventional cardiac catheterization were randomized to either general anesthesia with 50-65vol% xenon plus sevoflurane or sevoflurane alone. The primary outcome was the incidence of intraprocedural hemodynamic instability, defined as the occurrence of: (i) a heart rate change >20% from baseline; or (ii) a change in mean arterial blood pressure >20% from baseline; or (iii) the requirement of vasopressors, inotropes, chronotropes, or fluid boluses. Secondary endpoints included recovery characteristics, feasibility criteria, and safety (incidence of emergence agitation and postoperative vomiting. After inclusion of 40 children, the trial was stopped as an a priori planned blinded interim analysis revealed that the overall rate of hemodynamic instability did not differ between groups [100% in both the xenon-sevoflurane and the sevoflurane group. However, the adjuvant administration of xenon decreased vasopressor requirements, preserved better cerebral oxygen saturation, and resulted in a faster recovery. Xenon anesthesia was feasible (with no differences in the need for rescue anesthetics in both groups). Our observations suggest that combining xenon with sevoflurane in preschool children is safe, feasible, and facilitates hemodynamic management. Larger and adequately powered clinical trials are warranted to investigate the impact of xenon on short- and long-term outcomes in pediatric anesthesia.


Primary intra-aortic balloon support versus inotropes for decompensated heart failure and low output: a randomised trial.
The haemodynamic effects of primary implantation of an intra-aortic balloon pump (IABP) versus inotropes in decompensated heart failure and low output (DHF-LO), but without an acute coronary syndrome, have not been investigated. We therefore aimed to investigate the effect of primary IABP implantation as compared to inotropes on haemodynamics in DHF-LO with no acute ischaemia. Patients (n=32) with DHF-LO despite IV diuretics were randomised to primary 50 mL IABP or inotropes (INO: enoximone or dobutamine). The primary endpoint was the improvement of organ perfusion assessed by ∆ mixed-venous oxygen saturation (SvO2) at 3 hours; secondary endpoints included ∆ cardiac power output (CPO), NT-proBNP proportional change, cumulative fluid balance and ∆ dyspnoea severity score, all at 48 hours. Data are presented as median (IQR). Patients were 60 (48-69) years old and 72% were male. Baseline SvO2 was 44 (39-53)%. ∆SvO2 was higher in the IABP group (+17 [+9; +24] vs. +5 [+2; +9]%, p<0.05). IABP patients had a higher ∆CPO, a greater relative reduction in NT-proBNP, a more negative cumulative fluid balance, and a greater reduction in dyspnoea severity score. There were no IABP-related serious adverse events (SAEs). Thirty-day mortality was 23% (IABP) vs. 44% (INO). Primary circulatory support by IABP showed a significant increase in improved organ perfusion assessed by SvO2.


Incidence of Gonorrhea and Chlamydia Following Human Immunodeficiency Virus Preexposure Prophylaxis Among Men Who Have Sex With Men: A Modeling Study.
Preexposure prophylaxis (PrEP) is highly effective for preventing human immunodeficiency virus (HIV) infection, but risk compensation (RC) in men who have sex with men (MSM) raises concerns about increased sexually transmitted infections (STIs). The Center for Disease Control and Prevention's (CDC's) PrEP guidelines recommend biannual STI screening, which may reduce incidence by treating STIs that would otherwise remain undiagnosed. We investigated these two counteracting phenomena. With a network-based mathematical model of HIV, Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT) transmission dynamics among MSM in the United States, we simulated PrEP uptake following the prescription indications and HIV/STI screening recommendations in the CDC guidelines. Scenarios varied PrEP coverage (the proportion of MSM indicated for PrEP who received it), RC (a reduction in the per-act probability of condom use), and the STI screening interval. In our reference scenario (40% coverage, 40% RC), 42% of NG and 40% of CT infections would be averted over the next decade. A doubling of RC would still result in net STI prevention relative to no PrEP. STIs declined because PrEP-related STI screening resulted in a 17% and 16% absolute increase in the treatment of asymptomatic and rectal STIs, respectively. Screening and timely treatment at quarterly vs biannual intervals would reduce STI incidence an additional 50%. Implementation of the CDC PrEP guidelines while scaling up PrEP coverage could result in a significant decline in STI incidence among MSM. Our study highlights the design of PrEP not only as antiretroviral medication but as combination HIV/STI prevention incorporating STI screening.


Human biomonitoring assessment values: approaches and data requirements.
Human biomonitoring (HBM) data is a very useful metric for assessing human's exposures to chemicals in commerce. To assess the potential health risks associated with the presence of chemicals in blood, urine or other biological matrix requires HBM assessment values. While HBM assessment values based on human exposure-response data remain the most highly valuable and interpretable assessment values, enough data exists for such values for very few chemicals. As a consequence, efforts have been undertaken to derive HBM assessment values in which external dose based guidance values such as tolerable daily intakes have been translated into equivalent biomonitoring levels. The development of HBM values by the German HBM Commission and Biomonitoring Equivalents by Summit Toxicology has resulted in conceptually similar assessment values. The review of the development of these values provided here demonstrates examples and approaches that can be used to broaden the range of chemicals for which such assessment values can be derived. Efforts to date have resulted in the publication of HBM assessment values for more than 80 chemicals, and now provide tools that can be used for the evaluation of HBM data across chemicals and populations.


A clinical scale for the self-assessment of irritability.
To date there has been no suitable scale for the self-assessment of irritability in the clinical situation. Existing scales have either included aspects of personality trait together with present state or they have been constructed on non-clinical populations. A self-assessment scale has been constructed which seeks to overcome such faults. Measures of depression and of anxiety are included, together with measures of outwardly directed irritability and inwardly directed irritability. This scale should be known as the Irritability, Depression, Anxiety--or IDA--Scale.