Response of broiler chickens fed diets supplemented with a bioactive olive pomace extract from Olea europaea to an experimental coccidial vaccine challenge.
This study aimed to investigate an experimental procedure of coccidial challenge in battery cages and the anticoccidial effect of a bioactive olive pomace extract from Olea europaea (OE) in broiler chickens. To this end, four hundred 1-day-old male chicks were randomly assigned to 5 experimental treatments (10 cages/treatment; 8 birds/cage). One group was fed the control diet without any additives and not challenged (NCU). The other 4 groups were challenged and fed the control diet with no additives (NCC) or supplemented with 500 ppm of coccidiostat or with 500 or 1,500 ppm of OE. At 0, 7, and 14 d, all challenged birds, except the NCC group, were orally gavaged with a live Eimeria spp. oocyst vaccine at 1x, 4x, and 16x of the manufacturer's recommended dose, respectively. Feed intake (FI), body weight gain (BWG), and feed conversion ratio (FCR) were determined at 7, 14, 20, and 28 d. At 20 d of age, 1 bird per cage was euthanized to analyze duodenum and jejunum morphology, ileal mucosa gene expression, and plasma cytokine, alpha-1-acid glycoprotein, and carotenoid (CAR) concentrations. Coccidial vaccine challenge lowered BW (P < 0.05) throughout the trial, and reduced FI and BWG, except from 20 to 28d, and increased FCR from 0 to 7, 0 to 14, and 0 to 20 d. Birds in the NCC group had higher (P < 0.05) oocyst counts and lower (P < 0.05) CAR and villus height to crypt depth ratios compared with NCU birds. Overall, coccidia challenge caused the expected reductions in growth performance and gut integrity. While the coccidiostat reduced oocysts excretion, dietary OE or coccidiostat had no effects on performance or gut integrity. The attenuated inflammatory response observed for all the treatments following the third infection can be attributed to the adaptation or immunization to the repetitive exposure to Eimeria spp.


Application of confocal microscopy for surface and volume imaging of solid state nuclear track detectors.
Inhalation of radon gas is considered a risk factor in the development of lung cancer. Solid state nuclear track detectors (SSNTDs) are often used for monitoring radon levels. We have previously shown that 3D imaging can help distinguish real tracks from artefact. In this study, we investigated particle tracks in nine SSNTDs using surface and volume visualisation from confocal microscope imaging. An Olympus LEXT OLS 4000 confocal microscope equipped with the Olympus LEXT Remote Development Kit was used to acquire z-stack images and surface data from the SSNTDs. Surface and volume visualisation analysis methods were developed and applied to examine the data. The mean (standard deviation) depth of 45 tracks from the nine detectors was 9.5 (4.6) μm. The mean difference in track depth using the two analysis techniques was 0.08 μm, thus showing good agreement. Furthermore, volume visualisation should enable assessment of the structure of tracks deep in the detector.


The prevalence of atopy in children with antibodies against hepatitis A virus and hepatitis B virus.
To investigate the relationship between atopy and hepatitis A virus (HAV) and hepatitis B virus (HBV) infections, we studied 42 children who had had HAV infection (Group I), 28 children who had had HBV infection (Group II), and 31 children who were seronegative for both HAV and HBV infection (Control group). Serological tests for HAV and HBV infections (anti-HAV IgG, HBsAg, anti-HBc IgG) and allergic skin tests and specific IgE investigations for the detection of atopy were carried out. In this study, there was no significant divergence in the socio-demographic characteristics among the three groups. The rates of specific IgE positivity in children in the HAV seropositive group (11.9%) and in children in the HBV seropositive group (17.8%) were lower than in the control group (35.4%) (p = 0.03 and p = 0.22, respectively). Also, the number of children with respiratory allergic diseases (allergic rhinitis and/or asthma) both in the HAV seropositive group and in the HBV seropositive group were significantly lower than in the control group (p < 0.05). When atopy in all of the groups was evaluated, the prevalence of atopy was found to be more widespread in HAV seronegative children (Adjusted OR, 9.2; 95% CI, 1.7-48.2) and HBV seronegative children (Adjusted OR, 5.9; 95% CI, 1.1-31.8) than in HAV and HBV seropositive children, after adjustment for age, number of older siblings and education of the father. In conclusion, in this study, the prevalence of atopy in children who had had HAV or HBV infection was found to be low, and this situation was considered to be related to the relationship of HAV and HBV infections to poor hygiene and to the fact that these infections occur at early ages in Turkey.


Exploring early self-referential memory effects through ownership.
The self-reference effect (SRE) is the reliable memory advantage for information encoded about self over material encoded about other people. The developmental pathway of the SRE has proved difficult to chart, because the standard SRE task is unsuitable for young children. The current inquiry was designed to address this issue using an ownership paradigm, as encoding objects in the context of self-ownership have been shown to elicit self-referential memory advantages in adults. Pairs of 4- to 6-year-old children (n = 64) sorted toy pictures into self- and other-owned sets. A surprise recognition memory test revealed a significant advantage for toys owned by self, which decreased with age. Neither verbal ability nor theory of mind attainment predicted the size of the memory advantage for self-owned items. This finding suggests that contrary to some previous reports, memory in early childhood can be shaped by the same self-referential biases that pervade adult cognition.


Interpreting molecular monitoring results and international standardization in chronic myeloid leukemia.
Important advances in the understanding of the molecular basis of chronic myeloid leukemia have resulted in the development of new therapies and changed the paradigm for managing this myeloproliferative disease. Translocation of chromosomes 9 and 22 (known as the Philadelphia chromosome) results in a fusion BCR-ABL gene that produces a dysregulated BCR-ABL tyrosine kinase protein and triggers events leading to malignant transformation. The tyrosine kinase inhibitors imatinib, nilotinib, and dasatinib block the BCR-ABL protein and prevent activation of the transformation pathways. Molecular monitoring, the most sensitive approach currently available to assess treatment response, measures BCR-ABL messenger RNA levels and serves as a surrogate marker of disease. Further, molecular responses are predictive of patient outcomes. It is important for advanced practitioners to become familiar with the technology and interpretation of molecular monitoring results as well as efforts to standardize this type of testing so they can educate their patients and aid their understanding of test results. Undetectable BCR-ABL levels can bring feelings of relief, whereas an increasing level can lead to anxiety. Advanced practitioners, therefore, are an important resource for interpreting results for patients, answering questions, alleviating concerns, and encouraging continued adherence to treatment.


The molecular basis of canine melanoma: pathogenesis and trends in diagnosis and therapy.
Melanoma is a common neoplastic disease of dogs with variable presentation and biological behavior. Canine malignant melanoma is a rapidly metastatic disease that generally is incurable. The loss of function of cellular safeguards built into the genetic program and of immune surveillance systems that cooperate to prevent tumor formation and progression appear to be important underlying causes of canine malignant melanoma. In effect, many existing cancer treatments restore the function of 1 or the other of these mechanisms. For example, chemotherapy and radiotherapy often kill tumor cells by initiating a genetic suicide mechanism (apoptosis), and immunotherapy initiates or enhances a response by the body's immune cells to identify and destroy cancer cells by mechanisms that rely on direct cytotoxicity or apoptotic cell death. Nevertheless, standard therapeutic approaches have not proved effective in treatment of canine malignant melanoma, with only marginal improvement in the outcome of dogs with this disease. The advantages of an improved understanding of the molecular basis of canine cancer are underscored by recent promising advances in diagnosis and in immunologic and genetic therapies that may help reduce the mortality of dogs affected with malignant melanoma.


Hepatic acute phase response protects the brain from focal inflammation during postnatal window of susceptibility.
Perinatal inflammation is known to contribute to neurodevelopmental diseases. Animal models of perinatal inflammation have revealed that the inflammatory response within the brain is age dependent, but the regulators of this variation remain unclear. In the adult, the peripheral acute phase response (APR) is known to be pivotal in the downstream recruitment of leukocytes to the injured brain. The relationship between perinatal brain injury and the APR has not been established. Here, we generated focal inflammation in the brain using interleukin (IL)-1β at postnatal day (P)7, P14, P21 and P56 and studied both the central nervous system (CNS) and hepatic inflammatory responses at 4 h. We found that there is a significant window of susceptibility in mice at P14, when compared to mice at P7, P21 and P56. This was reflected in increased neutrophil recruitment to the CNS, as well as an increase in blood-brain barrier permeability. To investigate phenomena underlying this window of susceptibility, we performed a dose response of IL-1β. Whilst induction of endogenous IL-1β or intercellular adhesion molecule (ICAM)-1 in the brain and induction of a hepatic APR were dose dependent, the recruitment of neutrophils and associated blood-brain barrier breakdown was inversely proportional. Furthermore, in contrast to adult animals, an additional peripheral challenge (intravenous IL-1β) reduced the degree of CNS inflammation, rather than exacerbating it. Together these results suggest a unique window of susceptibility to CNS injury, meaning that suppressing systemic inflammation after brain injury may exacerbate the damage caused, in an age-dependent manner.


Striatal monoamine terminals in Lewy body dementia and Alzheimer's disease.
We used positron emission tomography (PET) with (+)-[(11)C]dihydrotetrabenazine ([+]-[(11)C]DTBZ) to examine striatal monoaminergic presynaptic terminal density in 20 patients with dementia with Lewy bodies (DLB), 25 with Alzheimer's disease (AD), and 19 normal elderly controls. Six DLB patients developed parkinsonism at least 1 year before dementia (DLB/PD) and 14 developed dementia before parkinsonism or at about the same time (DLB/AD). Striatal mean binding potential was decreased by 62 to 77% in the DLB/PD group and 45 to 67% in the DLB/AD compared to AD and control. Binding was lower in the DLB/PD group than the DLB/AD, but the differences reached only marginal significance in the caudate nucleus. No differences were found between AD and control groups though a few AD patients had binding values below the range of the controls. Subsequent neuropathological examination in one AD patient revealed both AD and DLB changes despite the absence of clinical parkinsonism. Both DLB groups had an anterior to posterior binding deficit gradient relative to controls, largest in posterior putamen, smaller in anterior putamen, smallest in caudate nucleus. The DLB/AD group showed significant binding asymmetry only in posterior putamen. We conclude that PET with (+)-[(11)C]DTBZ differentiates DLB from AD, and decreased binding in AD may indicate subclinical DLB pathology in addition to AD pathology.


Left temporal lobe structural and functional abnormality underlying auditory hallucinations in schizophrenia.
In this article, we have reviewed recent findings from our laboratory, originally presented in Hugdahl et al. (2008). These findings reveal that auditory hallucinations in schizophrenia should best be conceptualized as internally generated speech mis-representations lateralized to the left superior temporal gyrus and sulcus, not cognitively suppressed due to enhanced attention to the 'voices' and failure of fronto-parietal executive control functions. An overview of diagnostic questionnaires for scoring of symptoms is presented together with a review of behavioral, structural, and functional MRI data. Functional imaging data have either shown increased or decreased activation depending on whether patients have been presented an external stimulus during scanning. Structural imaging data have shown reduction of grey matter density and volume in the same areas in the temporal lobe. We have proposed a model for the understanding of auditory hallucinations that trace the origin of auditory hallucinations to neuronal abnormality in the speech areas in the left temporal lobe, which is not suppressed by volitional cognitive control processes, due to dysfunctional fronto-parietal executive cortical networks.


[Clinicopathologic and molecular genetic analysis of secretory carcinoma of salivary gland].
Objective: To investigate the clinicopathologic and molecular genetic features of secretory carcinoma of salivary gland (SCSG). Methods: Six cases of SCSG were collected from Zhejiang Provincial People's Hospital from January 2011 to March 2018. The clinical, histopathological and immunohistochemical features were analyzed and fluorescence in situ hybridization (FISH) was used to detect ETV6 gene rearrangement. Results: Four out of 6 tumors originated in the parotid gland and one of each in the minor salivary glands of soft palate and the buccal mucosa. Grossly, 4 cases were solid and 2 were partially cystic with maximum diameter ranging from 1.0 to 4.0 cm. Microscopically, 5 tumors showed typical features of low grade SCSG with tumor divided by thin fibrous septa into lobules composed of solid acinar, microcystic, follicular and papillary structures with abundant extracellular mucinous secretions. The tumor cells had cuolated or hobnail cytoplasm with low-grade nuclei and scarce mitoses. Perineural invasion was present in 1 case. The remaining tumor showed about 30% of the tumor areas with high-grade transformation characterized by proliferation of a distinct population of anaplastic cells arranged in irregular glandular, small nested and single cell patterns that were surrounded by desmoplastic stroma and invaded into surface mucosa with ulceration. Immunohistochemistry showed that all 6 tumors had diffuse and strong reactivities to S100 protein and cytokeratin 7, and 4 cases showed focal reactivity to gross cystic disease fluid protein 15 (GCDFP15), all were negative for discovered on gist 1 (DOG1), cytokeratin 20, p63 and calponin. High grade transformation cases were analysed, the high grade SCSG components showed a significantly increased Ki-67 index and cyclin D1 positive tumor cells compared to the conventional SCSG components. FISH analyses showed that 4 cases had ETV6 gene rearrangement. Eleven to seventy one months' follow-up showed no evidence of tumor recurrence nor metastasis. Conclusions: SCSG harbors characteristic genetic abnormalities with ETV6 gene rearrangement and typically shows a low grade morphology with occasionally, high grade transformation can be present.


Wet mammals shake at tuned frequencies to dry.
In cold wet weather, mammals face hypothermia if they cannot dry themselves. By rapidly oscillating their bodies, through a process similar to shivering, furry mammals can dry themselves within seconds. We use high-speed videography and fur particle tracking to characterize the shakes of 33 animals (16 animals species and five dog breeds), ranging over four orders of magnitude in mass from mice to bears. We here report the power law relationship between shaking frequency f and body mass M to be f ∼ M(-0.22), which is close to our prediction of f ∼ M(-0.19) based upon the balance of centrifugal and capillary forces. We also observe a novel role for loose mammalian dermal tissue: by whipping around the body, it increases the speed of drops leaving the animal and the ensuing dryness relative to tight dermal tissue.


Health risk assessment of chlorobenzenes in the air of residential houses using probabilistic techniques.
A human health risk assessment was performed to evaluate the risks due to chlorobenzenes in the air of residential houses. Chlorobenzenes found in the air in the toilets, rooms, and outdoors of three houses in Brisbane, Australia, were sampled by trapping on Tenax TA and analyzed using an automated thermal desorption (ATD)-gas chromatography/mass spectrometry (GC/MS) method. Concentrations of 1,4-dichlorobenzene (1,4-DCB) in the rooms, toilets, and outdoors were used as the exposure concentrations (E), while those in the toilets (microg/m3) were used as the high-exposure concentrations (HE). The exposure concentrations were transformed into exposure doses (EXD(E) and EXD(HE)). Dose-response data from the literature for a range of adverse effects in animals were obtained and exposure doses were expressed as human equivalent dose (HED). The HED values were higher than the EXD(E) and EXD(HE) values for all adverse effects, and a hazard quotient was calculated that indicated a low level of risk with the high-exposure environment. The lifetime average daily doses (LADDs) for a wide range of adverse effects observed in human case studies were estimated and compared to the doses in the high-exposure (HE) situation. Using the Monte Carlo simulation technique the probabilities of risk quotients higher than unity ranged from 0.02 to 0.26. This evaluation indicated that 1,4-DCB posed low risks to general residents; however, for individuals with susceptible characteristics and exposure to elevated 1,4-DCB, the probability of adverse responses was moderate to high.


Health care provider practices, barriers, and facilitators for weight management for individuals with spinal cord injuries and disorders.
Even though weight management is essential for the health of individuals with spinal cord injuries and disorders (SCI/D), little is known about current practices, barriers, and facilitators. To describe weight management delivery in the Veterans Affairs (VA) SCI/D System of Care, including barriers and facilitators experienced by health care providers. Qualitative focus groups were conducted in person at 4 geographically dispersed VA medical facilities delivering care to Veterans with SCI/D. Thirty-two employees involved in weight management efforts participated. Audio-recordings were transcribed and analyzed using qualitative content analysis techniques. Participants at SCI centers reported that weight management treatment was delivered through the center by a multidisciplinary team using education (eg, written materials) and counseling/consults. Participants at SCI spoke facilities generally depended on facility-level programs (eg, MOVE!) to deliver treatment. Spoke facilities discussed barriers to delivering treatment through their SCI team, including staff shortages and resource and structural issues. MOVE! staff discussed barriers, including limited wheelchair space in classrooms. Staff participants across facilities noted that Veterans with SCI/D were hesitant to use facility-level programs, because of nonspecific SCI-relevant information and discomfort attending sessions with general Veterans. Other barriers, for both centers and spoke facilities, included necessary medications that increase weight, lack of evidence-based guidelines for weight management, safety concerns, and facility layout/accessibility. Facilitators included facility leadership support, provider involvement/prioritization, and community resources. Weight management programs delivered through the SCI team, with peers and SCI-relevant content, are likely more acceptable and beneficial to individuals with SCI/D. Program classrooms should provide ample space for individuals with SCI/D.


Persistence of cholera in the United States.
In 1973, 1978, and 1981, cases of cholera were acquired along the Gulf Coast of the United States. The isolates from all of the cases were toxigenic Vibrio cholerae O-group 1, biotype El Tor, serotype Inaba, hemolytic, and of the same phage sensitivity pattern, and all had the same restriction endonuclease pattern by molecular genetic analysis. The strain from one of the two 1981 cases differed from the others in having a small plasmid and a negative Voges-Proskauer reaction. Multiple importations, chronic carriers, and continuous occurrence of undetected cases are unlikely explanations for these findings, which suggest that toxigenic V. cholerae 01 can multiply and persist for years in some environments, making eradication of cholera a formidable task.


Nutrition and health - the association between eating behavior and various health parameters: a matched sample study.
Population-based studies have consistently shown that our diet has an influence on health. Therefore, the aim of our study was to analyze differences between different dietary habit groups in terms of health-related variables. The sample used for this cross-sectional study was taken from the Austrian Health Interview Survey AT-HIS 2006/07. In a first step, subjects were matched according to their age, sex, and socioeconomic status (SES). After matching, the total number of subjects included in the analysis was 1320 (N = 330 for each form of diet - vegetarian, carnivorous diet rich in fruits and vegetables, carnivorous diet less rich in meat, and carnivorous diet rich in meat). Analyses of variance were conducted controlling for lifestyle factors in the following domains: health (self-assessed health, impairment, number of chronic conditions, vascular risk), health care (medical treatment, vaccinations, preventive check-ups), and quality of life. In addition, differences concerning the presence of 18 chronic conditions were analyzed by means of Chi-square tests. Overall, 76.4% of all subjects were female. 40.0% of the individuals were younger than 30 years, 35.4% between 30 and 49 years, and 24.0% older than 50 years. 30.3% of the subjects had a low SES, 48.8% a middle one, and 20.9% had a high SES. Our results revealed that a vegetarian diet is related to a lower BMI and less frequent alcohol consumption. Moreover, our results showed that a vegetarian diet is associated with poorer health (higher incidences of cancer, allergies, and mental health disorders), a higher need for health care, and poorer quality of life. Therefore, public health programs are needed in order to reduce the health risk due to nutritional factors.


Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life.
Aeroallergen sensitization and virus-induced wheezing are risk factors for asthma development during early childhood, but the temporal developmental sequence between them is incompletely understood. To define the developmental relationship between aeroallergen sensitization and virus-induced wheezing. A total of 285 children at high risk for allergic disease and asthma were followed prospectively from birth. The timing and etiology of viral respiratory wheezing illnesses were determined, and aeroallergen sensitization was assessed annually for the first 6 years of life. The relationships between these events were assessed using a longitudinal multistate Markov model. Children who were sensitized to aeroallergens had greater risk of developing viral wheeze than nonsensitized children (hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.2-3.1). Allergic sensitization led to an increased risk of wheezing illnesses caused by human rhinovirus (HRV) but not respiratory syncytial virus. The absolute risk of sensitized children developing viral wheeze was greatest at 1 year of age; however, the relative risk was consistently increased at every age assessed. In contrast, viral wheeze did not lead to increased risk of subsequent allergic sensitization (HR, 0.76; 95% CI, 0.50-1.1). Prospective, repeated characterization of a birth cohort demonstrated that allergic sensitization precedes HRV wheezing and that the converse is not true. This sequential relationship and the plausible mechanisms by which allergic sensitization can lead to more severe HRV-induced lower respiratory illnesses support a causal role for allergic sensitization in this developmental pathway. Therefore, therapeutics aimed at preventing allergic sensitization may modify virus-induced wheezing and the development of asthma.


Functional evaluation for adequacy of MDCK-lineage cells in influenza research.
Influenza is an acute respiratory disease caused by the influenza virus which circulates annually in populations of different species. Madin-Darby Canine Kidney (MDCK) is the most widely utilized cell-line for conducting influenza research. However, the infectivity of various influenza strains in MDCK cells is not equivalent and the productivity of viral propagation is also limited. We tested the functional adequacy of two MDCK-lineage cell lines, conventional MDCK and MDCK/London, were evaluated by assessing their infectivity of different influenza viral strains with focus forming assays and the cellular toxicity caused by influenza infections by lactate dehydrogenase assay. Moreover, the sensitivity of cells in the presence of the antiviral agent ribavirin was assessed by MTT assay. Our results showed that MDCK/London cells efficiently propagate virus across all influenza viruses tested, are comparable to the utility of Mv1Lu cells, and are superior to conventional MDCK cells in replicating virus as indicated by an increase in virus of three to four logs, particularly in H3N2 infection. Also, the MDCK/London cells were more sensitive to the presence of antiviral drug than conventional MDCK cells. In conclusion, MDCK/London cell line could be a better platform for influenza studies and vaccine development.


Estimating relative risks from significant family-based association studies.
Two approaches are described to estimate relative risks from significant family-based association studies. They can be used to obtain either point estimates or confidence regions. The approaches are evaluated by a simulation study and illustrated by application to a real data set. It is shown that both approaches largely reduce the bias in the relative risk estimates which can occur in case that the significant outcome of the study from which the relative risks are estimated is ignored.


First report of metallic elements in loggerhead and leatherback turtle eggs from the Indian Ocean.
Bio-monitoring of pollutants in long-lived animals such as sea turtles is an important tool in ecotoxicology. We present the first report on metallic elements in sea turtle eggs from the Indian Ocean. Eggs of the leatherback and loggerhead turtle that breed on the Indian Ocean coast of South Africa were analysed for 30 elements. The eggshells and egg contents of the loggerhead turtle, the smaller of the two species, had higher or significantly higher concentrations than leatherbacks, except for strontium - the reason is unknown. Elemental concentrations in eggshells and contents were the same or lower compared with other studies. The differences in concentrations in the egg contents and eggshells between the two species are likely due to different trophic levels, migration patterns, life histories, age, and growth, as well as differences in pollution sources and the uptake, retention and elimination characteristics of the different elements by the different species. We found no congruence between patterns in eggshells and corresponding egg contents, for both species. However, eggshells and egg contents showed congruence between species. The lack of congruence between eggshells and contents within each species precludes using eggshell concentrations as a proxy for egg content concentrations. Copper, strontium, and selenium occurred at concentrations higher than available toxic reverence values. Further research is warranted, including the analyses of POPs, as well as possible deme discrimination based on compositional pattern differences. Turtles serve as 'active samplers' returning to the same location to breed-something that is not practical with marine mammals or elasmobranchs.


Fitness costs of various mobile genetic elements in Enterococcus faecium and Enterococcus faecalis.
To determine the fitness effects of various mobile genetic elements (MGEs) in Enterococcus faecium and Enterococcus faecalis when newly acquired. We also tested the hypothesis that the biological cost of vancomycin resistance plasmids could be mitigated during continuous growth in the laboratory. Different MGEs, including two conjugative transposons (CTns) of the Tn916 family (18 and 33 kb), a pathogenicity island (PAI) of 200 kb and vancomycin-resistance (vanA) plasmids (80-200 kb) of various origins and classes, were transferred into common ancestral E. faecium and E. faecalis strains by conjugation assays and experimentally evolved (vanA plasmids only). Transconjugants were characterized by PFGE, S1 nuclease assays and Southern blotting hybridization analyses. Single specific primer PCR was performed to determine the target sites for the insertion of the CTns. The fitness costs of various MGEs in E. faecium and E. faecalis were estimated in head-to-head competition experiments, and evolved populations were generated in serial transfer assays. The biological cost of a newly acquired PAI and two CTns were both host- and insertion-locus-dependent. Newly acquired vanA plasmids may severely reduce host fitness (25%-27%), but these costs were rapidly mitigated after only 400 generations of continuous growth in the absence of antibiotic selection. Newly acquired MGEs may impose an immediate biological cost in E. faecium. However, as demonstrated for vanA plasmids, the initial costs of MGE carriage may be mitigated during growth and beneficial plasmid-host association can rapidly emerge.


Mitral-valve repair versus replacement for severe ischemic mitral regurgitation.
Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited. We randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank. At 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, -6.6 and -6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P=0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months. We observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.).


Peach Rusty Spot Is Caused by the Apple Powdery Mildew Fungus, Podosphaera leucotricha.
Peach rusty spot, an economically important disease of peach (Prunus persica var. persica), appears as necrotic spots on fruit. The etiology of the disease is still not well understood, although it has long been suspected that the causal agent is the apple powdery mildew pathogen, Podosphaera leucotricha. This work confirmed this hypothesis based on cross-inoculation experiments and analysis of rDNA internal transcribed spacer sequences polymerase chain reaction amplified from rusty spot and peach powdery mildew lesions. Cross-inoculations of apple and peach leaves with P. leucotricha and P. pannosa, the causal agent of peach powdery mildew, showed that (i) young peach fruit, up to 5 cm in diameter, developed symptoms typical of rusty spot following inoculation with P. leucotricha; (ii) leaves of 'Jonagold' apple seedlings developed powdery mildew infections when inoculated by touching young rusty spot lesions to their surfaces; (iii) P. leucotricha sporulated on young peach fruit up to 5 cm in diameter; and (iv) peach leaves and young shoots were not susceptible to P. leucotricha, whereas P. pannosa infected all the green parts of peach. A field experiment revealed that there was only a 2- to 3-week period of time during early peach fruit development when the epidermis was susceptible to P. leucotricha. An outcome of this study is that now a clear distinction can be made between the symptoms caused by P. pannosa and P. leucotricha on peach.


High-speed pattern projection for three-dimensional shape measurement using laser speckles.
We propose a high-speed projection system that is able to project statistical speckle patterns at a rate of 500Hz. Its purpose is to generate structured light for a real-time photogrammetry stereo vision setup. As conventional digital light projector (DLP) projection setups are limited in their maximum projection rate to 250Hz for gray-value patterns, stripe projection systems are usually applied for real-time three-dimensional (3D) measurements. However, these techniques can only be used on steady surfaces as phase unwrapping has to be done. In contrast, the proposed setup is able to measure the shape of multiple spatially separated objects at once. We compare the speckle setup with a system using a DLP projector and with other fast 3D shape measurement setups, like the widely used stripe projection methods, qualitatively and quantitatively.


Abiraterone in metastatic prostate cancer without previous chemotherapy.
Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival. The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone-prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone-prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P=0.01) but did not cross the efficacy boundary. Abiraterone-prednisone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone. Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.).


How well does the MESTT correlate with CTCAE scale for the grading of dermatological toxicities associated with oral tyrosine kinase inhibitors?
Dermatological toxicities associated with tyrosine kinase inhibitors (TKIs) are commonly graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). A new tool has been proposed by the Multinational Association for Supportive Care in Cancer (MASCC), namely the MASCC EGFRI Skin Toxicity Tool (MESTT), as a class-specific grading system. This study was designed to assess the correlation between the severity grading of the dermatological toxicities associated with TKIs using the NCI-CTCAE v4.0 and the MESTT. One hundred patients were interviewed at the National Cancer Centre Singapore with the criteria of being on erlotinib, gefitinib, lapatinib, sorafenib, or sunitinib over 2 weeks and manifested dermatological toxicities. Dermatological toxicities were graded using CTCAE and MESTT 1, respectively, by a single observer. Spearman's correlation test was performed on the results. Sixty-five patients (65%) experienced papulopustular rash, 72 patients (72%) had pruritus, 85 patients (85%) had xerosis, 33 patients (33%) experienced nail changes, and 24 patients (24%) had alopecia. There was significant positive correlation between the two grading systems for all investigated dermatological toxicities, namely rash (r = 0.734), pruritus (r = 0.917), xerosis (r = 0.635), and paronychia (r = 0.611) at 99% confidence level. Good correlation was observed between the scales, but there is a tendency for the MESTT tended to report higher toxicity grades for rash, xerosis, and paronychia. The MESTT was also found to be more useful to grade rash specific to TKIs and had similar usefulness for grading other studied toxicities.


Application of computational methods to the design and characterisation of porous molecular materials.
Composed from discrete units, porous molecular materials (PMMs) possess unique properties not observed for conventional, extended, solids, such as solution processibility and permanent porosity in the liquid phase. However, identifying the origin of porosity is not a trivial process, especially for amorphous or liquid phases. Furthermore, the assembly of molecular components is typically governed by a subtle balance of weak intermolecular forces that makes structure prediction challenging. Accordingly, in this review we canvass the crucial role of molecular simulations in the characterisation and design of PMMs. We will outline strategies for modelling porosity in crystalline, amorphous and liquid phases and also describe the state-of-the-art methods used for high-throughput screening of large datasets to identify materials that exhibit novel performance characteristics.


Evolutionary recombination hotspot around GSDML-GSDM locus is closely linked to the oncogenomic recombination hotspot around the PPP1R1B-ERBB2-GRB7 amplicon.
PPP1R1B-STARD3-TCAP-PNMT-PERLD1-ERBB2-MGC14832-GRB7 locus at human chromosome 17q12 is frequently amplified in human gastric cancer and breast cancer. Here, we compared human GSDML-GSDM locus with rodent genomes by using bioinformatics. Rodent ortholog of human GSDML was not identified. Rat Gsdm gene was identified within rat genome clone CH230-28N16 (AC119462.4), and was mapped to rat chromosome 10q31. Rat Gsdm gene, consisting of 12 exons, encoded a 446-amino-acid protein, which showed 86.3% and 32.3% total-amino-acid identities with human GSDM and GSDML, respectively. Mouse Gsdm-like 1 (Gsdml1) and Gsdml2 genes were identified within mouse genome clone RP23-438D7 (AL591125.20). Gsdml1 and Gsdml2 genes were found to encode 456- and 443-amino-acid proteins, respectively. Mouse 2200001G21Rik cDNA (AK008613.1) was a partial cDNA derived from mouse Gsdml2 gene. Mouse Gsdml1 and Gsdml2 were also more homologous to human GSDM than to human GSDML. Mouse Gsdml1, Gsdml2 and Gsdm genes, existing in the tandem homologous gene cluster, was mapped to mouse chromosome 11D. Mouse Gsdml1-Gsdml2-Gsdm gene cluster was predicted to be generated due to triplication of mouse Gsdm gene, while GSDML gene was predicted to be generated due to duplication of GSDM gene. Evolutionary recombination hotspot around the GSDML-GSDM locus was closely linked to the oncogenomic recombination hotspot around the PPP1R1B-ERBB2-GRB7 amplicon. The evolutionary recombination hotspot and oncogenomic recombination hotspot might be clustered around the fragile sites within the human genome.


Cervicocerebral artery dissections.
To determine the aetiology, frequency, presentation, and outcome of blunt cervicocerebral arterial dissection presentations. Cases were retrospectively identified through the stroke registers at Royal Melbourne Hospital (a tertiary teaching hospital) and Geelong Hospital (a regional referral centre). Medical notes were then reviewed. A total of 18 cases were identified, with ages ranging from 28 to 53 years. Fifty five per cent of the injuries sustained were to the internal carotid artery and 45% to the vertebral artery. The majority of the injuries were either spontaneous or associated with trivial forces. Other causes included motor vehicle accidents, falls, and cervical manipulations. Fifty five per cent of patients complained of significant neck pain before presentation. Most patients had delayed presentations, with only 39% presenting on the day of the incident. Seventy eight per cent presented with a neurological deficit. Initial computed tomography was normal in 71% of patients. The majority of patients were managed with anticoagulation, and had minimal functional deficit on discharge. Other treatment modalities included surgery (one patient) and thrombolysis (two patients). One patient was managed conservatively. The incidence of blunt cervicocerebral arterial dissection is unknown; however it is an uncommon diagnosis. The most common presentation is that of a delayed neurological event. Initial brain computed tomography is usually normal. Minimal adverse outcomes at discharge were noted in patients treated with anticoagulation only.


Application of High-Throughput Screening Raman Spectroscopy (HTS-RS) for Label-Free Identification and Molecular Characterization of Pollen.
Pollen studies play a critical role in various fields of science. In the last couple of decades, replacement of manual identification of pollen by image-based methods using pollen morphological features was a great leap forward, but challenges for pollen with similar morphology remain, and additional approaches are required. Spectroscopy approaches for identification of pollen, such as Raman spectroscopy has potential benefits over traditional methods, due to the investigation of the intrinsic molecular composition of a sample. However, current Raman-based characterization of pollen is complex and time-consuming, resulting in low throughput and limiting the statistical significance of the acquired data. Previously demonstrated high-throughput screening Raman spectroscopy (HTS-RS) eliminates the complexity as well as human interaction by incorporation full automation of the data acquisition process. Here, we present a customization of HTS-RS for pollen identification, enabling sampling of a large number of pollen in comparison to other state-of-the-art Raman pollen investigations. We show that using Raman spectra we are able to provide a preliminary estimation of pollen types based on growth habits using hierarchical cluster analysis (HCA) as well as good taxonomy of 37 different Pollen using principal component analysis-support vector machine (PCA-SVM) with good accuracy even for the pollen specimens sharing similar morphological features. Our results suggest that HTS-RS platform meets the demands for automated pollen detection making it an alternative method for research concerning pollen.


Chemotaxis-mediated scission contributes to efficient cytokinesis in Dictyostelium.
Interphase amoeba of Entamoeba invadens are attracted to the furrowing region of a neighboring dividing cell to assist with the division. A seemingly similar behavior has been observed in Dictyostelium discoideum, but in this case, it has not been shown whether the movements were truly directed toward the furrowing region or whether they have any relevance. We thus used myosin II-null cells, which spend more time than wild type cells in cytokinesis, and successfully demonstrated that nearly half of the division events involve the attraction of a neighbor cell to the furrowing region. Cells lacking the beta subunit of the trimeric G protein (Gbeta), which are incapable of chemotaxis, did not show such midwifery. Culturing wild type cells flattened under agarose sheets also slowed the cytokinesis process, and this allowed us to demonstrate that phosphatidylinositol trisphosphate was enriched in the anterior region of midwifing cells, consistent with the view that midwifery in D. discoideum is also chemotaxis. On substrates, while only 3.6% of wild type cells were multinucleate, 8.1% of Gbeta-null cells were multinucleate, and this was reduced to 3.4% when they were surrounded by wild type cells. Conversely, multinucleated wild type cells increased to 6.8% when they were surrounded by Gbeta-null cells. Thus, Gbeta-null cells frequently fail to divide because they cannot assist each other's division and midwifery ensures successful cytokinesis in Dictyostelium discoideum.


Outlier loci highlight the direction of introgression in oaks.
Loci considered to be under selection are generally avoided in attempts to infer past demographic processes as they do not fit neutral model assumptions. However, opportunities to better reconstruct some aspects of past demography might thus be missed. Here we examined genetic differentiation between two sympatric European oak species with contrasting ecological dynamics (Quercus robur and Quercus petraea) with both outlier (i.e. loci possibly affected by divergent selection between species or by hitchhiking effects with genomic regions under selection) and nonoutlier loci. We sampled 855 individuals in six mixed forests in France and genotyped them with a set of 262 SNPs enriched with markers showing high interspecific differentiation, resulting in accurate species delimitation. We identified between 13 and 74 interspecific outlier loci, depending on the coalescent simulation models and parameters used. Greater genetic diversity was predicted in Q. petraea (a late-successional species) than in Q. robur (an early successional species) as introgression should theoretically occur predominantly from the resident species to the invading species. Remarkably, this prediction was verified with outlier loci but not with nonoutlier loci. We suggest that the lower effective interspecific gene flow at loci showing high interspecific divergence has better preserved the signal of past asymmetric introgression towards Q. petraea caused by the species' contrasting dynamics. Using markers under selection to reconstruct past demographic processes could therefore have broader potential than generally recognized.


The unique effects of forgiveness on health: an exploration of pathways.
The relationship of forgiveness, both state and trait, to health was assessed. Eighty-one community adults completed a packet of questionnaires and participated in a laboratory interview about a time of hurt or betrayal. Heart rate and blood pressure were recorded during a 10 min baseline, the interview and during a recovery period; interviews were structured around a framework of questions and videotaped. Four measures of forgiveness were all statistically associated with five measures of health (physical symptoms, medications used, sleep quality, fatigue, and somatic complaints). Trait forgiveness was associated with decreased reactivity (rate-pressure product) to the interview, but sympathetic reactivity did not account for the trait forgiveness-health association. Four mechanisms or pathways by which forgiveness could lead to fewer physical symptoms were examined: spirituality, social skills, reduction in negative affect, and reduction in stress. All factors either partially or fully mediated the effect of forgiveness on health; however, the strongest mediator for both state and trait forgiveness was reduction in negative affect. For state forgiveness, the second strongest mediator was reduction in stress; for trait forgiveness, both conflict management and reduction in stress were strong contributors.


Risk management of excreta in a cancer unit.
Although many legal and clinical requirements are in effect for the preparation and administration of the antineoplasic drugs, limited data exist on the potential cytotoxic risk to healthcare personnel from exposure of excreta (urine, feces, expectorations, saliva, perspiration, and vomiting) from patients. A preliminary risk analysis was conducted with a multidisciplinary work group. The objectives were to identify all potential hazards and accidental events that may lead to an accident related to the excreta management and to implement a global risk reduction and quality improvement policy. The findings revealed the potential risks of excreta contamination in health service and led to recommendations for the healthcare team to optimize working conditions, ensure public protection and occupational health, and promote environmental and employee safety.


Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust.
Diesel exhaust is a common air pollutant made up of several gases, hydrocarbons, and particles. An experimental study was carried out which was designed to evaluate if a particle trap on the tail pipe of an idling diesel engine would reduce effects on symptoms and lung function caused by the diesel exhaust, compared with exposure to unfiltered exhaust. Twelve healthy non-smoking volunteers (aged 20-37) were investigated in an exposure chamber for one hour during light work on a bicycle ergometer at 75 W. Each subject underwent three separate double blind exposures in a randomised sequence: to air and to diesel exhaust with the particle trap at the tail pipe and to unfiltered diesel exhaust. Symptoms were recorded according to the Borg scale before, every 10 minutes during, and 30 minutes after the exposure. Lung function was measured with a computerised whole body plethysmograph. The ceramic wall flow particle trap reduced the number of particles by 46%, whereas other compounds were relatively constant. It was shown that the most prominent symptoms during exposure to diesel exhaust were irritation of the eyes and nose and an unpleasant smell increasing during exposure. Both airway resistance (R(aw)) and specific airway resistance (SR(aw)) increased significantly during the exposures to diesel exhaust. Despite the 46% reduction in particle numbers by the trap effects on symptoms and lung function were not significantly attenuated. Exposure to diesel exhaust caused symptoms and bronchoconstriction which were not significantly reduced by a particle trap.


Discovery of common and rare genetic risk variants for colorectal cancer.
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.


Are epilepsy patients bypassing primary care? A cross-sectional study from India.
Lack of epilepsy primary and secondary care and an arbitrary referral system causes many epilepsy patients to seek tertiary care even when they may not need it. This causes overcrowding, increased waiting times and also compromises the quality of tertiary care. We conducted this study to identify what proportion of epilepsy patients presenting to tertiary care actually needed it. To test appropriateness of candidacy for tertiary care, we formulated Modified NICE criteria (MNC) based on NICE criteria. Modified NICE criteria were used to dichotomize participants into two groups: a) those who needed tertiary care and b) those who did not need tertiary care. We also looked at agreement between MNC and original NICE criteria. Four hundred and twenty two patients were recruited. According to the MNC, 240 patients (57%) qualified for tertiary care while 182 (43%) did not. The agreement between MNC and original NICE criteria was 86.7%, kappa 0.73(95% CI 0.66-0.79, p < 0.001). The most frequently cited reason for seeking tertiary care was 'Unsatisfactory response to treatment', although; many of these patients were actually non-adherent to treatment. Amongst variables that predicted non-eligibility for tertiary care, the most important was not having been referred. Many epilepsy patients seeking tertiary care do not need it. Access and quality of epilepsy care can be improved if there is a rational and need-based distribution of patients between primary, secondary and tertiary care. Referral systems also need to be developed and used to transition patients from one level of care to another.


Platelet transfusions for patients with haematological malignancies: who needs them?
The goal of platelet transfusions is to prevent severe and life-threatening bleeding in patients with thrombocytopenia. This aim needs to be balanced against the risks associated with platelet transfusions as well as the challenge of maintaining an adequate supply. This review summarizes the recent evidence regarding the clinical use of platelet transfusions in haematology patients, concentrating on the topics that still continue to provoke debate. These include the optimal dose for platelet transfusions and the relative safety of a 'therapeutic only' platelet transfusion strategy compared to the use of prophylactic platelet transfusions. The type of platelet product has been the subject of two recent systematic reviews. The results of these reviews will be discussed as well as their implications for current practice.


Oxidation of dietary linoleate occurs to a greater extent than dietary palmitate in vivo in humans.
It has been suggested that dietary polyunsaturated fatty acids (PUFA) are partitioned into oxidation pathways to a greater extent than dietary saturated fatty acids (SFA). Whilst this has been demonstrated in animal models, evidence in humans is lacking. The potential divergence in the metabolic fate of these dietary fatty acids (FA) may explain some of the reported differences in ectopic fat deposition with SFA and PUFA enriched diets. To compare whole-body oxidation of dietary palmitate and linoleate after consumption of a single test meal. In a randomized, crossover design 24 healthy volunteers (12 males and 12 females, matched for age and BMI) underwent two study days separated by 2-week washout period. During each study day participants consumed a standardized test meal which contained [U13C]palmitate or [U13C]linoleate. Blood and breath samples were collected over the 6 h postprandial period and the 13C enrichment in breath CO2 samples and plasma lipid fractions was determined. Appearance of 13C in expired CO2 was significantly (p < 0.05) increased after consumption of the meal containing [U13C]linoleate compared to the meal containing [U13C]palmitate. The recovery of tracer was 8.9 ± 1.2% [U13C]linoleate vs. 5.6 ± 0.4% [U13C]palmitate (p < 0.05). The incorporation of 13C from [U13C]palmitate was greater in plasma triacylglycerol and non-esterified fatty acids than [U13C]linoleate, whereas the incorporation of 13C from [U13C]linoleate was greater than [U13C]palmitate in plasma phospholipids. Although 13CO2 was significantly (p < 0.05) higher in females compared to males after consumption of [U13C]palmitate, there was no difference in 13CO2 between sexes after consumption of [U13C]linoleate. We demonstrate that whole-body oxidation of dietary linoleate is comparatively higher than that of dietary palmitate in humans following consumption of a single mixed-test meal. We found indications of sexual dimorphism for dietary palmitate but not dietary linoleate. http://www.clinicaltrials.org/ ID number NCT03587753.


Kinetics of protein binding determine rates of uptake of drugs by brain.
A mathematical model describing the kinetics of binding and release of substances by plasma proteins is presented. The effects of protein binding on the uptake of substances such as drugs from the capillary network of the brain are discussed. The model assumes equilibration between bound and free forms of drug in arterial blood and incorporates the on-off rate constants for the drug-protein complex and rate constants for passage of free drug across the blood-brain barrier and for drug metabolism in the brain. Regional cerebral blood flow and the related capillary transit time are important parameters in the model. Analytical expressions for bound and free drug concentrations and for the net extraction of drug are derived where practicable, and numerical solutions also are presented. Effects of changes in the total drug and protein concentrations in the plasma are discussed with special reference to the uptake of bilirubin by the brain.


Peripheral dopamine in pathophysiology of hypertension. Interaction with aging and lifestyle.
Dopamine, an ancestral catecholamine, is physiologically natriuretic and vasodilating, thus essentially protecting against hypertension. Its actions are overshadowed by the opposite effects of its main biological partner, norepinephrine, and this is accentuated with aging. Clinical observations combined with molecular biology approaches to catecholamine-synthesizing and catecholamine-metabolizing enzymes and receptors permit the identification of some inborn defects. Subtle changes in the dopamine-norepinephrine balance may account for the enhanced peripheral noradrenergic activity seen in the setting of decreased dopaminergic activity in advanced age. These changes may contribute to the diminished ability of the aged kidney to excrete a salt load, as well as to the finding that systolic blood pressure increases with age in populations with a high, but not in those with a low, intake of salt. The attainment of advanced age in Western societies with adverse lifestyle changes (mental rather than physical stress, excess salt intake, overeating, sedentarism) appears to facilitate the development of hypertension. The adaptation to all the preceding lifestyle changes necessitates an increased dopamine generation, which may initially compensate to maintain appropriate natriuresis and vasodilation since many patients with initial borderline essential hypertension express their sympathetic hyperfunction, in addition to increased norepinephrine release, by excessive dopamine release. However, the progression of hypertension is accompanied by a peripheral dopaminergic deficiency and diminished ability to excrete salt. This may represent an eventual inadequacy of a phylogenetically redundant system resulting in decreased natriuresis and vasodilation and may account for the responsiveness of established chronic hypertension to salt restriction, diuretics, and dopaminomimetic medication.


PERIOD3 polymorphism is associated with sleep quality recovery after a mild traumatic brain injury.
Mild traumatic brain injury (mTBI) causes transient sleep disorders and circadian dysrhythmia. One of the clock genes, PERIOD3 (PER3), regulates the circadian rhythm and contains a genetic polymorphism, namely a variable-number tandem repeat in the coding area with either four or five repeats. PER3(5) carriers are inclined to have a morning preference and associated with higher risk of bipolar disorder and diabetes. This study investigated the effects of PER3 polymorphism on sleep quality changes after mTBI. From May 2012 to May 2014, a total of 96 mTBI patients completed the baseline (1 week after mTBI) and follow-up (6 weeks after mTBI) assessments, including the Pittsburgh Sleep Quality Index (PSQI) and anxiety and depression questionnaires. Statistics were analyzed using the Mann-Whitney U test, Wilcox signed-rank test or chi-squared test. Among the 96 patients, 24 were heterozygous PER3(5) carriers (PER3(4/5)), and the rest of 72 were PER3(5) noncarriers (PER3(4/4)). The subscale of PSQI questionnaire results indicated that the PER3(5) allele was associated with significant sleep duration shortening, but improvement in overall sleep quality. Furthermore, analyzing patients with sleep disturbance at the baseline (PSQI >5) revealed that only the PER3(5) noncarriers exhibited a significant improvement in overall PSQI scores. PER3(5) carriers exhibited sleep duration shortening and improved daytime function 6 weeks after mTBI compared with the baseline values. On the other hand, among poor sleepers, PER3(5) carriers did not embrace a significant improvement of overall PSQI scores as noncarriers. The underlying mechanisms and clinical significances must be investigated further.


Thiamine deficiency in Gambian women of reproductive age.
Thiamine deficiency disorders are associated with a variety of clinical symptoms affecting the nervous and cardiovascular systems. There is growing recognition that thiamine deficiency can occur in populations well beyond the classical region of South Asia, and at-risk populations include those who receive a large proportion of their energy from polished white rice (or other low-thiamine staple foods) and with low dietary diversity. Reports of thiamine deficiency in West Africa over the last century have suggested that this has historically been an issue in this population, but in more recent decades, these reports have been limited to prison populations. To understand if thiamine deficiency might be an unrecognized problem in the communities of this region, erythrocyte samples collected during the wet and dry seasons from 226 women of reproductive age (mean age = 28 years old) were assessed for thiamine status by measuring the erythrocyte transketolase activity coefficient (ETKac). Overall, 35.8% of the sample was at high risk of thiamine deficiency (ETKac ≥ 1.25). Risk of thiamine deficiency was significantly higher in the wet (47.9%) compared with the dry season (22.9%) (P < 0.001). To our knowledge, this is the first report of biochemical thiamine deficiency in a free-living population in West Africa in the 21st century and suggests that further investigation is warranted.


Unrelated donor transplants in adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission.
We report the retrospective outcomes of unrelated donor (URD) transplants in 169 patients with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) who received transplants between 1995 and 2004. Median age was 33 years (range, 16-59 years). A total of 50% had a white blood cell count (WBC) more than 30 x 10(9)/L, 18% extramedullary disease, 42% achieved CR more than 8 weeks from diagnosis, 25% had adverse cytogenetics, and 19% had T-cell leukemia. A total of 41% were HLA well-matched, 41% partially matched with their donors, and 18% were HLA-mismatched. At 54-month median follow-up, incidences of acute grade 2-IV, III to IV, and chronic graft-versus-host disease were 50%, 25%, and 43%, respectively. Five-year treatment-related mortality (TRM), relapse, and overall survival were 42%, 20%, and 39%, respectively. In multivariate analyses, TRM was significantly higher with HLA-mismatched donors and T-cell depletion. Relapse risk was higher if the diagnostic WBC was more than 100 x 10(9)/L. Factors associated with poorer survival included WBC more than 100 x 10(9)/L, more than 8 weeks to CR1, cytomegalovirus seropositivity, HLA mismatching, and T-cell depletion. Nearly 40% of adults with ALL in CR1 survive 5 years after URD transplantation. Relapse risks were modest; TRM is the major cause of treatment failure. Selecting closely HLA-matched URD and reducing TRM should improve results.


Outcome Comparison of Graft Bridging and Superior Capsule Reconstruction for Large to Massive Rotator Cuff Tears: A Systematic Review.
Graft bridging (GB) and superior capsule reconstruction (SCR) were developed to treat large to massive rotator cuff tears (RCTs); however, the outcome differences between GB and SCR remain unclear. To systematically review and compare the outcomes of GB and SCR for large to massive RCT. Systematic review. A systematic review was performed via a comprehensive search of PubMed, Embase, and the Cochrane Library. Studies of GB or SCR were included according to the inclusion and exclusion criteria. The primary outcome was Constant-Murley score at the final follow-up. Secondary outcomes included the American Shoulder and Elbow Surgeons score, visual analog scale score for pain, active shoulder range of motion, and graft healing rate. Complication rate was the safety outcome measure. Outcomes were summarized into group SCR and group GB, and the results were compared statistically (P < .05). A total of 23 studies were included in this review: 238 repairs from the 5 studies in group SCR and 593 repairs from the 18 studies in group GB. For group SCR and group GB, the mean age was 61.6 and 63.3 years, and the mean follow-up was 18.0 and 40.1 months, respectively. Overall, both procedures demonstrated improvement of clinical outcomes. When compared with group SCR, group GB had significantly higher mean differences of the Constant-Murley score (41.9 vs 19.8), American Shoulder and Elbow Surgeons score (39.3 vs 33.8), visual analog scale score for pain (4.4 vs 3.4), and active external rotation at side (15.3 vs 9.3). No statistically significant difference was detected in the mean difference of active forward flexion, internal rotation, abduction, and graft healing rate between the groups. The complication rates were 0.84% (2 of 238) in group SCR and 0.67% (4 of 593) in group GB. In general, GB showed significantly better clinical and functional outcomes postoperatively than SCR, with a similar complication rate. The available fair-quality evidence suggested that GB might be a better choice for large to massive RCT. More high-quality randomized controlled studies are required to further evaluate the relative benefits of the 2 procedures.


Microevolution of the Chibcha-speaking peoples of lower Central America: rare genes in an Amerindian complex.
Models are developed for the survival, history, and spread of variant alleles, in order to consider what can, and what cannot, be inferred from this type of data. The high variances of the processes involved, and questions of sampling, place severe limitations on inferences. Nonetheless, by combining information on a number of rare variants observed in a group of interrelated populations, reliable qualitative inferences are possible. These ideas and models are developed in the context of data on five rare variants and six private polymorphisms observed in eight Chibcha-speaking tribes of Costa Rica and Panama. The decline and fragmentation of the Amerindian populations of Central America over the last 300 years create considerable difficulties in attempting inference of past genetic events. However, these tribes have been well studied genetically, anthropologically, and linguistically and thus provide an excellent framework for the study of rare-variant spread.


Public support for conserving bird species runs counter to climate change impacts on their distributions.
There is increasing evidence that global climate change will alter the spatiotemporal occurrences and abundances of many species at continental scales. This will have implications for efficient conservation of biodiversity. We investigate if the general public in Denmark are willing to pay for the preservation of birds potentially immigrating and establishing breeding populations due to climate change to the same extent that they are for native species populations currently breeding in Denmark, but potentially emigrating due to climate change. We find that Danish citizens are willing to pay much more for the conservation of birds currently native to Denmark, than for bird species moving into the country--even when they are informed about the potential range shifts associated with climate change. The only exception is when immigrating species populations are under pressure at European level. Furthermore, people believing climate change to be man-made and people more knowledgeable about birds tended to have higher WTP for conservation of native species, relative to other people, whereas their preferences for conserving immigrant species generally resembled those of other people. Conservation investments rely heavily on public funding and hence on public support. Our results suggest that cross-country coordination of conservation efforts under climate change will be challenging in terms of achieving an appropriate balance between cost-effectiveness in adaptation and the concerns of a general public who seem mostly worried about protecting currently-native species.


A 4- to 6-year retrospective clinical study of cracked teeth restored with bonded indirect resin composite onlays.
The purpose of this study was to retrospectively evaluate the clinical performance of bonded indirect resin composite onlays for the treatment of painful, cracked teeth over a 6-year period. Forty-three posterior teeth diagnosed as having a crack were selected in the restorative department of the University of Genoa. Inclusion criteria were sensitivity to biting and cold and a clinically visible crack. Direct composite buildup after removal of the existing restoration was performed before definitive cavity preparation. All composite onlay restorations were cemented with an adhesive technique using a 3-step total etch system and a dual-cure composite cement. Patients were interviewed and clinically examined at 1 week, 4 weeks, and every 6 months. The effectiveness of bonded onlay restorations was evaluated for a mean observation time of 4.78 years. At 1 week, 38 (88.37%) restored teeth were free of pain, 3 (6.98%) still had sensitivity to cold, and 2 (4.65%) still had sensitivity to cold and chewing. At 4 weeks, 40 (93.02%) teeth were free of pain, 2 (4.65%) still had sensitivity to cold and chewing, and 1 (2.32%) needed endodontic treatment. Two other teeth (4.65%) also needed endodontic treatment, the first after 2 months and the second after 5 months. During the evaluation period, 3 restorations (6.98%) failed, and upon clinical examination, 40 (93.02%) teeth were free of symptoms with a 6-year survival rate of 93.02% (life table analysis). Bonded indirect resin composite onlays can be successful in treating painful, cracked teeth. From the findings of this study, it appears that cuspal protection should be incorporated into the design of coronal restorations.


Dietary gallic acid and anthocyanin cytotoxicity on human fibrosarcoma HT1080 cells. A study on the mode of action.
Gallic acid and anthocyanins are abundant plant food bioactives present in many fruits and vegetables, being especially important in the composition of berries. Gallic acid has been shown to possess cytotoxic properties in several cancer cell lines and to inhibit carcinogenesis in animal models. However, its mechanism of action is not yet fully understood. The aim of this study was to elucidate whether the observed inhibitory activity of gallic acid against gelatinases corresponds to its cytotoxic activity in HT1080 cells and to determine if anthocyanins could exhibit a similar behavior. Gallic acid and delphinidin-3-glucoside have shown selective cytotoxicity towards HT1080 cells. Further analysis by a migration and invasion assay showed anti-invasive activities of gallic acid, delphinidin and pelargonidin-3-glucosides. Zymographic analysis demonstrated the inhibitory activity of gallic acid at the level of secreted and activated gelatinases. Moreover, gallic acid inhibited MMP-2 and MMP-9 proteolytic activity with very similar potency. NMR and molecular modelling experiments confirmed the interaction of gallic acid with MMP-2, and suggested that it takes place within the catalytic center. In this work we give some new experimental data supporting the role of these compounds in the inhibition of metalloproteases as the mechanism for their cytotoxic activity against fibrosarcoma.


Optimized flocking of autonomous drones in confined environments.
We address a fundamental issue of collective motion of aerial robots: how to ensure that large flocks of autonomous drones seamlessly navigate in confined spaces. The numerous existing flocking models are rarely tested on actual hardware because they typically neglect some crucial aspects of multirobot systems. Constrained motion and communication capabilities, delays, perturbations, or the presence of barriers should be modeled and treated explicitly because they have large effects on collective behavior during the cooperation of real agents. Handling these issues properly results in additional model complexity and a natural increase in the number of tunable parameters, which calls for appropriate optimization methods to be coupled tightly to model development. In this paper, we propose such a flocking model for real drones incorporating an evolutionary optimization framework with carefully chosen order parameters and fitness functions. We numerically demonstrated that the induced swarm behavior remained stable under realistic conditions for large flock sizes and notably for large velocities. We showed that coherent and realistic collective motion patterns persisted even around perturbing obstacles. Furthermore, we validated our model on real hardware, carrying out field experiments with a self-organized swarm of 30 drones. This is the largest of such aerial outdoor systems without central control reported to date exhibiting flocking with collective collision and object avoidance. The results confirmed the adequacy of our approach. Successfully controlling dozens of quadcopters will enable substantially more efficient task management in various contexts involving drones.


Repbase Update, a database of eukaryotic repetitive elements.
Repbase Update is a comprehensive database of repetitive elements from diverse eukaryotic organisms. Currently, it contains over 3600 annotated sequences representing different families and subfamilies of repeats, many of which are unreported anywhere else. Each sequence is accompanied by a short description and references to the original contributors. Repbase Update includes Repbase Reports, an electronic journal publishing newly discovered transposable elements, and the Transposon Pub, a web-based browser of selected chromosomal maps of transposable elements. Sequences from Repbase Update are used to screen and annotate repetitive elements using programs such as Censor and RepeatMasker. Repbase Update is available on the worldwide web at http://www.girinst.org/Repbase_Update.html.


Testing Sleep Consolidation in Skill Learning: A Field Study Using an Online Game.
Using an observational sample of players of a simple online game (n > 1.2 million), we are able to trace the development of skill in that game. Information on playing time, and player location, allows us to estimate time of day during which practice took place. We compare those whose breaks in practice probably contained a night's sleep and those whose breaks in practice probably did not contain a night's sleep. Our analysis confirms experimental evidence showing a benefit of spacing for skill learning, but it fails to find any additional benefit of sleeping during a break from practice. We discuss reasons why the well-established phenomenon of sleep consolidation might not manifest in an observational study of skill development. We put the spacing effect into the context of the other known influences on skill learning: improvement with practice, and individual differences in initial performance. Analysis of performance data from games allows experimental results to be demonstrated outside of the lab and for experimental phenomenon to be put in the context of the performance of the whole task.


Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders.
To evaluate clinical features among patients with neuromyelitis optica spectrum disorders (NMOSD) who have myelin oligodendrocyte glycoprotein (MOG) antibodies, aquaporin-4 (AQP4) antibodies, or seronegativity for both antibodies. Sera from patients diagnosed with NMOSD in 1 of 3 centers (2 sites in Brazil and 1 site in Japan) were tested for MOG and AQP4 antibodies using cell-based assays with live transfected cells. Among the 215 patients with NMOSD, 7.4% (16/215) were positive for MOG antibodies and 64.7% (139/215) were positive for AQP4 antibodies. No patients were positive for both antibodies. Patients with MOG antibodies represented 21.1% (16/76) of the patients negative for AQP4 antibodies. Compared with patients with AQP4 antibodies or patients who were seronegative, patients with MOG antibodies were more frequently male, had a more restricted phenotype (optic nerve more than spinal cord), more frequently had bilateral simultaneous optic neuritis, more often had a single attack, had spinal cord lesions distributed in the lower portion of the spinal cord, and usually demonstrated better functional recovery after an attack. Patients with NMOSD with MOG antibodies have distinct clinical features, fewer attacks, and better recovery than patients with AQP4 antibodies or patients seronegative for both antibodies.


Dietary habits and pancreatic cancer risk in a cohort of middle-aged and elderly Japanese.
Few epidemiological studies have examined associations between diet and pancreatic cancer in Japan. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, we evaluated the relationship between dietary factors, including meat, vegetable, and fruit intake, and the risk of pancreatic cancer deaths. Among the original cohort established between 1988 and 1990, 46,465 men and 64,327 women aged 40-79 yr were followed-up through December 31,1999. During 1,042,608 person-years of follow-up, we documented 300 deaths from pancreatic cancer. A 33-item food-frequency questionnaire was used to assess dietary intake at the baseline survey. Cox proportional-hazards models were used to estimate the relative risks of pancreatic cancer death in relation to the intake frequency of food items. We did not observe an overall association between meat intake and pancreatic cancer risk. Except for a 50% decrease in risk associated with high fruit intake among men, we did not find other significant inverse relationships between vegetable and fruit intake and pancreatic cancer risk. Smoking did not modify the associations with dietary habits. Our study suggested that high consumption of pickles and wild edible plants, mainly bracken, might be related to increased pancreatic cancer risk; however, this finding should be confirmed in other epidemiological studies.


[Feeding and eating disorders in the DSM-5].
In the DSM-5, feeding disorders and eating disorders have been integrated into one single category. To review the rationale for changes in the criteria for feeding and eating disorders in DSM-5. The revised criteria were drafted and formulated by a DSM-5 workgroup. Next, professionals were given the opportunity to react to the proposed revisions by participating in several discussion rounds. The criteria for anorexia nervosa have been reworded and the amenorrhea criterion has been removed. The threshold for the diagnosis of bulimia nervosa has been lowered so that once-a-week binge eating and complementary behaviours are now sufficient for a patient to be diagnosed as having bulimia nervosa. Subtyping of bulimia nervosa has been removed. There are hardly any changes in the criteria for pica and rumination disorder. Two new official feeding and eating disorders have been introduced into DSM-5: avoidant/restrictive food intake disorder and binge eating disorder. The definition of and the criteria for feeding and eating disorders given in DSM-5 are an improvement on those used in dsm-iv and should help to reduce the eating disorders not otherwise specified (EDNOS).


Tobacco smoking and all-cause mortality in a large Australian cohort study: findings from a mature epidemic with current low smoking prevalence.
The smoking epidemic in Australia is characterised by historic levels of prolonged smoking, heavy smoking, very high levels of long-term cessation, and low current smoking prevalence, with 13% of adults reporting that they smoked daily in 2013. Large-scale quantitative evidence on the relationship of tobacco smoking to mortality in Australia is not available despite the potential to provide independent international evidence about the contemporary risks of smoking. This is a prospective study of 204,953 individuals aged ≥45 years sampled from the general population of New South Wales, Australia, who joined the 45 and Up Study from 2006-2009, with linked questionnaire, hospitalisation, and mortality data to mid-2012 and with no history of cancer (other than melanoma and non-melanoma skin cancer), heart disease, stroke, or thrombosis. Hazard ratios (described here as relative risks, RRs) for all-cause mortality among current and past smokers compared to never-smokers were estimated, adjusting for age, education, income, region of residence, alcohol, and body mass index. Overall, 5,593 deaths accrued during follow-up (874,120 person-years; mean: 4.26 years); 7.7% of participants were current smokers and 34.1% past smokers at baseline. Compared to never-smokers, the adjusted RR (95% CI) of mortality was 2.96 (2.69-3.25) in current smokers and was similar in men (2.82 (2.49-3.19)) and women (3.08 (2.63-3.60)) and according to birth cohort. Mortality RRs increased with increasing smoking intensity, with around two- and four-fold increases in mortality in current smokers of ≤14 (mean 10/day) and ≥25 cigarettes/day, respectively, compared to never-smokers. Among past smokers, mortality diminished gradually with increasing time since cessation and did not differ significantly from never-smokers in those quitting prior to age 45. Current smokers are estimated to die an average of 10 years earlier than non-smokers. In Australia, up to two-thirds of deaths in current smokers can be attributed to smoking. Cessation reduces mortality compared with continuing to smoke, with cessation earlier in life resulting in greater reductions.


[Body composition and polycystic ovary syndrome].
Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders of reproductive age women. The main signs of PCOS are as follows: androgen excess, menstrual dysfunction, infertility, obesity, and other numerous health problems. By different authors, the disorder affects 2-28% of reproductive age women. Polycystic ovary syndrome is characterized by presence of hyperandrogenism, anovulation, menstrual cycle disturbances, also by the other metabolic changes. The lack of well-defined and universally accepted diagnostic criteria makes identification of this syndrome confusing to many clinicians. There are only few studies concerning the correlations between phenotypic expression, body composition and PCOS, and relationship with the processes of growth and sexual maturation and various environmental factors (nutrition, physical activity, stress, and other factors). There is a lack of knowledge about further PCOS development and prognosis, considering the individual and environmental factors. Variation in human body composition and shape ranges considerably: many body size and shape indices (height, weight, body composition, and proportions) are the result of long evolution process and adaptation to environment. Obviously, the morphological body parameters, physiological and biochemical indices are complex and compound the interdependent system. By current literature, more than 50% of women are overweight or obese. If waist circumference and waist-to-hip ratio of women with PCOS increase, reproductive function and metabolic state of a woman is altered more than in cases when there are no changes in these parameters. The investigations of the strongest sexual dimorphism sign--the subcutaneous and visceral fat topography--showed that women with PCOS have greater adipose tissue mass in the areas of the abdomen, waist, and upper arms than control women. It is known that some indices of sexual dimorphism may be considered as the morphological signs of hyperandrogenism, for example handgrip, waist-to-hip ratio, hand and foot length, 2nd-to-4th digit (finger length) ratio (2D:4D), certain facial characteristics. Only 2D:4D ratio was investigated for the women with PCOS. The early changes of certain morphological and other indices of physical status could help to predict some metabolic characteristics, development of PCOS, and outcome of this syndrome.


Creative decision making and visual search behavior in skilled soccer players.
The ability to produce creative solutions is a key part of expert performance. The aim of this study was to identify the visual search behaviors that underpin superior creative performance of skilled soccer players during simulated 11-a-side match play. Players (N = 44) were required to interact with a representative life-size video-based simulation of attacking situations whilst in possession of the ball. Clips were occluded at a key moment and they were required to play the ball in response to each situation presented. Moreover, they were required to name other additional actions they could execute for each situation. Creative performance on the task was measured using the three criteria of originality, flexibility, and fluency of decisions. Visual search behaviors were examined using a portable eye-movement registration system. Players were classified as most- (n = 11) or least-creative (n = 11) based on their performance on the representative task. The most-creative players produced more appropriate, original, flexible, and fluid decisions compared to least-creative players. The creativity-based differences in judgment were underpinned by differences in visual search strategy. Most-creative players employed a broader attentional focus including more fixations of shorter duration and towards more informative locations of the display compared with least-creative players. Moreover, most-creative players detected teammates in threatening positions earlier in the attacking play. Creative performance is underpinned by different underlying visual processes when compared to less-creative performance, which appears to be crucial in facilitating more creative solutions.


Scrub Typhus in a Tertiary Care Hospital in North India.
Scrub typhus, a zoonotic disease caused by the bacterium Orientia tsutsugamushi, has become endemic in many parts of India. We studied the clinical profile of this infection in 228 patients that reported to this tertiary care center from July 2013 to December 2014. The median age of patients was 35 years (interquartile range = 24.5-48.5 years), and 111 were males and 117 females. A high-grade fever occurred in 85%, breathlessness in 42%, jaundice in 32%, abdominal pain in 28%, renal failure in 11%, diarrhea in 10%, rashes in 9%, and seizures in 7%. Common laboratory abnormalities at presentation were a deranged hepatic function in 61%, anemia in 54%, leukopenia in 15%, and thrombocytopenia in 90% of our patients. Acute kidney injury (32%), acute respiratory distress syndrome (ARDS) (25%), and disseminated intravascular coagulation (DIC) (16%) were the commonest complications. A hepatorenal syndrome was seen in 38% and multiple organ dysfunction syndrome (MODS) in 20% patients. The overall case fatality rate was 13.6%. In univariate analysis, ARDS requiring mechanical ventilation, acute kidney injury requiring hemodialysis, hypotension requiring inotropic support, central nervous system dysfunction at presentation, and MODS were inversely associated with survival. Survival was significantly higher in patients that presented with a duration of fever < 10 days compared with those that presented ≥ 12 days (P < 0.05) after onset. In conclusion, scrub typhus has become a leading infectious disease in north India and an important cause of infectious fever. An increasing awareness of this disease coupled with prompt management will go a long way in reducing both morbidity and mortality from this disease.


Young carers as social actors: coping strategies of children caring for ailing or ageing guardians in Western Kenya.
There is a vast body of research on the impact of HIV/AIDS on children, but little which acknowledges the role of children in providing care and support for ailing parents or ageing guardians. There has been a tendency to downplay the active role and agency of young carers, with young carers often represented as victims of damaging circumstances that compromise their psychosocial well-being. To counter-balance this tendency, and to develop the critical trend that views children as social actors, we explore how young carers cope with challenging circumstances, often with skill and ingenuity, drawing on data collected in Western Kenya in 2007. Forty-eight young carers (aged 11-17) used photography and drawing to provide accounts of their coping strategies. They described 240 of the resulting photographs and drawings in writing. In addition, 34 individual interviews and 2 group discussions were conducted with children to explore the findings further and 10 individual interviews with local adults were conducted to elucidate the dynamics between adults and children. Our data revealed that young carers cope by mobilising social support, engaging in income generating activities and constructing positive social identities around their caring roles. We conclude that children's ability to cope is determined by the extent to which they are able to participate in their community and negotiate support from it.


Time course of phosphorylated-tau181 in blood across the Alzheimer's disease spectrum.
Tau phosphorylated at threonine 181 (p-tau181) measured in blood plasma has recently been proposed as an accessible, scalable, and highly specific biomarker for Alzheimer's disease. Longitudinal studies, however, investigating the temporal dynamics of this novel biomarker are lacking. It is therefore unclear when in the disease process plasma p-tau181 increases above physiological levels and how it relates to the spatiotemporal progression of Alzheimer's disease characteristic pathologies. We aimed to establish the natural time course of plasma p-tau181 across the sporadic Alzheimer's disease spectrum in comparison to those of established imaging and fluid-derived biomarkers of Alzheimer's disease. We examined longitudinal data from a large prospective cohort of elderly individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) (n = 1067) covering a wide clinical spectrum from normal cognition to dementia, and with measures of plasma p-tau181 and an 18F-florbetapir amyloid-β PET scan at baseline. A subset of participants (n = 864) also had measures of amyloid-β1-42 and p-tau181 levels in CSF, and another subset (n = 298) had undergone an 18F-flortaucipir tau PET scan 6 years later. We performed brain-wide analyses to investigate the associations of plasma p-tau181 baseline levels and longitudinal change with progression of regional amyloid-β pathology and tau burden 6 years later, and estimated the time course of changes in plasma p-tau181 and other Alzheimer's disease biomarkers using a previously developed method for the construction of long-term biomarker temporal trajectories using shorter-term longitudinal data. Smoothing splines demonstrated that earliest plasma p-tau181 changes occurred even before amyloid-β markers reached abnormal levels, with greater rates of change correlating with increased amyloid-β pathology. Voxel-wise PET analyses yielded relatively weak, yet significant, associations of plasma p-tau181 with amyloid-β pathology in early accumulating brain regions in cognitively healthy individuals, while the strongest associations with amyloid-β were observed in late accumulating regions in patients with mild cognitive impairment. Cross-sectional and particularly longitudinal measures of plasma p-tau181 were associated with widespread cortical tau aggregation 6 years later, covering temporoparietal regions typical for neurofibrillary tangle distribution in Alzheimer's disease. Finally, we estimated that plasma p-tau181 reaches abnormal levels ∼6.5 and 5.7 years after CSF and PET measures of amyloid-β, respectively, following similar dynamics as CSF p-tau181. Our findings suggest that plasma p-tau181 increases are associated with the presence of widespread cortical amyloid-β pathology and with prospective Alzheimer's disease typical tau aggregation, providing clear implications for the use of this novel blood biomarker as a diagnostic and screening tool for Alzheimer's disease.


Comparison Of Digital Manometer And Water Column Manometer Pressures Measurements During Lumbar Puncture.
Cerebrospinal fluid (CSF) pressure measurement is routinely performed via a conventional water column manometer. There is increasing interest in using a digital manometer in measuring CSF pressures. The aim of this study is to compare column and digital manometers, in addition to measuring time to acquire the pressure readings. This prospective study included 27 patients who were referred for a fluoroscopically guided lumbar puncture. Opening pressure and closing pressure measurements were done with a digital manometer and then a traditional water column manometer. The time to obtain each pressure measurement was also recorded and compared. Mean time to obtain pressure reading was significantly lower in the digital manometer group when compared to the water column manometer group (8.1 seconds vs. 42.2 seconds, P<0.05 for opening pressure and 8.92 seconds vs. 45.15 seconds, P<0.05 for closing pressure). Correlation between the opening pressure measurements (Pearson coefficient r= 0.98) and closing pressure (Pearson coefficient r= 0.89) was strong. However, the digital manometer reading consistently read higher. Digital manometry during an LP yielded is faster however there might be a clinical difference between the devices. Clinicians must be careful in using the device across all cases.


Identification and analysis of a genomic strain cluster of mycoplasmalike organisms associated with Canadian peach (eastern) X disease, western X disease, and clover yellow edge.
Genetic interrelatedness among 13 strains of mycoplasmalike organisms (MLOs) from various sources was evaluated by dot hybridization and restriction fragment length polymorphism analyses using cloned DNA probes derived from Canadian peach X (CX) and western X (WX) MLOs. Dot hybridization analysis indicated that CX, WX, and clover yellow edge MLOs are closely related and form a distinct strain cluster that is only distantly related to the 10 other MLOs. Similarity coefficients derived from restriction fragment length polymorphism analysis revealed that CX, WX, and clover yellow edge MLOs represent three distinct genomic types.


The measurement of psychological literacy: a first approximation.
Psychological literacy, the ability to apply psychological knowledge to personal, family, occupational, community and societal challenges, is promoted as the primary outcome of an undergraduate education in psychology. As the concept of psychological literacy becomes increasingly adopted as the core business of undergraduate psychology training courses world-wide, there is urgent need for the construct to be accurately measured so that student and institutional level progress can be assessed and monitored. Key to the measurement of psychological literacy is determining the underlying factor-structure of psychological literacy. In this paper we provide a first approximation of the measurement of psychological literacy by identifying and evaluating self-report measures for psychological literacy. Multi-item and single-item self-report measures of each of the proposed nine dimensions of psychological literacy were completed by two samples (N = 218 and N = 381) of undergraduate psychology students at an Australian university. Single and multi-item measures of each dimension were weakly to moderately correlated. Exploratory and confirmatory factor analyses of multi-item measures indicated a higher order three factor solution best represented the construct of psychological literacy. The three factors were reflective processes, generic graduate attributes, and psychology as a helping profession. For the measurement of psychological literacy to progress there is a need to further develop self-report measures and to identify/develop and evaluate objective measures of psychological literacy. Further approximations of the measurement of psychological literacy remain an imperative, given the construct's ties to measuring institutional efficacy in teaching psychology to an undergraduate audience.