Use of and Adherence to Antiretroviral Therapy in a Large U.S. Sample of HIV-infected Adults in Care, 2007-2008.
Antiretroviral therapy (ART) is the cornerstone of HIV clinical care and is increasingly recognized as a key component of HIV prevention. However, the benefits of ART can be realized only if HIV-infected persons maintain high levels of adherence. We present interview data (collected from June 2007 through September 2008) from a national HIV surveillance system in the United States-the Medical Monitoring Project (MMP)-to describe persons taking ART. We used multivariate logistic regression to assess behavioral, sociodemographic, and medication regimen factors associated with three measures that capture different dimensions of nonadherence to ART: dose, schedule, and instruction. The use of ART among HIV-infected adults in care was high (85%), but adherence to ART was suboptimal and varied across the three measures of nonadherence. Of MMP participants currently taking ART, the following reported nonadherence during the past 48 hours: 13% to dose, 27% to schedule, and 30% to instruction. The determinants of the three measures also varied, although younger age and binge drinking were associated with all aspects of nonadherence. Our results support the measurement of multiple dimensions of medication-taking behavior in order to avoid overestimating adherence to ART.


Clinicopathological features of infiltrating lobular carcinomas comparing with infiltrating ductal carcinomas: a case control study.
Infiltrating lobular carcinoma (ILC) is the second most common type of invasive breast cancers and it has been reported to have some unique biologic and epidemiologic characteristics. Clinicopathological features of 95 patients with ILC, their relapse free survival (RFS) and overall survival (OS) were retrospectively investigated and compared with those of 3,621 patients with infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) between January 1984 and December 2005. ILC constitutes 2.3% of all invasive breast cancers. There were no difference between the ILC and the IDC-NOS groups regarding age at diagnosis, tumor size, nodal status, and treatment modalities except hormone therapy. The ILC group showed more estrogen receptor expression, less HER-2 expression and higher bilaterality. RFS and OS of the ILC patients were similar to those of the IDC. IDC-NOS metastasized more frequently to the lung and bone, whereas, ILC to the bone and ovary. The incidence of ILC was relatively low in Korean breast cancer patients. Comparing to IDC-NOS ILC showed some different features such as higher estrogen receptor expression, less HER-2 expression, higher bilaterality and preferred metastatic sites of bone and ovary. Contralateral cancers and bone and ovary evaluation should be considered when monitoring ILC patients.


Large-Scale Automatic Feature Selection for Biomarker Discovery in High-Dimensional OMICs Data.
The identification of biomarker signatures in omics molecular profiling is usually performed to predict outcomes in a precision medicine context, such as patient disease susceptibility, diagnosis, prognosis, and treatment response. To identify these signatures, we have developed a biomarker discovery tool, called BioDiscML. From a collection of samples and their associated characteristics, i.e., the biomarkers (e.g., gene expression, protein levels, clinico-pathological data), BioDiscML exploits various feature selection procedures to produce signatures associated to machine learning models that will predict efficiently a specified outcome. To this purpose, BioDiscML uses a large variety of machine learning algorithms to select the best combination of biomarkers for predicting categorical or continuous outcomes from highly unbalanced datasets. The software has been implemented to automate all machine learning steps, including data pre-processing, feature selection, model selection, and performance evaluation. BioDiscML is delivered as a stand-alone program and is available for download at https://github.com/mickaelleclercq/BioDiscML.


The effect of paclitaxel on the progression of polycystic kidney disease in rodents.
Woo et al (Nature 368:750-753) reported that parenteral administration of paclitaxel arrested the striking renal enlargement and prolonged life in C57BL/6J-cpk/cpk mice with a rapidly progressive form of polycystic kidney disease (PKD). In the current study, we sought to determine whether paclitaxel could alter the progression of other forms of hereditary PKD in rodents. Paclitaxel was administered by intraperitoneal injection to C57BL/6J-cpk/cpk mice and Han:SPRD-Cy/Cy rats with rapidly progressive PKD and to DBA/2FG-pcy/pcy mice and Han:SPRD-Cy/+ rats with slowly progressive PKD. Paclitaxel (150 micrograms/wk) prolonged the survival of cpk/cpk mice from 24.5 days to more than 65 days and decreased kidney weight relative to body weight from 16.5% at 21 days of age to 8.2% at more than 65 days of age. Mortality attributable to paclitaxel was 12%. By contrast, the administration of paclitaxel (0.1 to 15 mg/kg/wk) to 7- to 10-day-old Han:SPRD-Cy/Cy rats with rapidly progressive PKD had no effect on the course of the disease; moreover, paclitaxel caused severe side effects and premature death in all the Cy/Cy animals. Heterozygous male Cy/+ rats develop slowly progressive renal enlargement and azotemia. Paclitaxel, administered at 7, 15, or 27 mg/kg/wk to male Cy/+ rats from 4 until 10 weeks of age, reduced body weight gain, had an inconsistent effect on kidney weight relative to body weight, and had no effect on the serum urea nitrogen concentration. Mortality associated with the 7, 15, and 27 mg/kg/wk doses of paclitaxel was 0%, 15.4%, and 28.5%, respectively. DBA/2FG-pcy/pcy mice of either sex developed slowly progressive renal enlargement and azotemia. The administration of paclitaxel (100 to 150 micrograms/wk) from 2 to 10 weeks of age to DBA/2FG-pcy/pcy mice with cystic disease had no effect on the increase in kidney weight or on the level of serum urea nitrogen in comparison to untreated cystic animals. Mortality associated with 100- and 150-micrograms/wk doses of paclitaxel was 0% and 20%, respectively. We conclude that paclitaxel diminished the rate of renal enlargement and increased the life span of cpk/cpk mice but not Cy/Cy rats with rapidly progressive forms of PKD. Paclitaxel had no apparent benefit in Cy/+ rats nor pcy/pcy mice with slowly progressive PKD. On the basis of these studies in rodents, it appears that paclitaxel has limited potential usefulness as a therapeutic agent in the treatment of PKD.


Local anaesthetic wound infiltration after internal fixation of femoral neck fractures: a randomized, double-blind clinical trial in 33 patients.
Pain control may assist early mobilisation after internal fixation of femoral neck fractures. Systemic opioids have significant side effects in elderly patients. We present an evaluation of the effect of local anaesthetic infiltration in such cases , the objective being to decrease the need for postoperative opioids and to improve pain control for patients after surgery. 33 patients undergoing internal fixation with 2 parallel hook pins were randomized into 2 groups in a double blind study (ClinicalTrials.gov: NCT00529425). 33 patients received intraoperative infiltration followed by 6 postoperative injections through an intraarticular catheter in eight-hour intervals. 19 patients received ropivacaine and 14 received saline. The intervention period was 48 hours and the observation period was 5 days. In both groups there were no restrictions on the total daily dose of rescue analgesics. Pain was assessed at specific postoperative time-points and the daily consumption of opioid drugs needed for analgesia was registered. There was no significantly reduced consumption of standardized opioid rescue analgesics or pain in the study group receiving ropivacaine injections. Apart from a reduction in nausea in the study group on the second postoperative day, there were no significant differences in the occurrence of side effects between the groups. On day 2 the placebo group had less pain than the study group. Local anaesthetic infiltration after fixation of femoral neck fractures does not reduce opioid consumption or pain'.


Discriminant saliency, the detection of suspicious coincidences, and applications to visual recognition.
A discriminant formulation of top-down visual saliency, intrinsically connected to the recognition problem, is proposed. The new formulation is shown to be closely related to a number of classical principles for the organization of perceptual systems, including infomax, inference by detection of suspicious coincidences, classification with minimal uncertainty, and classification with minimum probability of error. The implementation of these principles with computational parsimony, by exploitation of the statistics of natural images, is investigated. It is shown that Barlow's principle of inference by the detection of suspicious coincidences enables computationally efficient saliency measures which are nearly optimal for classification. This principle is adopted for the solution of the two fundamental problems in discriminant saliency, feature selection and saliency detection. The resulting saliency detector is shown to have a number of interesting properties, and act effectively as a focus of attention mechanism for the selection of interest points according to their relevance for visual recognition. Experimental evidence shows that the selected points have good performance with respect to 1) the ability to localize objects embedded in significant amounts of clutter, 2) the ability to capture information relevant for image classification, and 3) the richness of the set of visual attributes that can be considered salient.


Characterization of monoclonal antibodies against Erwinia carotovora subsp. atroseptica serogroup I: specificity and epitope analysis.
The characteristics of two monoclonal antibodies (Mabs), A23/1221.59.44.d.3 (1221) and A23/1239.36.64.e.2 (1239), against Erwinia carotovora subsp. atroseptica serogroup I produced in this study were compared with those of two other independently obtained Mabs, 4G4 in Spain and 4F6 in Canada, using different strains as immunogen and different screening procedures. The reaction pattern of Mabs 1221 and 1239 determined by indirect ELISA on over 200 bacterial strains including five E.c. atroseptica and 36 E.c. carotovora serogroups, seven Erw. chrysanthemi biovars, 23 other plant bacterial pathogens and 33 saprophytic bacteria from potato was similar to that of 4G4. Specificity for E.c. atroseptica serogroup I was improved, especially when skimmed milk (Marvel) was used instead of bovine serum albumin as blocking agent. Mabs 1221, 1239 and 4G4 reacted positively with all 22 E.c. atroseptica serogroup I, the dominant E.c. atroseptica serogroup on potato, strains tested and only with two out of five E.c. atroseptica serogroup XXII strains, one E.c. carotovora serogroup XXI strain and one strain of a saprophytic bacterium, Comamonas sp. Essentially similar results were obtained when examined by immunofluorescence. Characterization of the four Mabs showed that they were IgG3 and SDS-PAGE/immunoblot results suggested that they were probably against the O-side chain of bacterial cell wall lipopolysaccharides. In competition ELISA between biotin-labelled and unlabelled Mabs, the competition pattern of the four Mabs was similar.(ABSTRACT TRUNCATED AT 250 WORDS)


Exploring patient-reported barriers to advance care planning in family practice.
Although patient-centred care has become increasingly important across all medical specialties, when it comes to end of life care, research has shown that treatments ordered are not often concordant with people's expressed preferences. Patient and family engagement in Advance Care Planning (ACP) in the primary care setting could improve the concordance between patients' wishes and the healthcare received when patients cannot speak for themselves. The aim of this study was to better understand the barriers faced by older patients regarding talking to their family members and family physicians about ACP. In this multi-site cross-sectional study, three free text questions regarding reasons patients found it difficult to discuss ACP with their families or their family physicians were part of a self-administered questionnaire about patients' knowledge of and engagement in ACP. The questionnaire, which included closed ended questions followed by three probing open ended questions, was distributed in 20 family practices across 3 provinces in Canada. The free text responses were analyzed using thematic analysis and form the basis of this paper. One hundred two participants provided an analyzable response to the survey when asked why they haven't talked to someone about ACP. Two hundred fifty-four answered the question about talking to their physician and 340 answered the question about talking to family members. Eight distinct themes emerged from the free text response analysis: 1. They were too young for ACP; 2. The topic is too emotional; 3. The Medical Doctor (MD) should be responsible for bringing up ACP 4. A fear of negatively impacting the patient-physician relationship; 5. Not enough time in appointments; 6. Concern about family dynamics; 7. It's not a priority; and 8. A lack of knowledge about ACP. Patients in our sample described many barriers to ACP discussions, including concerns about the effect these discussions may have on relationships with both family members and family physicians, and issues relating to patients' knowledge and interpretation of the importance, responsibility for, or relevance of ACP itself. Family physicians may be uniquely placed to leverage the longitudinal, person- centred relationship they have with patients to mitigate some of these barriers.


Toward a neurobiology of internal selective attention.
A recent study in non-human primates (NHPs) by Panichello and Buschman brings the investigation of selective attention within visual working memory to the systems and cellular neuroscience levels. We reflect on this breakthrough in light of nearly 20 years of related research in humans and highlight some of the lessons to help frame future work.


Health Pregnancy, Healthy Baby: testing the added benefits of pregnancy ultrasound scan for child development in a randomised control trial.
The 2016 World Health Organization Antenatal Guidelines and the 2015 South African Maternal and Child Health Guidelines recommend one early antenatal ultrasound scan to establish gestational age and to detect multiple pregnancies and fetal abnormalities. Prior research indicates that ultrasound scan can also increase parental-fetal attachment. We aim to establish whether, compared to routine care, messages to promote parental attachment and healthy child development, conducted during one or two pregnancy ultrasound scans, improve early child development and growth, exclusive breastfeeding, parental-child interactions and prenatal and postnatal clinic attendance. The effect of messages to sensitise mothers and fathers to fetal development will be tested in a three-armed randomised trial with 100 mothers and their partners from Soweto, Johannesburg in each arm. The primary outcome is child development at 6 months postnatally. Secondary outcomes include infant feeding, parental attachment and interaction, parental mental health and infant growth, assessed at 6 weeks and 6 months. Parents in Arm 1 receive a fetal ultrasound scan < 25 weeks during routine antenatal care at tertiary hospitals, and a second standard ultrasound scan at the research site within 2 weeks. Arm 2 participants receive the routine antenatal ultrasound scan and an additional ultrasound scan < 25 weeks at the research site, together with messages to promote parental attachment and healthy child development. Arm 3 participants receive the routine ultrasound scan and two additional ultrasound scans at the research site, < 25 weeks and < 36 weeks, together with messages to promote parental attachment and healthy child development. Evidence from high-income countries suggests that first-time prospective mothers and fathers enjoy seeing their fetus during ultrasound scan and that it is an emotional experience. A number of studies have found that ultrasound scan increases maternal attachment during pregnancy, a predictor of positive parent-infant interactions which, in turn, promotes healthy infant development. It is generally agreed that studies are needed which follow up parental-child behaviour and healthy child development postnatally, include fathers and examine the construct in a wider diversity of settings, especially in low and middle-income countries. Testing the added benefits of pregnancy ultrasound scan for child development is a gap that the proposed trial in South Africa seeks to address. Pan African Clinical Trials Registry, PACTR201808107241133. Registered on 15 August 2018.


IMMUNE-MEDIATED INTRAOCULAR INFLAMMATION. A REVIEW.
Immune mediated inflammatory diseases are categorized into autoimmune and autoinflammatory. Autoimmune etiology is represented by autoreactive lymphocytes or autoantibodies, e.g. primary Sjögrens syndrome or rheumatoid arthritis. Ocular specific diseases with presumed autoimmune origin are sympathetic ophthalmia or birdshot chorioretinopathy. Autoinflammatory diseases are caused by mutations in regulatory genes for specific immunity. Hereditary periodic fevers represent monogenic autoinflammatory diseases; eye specific is Blau syndrome also named sarcoidosis with early onset. This article reviews the actual knowledge about immune mediated uveitides, their immunological mechanisms and the possible trigger role of infection in autoimmune inflammation. Immune privilege provides a protection of the eye against any strong immune reaction to foreign antigen, based on physical, immune, humoral and molecular mechanisms. Antigens hidden within the eye are revealed in case of damage of hematoretinal barrier caused by infection or mechanical insult. These ocular antigens have not been set as tolerable during the development and immune reaction is initiated subsequently. Current studies demonstrate that uveogenic trigger might be generated by own microbiome, particularly when dysregulated, so called dysbiosis. There is a known association between idiopathic inflammatory bowel disease with ankylosing spondylitis and anterior uveitis in humans. Intensive research is focused on microbiome and immune mediated inflammatory disease to influence therapeutically the intestinal microbiome. The animal models are used to study the immunopathological mechanisms of uveitis and the new therapeutic strategies, because of relatively low incidence of immune mediated uveitis in humans.


The vibrational spectroscopy and dynamics of weakly bound neutral complexes.
A growing number of binary and tertiary van der Waals and hydrogen-bonded complexes are being studied by means of near-infrared laser spectroscopy. Studies of this type have generated a wealth of detailed structural and dynamical information that provides exacting tests of the corresponding theoretical methods. An additional incentive for the investigation of such clusters arises from the fact that they may be considered as intermediates between the gas and condensed phases of matter. As a result, these systems represent a fertile meeting ground for researchers from both fields and can often be studied with a variety of methods.


Sputum endothelin-1 is increased in cystic fibrosis and chronic obstructive pulmonary disease.
Many patients with cystic fibrosis (CF) have airflow obstruction, with peribronchial and peribronchiolar fibrosis. Endothelin (ET)-1 is a potent bronchoconstrictor with mitogenic activity for airway smooth muscle. Do the levels of ET-1 in sputum support the putative role of ET-1 in contributing to airway remodelling with airflow obstruction in CF? The levels of ET-1 in plasma, saliva and sputum from 12 adult patients with CF not in exacerbation (spontaneous sputum), 17 normal control subjects (induced sputum) and as an additional control population, nine patients with stable chronic obstructive pulmonary disease (COPD) (seven spontaneous sputum) were measured. Total and differential sputum cell counts were performed. Median (interquartile range) sputum ET-1 level was elevated in CF (77.6 (29.0-122.8) pg x mL(-1)) compared to normal subjects (6.00 (2.8-14.8) pg x mL(-1)) and COPD (16.4 (6.8-38.2) pg x mL(-1)), and in COPD compared to normal subjects. There was a slight elevation of plasma ET-1 level in CF (5.3 (3.2-6.0) pg x mL(-1)) compared to normal subjects (3.1 (1.7-4.4) pg x mL(-1)) and COPD (3.3 (2.7-4.2) pg x mL(-1)). Sputum and saliva ET-1 levels were significantly higher than plasma levels in all groups, suggesting local production or release in the respiratory tract. Sputum differential cell counts revealed pronounced neutrophilia in CF and COPD compared to normal subjects. Sputum endothelin-1 concentrations are elevated in cystic fibrosis sputum compared to chronic obstructive pulmonary disease, and in cystic fibrosis and chronic obstructive pulmonary disease compared to normal subjects. The role of endothelin-1 in contributing to airflow obstruction through bronchoconstriction and mitogenesis in cystic fibrosis needs now to be explored.


Avian Polyomavirus Genome Sequences Recovered from Parrots in Captive Breeding Facilities in Poland.
Eight genomes of avian polyomaviruses (APVs) were recovered and sequenced from deceased Psittacula eupatria, Psittacula krameri, and Melopsittacus undulatus from various breeding facilities in Poland. Of these APV-positive samples, six had previously tested positive for beak and feather disease virus (BFDV) and/or parrot hepatitis B virus (PHBV).


Routes of Acquisition of the Gut Microbiota of the Honey Bee Apis mellifera.
Studies of newly emerged Apis mellifera worker bees have demonstrated that their guts are colonized by a consistent core microbiota within several days of eclosure. We conducted experiments aimed at illuminating the transmission routes and spatiotemporal colonization dynamics of this microbiota. Experimental groups of newly emerged workers were maintained in cup cages and exposed to different potential transmission sources. Colonization patterns were evaluated using quantitative real-time PCR (qPCR) to assess community sizes and using deep sequencing of 16S rRNA gene amplicons to assess community composition. In addition, we monitored the establishment of the ileum and rectum communities within workers sampled over time from natural hive conditions. The study verified that workers initially lack gut bacteria and gain large characteristic communities in the ileum and rectum within 4 to 6 days within hives. Typical communities, resembling those of workers within hives, were established in the presence of nurse workers or nurse worker fecal material, and atypical communities of noncore or highly skewed compositions were established when workers were exposed only to oral trophallaxis or hive components (comb, honey, bee bread). The core species of Gram-negative bacteria, Snodgrassella alvi, Gilliamella apicola, and Frischella perrara, were dependent on the presence of nurses or hindgut material, whereas some Gram-positive species were more often transferred through exposure to hive components. These results indicate aspects of the colony life cycle and behavior that are key to the propagation of the characteristic honey bee gut microbiota.


Theta band power increases in the posterior hippocampus predict successful episodic memory encoding in humans.
Functional differences in the anterior and posterior hippocampus during episodic memory processing have not been examined in human electrophysiological data. This is in spite of strong evidence for such differences in rodent data, including greater place cell specificity in the dorsal hippocampus, greater sensitivity to the aversive or motivational content of memories in ventral regions, connectivity analyses identifying preferential ventral hippocampal connections with the amygdala, and gene expression analyses identifying a dorsal-ventral gradient. We asked if memory-related oscillatory patterns observed in human hippocampal recordings, including the gamma band and slow-theta (2.5-5 Hz) subsequent memory effects, would exhibit differences along the longitudinal axis and between hemispheres. We took advantage of a new dataset of stereo electroencephalography patients with simultaneous, robotically targeted anterior, and posterior hippocampal electrodes to directly compare oscillatory subsequent memory effects during item encoding. This same data set allowed us to examine left-right connectivity and hemispheric differences in hippocampal oscillatory patterns. Our data suggest that a power increase during successful item encoding in the 2.5-5 Hz slow-theta frequency range preferentially occurs in the posterior hippocampus during the first 1,000 ms after item presentation, while a gamma band power increase is stronger in the dominant hemisphere. This dominant-nondominant pattern in the gamma range appears to reverse during item retrieval, however. Intrahippocampal phase coherence was found to be stronger during successful item encoding. Our phase coherence data are also consistent with existing reports of a traveling wave for theta oscillations propagating along the septotemporal (longitudinal) axis of the human hippocampus. We examine how our findings fit with theories of functional specialization along the hippocampal axis.


Adaptation of Fire Blight Forecasting to Optimize the Use of Biological Controls.
We investigated adaptation of fire blight forecasting concepts to incorporate and optimize the use of biological agents for disease suppression. The effect of temperature on growth of the bacterial antagonists, Pseudomonas fluorescens A506 and Pantoea agglomerans C9-1S, and of the pathogen Erwinia amylovora153N, on pear and apple blossoms was evaluated in growth chamber and screenhouse experiments. New blossoms were inoculated with the strains and subsequent growth was measured over 96 h. Bacterial growth rates on blossoms were described as functions of temperature. A degree hour-based "bacterial growth index" (96-h moving total of degree hours >10°C) was created to assess conduciveness of orchard environments for antagonist colonization. A comparison of this index to a disease risk index indicated that biocon-trol treatments could be timed such that the antagonists could be expected to grow to an effective population size before the disease index shifted from "low" to "moderate" risk. For six pear- and apple-production areas of Oregon and Washington, regression of actual values of the bacterial growth and disease risk indices on index values derived from 4-day temperature forecasts resulted in coefficients of determination that averaged 0.75. The "bacterial growth index" and its estimation via temperature forecasts were incorporated into a decision matrix designed to guide optimal treatment timing.


Neurotoxicity effects of anesthetic exposure on the developing brain of non-human primates.
Mounting evidence has shown that general anesthetic agents commonly used clinically can cause anesthetic-related neurotoxicity in the developing brains of mammals, potentially causing long-term neurological impairment. This results in growing interest and concern among the public. Here, we present an overview of the relevant findings from non-human primates, arguably the very best model for studies of developmental neurotoxicity. These studies have shown that varying degrees of neurodegeneration occur as a result of anesthesia type, duration/dose of exposure, the timing of exposure, and brain region of interest, combined with subsequent alterations in cognitive assessments. Specifically, the rapid advancement of minimally or non-invasive neuroimaging methodologies and availability provided more sophisticated techniques for investigating brain structure and function. Neuroimaging methodologies have shown some of their most significant promise in studies of anesthetic-induced developmental neurotoxicity.


The expression of endothelial cell surface antigens by AIDS-associated Kaposi's sarcoma. Evidence for a vascular endothelial cell origin.
The authors investigated 19 cases of Kaposi's sarcoma (KS) obtained from patients with the acquired immune deficiency syndrome (AIDS) for their expression of Factor VIII-related antigen (FVIIIRAg), HLA-DR (Ia) antigens, OKM1, and three distinctive vascular, but not lymphatic, endothelial-cell-associated antigens, E92, OKM5, and HCl. Antigen expression was demonstrated by immunoperoxidase staining of cryostat sections. FVIIIRAg is strongly expressed by the cells lining the vascular spaces (VCs) but is absent, weakly or focally, and variably expressed by the spindle cell (SC) component of KS. The VC component of each KS lesion examined strongly expressed E92, moderately expressed HCl, and weakly expressed OKM5. In contrast, the entire SC component of each KS lesion studied strongly expressed E92 and OKM5 and weakly expressed HCl. Neither the VCs nor the SCs expressed OKM1. These studies provide strong and compelling evidence for the vascular endothelial cell histogenesis of both the vascular and spindle cell components of KS, demonstrate the intertumor and intratumor phenotypic heterogeneity of KS, and suggest that monoclonal antibodies OKM5 and anti-E92 are the best currently available immunohistochemical markers for identifying the spindle cell component of AIDS-associated KS in cryostat sections.


Ethics of emergent information and communication technology applications in humanitarian medical assistance.
New applications of information and communication technology (ICT) are shaping the way we understand and provide humanitarian medical assistance in situations of disaster, disease outbreak or conflict. Each new crisis appears to be accompanied by advancements in humanitarian technology, leading to significant improvements in the humanitarian aid sector. However, ICTs raise ethical questions that warrant attention. Focusing on the context of humanitarian medical assistance, we review key domains of ICT innovation. We then discuss ethical challenges and uncertainties associated with the development and application of new ICTs in humanitarian medical assistance, including avoiding harm, ensuring privacy and security, responding to inequalities, demonstrating respect, protecting relationships, and addressing expectations. In doing so, we emphasize the centrality of ethics in humanitarian ICT design, application and evaluation.


Characterisation and evaluation of a miniaturised polyphenylene oxide dosimeter for ultraviolet exposures.
Dosimeters are used in measuring received ultraviolet (UV) radiation by humans and plants. Previously dosimeters 3.0cm×3.0cm weighing 0.6g, using poly(2,6-dimethyl-1,4-phenylene oxide) (PPO)(1) as the photoactive material have been used. A smaller 1.0cm×1.5cm flexible PPO dosimeter weighing 0.05g has been developed and characterised in this research. Laboratory and field studies show that the miniaturised dosimeter measures comparative results to the larger dosimeters for cosine response, dark reaction and dose response. The smaller, flexible dosimeters are also more applicable for use on curved surfaces and have less impact on the orientation of plant leaves due to their decreased mass. This research has also shown that miniaturised PPO dosimeters can be successfully employed on plant and human subjects to accurately determine biologically active UV distributions. The miniaturised PPO dosimeters allow for more measurements over an exposed area and the PPO film allows for measurements to be made for periods longer than 1day. The combination of smaller size and longevity of the photoactive material allows for more flexibility in future UV field research resulting in an increase in the potential number of environments where UV dosimeters can be deployed.


Indirect Evidence Link PCB Dehalogenation with Geobacteraceae in Anaerobic Sediment-Free Microcosms.
Although polychlorinated biphenyls (PCBs) production was brought to a halt 30 years ago, recalcitrance to degradation makes them a major environmental pollutant at a global scale. Previous studies confirmed that organohalide-respiring bacteria (OHRB) were capable of utilizing chlorinated congeners as electron acceptor. OHRB belonging to the Phyla Chloroflexi and Firmicutes are nowadays considered as the main PCB-dechlorinating organisms. In this study, we aimed at exploring the involvement of other taxa in PCB dechlorination using sediment-free microcosms (SFMs) and the Delor PCB mixture. High rates of congener dehalogenation (up to 96%) were attained in long-term incubations of up to 692 days. Bacterial communities were dominated by Chloroflexi, Proteobacteria, and Firmicutes, among strictly simplified community structures composed of 12 major phyla only. In a first batch of SFMs, Dehalococcoides mccartyi closely affiliated with strains CG4 and CBDB1 was considered as the main actor associated with congener dehalogenation. Addition of 2-bromoethanesulfonate (BES), a known inhibitor of methanogenic activity in a second batch of SFMs had an adverse effect on the abundance of Dehalococcoides sp. Only two sequences affiliated to this Genus could be detected in two (out of six) BES-treated SFMs, contributing to a mere 0.04% of the communities. BES-treated SFMs showed very different community structures, especially in the contributions of organisms involved in fermentation and syntrophic activities. Indirect evidence provided by both statistical and phylogenetic analysis validated the implication of a new cluster of actors, distantly affiliated with the Family Geobacteraceae (Phylum δ-Proteobacteria), in the dehalogenation of low chlorinated PCB congeners. Members of this Family are known already for their dehalogenation capacity of chlorinated solvents. As a result, the present study widens the knowledge for the phylogenetic reservoir of indigenous PCB dechlorinating taxa.


SU-E-T-20: Removal of Electron Contamination in Longitudinal Field MRI-Linac Systems: A Monte Carlo Study.
The prototype inline MRI-linac system has some advantages over perpendicular models including avoiding the electron return effect. One of the disadvantages of the inline approach is the increased skin dose, estimated to be 400-1000% of the dmax dose. The purpose of this work was to design a feasible method to reduce this skin dose to acceptable levels. Magnetic modeling of proposed MRI-linac designs have been simulated with the inclusion of an optimized permanent magnet system to purge/deflect the electron contamination. The region of air above the phantom was also replaced with a helium bag (region of helium gas) and a beam scrapper below the deflector was added to collect deflected off-axis contamination. Monte Carlo simulations were then performed including the accurate 3D magnetic field maps. Surface dosimetry was recorded to verify the changes to the skin doses. Magnetic modelling showed that an optimized NdFeB permanent magnet system located outside the MRI coils (below the MLC's) can provide a strong enough region to purge/deflect a significant portion of the electron contamination from the x-ray beam. The impact on the MRI uniformity is around 100 ppm and hence is correctable via active/passive shimming of the MRI. The helium region also significantly limits the production of contamination traveling towards the phantom surface. Entry doses near CAX are predicted to be similar to the 0 T case. Magnetic and Monte Carlo modeling were performed to estimate the effect that a permanent magnet purging system, beam scrapper, and helium bag would have on lowering the skin doses in an inline MRI-Linac system. MRI non-uniformities introduced by the deflector could be corrected, contamination is mostly purged or blocked, and the helium bag minimizes air-generated contamination. As a result skin doses are comparable to having zero magnetic field.


Two homeobox genes define the domain of EphA3 expression in the developing chick retina.
Graded expression of the Eph receptor EphA3 in the retina and its two ligands, ephrin A2 and ephrin A5 in the optic tectum, the primary target of retinal axons, have been implicated in the formation of the retinotectal projection map. Two homeobox containing genes, SOHo1 and GH6, are expressed in a nasal-high, temporal-low pattern during early retinal development, and thus in opposing gradients to EphA3. Retroviral misexpression of SOHo1 or GH6 completely and specifically repressed EphA3 expression in the neural retina, but not in other parts of the central nervous system, such as the optic tectum. Under these conditions, some temporal ganglion cell axons overshot their expected termination zones in the rostral optic tectum, terminating aberrantly at more posterior locations. However, the majority of ganglion cell axons mapped to the appropriate rostrocaudal locations, although they formed somewhat more diffuse termination zones. These findings indicate that other mechanisms, in addition to differential EphA3 expression in the neural retina, are required for retinal ganglion axons to map to the appropriate rostrocaudal locations in the optic tectum. They further suggest that the control of topographic specificity along the retinal nasal-temporal axis is split into several independent pathways already at a very early time in development.


Critical behavior in tetragonal antiperovskite GeNFe3 with a frustrated ferromagnetic state.
Tetragonal GeNFe3 has a second-order ferromagnetic (FM) to paramagnetic transition at 76 K. Our integrated investigations indicate that the ground FM state is frustrated and the tetragonal symmetry is retained below 550 K based on the results of variable temperature X-ray diffraction. Critical behavior was analyzed by a systematic bulk magnetization study. The estimated critical exponents by three different methods (modified Arrott plot, the Kouvel-Fisher method, and critical isotherm analysis) conformably suggest that long-range magnetic coupling described by mean-field (MF) theoretical model is dominant in GeNFe3. The experimental M-T-H data collapse into two independent branches according to the scaling equations m = f±(h) with the renormalized magnetization m = ε-βM(H, ε) and the magnetic field h = Hε-(β+γ). The exchange distance is estimated as J(r) ∼ r-4.8 on the basis of the β and γ values, which lies between the long-range MF model (r-4.5) and the short-range 3D Heisenberg (3DH) model (r-5). Our results indicate that the competition between local magnetic moments of iron 3d electronic state and itinerant covalent interactions of N-Fe bonds should be responsible for critical behavior in this system.


Mathematical Talent is Linked to Autism.
A total of 378 mathematics undergraduates (selected for being strong at "systemizing") and 414 students in other (control) disciplines at Cambridge University were surveyed with two questions: (1) Do you have a diagnosed autism spectrum condition? (2) How many relatives in your immediate family have a diagnosed autism spectrum condition? Results showed seven cases of autism in the math group (or 1.85%) vs one case of autism in the control group (or 0.24%), a ninefold difference that is significant. Controlling for sex and general population sampling, this represents a three- to sevenfold increase for autism spectrum conditions among the mathematicians. There were 7 of 1,405 (or 0.5%) cases of autism in the immediate families of the math group vs 2 of 1,669 (or 0.1%) cases in the immediate families of the control group, which again is a significant difference. These results confirm a link between autism and systemizing, and they suggest this link is genetic given the association between autism and first-degree relatives of mathematicians.


Electrochemical immunoassay for vitellogenin based on sequential injection using antigen-immobilized magnetic microbeads.
A rapid and sensitive immunoassay for the determination of vitellogenin (Vg) is described. The method involves a sequential injection analysis (SIA) system equipped with an amperometric detector and a neodymium magnet. Magnetic beads, onto which an antigen (Vg) was immobilized, were used as a solid support in an immunoassay. The introduction, trapping and release of magnetic beads in an immunoreaction cell were controlled by means of the neodymium magnet and by adjusting the flow of the carrier solution. The immunoassay was based on an indirect competitive immunoreaction of an alkaline phosphatase (ALP) labeled anti-Vg monoclonal antibody between the fraction of Vg immobilized on the magnetic beads and Vg in the sample solution. The immobilization of Vg on the beads involved coupling an amino group moiety of Vg with the magnetic beads after activation of a carboxylate moiety on the surface of magnetic beads that had been coated with a polylactate film. The Vg-immobilized magnetic beads were introduced and trapped in the immunoreaction cell equipped with the neodymium magnet; a Vg sample solution containing an ALP labeled anti-Vg antibody at a constant concentration and a p-aminophenyl phosphate (PAPP) solution were sequentially introduced into the immunoreaction cell. The product of the enzyme reaction of PAPP with ALP on the antibody, paminophenol, was transported to an amperometric detector, the applied voltage of which was set at +0.2 V vs. an Ag/AgCl reference electrode. A sigmoid calibration curve was obtained when the logarithm of the concentration of Vg was plotted against the peak current of the amperometric detector using various concentrations of standard Vg sample solutions (0-500 ppb). The time required for the analysis is less than 15 min.


Development of improved pertussis vaccine.
Rates of infection with Bordetella pertussis, the gram-negative bacterium that causes the respiratory disease called whooping cough or pertussis, have not abated and 16 million cases with almost 200,000 deaths are estimated by the WHO to have occurred worldwide in 2008. Despite relatively high vaccination rates, the disease has come back in recent years to afflict people in numbers not seen since the pre-vaccine days. Indeed, pertussis is now recognized as a frequent infection not only in newborn and infants but also in adults. The disease symptoms also can be induced by the non-vaccine-preventable infection with the close species B. parapertussis for which an increasing number of cases have been reported. The epidemiologic situation and current knowledge of the limitations of pertussis vaccine point out the need to design improved vaccines. Several alternative approaches and their challenges are summarized.


Endodermal sinus tumor and embryonal carcinoma of the ovary in a 53-year-old woman.
Germ cell tumors, the most common ovarian malignancies in females under the age of 21, are rare in older women. We report an unusual case of a mixed embryonal carcinoma and endodermal sinus germ cell tumor in a perimenopausal patient and review the differential diagnosis and management of these malignancies with respect to age. A 53-year-old woman complaining of irregular menses and pelvic pain was found to have a large pelvic mass and a positive pregnancy test. Subsequent investigation revealed a large left adnexal mass, and an elevated beta-HCG and alpha-AFP. At laparotomy, a mixed germ cell tumor was found. The patient was treated with multiagent chemotherapy and currently is without evidence of disease. Although rare, the diagnosis of germ cell tumor should be considered in older women presenting with a large pelvic mass. The treatment and prognosis is similar regardless of age, except that reproductive-sparing surgery is not a priority in the older patient.


Bacterial infection of mudfish Clarias gariepinus (Siluriformes: Clariidae) fingerlings in tropical nursery ponds.
Bacterial infection among the most common cultured mudfish Clarias gariepinus in Africa, has become a cause of concern, because it constitutes the largest economic loss in fish farms. In order to provide useful biological data of the pathogens for good management practices, samples were collected monthly between January 2008 and December 2009 in three monoculture nursery ponds, located in three different positions: upriver (A, grassland), mid-river (B, mixed forest and grassland) and downriver (C, rainforest) along 200 km length of Cross River floodplains, Nigeria. A total of 720 fingerlings between 15.1 and 20.7 g were analyzed to determine the degree of infection. The bacterial pathogens were taken from their external surfaces, and were isolated and identified by standard methods. The caudal fins of fingerlings from pond A had the highest bacterial load (5.8 x 10(3) cfu/g), while the least counts (1.2 x 103 cfu/g) were identified on the head of fish from pond C, with Flexibacter columnaris as the major etiological agent. Pseudomonas fluorescens, Aeromonas hydrophila, Escherichia coli, Staphylococcus aureus and Micrococcus luteus were identified as co-isolates with P. fluorescens as dominant (0.7 x 10(2) cfu/mL) co-isolates in pond water. Clinical signs of five white spots with red periphery appeared on the external surface of infected fish. All the fish sampled, died after 4 to 9 days. There was no significant difference in the bacterial counts between different ponds, but the difference between fish organs/parts examined was significant. Fish from these ponds are therefore potentially dangerous to consumers and highly devalued, with the economic impact to producers. Preventive methods to avoid these infections are recommended.


Genome-Wide Association Study for Identification and Validation of Novel SNP Markers for Sr6 Stem Rust Resistance Gene in Bread Wheat.
Stem rust (caused by Puccinia graminis f. sp. tritici Erikss. & E. Henn.), is a major disease in wheat (Triticum aestivium L.). However, in recent years it occurs rarely in Nebraska due to weather and the effective selection and gene pyramiding of resistance genes. To understand the genetic basis of stem rust resistance in Nebraska winter wheat, we applied genome-wide association study (GWAS) on a set of 270 winter wheat genotypes (A-set). Genotyping was carried out using genotyping-by-sequencing and ∼35,000 high-quality SNPs were identified. The tested genotypes were evaluated for their resistance to the common stem rust race in Nebraska (QFCSC) in two replications. Marker-trait association identified 32 SNP markers, which were significantly (Bonferroni corrected P < 0.05) associated with the resistance on chromosome 2D. The chromosomal location of the significant SNPs (chromosome 2D) matched the location of Sr6 gene which was expected in these genotypes based on pedigree information. A highly significant linkage disequilibrium (LD, r2 ) was found between the significant SNPs and the specific SSR marker for the Sr6 gene (Xcfd43). This suggests the significant SNP markers are tagging Sr6 gene. Out of the 32 significant SNPs, eight SNPs were in six genes that are annotated as being linked to disease resistance in the IWGSC RefSeq v1.0. The 32 significant SNP markers were located in nine haplotype blocks. All the 32 significant SNPs were validated in a set of 60 different genotypes (V-set) using single marker analysis. SNP markers identified in this study can be used in marker-assisted selection, genomic selection, and to develop KASP (Kompetitive Allele Specific PCR) marker for the Sr6 gene. Novel SNPs for Sr6 gene, an important stem rust resistant gene, were identified and validated in this study. These SNPs can be used to improve stem rust resistance in wheat.


The Hospital for Special Surgery affiliates with Cornell University Medical College and New York Hospital, 1951; Philip D. Wilson retires as Surgeon-in-Chief, 1955.
When World War II ended in 1945, the Hospital for Special Surgery (HSS), the oldest orthopedic hospital in the country, was entering its eighth decade. Only 5 years previously, its name was changed from the Hospital for the Ruptured and Crippled (R & C). In 1934, Dr. Philip D. Wilson (1886-1969) had been recruited to fill the office of the fifth Surgeon-in-Chief with a key charge to restore the hospital as the leading orthopedic institution in our country, a role it originally held for over half a century since its founding in 1863. Wilson believed that a close affiliation with a university center having a medical school and hospital, while maintaining independence, was vital to achieve this objective. In 1948, negotiations between representatives of the Board of the New York Society for the Relief of the Ruptured and Crippled and representatives of the Society of the New York Hospital and Cornell Medical Center began and a preliminary written agreement was reached in March, the next year. The affiliation called for construction of a new building to house approximately 170 inpatient beds for orthopedics and arthritis. The land on the East River between 70th and 71st Streets, owned by New York Hospital, was to be given, without monetary exchange, to the Hospital for Special Surgery for construction of its new hospital. Finally, on November 1, 1951, a new non-proximate agreement was ratified. On May 25, 1955, after 43 years at 321 East 42nd Street, the Hospital for Special Surgery moved to its new six million dollar building at 535 East 70th Street where it formally became affiliated with New York Hospital-Cornell Medical Center. Two months later, on July 1, 1955, Philip D. Wilson retired as Surgeon-in-Chief to become the Hospital for Special Surgery's new Director of Research and Surgeon-in-Chief Emeritus.


Hypertension-induced remodelling: on the interactions of cardiac risk factors.
Hypertension induces considerable cardiac remodelling, such as hypertrophy, interstitial fibrosis, and abnormal activity of the cardiac sympathetic nervous system, which are established risk factors in several highly dangerous heart diseases, such as ventricular fibrillation and congestive heart failure. All these risk factors and heart diseases are studied extensively in isolation, but to our knowledge, there is no comprehensive review of their interactions. At the same time, there is growing evidence suggesting that such interactions are numerous and that a successful therapy against a particular condition may have unexpectedly weak effects on mortality, as treated patients may die of a different cause exacerbated by the therapy. In this article, we present a multiscale review of the literature focusing on the relationships between the above-mentioned risk factors and heart diseases, and introduce a framework that gives insight into their possible interactions. We use this framework to demonstrate that conditions such as fibrosis and elevated activity of the sympathetic nervous system may be compensatory, rather than purely pathological, mechanisms in certain contexts. Finally, we show why the described mechanisms are relevant not only in hypertension, but also in the case of healed myocardial infarction.


Simple vertebrate models for chemical genetics and drug discovery screens: lessons from zebrafish and Xenopus.
Chemical genetics uses small molecules to modulate protein function and, in principle, has the potential to perturb any biochemical event in a complex cellular context. The application of chemical genetics to dissect biological processes has become an attractive alternative to mutagenesis screens due to its technical simplicity, inexpensive reagents, and low-startup costs. In vertebrates, only fish and amphibians are amenable to chemical genetic screens. Xenopus frogs share a long evolutionary history with mammals and so represent an excellent model to predict human biology. In this review, we discuss the lessons learned from chemical genetic studies carried out in zebrafish and Xenopus. We highlight how Xenopus can be employed as a convenient first-line animal model at various stages of the drug discovery and development process and comment on how they represent much-needed tools to bridge the gap between traditional in vitro and preclinical mammalian assays in biomedical research and drug development. Developmental Dynamics 238:1287-1308, 2009. (c) 2009 Wiley-Liss, Inc.


Dual-memory neural networks for modeling cognitive activities of humans via wearable sensors.
Wearable devices, such as smart glasses and watches, allow for continuous recording of everyday life in a real world over an extended period of time or lifelong. This possibility helps better understand the cognitive behavior of humans in real life as well as build human-aware intelligent agents for practical purposes. However, modeling the human cognitive activity from wearable-sensor data stream is challenging because learning new information often results in loss of previously acquired information, causing a problem known as catastrophic forgetting. Here we propose a deep-learning neural network architecture that resolves the catastrophic forgetting problem. Based on the neurocognitive theory of the complementary learning systems of the neocortex and hippocampus, we introduce a dual memory architecture (DMA) that, on one hand, slowly acquires the structured knowledge representations and, on the other hand, rapidly learns the specifics of individual experiences. The DMA system learns continuously through incremental feature adaptation and weight transfer. We evaluate the performance on two real-life datasets, the CIFAR-10 image-stream dataset and the 46-day Lifelog dataset collected from Google Glass, showing that the proposed model outperforms other online learning methods.


Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R).
Although depression appears to decrease in late life, this could be due to misattribution of depressive symptom to physical disorders that increase in late life. We studied age differences in major depressive episodes (MDE) in the National Comorbidity Survey Replication, a national survey of the US household population. DSM-IV MDE was defined without organic exclusions or diagnostic hierarchy rules to facilitate analysis of co-morbidity. Physical disorders were assessed with a standard chronic conditions checklist and mental disorders with the WHO Composite International Diagnostic Interview (CIDI) version 3.0. Lifetime and recent DSM-IV/CIDI MDE were significantly less prevalent among respondents aged 65 years than among younger adults. Recent episode severity, but not duration, was also lower among the elderly. Despite prevalence of mental disorders decreasing with age, co-morbidity of hierarchy-free MDE with these disorders was either highest among the elderly or unrelated to age. Co-morbidity of MDE with physical disorders, in comparison, generally decreased with age despite prevalence of co-morbid physical disorders usually increasing. Somewhat more than half of respondents with 12-month MDE received past-year treatment, but the percentage in treatment was lowest and most concentrated in the general medical sector among the elderly. Given that physical disorders increase with age independent of depression, their lower associations with MDE in old age argue that causal effects of physical disorders on MDE weaken in old age. This result argues against the suggestion that the low estimated prevalence of MDE among the elderly is due to increased confounding with physical disorders.


Regional differences in the psychological recovery of Christchurch residents following the 2010/2011 earthquakes: a longitudinal study.
We examined changes in psychological distress experienced by residents of Christchurch following two catastrophic earthquakes in late 2010 and early 2011, using data from the New Zealand Attitudes and Values Study (NZAVS), a national probability panel study of New Zealand adults. Analyses focused on the 267 participants (172 women, 95 men) who were living in central Christchurch in 2009 (i.e., before the Christchurch earthquakes), and who also provided complete responses to our yearly panel questionnaire conducted in late 2010 (largely between the two major earthquakes), late 2011, and late 2012. Levels of psychological distress were similar across the different regions of central Christchurch immediately following the September 2010 earthquake, and remained comparable across regions in 2011. By late 2012, however, average levels of psychological distress in the regions had diverged as a function of the amount of property damage experienced within each given region. Specifically, participants in the least damaged region (i.e., the Fendalton-Waimairi and Riccarton-Wigram wards) experienced greater drops in psychological distress than did those in the moderately damaged region (i.e., across the Spreydon-Heathcote and Hagley-Ferrymead wards). However, the level of psychological distress reported by participants in the most damaged region (i.e., across Shirley-Papanui and Burwood-Pegasus) were not significantly different to those in the least damaged region of central Christchurch. These findings suggest that different patterns of psychological recovery emerged across the different regions of Christchurch, with the moderately damaged region faring the worst, but only after the initial shock of the destruction had passed.


Identifying and assessing the application of ecosystem services approaches in environmental policies and decision making.
The presumption is that ecosystem services (ES) approaches provide a better basis for environmental decision making than do other approaches because they make explicit the connection between human well-being and ecosystem structures and processes. However, the existing literature does not provide a precise description of ES approaches for environmental policy and decision making, nor does it assess whether these applications will make a difference in terms of changing decisions and improving outcomes. We describe 3 criteria that can be used to identify whether and to what extent ES approaches are being applied: 1) connect impacts all the way from ecosystem changes to human well-being, 2) consider all relevant ES affected by the decision, and 3) consider and compare the changes in well-being of different stakeholders. As a demonstration, we then analyze retrospectively whether and how the criteria were met in different decision-making contexts. For this assessment, we have developed an analysis format that describes the type of policy, the relevant scales, the decisions or questions, the decision maker, and the underlying documents. This format includes a general judgment of how far the 3 ES criteria have been applied. It shows that the criteria can be applied to many different decision-making processes, ranging from the supranational to the local scale and to different parts of decision-making processes. In conclusion we suggest these criteria could be used for assessments of the extent to which ES approaches have been and should be applied, what benefits and challenges arise, and whether using ES approaches made a difference in the decision-making process, decisions made, or outcomes of those decisions. Results from such studies could inform future use and development of ES approaches, draw attention to where the greatest benefits and challenges are, and help to target integration of ES approaches into policies, where they can be most effective. Integr Environ Assess Manag 2017;13:41-51. © 2016 SETAC.


Repetitive Nerve Stimulation in Amyotrophic Lateral Sclerosis.
Nowadays, it is widely known that decremental responses in low-frequency repetitive nerve stimulation (LF-RNS) are frequently observed in patients with amyotrophic lateral sclerosis (ALS). The pathological mechanism of this phenomenon remains unknown. This study aimed to illuminate the features of RNS in Chinese patients with ALS. Clinical and electrophysiological data of 146 probable and definite ALS patients who underwent RNS were retrospectively enrolled and analyzed. LF-RNS (3 Hz) was performed in trapezius, deltoid, abductor digiti minimi (ADM), quadriceps femoris, and tibialis anterior. High-frequency RNS (HF-RNS, 10 Hz) was performed only in ADM. The two-sample t-test and Chi-squared test were used for statistical analysis. Decremental responses to LF-RNS (≥10%) in at least one muscle were detected in 83 (56.8%) of the cases and were most commonly seen in trapezius and deltoid. The incidence of decremental response was higher in patients with upper limb onset. Incremental responses to HF-RNS (≥60%) in ADM were observed in 6 (5.6%) of the cases. In 106 muscles with decremental response, 62 (57.4%) muscles had a continuous decremental pattern, more than a U-shape pattern (37 cases, 34.3%). Nineteen cases showed definite decrements in LF-RNS tests in trapezius, while no abnormalities were found in the electromyography and neurological examination of the sternocleidomastoid muscle, supplied by the accessory nerve as well. Decremental responses in the RNS are commonly observed in ALS patients. The findings regarding the trapezius indicated that some ALS onsets could be initiated by a "dying back" process, with destruction of neuromuscular junctions (NMJs) before motor neurons. Incremental responses in the ADM implied damage of the NMJs involved both the post and presynaptic membranes.


Open, randomized therapeutic trial of six antimicrobial regimens in the treatment of human brucellosis.
This report describes the results of six antimicrobial regimens used for the treatment of brucellosis in an open, randomized study performed over two periods (1980-1983 and 1984-1987). In the first period, rifampicin and doxycycline were used for 4 weeks, trimethoprim-sulfamethoxazole for 6 months, and doxycycline for 6 weeks. During the second period, we used streptomycin for 2 or 3 weeks together with doxycycline for 6 weeks and rifampicin with doxycycline for 6 weeks. Comparison of the results showed the following: (1) no statistically significant findings were revealed when the different regimens were compared and (2) the regimens containing streptomycin yielded statistically more favorable results than those consisting of rifampicin and monotherapy when the patients treated with rifampicin were compared with those taking streptomycin and those receiving single-agent therapy. No significant differences were observed between monotherapeutic regimens and those including rifampicin.


Metabolism and disposition of gemcitabine, and oncolytic deoxycytidine analog, in mice, rats, and dogs.
Gemcitabine, 2'-deoxy-2',2'-difluorocytidine, is a broad spectrum oncolytic compound with antitumor activity in solid tumor models. The pharmacokinetics, metabolism, and disposition of gemcitabine was examined in mice, rats, and dogs. All three species metabolize gemcitabine by deamination to the uracil metabolite. However, deamination in the mouse and dog was more extensive than in the rat. The mouse deaminated gemcitabine rapidly with the plasma concentration maximum of the uracil metabolite of gemcitabine being attained at 15 min postdosing compared with approximately 3 and 6 hr in the dog and rat, respectively. The rapid deamination in the mouse was also reflected in the plasma half-life of the parent compound. The mouse exhibited the shortest plasma half-life, approximately 0.28 hr, contrasted with 2.14 and 1.38 hr half-lives in rat and dog, respectively. Plasma AUC for the uracil metabolite of gemcitabine was 73%, 10.5%, and 315% of that for gemcitabine in the mouse, rat, and dog, respectively. Tissue concentrations of gemcitabine-derived radioactivity in the rat and mouse indicated that gemcitabine was rapidly distributed throughout the body. Half-lives of radioactivity in tissues of both the rat and mouse were relatively short, with the longest tissue half-lives of 5.7 and 3.0 hr, respectively. Plasma protein binding is negligible in all three species. The major route of elimination is via the urine in all three species with 76-86% of the dose excreted in the first 24 hr. The predominant radiolabeled component isolated from urine was gemcitabine in the rat and its uracil metabolite in the mouse and dog.


The Prostate Cancer Intervention Versus Observation Trial (PIVOT).
The Prostate Cancer Intervention Versus Observation Trial (PIVOT) is a randomized trial designed to determine whether radical prostatectomy or expectant management provides superior length and quality of life for men with clinically localized prostate cancer. Conducted at Department of Veterans Affairs and National Cancer Institute medical centers, PIVOT will enroll over 1,000 individuals < 75 years of age. The primary study end point is all-cause mortality. Secondary outcomes include prostate cancer- and treatment-specific morbidity and mortality, health status, predictors of disease-specific outcomes, and cost-effectiveness. Within the first 3 years of enrollment, over 400 men have been randomized. Early analysis of participants' baseline characteristics indicate that enrollees are representative of men diagnosed with clinically localized prostate cancer throughout the United States. Therefore, results of PIVOT will be generalizable. These results are necessary in order to determine the preferred therapy for clinically localized prostate cancer.


A novel CCR5 mutation common in sooty mangabeys reveals SIVsmm infection of CCR5-null natural hosts and efficient alternative coreceptor use in vivo.
In contrast to HIV infection in humans and SIV in macaques, SIV infection of natural hosts including sooty mangabeys (SM) is non-pathogenic despite robust virus replication. We identified a novel SM CCR5 allele containing a two base pair deletion (Δ2) encoding a truncated molecule that is not expressed on the cell surface and does not support SIV entry in vitro. The allele was present at a 26% frequency in a large SM colony, along with 3% for a CCR5Δ24 deletion allele that also abrogates surface expression. Overall, 8% of animals were homozygous for defective CCR5 alleles and 41% were heterozygous. The mutant allele was also present in wild SM in West Africa. CD8+ and CD4+ T cells displayed a gradient of CCR5 expression across genotype groups, which was highly significant for CD8+ cells. Remarkably, the prevalence of natural SIVsmm infection was not significantly different in animals lacking functional CCR5 compared to heterozygous and homozygous wild-type animals. Furthermore, animals lacking functional CCR5 had robust plasma viral loads, which were only modestly lower than wild-type animals. SIVsmm primary isolates infected both homozygous mutant and wild-type PBMC in a CCR5-independent manner in vitro, and Envs from both CCR5-null and wild-type infected animals used CXCR6, GPR15 and GPR1 in addition to CCR5 in transfected cells. These data clearly indicate that SIVsmm relies on CCR5-independent entry pathways in SM that are homozygous for defective CCR5 alleles and, while the extent of alternative coreceptor use in SM with CCR5 wild type alleles is uncertain, strongly suggest that SIVsmm tropism and host cell targeting in vivo is defined by the distribution and use of alternative entry pathways in addition to CCR5. SIVsmm entry through alternative pathways in vivo raises the possibility of novel CCR5-negative target cells that may be more expendable than CCR5+ cells and enable the virus to replicate efficiently without causing disease in the face of extremely restricted CCR5 expression seen in SM and several other natural host species.


Trunk muscle activation during dynamic weight-training exercises and isometric instability activities.
The purpose of this study was to examine the extent of activation in various trunk muscles during dynamic weight-training and isometric instability exercises. Sixteen subjects performed squats and deadlifts with 80% 1 repetition maximum (1RM), as well as with body weight as resistance and 2 unstable calisthenic-type exercises (superman and sidebridge). Electromyographic (EMG) activity was measured from the lower abdominals (LA), external obliques (EO), upper lumbar erector spinae (ULES), and lumbar-sacral erector spinae (LSES) muscle groups. Results indicated that the LSES EMG activity during the 80% 1RM squat significantly exceeded 80% 1RM deadlift LSES EMG activity by 34.5%. The LSES EMG activity of the 80% 1RM squat also exceeded the body weight squat, deadlift, superman, and sidebridge by 56, 56.6, 65.5, and 53.1%, respectively. The 80% 1RM deadlift ULES EMG activity significantly exceeded the 80% 1RM squat exercise by 12.9%. In addition, the 80% 1RM deadlift ULES EMG activity also exceeded the body weight squat, deadlift, superman, and sidebridge exercises by 66.7, 65.5, 69.3, and 68.6%, respectively. There were no significant changes in EO or LA activity. Therefore, the augmented activity of the LSES and ULES during 80% 1RM squat and deadlift resistance exercises exceeded the activation levels achieved with the same exercises performed with body weight and selected instability exercises. Individuals performing upright, resisted, dynamic exercises can achieve high trunk muscle activation and thus may not need to add instability device exercises to augment core stability training.


Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics.
An unaddressed and important issue is the role age plays in modulating response to short acting β2-agonists in individuals with asthma. The objective of this study was to identify whether age modifies genetic associations of single nucleotide polymorphisms (SNPs) with bronchodilator response (BDR) to β2-agonists. Using three cohorts with a total of 892 subjects, we ran a genome wide interaction study (GWIS) for each cohort to examine SNP by age interactions with BDR. A fixed effect meta-analysis was used to combine the results. In order to determine if previously identified BDR SNPs had an age interaction, we also examined 16 polymorphisms in candidate genes from two published genome wide association studies (GWAS) of BDR. There were no significant SNP by age interactions on BDR using the genome wide significance level of 5 × 10-8. Using a suggestive significance level of 5 × 10-6, three interactions, including one for a SNP within PRAG1 (rs4840337), were significant and replicated at the significance level of 0.05. Considering candidate genes from two previous GWAS of BDR, three SNPs (rs10476900 (near ADRB2) [p-value = 0.009], rs10827492 (CREM) [p-value = 0.02], and rs72646209 (NCOA3) [p-value = 0.02]) had a marginally significant interaction with age on BDR (p < 0.05). Our results suggest age may be an important modifier of genetic associations for BDR in asthma.


Molecular profiling of tumor progression in head and neck cancer.
To assess gene expression changes associated with tumor progression in patients with squamous cell carcinoma of the oral cavity. A microarray containing 17 840 complementary DNA clones was used to measure gene expression changes associated with tumor progression in 9 patients with squamous cell carcinoma of the oral cavity. Samples were taken for analysis from the primary tumor, nodal metastasis, and "normal" mucosa from the patients' oral cavity. Tertiary care facility. Patients Nine patients with stage III or stage IV untreated oral cavity squamous cell carcinoma. Our analysis to categorize genes based on their expression patterns has identified 140 genes that consistently increased in expression during progression from normal tissue to invasive tumor and subsequently to metastatic node (in at least 4 of the 9 cases studied). A similar list of 94 genes has been identified that decreased in expression during tumor progression and metastasis. We validated this gene discovery approach by selecting moesin (a member of the ezrin/radixin/moesin [ERM] family of cytoskeletal proteins) and one of the genes that consistently increased in expression during tumor progression for subsequent immunohistochemical analysis using a head and neck squamous cell carcinoma tissue array. A distinct pattern of gene expression, with progressive up- or down-regulation of expression, is found during the progression from histologically normal tissue to primary carcinoma and to nodal metastasis.


Improving information technology competencies: implications for psychiatric mental health nursing.
While substantial evidence links information technology (IT) with improved patient safety, care quality, access, and efficiency, nurses must demonstrate competencies in computers, informatics, and information literacy in order to use IT for practice, education, and research. The nursing profession has established IT competencies for all nurses at beginning and experienced levels. Newly revised standards also articulate role-specific expectations for advanced practice nurses. Unfortunately, there is a concern that many nurses may not possess these capabilities and that nurse educators are not prepared to teach them. IT competency evaluations, which have focused predominately on nursing education, indicate novice skill levels for most faculty and students. In numerous studies, again conducted largely in nursing education, significant improvement in IT competencies has been achieved only with intensive interventions. Deficits in IT competencies are a significant concern, because the federal government has mandated full implementation of Electronic Health Records (EHR) by 2014. EHR will require all nurses to use IT to deliver, document, and obtain reimbursement for patient care. In response to these concerns, two recent initiatives, the "Health Information Technology Scholars (HITS)" and "Technology Informatics Guiding Education Reform (TIGER)" projects, have been launched. By enhancing IT competencies, these projects will enable nurses to use evidence-based practice and other innovations to transform clinical care, education, and research. This report updates psychiatric-mental health nurses on the IT competencies literature, recent enhancement initiatives and innovations, and their implications for the specialty.


Cardiac reflexes conducted by vagal afferents in normotensive and renal hypertensive dogs.
1. The renal sympathetic reflex responses to transient balloon occlusion of the descending aorta (systemic baroreceptor activation) and the ascending aorta (cardiac stretch-receptor activation) have been studied together with blood pressure increases after successive cutting of carotid sinus, aortic and vagus nerves in acute experiments in the dog. 2. Results from these experiments provide evidence for cardiac vagal afferent participation in the tonic regulation of systemic blood pressure. 3. In other experiments the reflex pressure-response curve of the isolated gracilis muscle at constant flow to transient ascending aorta occlusion was measured. This curve was moved to the right in renal hypertensive dogs as compared with normotensive dogs. The threshold response of left ventricular vagal afferent nerves was shifted to higher left ventricular pressure in the former. 3. These findings indicate resetting of ventricular receptors in hypertensive animals.


Nonverbal imitation skills in children with specific language delay.
Research in children with language problems has focussed on verbal deficits, and we have less understanding of children's deficits with nonverbal sociocognitive skills which have been proposed to be important for language acquisition. This study was designed to investigate elicited nonverbal imitation in children with specific language delay (SLD). It is argued that difficulties in nonverbal imitation, which do not involve the processing of structural aspects of language, may be indicative of sociocognitive deficits. Participants were German-speaking typically developing children (n=60) and children with SLD (n=45) aged 2-3 ½ years. A novel battery of tasks measured their ability to imitate a range of nonverbal target acts that to a greater or lesser extent involve sociocognitive skills (body movements, instrumental acts on objects, pretend acts). Significant group differences were found for all body movement and pretend act tasks, but not for the instrumental act tasks. The poorer imitative performance of the SLD sample was not explained by motor or nonverbal cognitive skills. Thus, it appeared that the nature of the task affected children's imitation performance. It is argued that the ability to establish a sense of connectedness with the demonstrator was at the core of children's imitation difficulty in the SLD sample.


Developments in the Collection of Statistical Information on the Number of Animals used in Experiments and other Scientific Purposes in the European Union.
In 1999, the European Commission presented its second report on the numbers of laboratory animals used in the European Union (EU). The plausibility of the data and the usefulness of the format of the registration tables remain questionable, for reasons previously discussed in connection with the Commission` s first statistical report. In addition, it is impossible to derive sound information on trends in animal use in the EU and its Member States from the second statistical report. The European Commission and the Member States have agreed on new tables to be used for future statistics on the use of experimental animals in the EU. These new tables have been significantly extended and improved. Several categories of little relevance have been revised, and ambiguous expressions have been clarified. However, several problems either persist or have been newly created. Moreover, some important data (i.e. categories for pain and distress, as well as for several specific purposes of use; the origin of some animal species; types of institutions; and the use of genetically engineered animals) are still not required. Nevertheless, these are highly relevant to animal welfare and must be regarded as indispensable for a well-aimed application of the statistics to set priorities concerning the Three Rs.


In-vitro culture with a tilting device in chemically defined media during meiotic maturation and early development improves the quality of blastocysts derived from in-vitro matured and fertilized porcine oocytes.
Under physiological conditions, mammalian oocytes and embryos appear to be stimulated not only chemically but also mechanically, such as by compression, shear stress and/or friction force in the follicle and female reproductive tract. The present study was undertaken to examine the effects of kinetic culture with a tilting device in chemically defined media during in vitro maturation (IVM) of porcine oocytes and in vitro culture (IVC) following in vitro fertilization (IVF) on the early developmental competence and quality of blastocysts. After culture in a chemically defined IVM medium, modified porcine oocyte medium (mPOM) containing gonadotropins and dibutyryl cAMP for 20 h, the mean diameter of the cumulus-oocyte complexes (COCs) was larger in the tilting culture than in the static controls, whereas the diameter of the oocytes did not differ. When culture of the COCs was continued additionally in a fresh medium without gonadotropins and dibutyryl cAMP for 24 h, the incidences of oocytes completing GVBD and developing to the metaphase-II stage did not differ between the tilting and static culture systems. Furthermore, the sperm penetration after IVF and developmental competence of the oocytes to the blastocyst stage were not different between the tilting and static systems during IVM and IVC. However, tilting culture during both IVM and IVC had a significant positive effect on the number of cells per blastocyst (P<0.05). These observations indicate that tilting culture during IVM and IVC in chemically defined media improves the quality of blastocyst, as determined by the number of cells per blastocyst, without any effects on penetrability and developmental competence.


Exposure to nicotine enhances acquisition of ethanol drinking by laboratory rats in a limited access paradigm.
Observations in humans suggest that the initial use of tobacco occurs in close temporal proximity to experimentation with alcohol. There have been relatively few research reports, however, examining possible interactions between these two agents. The present experiments examined the effect of nicotine exposure on the acquisition of ethanol drinking behavior in a limited access procedure. In experiment 1, rats were presented with 1-h access to ethanol solutions of increasing concentration for a period of 20 days. Subcutaneous injections of nicotine (0.6 or 1.2 mg/kg salt) or vehicle were administered 30 min prior to each ethanol presentation. Experiment 2 used a similar method, but rats were presented with water along with ethanol during the 1-h test session. Mecamylamine, a nicotinic receptor antagonist, was administered 30 min prior to the nicotine treatment. Nicotine was seen to produce a dose-dependent increase in ethanol drinking behavior which commenced at the 5% ethanol concentration and continued at 8% and again at 10%. In the second experiment, mecamylamine was observed to block completely the nicotine-induced increase in ethanol drinking behavior. The findings suggest that exposure to nicotine can facilitate the acquisition of ethanol drinking behavior in naive rats and that this effect is mediated by nicotine's interaction at the nicotinic-cholinergic receptor.


Enhanced prediction of atrial fibrillation and mortality among patients with congenital heart disease using nationwide register-based medical hospital data and neural networks.
To improve short-and long-term predictions of mortality and atrial fibrillation (AF) among patients with congenital heart disease (CHD) from a nationwide population using neural networks (NN). The Swedish National Patient Register and the Cause of Death Register were used to identify all patients with CHD born from 1970 to 2017. A total of 71 941 CHD patients were identified and followed-up from birth until the event or end of study in 2017. Based on data from a nationwide population, a NN model was obtained to predict mortality and AF. Logistic regression (LR) based on the same data was used as a baseline comparison. Of 71 941 CHD patients, a total of 5768 died (8.02%) and 995 (1.38%) developed AF over time with a mean follow-up time of 16.47 years (standard deviation 12.73 years). The performance of NN models in predicting the mortality and AF was higher than the performance of LR regardless of the complexity of the disease, with an average area under the receiver operating characteristic of >0.80 and >0.70, respectively. The largest differences were observed in mortality and complexity of CHD over time. We found that NN can be used to predict mortality and AF on a nationwide scale using data that are easily obtainable by clinicians. In addition, NN showed a high performance overall and, in most cases, with better performance for prediction as compared with more traditional regression methods.


Prevalence of coeliac disease among adult patients with autoimmune hypothyroidism in Jordan.
The prevalence of coeliac disease among patients with autoimmune hypothyroidism has not been studied before in Jordan and other Arab countries. A cross-sectional record-based review was made of all adult autoimmune hypothyroidism patients who attended a referral centre in Jordan, during an 8-month period. Coeliac disease in these patients was diagnosed by the attending physician based on positive serological tests for anti-endomysial antibodies IgA and IgG followed by duodenal biopsy to confirm the diagnosis of coeliac disease. Of 914 patients recruited, 117 (12.8%) were seropositive for coeliac disease. Of 87 seropositive patients who underwent duodenal biopsy, 39 had positive histological findings of coeliac disease (44.8%). Extrapolating from these findings the overall rate of coeliac disease among autoimmune hypothyroidism patients was estimated to be 5.7%. In multivariate logistic regression coeliac disease was significantly associated with older age (> 40 years), presence of other autoimmune diseases, vitamin B12 deficiency and anaemia.


Religious Involvement, Anxiety/Depression, and PTSD Symptoms in US Veterans and Active Duty Military.
Religious involvement is associated with mental health and well-being in non-military populations. This study examines the relationship between religiosity and PTSD symptoms, and the mediating effects of anxiety and depression in Veterans and Active Duty Military (V/ADM). This was a cross-sectional multi-site study involving 585 V/ADM recruited from across the USA. Inclusion criteria were having served in a combat theater and PTSD symptoms. Demographics, military characteristics, and social factors were assessed, along with measurement of religiosity, PTSD symptoms, depression, and anxiety. Bivariate and multivariate analyses examined the religiosity-PTSD relationship and the mediating effects of anxiety/depression on that relationship in the overall sample and stratified by race/ethnic group (White, Black, Hispanic). In bivariate analyses, the religiosity-PTSD relationship was not significant in the overall sample or in Whites. However, the relationship was significant in Blacks (r = - 0.16, p = 0.01) and in Hispanics (r = 0.30, p = 0.03), but in opposite directions. In the overall sample, religiosity was inversely related to anxiety (r = - 0.07, p = 0.07) and depression (r = - 0.21, p < 0.0001), especially in Blacks (r = - 0.21, p = 0.001, and r = - 0.34, p < 0.0001, respectively); however, in Hispanics, religiosity was positively related to anxiety (r = 0.32, p = 0.02) as it was to PTSD symptoms. When anxiety/depression was controlled for in multivariate analyses, the religiosity-PTSD relationship in the overall sample reversed from negative to positive, approaching statistical significance (B = 0.05, SE = 0.03, p = 0.079). In Blacks, the inverse association between religiosity and PTSD was explained by quality of relationships, whereas the positive relationship in Hispanics was explained by anxiety symptoms. In conclusion, religiosity was inversely related to PTSD symptoms in Blacks, positively related to PTSD in Hispanics, and unrelated to PTSD in the overall sample and in Whites. Anxiety/depression partially mediated the relationship in the overall sample and in Hispanics. Although longitudinal studies will be necessary to determine how these relationships come about, consideration should be given to spiritual/religious interventions that target anxiety/depression in V/ADM with PTSD.


The work place educational climate in gynecological oncology fellowships across Europe: the impact of accreditation.
A good educational climate/environment in the workplace is essential for developing high-quality medical (sub)specialists. These data are lacking for gynecological oncology training. This study aims to evaluate the educational climate in gynecological oncology training throughout Europe and the factors affecting it. A Web-based anonymous survey sent to ENYGO (European Network of Young Gynecological Oncologists) members/trainees to assess gynecological oncology training. This included sociodemographic information, details regarding training posts, and a 50-item validated Dutch Residency Educational Climate Test (D-RECT) questionnaire with 11 subscales (1-5 Likert scale) to assess the educational climate. The χ test was used for evaluating categorical variables, and the Mann-Whitney U (nonparametric) test was used for continuous variables between 2 independent groups. Cronbach α assessed the questionnaire reliability. Multivariable linear regression assessed the effect of variables on D-RECT outcome subscales. One hundred nineteen gynecological oncological fellows responded. The D-RECT questionnaire was extremely reliable for assessing the educational environment in gynecological oncology (subscales' Cronbach α, 0.82-0.96). Overall, trainees do not seem to receive adequate/effective constructive feedback during training. The overall educational climate (supervision, coaching/assessment, feedback, teamwork, interconsultant relationships, formal education, role of the tutor, patient handover, and overall consultant's attitude) was significantly better (P = 0.001) in centers providing accredited training in comparison with centers without such accreditation. Multivariable regression indicated the main factors independently associated with a better educational climate were presence of an accredited training post and total years of training. This study emphasizes the need for better feedback mechanisms and the importance of accreditation of centers for training in gynecological oncology to ensure training within higher quality clinical learning climates.


Location, Location, Location: Alterations in the Functional Topography of Face- but not Object- or Place-Related Cortex in Adolescents with Autism.
In autism, impairments in face processing are a relatively recent discovery, but have quickly become a widely accepted aspect of the behavioral profile. Only a handful of studies have investigated potential atypicalities in autism in the development of the neural substrates mediating face processing. High-functioning individuals with autism (HFA) and matched typically developing (TD) controls watched dynamic movie vignettes of faces, common objects, buildings, and scenes of navigation while undergoing an fMRI scan. With these data, we mapped the functional topography of category-selective activation for faces bilaterally in the fusiform gyrus, occipital face area, and posterior superior temporal sulcus. Additionally, we mapped category-selective activation for objects in the lateral occipital area and for places in the parahippocampal place area in the two groups. Our findings do not indicate a generalized disruption in the development of the entire ventral visual pathway in autism. Instead, our results suggest that the functional topography of face-related cortex is selectively disrupted in autism and that this alteration is present in early adolescence. Furthermore, for those HFA adolescents who do exhibit face-selective activation, this activation tends to be located in traditionally object-related regions, which supports the hypothesis that perceptual processing of faces in autism may be more akin to the perceptual processing of common objects in TD individuals.


The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey.
To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action. All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1%). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies. Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 +/- 0.20 vs. 0.53 +/- 0.18 microL.min(-1). After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1% dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes. The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar.


Disinfection of meticillin-resistant Staphylococcus aureus and Staphylococcus epidermidis biofilms using a remote non-thermal gas plasma.
The effective disinfection of hospital surfaces is recognised as an important factor in preventing hospital-acquired infections. The purpose of this study was to quantify the disinfection rate of a novel gas plasma system on clinically relevant biofilms. Clinical isolates of Staphylococcus epidermidis and meticillin-resistant Staphylococcus aureus (MRSA) were grown as biofilms on glass surfaces and tested in a disinfection container remote from the plasma source. The strains used in this study were known to produce substantial quantities of biofilm and average log₁₀ counts were 9.0 and 9.1 cfu/cm(2) for S. epidermidis and MRSA respectively. Counts were reduced by between 4 and 4.5 log₁₀ after 1h of exposure for MRSA and S. epidermidis respectively. More prolonged treatment in the case of MRSA biofilms resulted in a 5.5 log₁₀ reduction after 90 min. Biofilm samples were also placed in medical device packaging bags and similar rates of disinfection were observed.


Stroke in a patient with pulmonary arteriovenous fistula: A case report study.
Pulmonary arteriovenous fistula (PAVF) is a venous malformation that permits right to left shunting of blood, bypassing the pulmonary capillary bed. Often PAVFs are seen in association with hereditary conditions. On the other hand, isolated PAVFs are rare and asymptomatic. There have been few reports of isolated PAVF related complications. A patient was referred to us with dysarthria and diplopia and history of surgically-treated PAVF. Further evaluations revealed a stroke in thalamic region. We found an open PAVF in a case of thalamic stroke.


The management of acute distal tibio-fibular syndesmotic injuries: results of a nationwide survey.
Ankle fractures are one of the most frequently encountered musculoskeletal injuries, and 10% of patients have a concomitant distal tibiofibular syndesmotic disruption necessitating surgical repair. A national survey was conducted to gain more insight into the current approaches in the management of syndesmotic injuries in the Netherlands. A postal survey was sent to one or two staff members of the trauma and orthopaedic surgery departments in each of the 86 hospitals in the Netherlands. Questions concerned the pre-, per- and postoperative strategies and the different ideas on the type, number and placement of the syndesmotic screw. A total of 85.2% of the trauma surgeons and 61.9% of the orthopaedic surgeons responded (representing 87% of all hospitals). Syndesmotic injury was judged mainly using the 'Hook test'. Syndesmotic injuries in a Weber-B ankle fracture were treated with one screw in 81.2% of cases and in Maisonneuve injuries mainly with two screws. The 3.5-mm screw was used most frequently over three cortices at 2.1-4.0cm above the tibial plafond. Removal of the syndesmotic screw was routinely done by 87.0% of surgeons, mostly between 6 and 8 weeks. Of all respondents, 62.3% showed interest in participating in a randomised controlled trial comparing standard removal with removal on indication. Compared with previous surveys our survey is more complete, has the highest response rate and has almost national coverage. Most individual items reviewed compare well with current literature, except for the routine removal of the syndesmotic screw, which might not be encouraged from a literature point of view. For this reason, the results of the current survey will be used in the development of a multicentre randomised controlled trial comparing the functional outcome in routine removal of the syndesmotic screw compared with removal on indication.


Evaluating the Utility of EPIK in a Finger Tapping fMRI Experiment using BOLD Detection and Effective Connectivity.
EPI with Keyhole (EPIK) is a hybrid imaging technique that overcomes many of the performance disadvantages associated with EPI. Previously, EPIK was shown to provide a higher temporal resolution and fewer image distortions than EPI whilst maintaining comparable performance for the detection of BOLD-based signals. This work carefully examines the putative enhanced sensitivity of EPIK in a typical fMRI setting by using a robust fMRI paradigm - visually guided finger tapping - to demonstrate the advantages of EPIK for fMRI at 3 T. The data acquired were directly compared to the community standard fMRI protocol using single-shot EPI to ascertain a clear comparison. Each sequence was optimised to offer its highest possible spatial resolution for a given set of imaging conditions, i.e., EPIK and EPI achieved an in-planar resolution of 2.08 × 2.08 mm2 with 32 slices and 3.13 × 3.13 mm2 with 36 slices, respectively. EPIK demonstrated a number of clear improvements, such as superior spatial resolution with favourable robustness against susceptibility artefacts. Both imaging sequences revealed robust activation within primary motor, premotor and visual regions, although significantly higher BOLD amplitudes were detected using EPIK within the primary and supplementary motor areas. Dynamic causal modelling, in combination with Bayesian model selection, identified identical winning models for EPIK and EPI data. Coupling parameters reflecting task-related modulations and the connectivity of fixed connections were comparably robust for both sequences. However, fixed connections from the left motor cortex to the right visual cortex were estimated as being significantly more robust for EPIK data.