Level dependence of spatial processing in the primate auditory cortex.
Sound localization in both humans and monkeys is tolerant to changes in sound levels. The underlying neural mechanism, however, is not well understood. This study reports the level dependence of individual neurons' spatial receptive fields (SRFs) in the primary auditory cortex (A1) and the adjacent caudal field in awake marmoset monkeys. We found that most neurons' excitatory SRF components were spatially confined in response to broadband noise stimuli delivered from the upper frontal sound field. Approximately half the recorded neurons exhibited little change in spatial tuning width over a ~20-dB change in sound level, whereas the remaining neurons showed either expansion or contraction in their tuning widths. Increased sound levels did not alter the percent distribution of tuning width for neurons collected in either cortical field. The population-averaged responses remained tuned between 30- and 80-dB sound pressure levels for neuronal groups preferring contralateral, midline, and ipsilateral locations. We further investigated the spatial extent and level dependence of the suppressive component of SRFs using a pair of sequentially presented stimuli. Forward suppression was observed when the stimuli were delivered from "far" locations, distant to the excitatory center of an SRF. In contrast to spatially confined excitation, the strength of suppression typically increased with stimulus level at both the excitatory center and far regions of an SRF. These findings indicate that although the spatial tuning of individual neurons varied with stimulus levels, their ensemble responses were level tolerant. Widespread spatial suppression may play an important role in limiting the sizes of SRFs at high sound levels in the auditory cortex.


The Glasgow Outcome at Discharge Scale: an inpatient assessment of disability after brain injury.
This study assesses the validity and reliability of the Glasgow Outcome at Discharge Scale (GODS), which is a tool that is designed to assess disability after brain injury in an inpatient setting. It is derived from the Glasgow Outcome Scale-Extended (GOS-E), which assesses disability in the community after brain injury. Inter-rater reliability on the GODS is high (quadratic-weighted kappa 0.982; 95% confidence interval [CI] 0.968, 0.996) as is concurrent validity with the Disability Rating Scale (DRS) (Spearman correlation -0.728; 95% CI -0.819, -0.601). The GODS is significantly associated with physical and fatigue subscales of the short form (SF)-36 in hospital. In terms of predictive validity the GODS is highly associated with the GOS-E after discharge (Spearman correlation 0.512; 95% CI 0.281, 0.687), with the DRS, and with physical, fatigue, and social subscales of the SF-36. The GODS is recommended as an assessment tool for disability after brain injury pre-discharge and can be used in conjunction with the GOS-E to monitor disability between hospital and the community.


Congenital dysfibrinogenemias. A review.
Inherited qualitative abnormalities of fibrinogen have been documented in 144 families. These dysfibrinogenemias have been inherited as autosomal dominant traits and usually are clinically silent, but in some cases are associated with bleeding, thrombosis, or defective wound healing. Dysfibrinogenemias may be associated with defects in any of the three basic steps in the thrombin-fibrinogen reaction, i.e., cleavage of the fibrinopeptides by thrombin, polymerization, and fibrin cross-linking. Biochemical studies of several abnormal fibrinogens have demonstrated that the functional defects are the result of single amino acid substitutions. Most of the reported cases may be distinguished by functional criteria and by the physicochemical behavior and biochemical nature of the abnormal protein.


Modelling memory decay after injuries using household survey data from Khartoum State, Sudan.
Injuries represent an important cause of morbidity and mortality worldwide. In retrospective epidemiological studies, estimated rates of reported injuries often decline considerably when information is included from periods more than a few months before the data collection. Such low rates are usually regarded as a consequence of memory decay. It is largely unknown whether the extent of memory decay depends on external factors otherwise affecting injury rates. A statistical model was introduced to separate the influence of external factors on true injury rates from effects on memory decay. The relationship between apparent rates and time elapsed between injury occurrence and data collection was described by a parametric regression model. Relationships between memory decay and external factors were modelled by effect modification of the relationship with time. The procedure was applied to data collected in a retrospective household survey, carried out in Khartoum State in 2010, which elicited information about injuries that had occurred during the last year. The survey included 5661 individuals in 973 households, reporting a total of 481 non-fatal injuries. In the data from Khartoum State, differences in memory recall were observed between socioeconomic groups, with considerably faster memory decay in the lower socioeconomic tertile. In this tertile the estimated probability that an injury which occurred 6 months ago was reported was only 18%, compared to probabilities of about 35% in the remainder of the population. In the lower socioeconomic tertile, in contrast to other groups, a simple exponential model was not sufficient for describing memory decay. Memory decay did not depend on sex, age, urban/rural status or education. Road traffic injuries were subject to less memory decay than injuries due to falls, mechanical causes and burns. Memory decay seriously affected crude overall injury rates and also to some degree estimated relative rates. In the statistical analysis of retrospective injury data it is important to take into account the effects of memory decay.


Association of Radiographically Diagnosed Apical Periodontitis and Cardiovascular Disease: A Hospital Records-based Study.
Numerous studies have demonstrated an association between oral health status and systemic diseases. However, reports examining apical periodontitis (AP) and cardiovascular disease (CVD) are few. This study investigates whether an association exists between AP and CVD. The present study was a pair-matched, cross-sectional design that used medical and dental chart review. The AP group (n = 182) was defined as subjects with radiographic AP, and the non-AP group (n = 182) was defined as subjects without any radiographic AP. Samples for both groups were pair-matched by age and gender. Diagnosis for CVD, hypercholesterolemia, hypertension, and diabetes were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification and collected from electronic medical records. Documentation of alcohol use, smoking, race, and body mass index within the electronic medical records was also collected. Presence or absence of AP, missing teeth, teeth with root canal treatment, caries experience, and history of periodontal disease were collected from the electronic dental records. Analysis was performed by using Pearson χ(2), the paired t test, and conditional multivariate logistic regression. AP was significantly associated with CVD, hypercholesterolemia, race, missing teeth, caries experience, and number of root canal treatments in our bivariate analysis. Our final adjusted conditional logistic regression model showed statistically significant positive associations between AP and CVD (odds ratio, 5.3; 95% confidence interval, 1.5-18.4). Subjects with AP were more likely to have CVD than subjects without AP by 5.3-fold. However, further research is needed to elucidate temporality and reinforce association between CVD and AP.


Performance evaluation of Maxwell and Cercignani-Lampis gas-wall interaction models in the modeling of thermally driven rarefied gas transport.
A systematic study on the performance of two empirical gas-wall interaction models, the Maxwell model and the Cercignani-Lampis (CL) model, in the entire Knudsen range is conducted. The models are evaluated by examining the accuracy of key macroscopic quantities such as temperature, density, and pressure, in three benchmark thermal problems, namely the Fourier thermal problem, the Knudsen force problem, and the thermal transpiration problem. The reference solutions are obtained from a validated hybrid DSMC-MD algorithm developed in-house. It has been found that while both models predict temperature and density reasonably well in the Fourier thermal problem, the pressure profile obtained from Maxwell model exhibits a trend that opposes that from the reference solution. As a consequence, the Maxwell model is unable to predict the orientation change of the Knudsen force acting on a cold cylinder embedded in a hot cylindrical enclosure at a certain Knudsen number. In the simulation of the thermal transpiration coefficient, although all three models overestimate the coefficient, the coefficient obtained from CL model is the closest to the reference solution. The Maxwell model performs the worst. The cause of the overestimated coefficient is investigated and its link to the overly constrained correlation between the tangential momentum accommodation coefficient and the tangential energy accommodation coefficient inherent in the models is pointed out. Directions for further improvement of models are suggested.


Evolution of proneural atonal expression during distinct regulatory phases in the developing Drosophila eye.
Receptors of the Notch family affect the determination of many cell types. In the Drosophila eye, Notch antagonises the basic helix-loop-helix (bHLH) protein atonal, which is required for R8 photoreceptor determination. Similar antagonism between Notch and proneural bHLH proteins regulates most neural cell determination, however, it is uncertain whether the mechanisms are similar in all cases. Here, we have analyzed the sensitivity of atonal expression to Notch signalling using a temperature-sensitive Notch allele, by the expression of activated Notch or of the ligand Serrate, and by monitoring expression of the atonal-dependant gene scabrous and of the Notch-dependent Enhancer of split genes. The atonal expression pattern evolves from general "prepattern' expression, through transient "intermediate groups' to R8 precursor-specific expression. Successive phases of atonal expression differ in sensitivity to Notch. Prepattern expression of atonal is not inhibited. Inhibition begins at the intermediate group stage, corresponding to the period when atonal gene function is required for its own expression. At the transition to R8 cell-specific expression, Notch is activated in all intermediate group cells except the R8 cell precursor. R8 cells remain sensitive to inhibition in columns 0 and 1, but become less sensitive thereafter; non-R8 cells do not require Notch activity to keep atonal expression inactive. Thus, Notch signaling is coupled to atonal repression for only part of the atonal expression pattern. Accordingly, the Enhancer-of-split m delta protein is expressed reciprocally to atonal at the intermediate group and early R8 stages, but is expressed in other patterns before and after. In eye development, inhibition by Notch activity is restricted to specific phases of proneural gene expression, beginning when prepattern decays and is replaced by autoregulation. We suggest that Notch signalling inhibits atonal autoregulation, but not expression by other mechanisms, and that a transition from prepattern to autoregulation is necessary for patterning neural cell determination. Distinct neural tissues might differ in their proneural prepatterns, but use Notch in a similar mechanism.


Insights into the infective properties of YpfΦ, the Yersinia pestis filamentous phage.
YpfΦ is a filamentous phage that infected Yersinia pestis, the plague bacillus, during its emergence. Using an experimental transduction approach, we show here that this phage has the capacity to infect with variable efficiencies, all three pathogenic Yersinia species as well as Escherichia coli. Like other Inovirus phages, its genetic organization comprises three functional modules necessary for the production of infectious virions. Upon infection, YpfΦ integrates into the chromosomal dif site, but extrachromosomal forms are also frequently observed. Several pieces of evidence suggest that the absence of chromosomal YpfΦ in natural non-Orientalis Y. pestis isolates results from a higher chromosomal excision rate rather than from a defective integration machinery. A resident YpfΦ confers some protection against a superinfection. In contrast to other filamentous phages, the incoming YpfΦ genome inserts itself between two copies of the resident prophage. This analysis thus unravels infective properties specific to YpfΦ.


Business Process Modelling is an Essential Part of a Requirements Analysis. Contribution of EFMI Primary Care Working Group.
To perform a requirements analysis of the barriers to conducting research linking of primary care, genetic and cancer data. We extended our initial data-centric approach to include socio-cultural and business requirements. We created reference models of core data requirements common to most studies using unified modelling language (UML), dataflow diagrams (DFD) and business process modelling notation (BPMN). We conducted a stakeholder analysis and constructed DFD and UML diagrams for use cases based on simulated research studies. We used research output as a sensitivity analysis. Differences between the reference model and use cases identified study specific data requirements. The stakeholder analysis identified: tensions, changes in specification, some indifference from data providers and enthusiastic informaticians urging inclusion of socio-cultural context. We identified requirements to collect information at three levels: micro- data items, which need to be semantically interoperable, meso- the medical record and data extraction, and macro- the health system and socio-cultural issues. BPMN clarified complex business requirements among data providers and vendors; and additional geographical requirements for patients to be represented in both linked datasets. High quality research output was the norm for most repositories. Reference models provide high-level schemata of the core data requirements. However, business requirements' modelling identifies stakeholder issues and identifies what needs to be addressed to enable participation.


Immunoglobulin VH usage analysis by fluorescent in situ hybridization and flow cytometry.
We have devised a flow cytometry-based fluorescent in situ hybridization assay that permits analysis of gene expression in a large number of single cells. In this technique, fixed and permeabilized cells are incubated with biotinylated single-stranded RNA probes and by means of a fluorescently labelled second-step reagent, the cells are analyzed by flow cytometry. This is a rapid and simple method that allows all of the steps in the procedure to be performed on cells in suspension. Using this approach, we demonstrate here that immunoglobulin heavy chain variable region (VH) gene expression can be analyzed among individual cells using particular VH family-specific probes. This technique has a high degree of accuracy (greater than 97%) in detecting the fraction of cells expressing a specific message in a population and is sensitive enough to detect immunoglobulin message in LPS activated B cells. The technique has been applied successfully to monitor gene expression in homogeneous and heterogeneous populations. It also allows concurrent analysis of cell surface proteins and gene expression through two-color flow cytometry. This method of monitoring gene expression in individual cells may have a number of applications in immunology and cell biology.


Antifungal Drug Use for Onychomycosis.
Onychomycoses are fungal nail infections affecting predominantly toenails, and mainly caused by dermatophyte fungi, molds and some Candida species. Nail infections can be mild with purely cosmetic implications, but they can also negatively influence quality of life. The deep-seated nature of fungi within the nail plate, prolonged treatment, poor patient adherence, frequent recurrences, and development of resistance to various antimicrobial agents make onychomycosis difficult to successfully treat. When and how should clinicians prescribe systemic and topical antifungal drugs for onychomycosis? A narrative review was undertaken of the current literature identified in Medline, Scopus, CINAHL, the Cochrane library, and Google Scholar. Treatment is often lengthy and requires persistence and patient education. Definitive mycological diagnosis, and an individualized evaluation of risks and benefits of different treatments are imperative before initiating therapy. The choice of treatment can be influenced by the age and general health of the patient, the causative organism, the number of affected nails, and the extent of nail involvement. Oral antifungals offer greater likelihood of a cure than topicals, but oral therapy carries greater risks and requires closer monitoring. Oral terbinafine is the treatment of choice, followed by itraconazole pulse regimen. The newly approved topical agents, efinaconazole and tavaborole, were superior to placebo in clinical trials and appear to produce slightly improved mycological cure rates compared to previous topicals, but further direct comparisons are needed. The treatment of onychomycosis can be challenging, as most therapeutic options are lengthy, expensive and potentially unsuccessful.


Exploiting CRISPR/Cas systems for biotechnology.
The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system, a prokaryotic adaptive restriction system against invading nucleic acids, such as those originating from bacteriophages and plasmids. Recently, this RNA-directed DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site-specific transcriptional repression or activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in this regard. Thus, CRISPR/Cas systems represent an effective and versatile biotechnological tool, which will have significant impact on future advancements in genome engineering.


Oxidative stress promotes autophagic cell death in human neuroblastoma cells with ectopic transfer of mitochondrial PPP2R2B (Bbeta2).
The multifunctional protein phosphatase 2A (PP2A) is a heterotrimeric serine/threonine protein phosphatase composed of a scaffolding, catalytic and regulatory subunits. By modifying various downstream signal transducers, the aberrant expression of the brain-targeted regulatory subunit PPP2R2B is associated with the onset of a panel of neuronal disorders. The alternatively splicing of PPP2R2B encodes two regulatory subunit isoforms that determine cellular distribution of the neuron-specific holoenzyme to mitochondria (Bbeta2) and cytoplasm (Bbeta1), respectively. Human neuroblastoma cells were transfected with PPP2R2B constructs encoding the complete sequences of Bbeta2 and Bbeta1, respectively. The colonies with antibiotic resistance were selected as stable cell lines. Both ectopic Bbeta1 and Bbeta2 clones exhibited characteristics of autophagy. To test how cells respond to reactive oxygen species generators, the cells were treated with either hydrogen peroxide or t-butyl hydroperoxide and Bbeta2 clones induced cell death. Suppression of autophagy using either RNA interference of the essential autophagy gene or pharmacological inhibitor rescued cell death caused by oxidative stress. Cells with ectopically expressed mitochondria-targeted regulatory subunit PPP2R2B of the holoenzyme PP2A were shown predisposed to autophagy and oxidative stress induced cell death that is related to apoptosis. The results promised a model for studying the mechanism and function of aberrant PPP2R2B expression in neuronal cells. The work provided a new target for understanding and prevention of neuropathogenesis.


Trends in methadone-related deaths in Zurich.
Methadone has a long and successful history in the treatment of opioid addiction. In recent years, it has become popular again--as potent and inexpensive analgesic in patients with chronic pain. Since methadone has been used fatalities have been reported. In our study all methadone-associated deaths in Zurich from 1998 to 2007 were analysed. Most of the 146 detected deaths of the past 10 years occurred during substitution programmes or illicit intake of methadone while only three of them could be attributed to methadone used as an analgesic. Noticeable in our study was the high percentage of cases of combined drug intoxication (76%). The most frequent co-intoxicants were alcohol and cocaine. Mortalities attributed to methadone intoxication alone were a rare finding and could only be detected in five cases of deceased who had received methadone maintenance treatment. The aim of our study is to assess the trends in the number and nature of methadone-related fatalities in Zurich during the last 19 years. For this purpose a previous study from Zurich (1989-1997) was included, whereby a very long observation period and large number of cases resulted.


Evidence for hepatitis E virus quasispecies.
The genetic diversity of hepatitis E virus (HEV) has been extensively analysed during the last decade. Most sporadic and epidemic HEV strains are distributed into genotypes or groups. Nevertheless, few studies have looked at the polymorphism of HEV strains isolated from a given outbreak. A serum bank collected in Tanefdour, Algeria, during an acute hepatitis epidemic (1986-1987), retrospectively confirmed as hepatitis E, was analysed. Of the 69 serum samples collected within an 8-week period, 23 were positive for both partial ORF1 (replicase gene) and ORF2 (capsid gene) sequences. Inter- and intra-patient diversities were assessed by RFLP, and by sequencing a 448 bp sequence corresponding to ORF2. RFLP analysis distinguished three profiles: A (18/23), B (3/23) and C (2/23). Most isolates (18/23) shared 99.7-100 % sequence identity and the remainder showed 1-1.3 % divergence. HEV intra-patient diversity was studied using 12 isolates (seven displaying the major RFLP profile and five displaying minor RFLP profiles). For 9 of 12 isolates, additional intra-patient heterogeneity was revealed by RFLP analysis of 100 clones from each isolate and sequence diversity ranging from 0.11 to 3.4 %. These data strongly support the quasispecies organization of HEV during epidemics and could explain the adaptable behaviour of the virus in the host-pathogen interrelations.


Corp Regulates P53 in Drosophila melanogaster via a Negative Feedback Loop.
The tumor suppressor P53 is a critical mediator of the apoptotic response to DNA double-strand breaks through the transcriptional activation of pro-apoptotic genes. This mechanism is evolutionarily conserved from mammals to lower invertebrates, including Drosophila melanogaster. P53 also transcriptionally induces its primary negative regulator, Mdm2, which has not been found in Drosophila. In this study we identified the Drosophila gene companion of reaper (corp) as a gene whose overexpression promotes survival of cells with DNA damage in the soma but reduces their survival in the germline. These disparate effects are shared by p53 mutants, suggesting that Corp may be a negative regulator of P53. Confirming this supposition, we found that corp negatively regulates P53 protein level. It has been previously shown that P53 transcriptionally activates corp; thus, Corp produces a negative feedback loop on P53. We further found that Drosophila Corp shares a protein motif with vertebrate Mdm2 in a region that mediates the Mdm2:P53 physical interaction. In Corp, this motif mediates physical interaction with Drosophila P53. Our findings implicate Corp as a functional analog of vertebrate Mdm2 in flies.


Production of anti-peptide antibodies against trypanopain-Tb from Trypanosoma brucei brucei: effects of antibodies on enzyme activity against Z-Phe-Arg-AMC.
Anti-peptide antibodies were produced against the cysteine proteinase trypanopain-Tb from Trypanosoma brucei brucei and the effects of these antibodies on enzyme activity against carboxybenzoyl (Z)-Phe-Arg-aminomethylcoumarin (AMC) investigated. A peptide was synthesised corresponding to a region of the trypanopain-Tb active site around the active site histidine so that the resulting anti-peptide antibodies specifically targeted the active site of the enzyme. Such antibodies were considered more likely to modulate enzyme activity compared with antibodies directed against other regions of the enzyme. Trypanopain-Tb activity was modulated by rabbit and chicken antibodies produced against both the free and conjugated peptide. Rabbit anti-peptide antibodies enhanced trypanopain-Tb activity by up to 64% at 500 micrograms/ml relative to non-immune antibodies. Chicken antibodies on the other hand, both enhanced (by up to 176% at 500 mg/ml) and inhibited (by up to 85% at 250 mg/ml) trypanopain-Tb activity against Z-Phe-Arg-AMC. The nature of the antibody effect depended on the stage during the immunisation protocol at which the antibodies were produced. Chicken antibodies also modulated trypanopain-Tb activity in lysates of T.b. brucei, while rabbit antibodies were only effective against the purified enzyme. Anti-trypanopain-Tb peptide antibodies were thus shown to have the potential to affect trypanopain-Tb activity.


Socioeconomic status and incidence of sudden cardiac arrest.
Low socioeconomic status is associated with poor cardiovascular health. We evaluated the association between socioeconomic status and the incidence of sudden cardiac arrest, a condition that accounts for a substantial proportion of cardiovascular-related deaths, in seven large North American urban populations. Using a population-based registry, we collected data on out-of-hospital sudden cardiac arrests occurring at home or at a residential institution from Apr. 1, 2006, to Mar. 31, 2007. We limited the analysis to cardiac arrests in seven metropolitan areas in the United States (Dallas, Texas; Pittsburgh, Pennsylvania; Portland, Oregon; and Seattle-King County, Washington) and Canada (Ottawa and Toronto, Ontario; and Vancouver, British Columbia). Each incident was linked to a census tract; tracts were classified into quartiles of median household income. A total of 9235 sudden cardiac arrests were included in the analysis. For all sites combined, the incidence of sudden cardiac arrestin the lowest socioeconomic quartile was nearly double that in the highest quartile (incidence rate ratio [IRR] 1.9, 95% confidence interval [CI] 1.8-2.0). This disparity was greater among people less than 65 years old (IRR 2.7, 95% CI 2.5-3.0) than among those 65 or older (IRR 1.3, 95% CI 1.2-1.4). After adjustment for study site and for population age structure of each census tract, the disparity across socioeconomic quartiles for all ages combined was greater in the United States (IRR 2.0, 95% CI 1.9-2.2) than in Canada (IRR 1.8, 95% CI 1.6-2.0) (p<0.001 for interaction). The incidence of sudden cardiac arrest at home or at a residential institution was higher in poorer neighbourhoods of the US and Canadian sites studied, although the association was attenuated in Canada. The disparity across socioeconomic quartiles was greatest among people younger than 65. The association between socioeconomic status and incidence of sudden cardiac arrest merits consideration in the development of strategies to improve survival from sudden cardiac arrest, and possibly to identify opportunities for prevention.


Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans.
An underlying complex genetic susceptibility exists in multiple sclerosis (MS), and an association with the HLA-DRB1*1501-DQB1*0602 haplotype has been repeatedly demonstrated in high-risk (northern European) populations. It is unknown whether the effect is explained by the HLA-DRB1 or the HLA-DQB1 gene within the susceptibility haplotype, which are in strong linkage disequilibrium (LD). African populations are characterized by greater haplotypic diversity and distinct patterns of LD compared with northern Europeans. To better localize the HLA gene responsible for MS susceptibility, case-control and family-based association studies were performed for DRB1 and DQB1 loci in a large and well-characterized African American data set. A selective association with HLA-DRB1*15 was revealed, indicating a primary role for the DRB1 locus in MS independent of DQB1*0602. This finding is unlikely to be solely explained by admixture, since a substantial proportion of the susceptibility chromosomes from African American patients with MS displayed haplotypes consistent with an African origin.


Lateralisation of auditory processing in Down syndrome: a study of T-complex peaks Ta and Tb.
It has long been argued that abnormal cerebral lateralisation might underlie the language problems that characterise Down syndrome, but to date only behavioural evidence has been provided. We used the auditory event-related potentials Ta and Tb of the T-complex to investigate lateralised processing of speech (vowels) and non-speech (simple and complex tones) sounds in children with Down syndrome and age-matched typically developing children. We also explored associations with speech and language abilities. Although changes in the Ta and Tb in response to increases in stimulus complexity and 'speechness' were similar across group, the Tb peak was delayed in children with Down syndrome across conditions. In addition, marked differences in the patterns of lateralisation of Ta latency and Tb amplitude were observed in children with Down syndrome, in response to both speech and non-speech sounds. No associations were found between Ta and Tb characteristics and speech and language abilities in children with DS.


Factors related to the academic attainments of children with Down's syndrome.
The attainments in reading, number and writing skills, of 117 children with Down's syndrome, aged 6 to 14 years, were assessed using checklists completed by teachers. In a study of child and family functioning a wide range of variables was measured and the relationships of these to academic attainments were investigated using multivariable analysis. The children's mental age scores were most strongly related to academic attainments scores, but, in addition, type of school attended, gender, chronological age and fathers' scores on a measure of locus of control were significantly related. The results are discussed in terms of their implications for educational placement and curriculum, and the role of fathers in their children's education.


A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigen-positive and -negative erythrocytes.
Ring-infected erythrocyte surface antigen (RESA)-positive, Plasmodium falciparum-negative red blood cells (RBCs) are cells from which the malaria parasite has been removed by the host without the destruction of the erythrocyte ("pitting"). The survival of RESA-RBCs in vivo was assessed in 14 severe and 6 uncomplicated falciparum malaria patients. The mean RESA-RBC life of 183 hours (95% confidence interval [CI], 136-246) was longer than the median parasite clearance time of 66 hours (range, 30-108 hours) but shorter than the mean red cell life of 1027 hours (95% CI, 840-1213) (P =.0004), with a median ratio of 0.2:1.0 (range, 0.1-0.7). The estimated median percentage of parasites pitted/body transit was 0.003% (range, 0.001%-0.05%). The rate of rise of the RESA-RBC count during the first 24 hours after antimalarial treatment was significantly faster (P =.036) and the subsequent RESA-RBC survival significantly shorter (P =.017) after treatment with an artemisinin derivative than after treatment with quinine. Parasitization of red cells leads to changes in the erythrocyte that shorten their survival even if the parasite is removed subsequently.


MUTANT GENE THAT CHANGES PROTEIN COMPOSITION AND INCREASES LYSINE CONTENT OF MAIZE ENDOSPERM.
Preliminary tests have shown that the endosperms of maize seeds homozygous for the opaque-2 mutant gene have a higher lysine content than normal kernels. As a critical test, a backcross progeny was divided into opaque-2 and normal kernels, the endosperms separated, and the amino acids determined. The opaque-2 endosperms had a different amino acid pattern and 69 percent more lysine than the normal seeds. The major reason for these changes is the synthesis of proteins with a greater content of basic amino acids in the acid-soluble fraction of the mutant endosperm. This is accompanied by a reduction in the ratio of zein to glutelin.


Quantum Simulation Logic, Oracles, and the Quantum Advantage.
Query complexity is a common tool for comparing quantum and classical computation, and it has produced many examples of how quantum algorithms differ from classical ones. Here we investigate in detail the role that oracles play for the advantage of quantum algorithms. We do so by using a simulation framework, Quantum Simulation Logic (QSL), to construct oracles and algorithms that solve some problems with the same success probability and number of queries as the quantum algorithms. The framework can be simulated using only classical resources at a constant overhead as compared to the quantum resources used in quantum computation. Our results clarify the assumptions made and the conditions needed when using quantum oracles. Using the same assumptions on oracles within the simulation framework we show that for some specific algorithms, such as the Deutsch-Jozsa and Simon's algorithms, there simply is no advantage in terms of query complexity. This does not detract from the fact that quantum query complexity provides examples of how a quantum computer can be expected to behave, which in turn has proved useful for finding new quantum algorithms outside of the oracle paradigm, where the most prominent example is Shor's algorithm for integer factorization.


Stigmatizing attitudes and low levels of knowledge but high willingness to participate in HIV management: a community-based survey of pharmacies in Pune, India.
The World Health Organization (WHO) recommends that the role of pharmacists in low-income settings be expanded to address the increasing complexity of HIV antiretroviral (ARV) and co-infection drug regimens. However, in many such settings including in India, many pharmacists and pharmacy workers are often neither well trained nor aware of the intricacies of HIV treatment. The aims of our study were; to determine the availability of ARVs, provision of ARVs, knowledge about ARVs, attitudes towards HIV-infected persons and self-perceived need for training among community-based pharmacies in an urban area of India. We performed a survey of randomly selected, community-based pharmacies located in Pune, India, in 2004-2005 to determine the availability of ARVs at these pharmacies, how they were providing ARVs and their self-perceived need for training. We also assessed knowledge, attitudes and perceptions on HIV and ARVs and factors associated with stocking ARVs. Of 207 pharmacies included in the survey, 200 (96.6%) were single, private establishments. Seventy-three (35.3%) pharmacies stocked ARVs and 38 (18.4%) ordered ARVs upon request. The reported median number of ARV pills that patients bought at one time was 30, a two week supply of ARVs (range: 3-240 pills). Six (2.9%) pharmacy respondents reported selling non-allopathic medicines (i.e. Ayurvedic, homeopathy) for HIV. Ninety (44.2%) pharmacy respondents knew that ARVs cannot cure HIV, with those stocking ARVs being more likely to respond correctly (60.3% vs. 34.8%, p = 0.001). Respondents of pharmacies which stocked ARVs were also more likely to believe it was a professional obligation to provide medications to HIV-infected persons (91.8% vs. 78.8%, p = 0.007) but they were also more likely to believe that HIV-infected persons are unable to adhere to their medicines (79.5% vs. 40.9%, p < 0.01). Knowledge of the most common side effects of nevirapine, abnormal liver enzyme profile and skin rash, was reported correctly by 8 (3.9%) and 23 (11.1%) respondents, respectively. Seven (3.4%) respondents reported that they had received special training on HIV, 3 (1.5%) reported receipt of special training on ART and 167 (80.7%) reported that they believed that pharmacy staff should get special training on ART. There is a high willingness to participate in HIV management among community-based pharmacies but there is a tremendous need for training on HIV therapies. Furthermore, stigmatizing attitudes towards HIV-infected persons persist and interventions to reduce stigma are needed, particularly among those that stock ARVs.


Phylogenetic analysis of the bacterial communities in marine sediments.
For the phylogenetic analysis of microbial communities present in environmental samples microbial DNA can be extracted from the sample, 16S rDNA can be amplified with suitable primers and the PCR, and clonal libraries can be constructed. We report a protocol that can be used for efficient cell lysis and recovery of DNA from marine sediments. Key steps in this procedure include the use of a bead mill homogenizer for matrix disruption and uniform cell lysis and then purification of the released DNA by agarose gel electrophoresis. For sediments collected from two sites in Puget Sound, over 96% of the cells present were lysed. Our method yields high-molecular-weight DNA that is suitable for molecular studies, including amplification of 16S rRNA genes. The DNA yield was 47 micrograms per g (dry weight) for sediments collected from creosote-contaminated Eagle Harbor, Wash. Primers were selected for the PCR amplification of (eu)bacterial 16S rDNA that contained linkers with unique 8-base restriction sites for directional cloning. Examination of 22 16S rDNA clones showed that the surficial sediments in Eagle Harbor contained a phylogenetically diverse population of organisms from the Bacteria domain (G. J. Olsen, C. R. Woese, and R. Overbeek, J. Bacteriol. 176:1-6, 1994) with members of six major lineages represented: alpha, delta, and gamma Proteobacteria; the gram-positive high G+C content subdivision; clostridia and related organisms; and planctomyces and related organisms. None of the clones were identical to any representatives in the Ribosomal Database Project small subunit RNA database. The analysis of clonal representives in the first report using molecular techniques to determine the phylogenetic composition of the (eu)bacterial community present in coastal marine sediments.


Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma.
SPARC (secreted protein acidic and rich in cysteine) is a protein involved in cell matrix interactions, wound repair, and cell migration, and has been reported to inhibit cancer growth. SPARC undergoes epigenetic silencing in many pancreatic cancers, but stromal fibroblasts adjacent to infiltrating pancreatic adenocarcinomas frequently express SPARC. We evaluated the prognostic significance of tumor and peritumoral SPARC expression in patients with pancreatic adenocarcinoma. The expression patterns of SPARC were characterized by immunohistochemistry in 299 primary pancreatic ductal adenocarcinoma resection specimens from patients who underwent pancreaticoduodenectomy at Johns Hopkins Hospital (Baltimore, MD) between 1998 and 2003. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk associated with the presence or absence of tumor SPARC and peritumoral SPARC status. By Kaplan-Meier analysis, patients whose pancreatic cancer stromal fibroblasts expressed SPARC (median survival, 15 months) had a significantly worse prognosis than patients whose tumor stroma did not express SPARC (median survival, 30 months; log-rank P < .001). In contrast, the expression of SPARC in pancreatic cancer cells was not associated with prognosis (log-rank P = .13). Controlling for other prognostic factors (tumor size, positive lymph nodes, margin status, tumor grade, and age), the relative hazard for patients whose stroma expressed SPARC compared with those whose stroma did not was 1.89 (95% CI, 1.31 to 2.74); the expression of SPARC in pancreatic cancer cells remained unrelated to prognosis (relative hazard, 1.02; 95% CI, 0.73 to 1.42). The expression of SPARC by peritumoral fibroblasts portends a poorer prognosis for patients with pancreatic cancer.


Self-other control processes in social cognition: from imitation to empathy.
We review the evidence that an ability to achieve a precise balance between representing the self and representing other people is crucial in social interaction. This ability is required for imitation, perspective-taking, theory of mind and empathy; and disruption to this ability may contribute to the symptoms of clinical and sub-clinical conditions, including autism spectrum disorder and mirror-touch synaesthesia. Moving beyond correlational approaches, a recent intervention study demonstrated that training participants to control representations of the self and others improves their ability to control imitative behaviour, and to take another's visual perspective. However, it is unclear whether these effects apply to other areas of social interaction, such as the ability to empathize with others. We report original data showing that participants trained to increase self-other control in the motor domain demonstrated increased empathic corticospinal responses (Experiment 1) and self-reported empathy (Experiment 2), as well as an increased ability to control imitation. These results suggest that the ability to control self and other representations contributes to empathy as well as to other types of social interaction.


Ambient temperature and activation of implantable cardioverter defibrillators.
The degree to which weather influences the occurrence of serious cardiac arrhythmias is not fully understood. To investigate, we studied the timing of activation of implanted cardiac defibrillators (ICDs) in relation to daily outdoor temperatures using a fixed stratum case-crossover approach. All patients attending ICD clinics in London between 1995 and 2003 were recruited onto the study. Temperature exposure for each ICD patient was determined by linking each patient's postcode of residence to their nearest temperature monitoring station in London and the South of England. There were 5,038 activations during the study period. Graphical inspection of ICD activation against temperature suggested increased risk at lower but not higher temperatures. For every 1 °C decrease in ambient temperature, risk of ventricular arrhythmias up to 7 days later increased by 1.2 % (95 % CI -0.6 %, 2.9 %). In threshold models, risk of ventricular arrhythmias increased by 11.2 % (0.5 %, 23.1 %) for every 1° decrease in temperature below 2 °C. Patients over the age of 65 exhibited the highest risk. This large study suggests an inverse relationship between ambient outdoor temperature and risk of ventricular arrhythmias. The highest risk was found for patients over the age of 65. This provides evidence about a mechanism for some cases of low-temperature cardiac death, and suggests a possible strategy for reducing risk among selected cardiac patients by encouraging behaviour modification to minimise cold exposure.


"Wolf-in-Sheep's-Clothing" Strategy of a Predaceous Insect Larva.
The larva of the green lacewing Chrysopa slossonae lives in colonies of the wooly alder aphid Prociphilus tesselatus upon which it feeds. It disguises itself as its prey by plucking some of the waxy "wool" from the bodies of the aphids and applying this material to its own back. The investiture protects it from assault by the ants that ordinarily "shepherd" the aphids. Larvae artifically denuded are seized by the ants and removed from the aphid colonies. A larva requires on the average less than 20 minutes to coat itself with wax. A hungry denuded larva gives the coating procedure about the same behavioral priority as feeding.


Atypical hemolytic uremic syndrome due to factor H autoantibody.
Atypical hemolytic uremic syndrome (aHUS) is a disease caused by pathologies in the alternative complement system. The prevalence of aHUS is 10% of all aHUS cases. The subgroup of aHUS designated as DEAP (DEficiency of CFHR Proteins and CFH Autoantibody Positive)-HUS because of autoantibody to complement factor H (CFH) and CFH-related protein deficiency is seen very rarely, and the prevalence is 6% of all aHUS cases in the literature. We present here a female patient with DEAP-HUS. A 7.5-year-old girl with recurrent attacks of HUS had low C3 level. We initiated plasmapheresis treatment. After further analysis of the complement system, the result was compatible with DEAP-HUS, so we initiated immunosuppressive treatment. There were also family members with deficiency of CFHR-1 and CFHR-3, but they had no CFH autoantibody and no symptoms of HUS. In atypical cases of HUS, we should investigate complement status, especially for factor H autoantibody, for which treatment options differ from those of the other types of aHUS.


PUF60 variants cause a syndrome of ID, short stature, microcephaly, coloboma, craniofacial, cardiac, renal and spinal features.
PUF60 encodes a nucleic acid-binding protein, a component of multimeric complexes regulating RNA splicing and transcription. In 2013, patients with microdeletions of chromosome 8q24.3 including PUF60 were found to have developmental delay, microcephaly, craniofacial, renal and cardiac defects. Very similar phenotypes have been described in six patients with variants in PUF60, suggesting that it underlies the syndrome. We report 12 additional patients with PUF60 variants who were ascertained using exome sequencing: six through the Deciphering Developmental Disorders Study and six through similar projects. Detailed phenotypic analysis of all patients was undertaken. All 12 patients had de novo heterozygous PUF60 variants on exome analysis, each confirmed by Sanger sequencing: four frameshift variants resulting in premature stop codons, three missense variants that clustered within the RNA recognition motif of PUF60 and five essential splice-site (ESS) variant. Analysis of cDNA from a fibroblast cell line derived from one of the patients with an ESS variants revealed aberrant splicing. The consistent feature was developmental delay and most patients had short stature. The phenotypic variability was striking; however, we observed similarities including spinal segmentation anomalies, congenital heart disease, ocular colobomata, hand anomalies and (in two patients) unilateral renal agenesis/horseshoe kidney. Characteristic facial features included micrognathia, a thin upper lip and long philtrum, narrow almond-shaped palpebral fissures, synophrys, flared eyebrows and facial hypertrichosis. Heterozygote loss-of-function variants in PUF60 cause a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function.


Qualitative changes in ultrasonic vocalization in rats after unilateral dopamine depletion or haloperidol: a preliminary study.
The sensorimotor speech/voice deficits associated with Parkinson disease have been well documented in humans. They are largely resistant to pharmacological and surgical treatment, but respond to intensive speech therapy. The mechanisms underlying this phenomenon are not well understood and are difficult to systematically test in humans. Thus, we turn to the rat as a model. The purpose of this study is to compare the ultrasonic vocalization (USV) of rats in three conditions: control, haloperidol-induced transient dopamine depletion, and unilateral 6-hydroxydopamine (6-OHDA) induced moderately-severe degeneration of dopamine neurons. It was hypothesized that both dopamine-altered conditions would lead to a change in the features of the USV acoustic signal. Results demonstrated that bandwidth decreased in the dopamine-altered rats. This is the first study to document a degradation of the acoustic signal of frequency-modulated 50-kHz calls as a result of interfering with dopamine synaptic transmission in rats. The data suggest that mild transient dopamine depletion with haloperidol or even unilateral degeneration of dopamine neurons is associated with changes in the USV acoustic signal. Dopaminergic dysfunction influences USV quality without reducing the number of calls. This study provides a foundation to examine the role of dopamine in sensorimotor processes underlying USV production and potentially to explore treatments for dopamine deficiency-related impaired vocal outcome.


Activation energy of electron transport in dye-sensitized TiO2 solar cells.
Various characteristics of dye-sensitized nanostructured TiO2 solar cells, such as electron transport and electron lifetime, were studied in detail using monochromatic illumination conditions. The electron transport was found to be a thermally activated process with activation energies in the range of 0.10-0.15 eV for light intensities that varied 2 orders of magnitude. Electron lifetimes were determined using a new method and found to be significantly larger (>1 s) than previously determined. An average potential was determined for electrons in the nanostructured TiO2 under illumination in short-circuit conditions. This potential is about 0.2 V lower than the open-circuit potential at the same light intensity. The electron transport time varies exponentially with the internal potential at short-circuit conditions, indicating that the gradient in the electrochemical potential is the driving force for electron transport in the nanostructured TiO2 film. The applicability of the conventionally used trapping/detrapping model is critically analyzed. Although experimental results can be fitted using a trapping/detrapping model with an exponential distribution of traps, the distribution parameters differ significantly between different types of experiment. Furthermore, the experimental activation energies for electron transport are smaller than those expected in a trapping/detrapping model.


Does smoking status affect the likelihood of consulting a doctor about respiratory symptoms? A pilot survey in Western Australia.
Smokers attribute respiratory symptoms, even when severe, to everyday causes and not as indicative of ill-health warranting medical attention. The aim of this pilot study was to conduct a structured vignette survey of people attending general practice to determine when they would advise a person with respiratory symptoms to consult a medical practitioner. Particular reference was made to smoking status and lung cancer. Participants were recruited from two general practices in Western Australia. Respondents were invited to complete self-administered questionnaires containing nine vignettes chosen at random from a pool of sixty four vignettes, based on six clinical variables. Twenty eight vignettes described cases with at least 5% risk of cancer. For analysis these were dubbed 'cancer vignettes'. Respondents were asked if they would advise a significant other to consult a doctor with their respiratory symptoms. Logistic regression and non-parametric tests were used to analyse the data. Three hundred questionnaires were distributed and one hundred and forty completed responses were collected over six weeks. The majority (70.3%) of respondents were female aged forty and older. A history of six weeks' of symptoms, weight loss, cough and breathlessness independently increased the odds of recommending a consultation with a medical practitioner by a factor of 11.8, 2.11, 1.40 and 4.77 respectively. A history of smoking independently increased the odds of the person being thought 'likely' or 'very likely' to have cancer by a factor of 2.46. However only 32% of cancer vignettes with a history of cigarette smoking were recognised as presentations of possible cancer. Even though a history of cigarette smoking was more likely to lead to the suggestion that a symptomatic person may have cancer we did not confirm that smokers would be more likely to be advised to consult a doctor, even when presenting with common symptoms of lung cancer.


Efficacy and Patient Satisfaction of Dipeptidyl Peptidase-4 Inhibitor After Switching From Once-Daily DPP-4 Inhibitor to Once-Weekly Regimen.
We administered once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor (W) (used omarigliptin as W in this study) to patients with type 2 diabetes taking once-daily DPP-4 inhibitor (D), and investigated efficacy, safety and patient satisfaction before and after switching to W. W was administered to 182 patients with type 2 diabetes taking D (used sitagliptin as D in this study), who had been visiting our hospital on an outpatient basis; 164 (90.6%) of these patients requested to switch medications. Of these 164 patients, this study investigated 153 who requested to continue taking W. Hemoglobin A1c (HbA1c) levels, body weight, blood pressure and a questionnaire survey (Diabetes Treatment Satisfaction Questionnaire (DTSQ)) were evaluated in these patients. Patient characteristics were as follows: age, 63.9 ± 10.3; male/female ratio, 93:60; duration of diabetes, 14.9 ± 7.7 years; and body mass index (BMI), 25.5 ± 4.2 kg/m2. After switching to W, HbA1c levels changed from 7.41 ± 0.7% to 7.36 ± 0.9%, which was not statistically significant. Changes in body weight, BMI, and systolic and diastolic blood pressure were also not significant. On the DTSQ, satisfaction of Q1 significantly increased (P < 0.01). The score for lifestyle assessment did not significantly change, but compliance significantly improved (P < 0.001). This study revealed that 90% of patients taking D elected to switch to W. Moreover, patient satisfaction and compliance improved after switching to W. Increased satisfaction appeared to be influenced by improved blood glucose control, but was not associated with compliance. Switching from D to W did not affect HbA1c levels but improved patient adherence.


Human cytomegalovirus pp71 stimulates cell cycle progression by inducing the proteasome-dependent degradation of the retinoblastoma family of tumor suppressors.
The oncoproteins of the DNA tumor viruses, adenovirus E1A, simian virus 40 T antigen, and papillomavirus E7, each interact with the retinoblastoma family of tumor suppressors, leading to cell cycle stimulation, apoptosis induction, and cellular transformation. These proteins utilize a conserved LXCXE motif, which is also found in cellular proteins, to target the retinoblastoma family. Here, we describe a herpesvirus protein that shares a subset of the properties of the DNA tumor virus oncoproteins but maintains important differences as well. The human cytomegalovirus pp71 protein employs an LXCXD motif to attack the retinoblastoma family members and induce DNA synthesis in quiescent cells. pp71 binds to and induces the degradation of the hypophosphorylated forms of the retinoblastoma protein and its family members p107 and p130 in a proteasome-dependent manner. However, pp71 does not induce apoptosis and fails to transform cells. Thus, the similarities and differences in comparison to E1A, T antigen, and E7 make pp71 an interesting new tool with which to further dissect the role of the retinoblastoma/E2F pathway in cellular growth control and carcinogenesis.


Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition.
The signals and mechanisms that synchronize the timing of human parturition remain a mystery and a better understanding of these processes is essential to avert adverse pregnancy outcomes. Although our insights into human labor initiation have been informed by studies in animal models, the timing of parturition relative to fetal maturation varies among viviparous species, indicative of phylogenetically different clocks and alarms; but what is clear is that important common pathways must converge to control the birth process. For example, in all species, parturition involves the transition of the myometrium from a relaxed to a highly excitable state, where the muscle rhythmically and forcefully contracts, softening the cervical extracellular matrix to allow distensibility and dilatation and thus a shearing of the fetal membranes to facilitate their rupture. We review a number of theories promulgated to explain how a variety of different timing mechanisms, including fetal membrane cell senescence, circadian endocrine clocks, and inflammatory and mechanical factors, are coordinated as initiators and effectors of parturition. Many of these factors have been independently described with a focus on specific tissue compartments.In this review, we put forth the core hypothesis that fetal membrane (amnion and chorion) senescence is the initiator of a coordinated, redundant signal cascade leading to parturition. Whether modified by oxidative stress or other factors, this process constitutes a counting device, i.e. a clock, that measures maturation of the fetal organ systems and the production of hormones and other soluble mediators (including alarmins) and that promotes inflammation and orchestrates an immune cascade to propagate signals across different uterine compartments. This mechanism in turn sensitizes decidual responsiveness and eventually promotes functional progesterone withdrawal in the myometrium, leading to increased myometrial cell contraction and the triggering of parturition. Linkage of these processes allows convergence and integration of the gestational clocks and alarms, prompting a timely and safe birth. In summary, we provide a comprehensive synthesis of the mediators that contribute to the timing of human labor. Integrating these concepts will provide a better understanding of human parturition and ultimately improve pregnancy outcomes.


Chemical composition of organic matter in extremely acid, lignite-containing lake sediments impacted by fly ash contamination.
In the Lusatian lignite mining district of eastern Germany, extremely acid lakes developed during ground water rising after exploitation of lignite in open-cast mines. The reasons of plant colonization (Juncus bulbosus L.) of some lakes exhibiting moderate pH values while others remain extremely acid and unvegetated are unknown. Alkalinity gain may be achieved by addition of alkaline materials and/or decomposition of organic matter. Our objective was to examine fly ash deposition and the resulting changes in organic matter composition in the uppermost 0 to 5 cm of the sediment sampled from vegetated and unvegetated lakes. Bulk soil and particle size fractions were analyzed for elemental composition, magnetic susceptibility, and chemical structure of the organic matter by 13C solid-state nuclear magnetic resonance (NMR) spectroscopy. The lignite content of the samples was estimated by 14C activity measurements. The pH values decreased with increasing depth and the changes in pH were found to be correlated with changes in magnetic susceptibility. Carbon and nitrogen contents were found to decrease with increasing depth. The C to N ratios are consistent with the (i) the presence of decomposing plant residues and/or microbial material such as algae in the upper 0 to 5 cm of the sediment and (ii) the dominance of lignite in the layers below this depth as confirmed by 14C activity measurements. The structural analyses of the particle size separates from the 0- to 5-cm depth were consistent with the presence of organic matter derived from plant material. This study confirms that fly ash is an important source of alkalinity in the upper 0 to 5 cm of the sediment that enhanced plant growth and led to enrichment of the sediment with organic matter derived from plant material.


History of simulation in medicine: from Resusci Annie to the Ann Myers Medical Center.
Medical and surgical graduate medical education has historically used a halstedian approach of "see one, do one, teach one." Increased public demand for safety, quality, and accountability in the setting of regulated resident work hours and limited resources is driving the development of innovative educational tools. The use of simulation in nonmedical, medical, and neurosurgical disciplines is reviewed in this article. Simulation has been validated as an educational tool in nonmedical fields such as aviation and the military. Across most medical and surgical subspecialties, simulation is recognized as a valuable tool that will shape the next era of medical education, postgraduate training, and maintenance of certification.


Palliative care education in Swiss undergraduate medical curricula: a case of too little, too early.
Palliative medicine education is an important strategy in ensuring that the needs of terminally ill patients are met. A review was conducted in 2007 of the undergraduate curricula of all five of Switzerland's medical schools to identify their palliative care-related content and characteristics. The average number of mandatory hours of palliative care education is 10.2 h (median 8 h; range 0-27 h), significantly short of the 40 h recommended by the European Palliative Care Association's Education Expert Group. The median time allocated to designated palliative care blocks is 3 h (range 0-8 h). Most of the education occurs before the clinical years, and there are no mandatory clinical rotations. Three schools offer optional clinical rotations but these are poorly attended (<10% of students). Although a number of domains are covered, ethics-related content predominates; 21 of a total of 51 obligatory hours (41%). Communication related to palliative care is largely limited to 'breaking bad news'. In two of the schools, the teaching is done primarily by palliative care physicians and nurses (70% or more of the teaching). In the others, it is done mostly by educators in other clinical specialties and ethics (approximately 90% of the teaching). These findings show significant deficiencies.


Understanding the mechanism of action of pyrrolo[3,2-b]quinoxaline-derivatives as kinase inhibitors.
The X-ray structure of the catalytic domain of the EphA3 tyrosine kinase in complex with a previously reported type II inhibitor was used to design two novel quinoxaline derivatives, inspired by kinase inhibitors that have reached clinical development. These two new compounds were characterized by an array of cell-based assays and gene expression profiling experiments. A global chemical proteomics approach was used to generate the drug-protein interaction profile, which suggested suitable therapeutic indications. Both inhibitors, studied in the context of angiogenesis and in vivo in a relevant lymphoma model, showed high efficacy in the control of tumor size.


First Report of the Cereal Cyst Nematode Heterodera filipjevi on Wheat in Serbia.
The most globally recognized and economically important nematode on wheat is the cereal cyst nematode (CCN) complex (1). One of the most important species of this group is Heterodera filipjevi (Madžidov, 1981) Mulvey and Golden, 1983. During regular soil quarantine control in September 2010, Heterodera sp. cysts were found in soil samples originating from a wheat field in Gunaroš, Vojvodina Province, in northern Serbia. The wheat was a winter crop grown in a dryland production system and had an average cyst density of 2.50/100 cm3 of soil. Morphologically, the cysts were golden brown and lemon shaped with a posterior protuberance. The vulval cone was bifenestrate with horseshoe-shaped semifenestra, bullae, and underbridge. Cyst measurements (n = 30) ranged as follows: cyst length (without neck): 511.50 to 899.00 μm, cyst width: 201.50 to 682.00 μm, fenestral length: 44.80 to 65.60 μm, fenestral width: 24.00 to 40.00 μm, vulval bridge length: 12.80 to 20.80 μm, vulval bridge width: 6.40 to 14.40 μm, vulval slit: 6.00 to 12.80 μm, and underbridge length: 60.00 to 112.00 μm. The second-stage juveniles had an offset head, stylet with characteristic anchor-shaped basal knobs, four incisures, and a conical tail with a rounded tip. The J2 morphometrics (n = 30) were: length: 447.30 to 611.10 μm, width: 22.40 to 25.60 μm, stylet: 20.80 to 24.00 μm, tail length: 56.00 to 68.80 μm, tail width: 14.40 to 19.20 μm, and hyaline length: 35.20 to 44.80 μm. The ITS region was used for molecular analysis. Each DNA sample was extracted from a single cyst. Sequencing was done with primers TW81 and AB28 (2). In comparison with other H. filipjevi populations, the obtained sequence (GenBank Accession No. JX235959) revealed 99 to 100% similarity. Morphological and molecular data confirmed the existence of H. filipjevi. This is, to our knowledge, the first report of H. filipjevi from Serbia. Since wheat has important socioeconomic value for Serbia, after extensive surveys, additional phytosanitary measures may be necessary to prevent the spread of this parasite. References: (1) J. M. Nicol et al. Current Nematode Threats to World Agriculture. Genomics and Molecular Genetics of Plant-Nematode Interactions, Springer, New York, 2011. (2) A. M. Skantar et al. J. Nematol. 39:133, 2007.


Shear stress, tip cells and regulators of endothelial migration.
We have in recent years described several endothelial-specific genes that mediate cell migration. These include Robo4 (roundabout 4), CLEC14A (C-type lectin 14A) and ECSCR (endothelial cell-specific chemotaxis regulator) [formerly known as ECSM2 (endothelial cell-specific molecule 2)]. Loss of laminar shear stress induces Robo4 and CLEC14A expression and an endothelial 'tip cell' phenotype. Low shear stress is found not only at sites of vascular occlusion such as thrombosis and embolism, but also in the poorly structured vessels that populate solid tumours. The latter probably accounts for strong expression of Robo4 and CLEC14A on tumour vessels. The function of Robo4 has, in the past, aroused controversy. However, the recent identification of Unc5B as a Robo4 ligand has increased our understanding and we hypothesize that Robo4 function is context-dependent. ECSCR is another endothelial-specific protein that promotes filopodia formation and migration, but, in this case, expression is independent of shear stress. We discuss recent papers describing ECSCR, including intracellular signalling pathways, and briefly contrast these with signalling by Robo4.


A bipartite element with allele-specific functions safeguards DNA methylation imprints at the Dlk1-Dio3 locus.
Loss of imprinting (LOI) results in severe developmental defects, but the mechanisms preventing LOI remain incompletely understood. Here, we dissect the functional components of the imprinting control region of the essential Dlk1-Dio3 locus (called IG-DMR) in pluripotent stem cells. We demonstrate that the IG-DMR consists of two antagonistic elements: a paternally methylated CpG island that prevents recruitment of TET dioxygenases and a maternally unmethylated non-canonical enhancer that ensures expression of the Gtl2 lncRNA by counteracting de novo DNA methyltransferases. Genetic or epigenetic editing of these elements leads to distinct LOI phenotypes with characteristic alternations of allele-specific gene expression, DNA methylation, and 3D chromatin topology. Although repression of the Gtl2 promoter results in dysregulated imprinting, the stability of LOI phenotypes depends on the IG-DMR, suggesting a functional hierarchy. These findings establish the IG-DMR as a bipartite control element that maintains imprinting by allele-specific restriction of the DNA (de)methylation machinery.


Total creatinine appearance as indicator of risk of infectious complication in peritoneal dialysis.
Peritonitis and exit-site infections are the main causes of complications in peritoneal dialysis. Death due to infectious complication is also one of the major causes of drop-out. The underlying cause of infection may include malnutrition. Total creatinine appearance (TCA) may reflect overall nutritional status. We determined TCA from the daily dialysate, urine, and estimated gut creatinine of patients and normalized it to actual body weight (nTCA). We examined the relationship between nTCA and the incidence of infection, and between nTCA and infection-related survival. The study included 323 adult patients in a single dialysis center. The mean nTCA of all patients was 19.73 +/- 4.75 mg/kg/day. The patients with an nTCA below 1 standard deviation from the mean (nTCA < 14.98 mg/kg/day) had a significantly higher peritonitis and exit-site infection rate (p < 0.01) and a higher chance of drop-out owing to infection-related complications (p < 0.0001). Our study concluded that the adult patient with malnutrition (nTCA < 14.98 mg/kg/day) has higher risk of infection.


Design principles of multifiber resonant directional couplers with hollow Bragg fibers: example of a 3 x 3 coupler.
When several hollow photonic crystal fibers (HPCFs) are placed in proximity to each other, radiation-induced interfiber coupling between their core guided modes is observed. Under certain conditions coupling between the core modes of two touching collinear fibers can have a resonant increase via excitation of a low-quality intermirror cavity resonant state. Such coupling, however, decreases dramatically within the first micrometer of intermirror separation. Moreover, when fibers are touching, in the frequency domain a large number of accidental degeneracies with fiber surface and mirror states complicate the design of a stable 2 x 2 coupler. To alleviate these problems we consider coupling among three hollow Bragg fibers. When placed in the vertices of an isosceles triangle, even for a finite separation between fibers, triangular interfiber cavity forms a high-quality resonator that can be tuned via additional structural elements to a particular frequency of interest. Interfiber surface states are suppressed by keeping the fiber separation finite, thus allowing stable coupling conditions in a 3 x 3 HPCF coupler configuration.


Flow variability and its physical causes in infusion technology: a systematic review of in vitro measurement and modeling studies.
Infusion therapy is medically and technically challenging and frequently associated with medical errors. When administering pharmaceuticals by means of infusion, dosing errors can occur due to flow rate variability. These dosing errors may lead to adverse effects. We aimed to systematically review the available biomedical literature for in vitro measurement and modeling studies that investigated the physical causes of flow rate variability. Special focus was given to syringe pump setups, which are typically used if very accurate drug delivery is required. We aimed to extract from literature the component with the highest mechanical compliance in syringe pump setups. We included 53 studies, six of which were theoretical models, two articles were earlier reviews of infusion literature, and 45 were in vitro measurement studies. Mechanical compliance, flow resistance, and dead volume of infusion systems were stated as the most important and frequently identified physical causes of flow rate variability. The syringe was indicated as the most important source of mechanical compliance in syringe pump setups (9.0×10-9 to 2.1×10-8 l/Pa). Mechanical compliance caused longer flow rate start-up times (from several minutes up to approximately 70 min) and delayed occlusion alarm times (up to 117 min).


Poly(3-hydroxybutyrate) multifunctional composite scaffolds for tissue engineering applications.
Poly(3-hydroxybutyrate) (P(3HB)) foams exhibiting highly interconnected porosity (85% porosity) were prepared using a unique combination of solvent casting and particulate leaching techniques by employing commercially available sugar cubes as porogen. Bioactive glass (BG) particles of 45S5 Bioglass grade were introduced in the scaffold microstructure, both in micrometer ((m-BG), <5 microm) and nanometer ((n-BG), 30 nm) sizes. The in vitro bioactivity of the P(3HB)/BG foams was confirmed within 10 days of immersion in simulated body fluid and the foams showed high level of protein adsorption. The foams interconnected porous microstructure proved to be suitable for MG-63 osteoblast cell attachment and proliferation. The foams implanted in rats as subcutaneous implants resulted in a non-toxic and foreign body response after one week of implantation. In addition to showing bioactivity and biocompatibility, the P(3HB)/BG composite foams also exhibited bactericidal properties, which was tested on the growth of Staphylococcus aureus. An attempt was made at developing multifunctional scaffolds by incorporating, in addition to BG, selected concentrations of Vitamin E or/and carbon nanotubes. P(3HB) scaffolds with multifunctionalities (viz. bactericidal, bioactive, electrically conductive, antioxidative behaviour) were thus produced, which paves the way for next generation of advanced scaffolds for bone tissue engineering.


Genome sequence of the ethanol-producing Zymomonas mobilis subsp. pomaceae lectotype strain ATCC 29192.
Zymomonas mobilis is an alphaproteobacterium studied for bioethanol production. Different strains of this organism have been hitherto sequenced; they all belong to the Z. mobilis subsp. mobilis taxon. Here we report the finished and annotated genome sequence of strain ATCC 29192, a cider-spoiling agent isolated in the United Kingdom. ATCC 29192 is the lectotype of the second-best-characterized subspecies of Z. mobilis, Z. mobilis subsp. pomaceae. The nucleotide sequence of ATCC 29192 deviates from that of Z. mobilis subsp. mobilis representatives, which justifies its distinct taxonomic positioning and proves particularly useful for comparative and functional genomic analyses.


Predictors of hospital readmission two years after coronary artery bypass grafting.
To determine the clinical factors before, and in association with, coronary artery bypass grafting (CABG) that increase the risk of readmission to hospital in the first two years after surgery. All patients in western Sweden who had CABG without simultaneous valve surgery between 1 June 1988 and 1 June 1991. All patients who were readmitted to hospital were evaluated by postal inquiry and hospital records. A total of 2121 patients were operated on, of whom 2037 were discharged from hospital. Information regarding readmission was missing in four patients, leaving 2033 patients; 44% were readmitted to hospital. The most common reasons for readmission were angina pectoris and congestive heart failure. There were 12 independent significant predictors for readmission: clinical history (a previous history of either congestive heart failure or myocardial infarction, or CABG); acute operation; postoperative complications (time in intensive care unit greater than two days, neurological complications); clinical findings four to seven days after the operation (arrhythmia, systolic murmur equivalent to mitral regurgitation); medication four to seven days after the operation (antidiabetics, diuretics for heart failure, other antiarrhythmics (other than beta blockers, calcium antagonists, and digitalis), and lack of treatment with aspirin). 44% of patients were readmitted to hospital two years after CABG. The most common reasons for readmission were angina pectoris and congestive heart failure. Four clinical markers predicted readmission: clinical history; acute operation status; postoperative complications; and clinical findings and medication four to seven days after operation.


Time course of EEG oscillations during repeated listening of a well-known aria.
While previous studies have analyzed mean neurophysiological responses to musical stimuli, the current study aimed to identify specific time courses of electroencephalography (EEG) oscillations, which are associated with dynamic changes in the acoustic features of the musical stimulus. In addition, we were interested in whether these time courses change during a repeated presentation of the same musical piece. A total of 16 subjects repeatedly listened to the well-known aria "Nessun dorma," sung by Paul Potts, while continuous 128-channel EEG and heart rate, as well as electrodermal responses, were recorded. The time courses for the EEG oscillations were calculated using a time resolution of 1 second for several frequency bands, on the basis of individual alpha-peak frequencies (theta, low alpha-1, low alpha-2, upper alpha, and beta). For all frequency bands, we identified a more or less continuous increase in power relative to a baseline period, indicating strong event-related synchronization (ERS) during music listening. The ERS time courses, however, did not correlate strongly with the time courses of the acoustic features of the aria. In addition, we did not observe changes in EEG oscillations after repeated presentation of the same musical piece. Aside from this distinctive feature, we identified a remarkable variability in EEG oscillations, both within and between the repeated presentations of the aria. We interpret the continuous increase in ERS observed in all frequency bands during music listening as an indicator of a particular neurophysiological and psychological state evoked by music listening. We suggest that this state is characterized by increased internal attention (accompanied by reduced external attention), increased inhibition of brain networks not involved in the generation of this internal state, the maintenance of a particular level of general alertness, and a type of brain state that can be described as "mind wandering." The overall state can be categorized as a psychological process that may be seen as a "drawing in" to the musical piece. However, this state is not stable and varies considerably throughout the music listening session and across subjects. Most important, however, is the finding that the neurophysiological activations occurring during music listening are dynamic and not stationary.


How Do Legal Experts Cope With Medical Reports and Forensic Evidence? The Experiences, Perceptions, and Narratives of Swiss Judges and Other Legal Experts.
Expert scientific knowledge, including medical knowledge, is relevant for the legal profession and can strongly influence rulings and sentencing in criminal law, civil law, and insurance law. The way in which this medical evidence is understood and evaluated thus has an impact both on individuals and on society as a whole. It enters legal procedures in various forms, for example, as expert witness statements and/or as a legal expert's own acquired medical knowledge. On the other hand, a legal expert may be confronted with expert medical opinions that differ in quality or content and thus have to decide which ones to follow. The aim of this qualitative study was to investigate legal experts' perceptions, experiences, and narratives regarding medical knowledge, particularly the skills and general knowledge used in their branch of the legal profession. A total of 51 semi-structured interviews with judges and prosecutors from different courts of law and from the public prosecutor's office in six different German-speaking (Zurich, Luzern, Aagrau, Obwalden, Nidwalden, Zug) and German/French-speaking (Bern) cantons of Switzerland were conducted, coded, and analyzed using Nvivo. We used a comparison thematic approach identifying common and new themes related to the research aims. Our findings suggest that Swiss judges and prosecutors believe that possessing and developing the skills and terminology required for processing medical information is important but complex, and time-consuming for their work. Additionally, several legal experts reported that their understanding of medical evidence was limited or even non-existent. Moreover, the acquisition of skills related to the assessment of medical reports and forensic evidence appeared to be unstructured. Participants reported having no formal instruction in how to evaluate or deal with medical knowledge. The sources they used to answer questions arising appeared to be in part problematic and non-standardized (internet, newspapers, etc.). Medical literature from peer-reviewed journals was used only rarely. The findings from this study suggest that law departments might wish to evaluate whether their graduates are sufficiently equipped with scientific literacy skills and appropriate skills to evaluate medical information for their later careers. At the same time, medical knowledge pertinent to forensics published in local legal journals may be more effective in reaching the legal expert audience than in medical journals.


Heteroclinic dynamics of coupled semiconductor lasers with optoelectronic feedback.
Generalized Lotka-Volterra (GLV) equations are important equations used in various areas of science to describe competitive dynamics among a population of N interacting nodes in a network topology. In this Letter, we introduce a photonic network consisting of three optoelectronically cross-coupled semiconductor lasers to realize a GLV model. In such a network, the interaction of intensity and carrier inversion rates, as well as phases of laser oscillator nodes, result in various dynamics. We study the influence of asymmetric coupling strength and frequency detuning between semiconductor lasers and show that inhibitory asymmetric coupling is required to achieve consecutive amplitude oscillations of the laser nodes. These studies were motivated primarily by the dynamical models used to model brain cognitive activities and their correspondence with dynamics obtained among coupled laser oscillators.


Theory of unconventional Smith-Purcell radiation in finite-size photonic crystals.
Unusual emission of light, called the unconventional Smith- Purcell radiation (uSPR) in this paper, was demonstrated from an electron traveling near a finite photonic crystal (PhC) at an ultra-relativistic velocity. This phenomenon is not related to the accepted mechanism of the conventional SPR and arises because the evanescent light from the electron has such a small decay constant in the ultra-relativistic regime that it works practically as a plane-wave probe entering the PhC from one end. We analyze the dependence of the SPR spectrum on the velocity of electron and on the parity of excited photonic bands and show, for PhCs made up of a finite number of cylinders, that uSPR probes the photonic band structure very faithfully.


Evolution of a plant growth-regulatory protein interaction specificity.
Specific protein-protein interactions (PPIs) enable biological regulation. However, the evolution of PPI specificity is little understood. Here we trace the evolution of the land-plant growth-regulatory DELLA-SLY1/GID2 PPI, revealing progressive increase in specificity of affinity of SLY1/GID2 for a particular DELLA form. While early-diverging SLY1s display relatively broad-range DELLA affinity, later-diverging SLY1s tend towards increasingly stringent affinity for a specific DELLA A' form generated by the growth-promoting phytohormone gibberellin (GA). Our novel mutational strategy reveals amino acid substitutions contributing to the evolution of Arabidopsis thaliana SLY1 A' specificity, also showing that routes permitting reversion to broader affinity became increasingly constrained over evolutionary time. We suggest that progressive affinity narrowing may be an important evolutionary driver of PPI specificity and that increase in SLY1/GID2-DELLA specificity enabled the enhanced flexibility of plant physiological environmental adaptation conferred by the GA-DELLA growth-regulatory mechanism.


Indications of enucleations and eviscerations performed at a tertiary eye care unit: A case series.
The retrospective study was planned to look at the indications of eye enucleations and eviscerations, and comprised all such procedures done at the Aga Khan University Hospital, Karachi, from January 2006 to December 2015. Data was collected regarding age at the time of procedure, gender, procedure type, indication for enucleation or evisceration, type of implant if used and complications. Of the 66 eyes of 65 individuals, 47 (71.2%) underwent evisceration and 19 (28.8%) enucleation. The mean age at the time of the procedures was 37.86±23.09 years. The indication for enucleation or evisceration were keratitis 14(21.2%), introcular tumours 13(19.7%), trauma 10(15.2%), endophthalmitis 10(15.2%), cosmesis 10(15.2%) and painful blind eye 9(13.6%). Only 5(7.5%) procedures had postoperative complications such as wound dehiscence, infected socket, loose suture, or stich abscess. Most of causes of enucleation and evisceration in this case series could have prevented through the application of evidence-based safety practices.


Structure of Arp2/3 complex in its activated state and in actin filament branch junctions.
The seven-subunit Arp2/3 complex choreographs the formation of branched actin networks at the leading edge of migrating cells. When activated by Wiskott-Aldrich Syndrome protein (WASp), the Arp2/3 complex initiates actin filament branches from the sides of existing filaments. Electron cryomicroscopy and three-dimensional reconstruction of Acanthamoeba castellanii and Saccharomyces cerevisiae Arp2/3 complexes bound to the WASp carboxy-terminal domain reveal asymmetric, oblate ellipsoids. Image analysis of actin branches indicates that the complex binds the side of the mother filament, and Arp2 and Arp3 (for actin-related protein) are the first two subunits of the daughter filament. Comparison to the actin-free, WASp-activated complexes suggests that branch initiation involves large-scale structural rearrangements within Arp2/3.


Prediction of CsrA-regulating small RNAs in bacteria and their experimental verification in Vibrio fischeri.
The role of small RNAs as critical components of global regulatory networks has been highlighted by several recent studies. An important class of such small RNAs is represented by CsrB and CsrC of Escherichia coli, which control the activity of the global regulator CsrA. Given the critical role played by CsrA in several bacterial species, an important problem is the identification of CsrA-regulating small RNAs. In this paper, we develop a computer program (CSRNA_FIND) designed to locate potential CsrA-regulating small RNAs in bacteria. Using CSRNA_FIND to search the genomes of bacteria having homologs of CsrA, we identify all the experimentally known CsrA-regulating small RNAs and also make predictions for several novel small RNAs. We have verified experimentally our predictions for two CsrA-regulating small RNAs in Vibrio fischeri. As more genomes are sequenced, CSRNA_FIND can be used to locate the corresponding small RNAs that regulate CsrA homologs. This work thus opens up several avenues of research in understanding the mode of CsrA regulation through small RNAs in bacteria.


Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis.
Bacterial vaginosis (BV) is an ecological disorder of the vaginal microbiota that affects millions of women annually, and is associated with numerous adverse health outcomes including pre-term birth and the acquisition of sexually transmitted infections. However, little is known about the overall structure and composition of vaginal microbial communities; most of the earlier studies focused on predominant vaginal bacteria in the process of BV. In the present study, the diversity and richness of vaginal microbiota in 50 BV positive and 50 healthy women from China were investigated using culture-independent PCR-denaturing gradient gel electrophoresis (DGGE) and barcoded 454 pyrosequencing methods, and validated by quantitative PCR. Our data demonstrated that there was a profound shift in the absolute and relative abundances of bacterial species present in the vagina when comparing populations associated with healthy and diseased conditions. In spite of significant interpersonal variations, the diversity of vaginal microbiota in the two groups could be clearly divided into two clusters. A total of 246,359 high quality pyrosequencing reads was obtained for evaluating bacterial diversity and 24,298 unique sequences represented all phylotypes. The most predominant phyla of bacteria identified in the vagina belonged to Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria. The higher number of phylotypes in BV positive women over healthy is consistent with the results of previous studies and a large number of low-abundance taxa which were missed in previous studies were revealed. Although no single bacterium could be identified as a specific marker for healthy over diseased conditions, three phyla - Bacteroidetes, Actinobacteria and Fusobacteria, and eight genera including Gardnerella, Atopobium, Megasphaera, Eggerthella, Aerococcus, Leptotrichia/Sneathia, Prevotella and Papillibacter were strongly associated with BV (p < 0.05). These genera are potentially excellent markers and could be used as targets for clinical BV diagnosis by molecular approaches. The data presented here have clearly profiled the overall structure of vaginal communities and clearly demonstrated that BV is associated with a dramatic increase in the taxonomic richness and diversity of vaginal microbiota. The study also provides the most comprehensive picture of the vaginal community structure and the bacterial ecosystem, and significantly contributes to the current understanding of the etiology of BV.


Physical activity during school in urban minority kindergarten and first-grade students.
To determine if physical activity (PA) during the school day varied by school, grade level, gender, weight status, and physical education (PE) and recess participation among urban kindergarten and first-grade students. Cross-sectional study at 4 Bronx, NY, schools. Student PA was measured by a Yamax Digi-Walker pedometer, an objective and validated measure of PA in children. Each student wore a sealed pedometer during school for 5 consecutive days. Hierarchical models were fit to identify variables predictive of PA. A total of 916 had valid pedometer data (53% male, 70% Hispanic, mean age 5.98 years [SD 0.66], 45% overweight). PA varied by school (P < .0001). First-grade students took a significantly greater mean number of steps during school than kindergarten students. Overall, students took an average of 2479.7 (SD 961.8) steps/school day. PA did not differ by BMI status. Students took on average 724 more steps on PE days than on non-PE days and 490 more steps on days with outdoor recess than nonrecess days (P < .05 for both). Fewer than 1% of all students achieved lower cut points for previously published mean range of steps/school day for boys and girls. Multivariable analysis revealed higher grade level, participation in PE class, and outdoor recess as independent predictors of PA. PA levels were low in kindergarten and first-grade students. Future interventions incorporating classroom-based PA and outdoor recess may increase PA in resource-poor urban schools with limited PE facilities.


[The protective effects of baicalin on pertussis bacilli-induced brain edema in rats].
To evaluate the inhibitory effect of baicalin on iron-dependent lipid peroxidation (IDLPO) and the protective effect on pertussis bacilli-induced brain edema in rats. In vitro, the inhibitory effect of baicalin and deferoxamine (DFX) was studied at different concentrations on IDLPO in brain homogenates of Sprague-Dawley rats. In vivo, the protective effect was studied of baicalin and DFX on brain edema induced by injecting purtussis bacilli into the left internal carotid artery in rats. Forty Sprague-Dawley rats were randomly divided into four groups. Group 1 (NS, n = 10), as control; Group 2 (PB, n = 10), pertussis bacilli control; Group 3 (DFX, n = 10), PB + deferoxamine; and Group 4 (BAI, n = 10), PB + baicalin. The baicalin was possessed of an inhibitory effect on IDLPO in rat brain homogenate, moreover, the inhibitory potency of baicalin was approximately 20 times higher than DFX treated alone. In vivo, the increase in the content of water(CW) and Evans blue (EB) was attenuated in groups DFX and BAI (CW: 79.8 +/- 0.7)% and (79.5 +/- 0.6)%; (EB: 11 +/- 7 micrograms/g and 12 +/- 5 micrograms/g) as compared with the group PB (CW: 80.4 +/- 0.9%, EB: 24 +/- 10 micrograms/g). The content of iron was significantly lower than in the left hemispheres (injected side) in the group DFX and the group BAI (79 +/- 9 micrograms/g and 77 +/- 10 micrograms/g) than in the left hemispheres in the group PB(132 +/- 28 micrograms.d-1.g), P < 0.05. The activation of CuZn-SOD (L155 +/- 36 U/mg pr, R177 +/- 75 U/mg pr) was decreased in the group BP compared with the group NS(L 201 +/- 49 U/mg pr, R 249 +/- 49 U/mg pr), P < 0.05. The activation of CuZn-SOD was significantly higher in the left brain tissues in the groups DFX and BAI (222 +/- 49 U/mg pr and 230 +/- 45 U/mg pr, respectively) than in the left brain tissues of the group of PB (P < 0.05). The baicalin and DFX have a protective effects on the pertussis bacilli-induced brain edema in rats, and the protective effects are related to the inhibitory effect on IDLPO, chelating Fe2+, and activated CuZn-SOD.


Bioleaching review part B: progress in bioleaching: applications of microbial processes by the minerals industries.
This review describes the historical development and current state of metals leaching and sulfide mineral biooxidation by the minerals industries. During the past 20 years commercial processes employing microorganisms for mineral recovery have progressed from rather uncontrolled copper dump leaching to mineral oxidation and leaching in designed bioheaps for oxidation of refractory gold ores and for copper recovery. Also during this period of time, stirred tank bioleaching has been commercialized for cobalt recovery and for biooxidation of refractory gold ores. Chalcopyrite bioleaching in stirred tanks is on the verge of commercialization. Commercial applications of biohydrometallurgy have advanced due to favorable process economics and, in some cases, reduced environmental problems compared to conventional metal recovery processes such as smelting. Process development has included recognition of the importance of aeration of bioheaps, and improvements in stirred tank reactor design and operation. Concurrently, knowledge of the key microorganisms involved in these processes has advanced, aided by advances in molecular biology to characterize microbial populations.


The efficacy and safety of targeted narrowband UVB therapy: a retrospective cohort study
Phototherapy is a safe and effective treatment modality for numerous dermatological conditions. Recently, targeted phototherapy modalities have gained importance due to their advantages over conventional phototherapy.This retrospective study aimed to evaluate the safety and efficacy of targeted narrowband UVB phototherapy in patients with dermatological disorders This single-center study included 173 patients who were treated with targeted narrowband UVB phototherapy. Demographic features, phototherapy parameters, and adverse effects were evaluated in all patients, and the treatment response was assessed in patients who attended at least one follow-up visit. A total of 173 patients (102 females; 71 males) with vitiligo, alopecia areata, lichen simplex chronicus, palmoplantar psoriasis, and psoriasis vulgaris were included in the study. Among 73 patients, with whom the treatment was finalized by physician, an excellent response was obtained in 10%, 52.9%, 53.8%, 28.6%, and 40% of patients with vitiligo, alopecia areata, lichen simplex chronicus, palmoplantar psoriasis, and psoriasis, respectively. The treatment was generally well tolerated and was discontinued in only two patients due to adverse effects. This study demonstrates that targeted narrowband UVB therapy is a safe and effective treatment alternative, particularly for alopecia areata, lichen simplex chronicus, and palmoplantar and plaque-type psoriasis.


A community health nursing approach to the problem of antibiotic over-prescribing.
Antibiotic resistance due to over-prescribing is a critical problem for society. The purpose of this study was to examine the effect of a nurse-led quality-assurance-based program designed to decrease inappropriate antibiotic prescribing rates in patients suffering from viral upper respiratory tract infections. The study was based in a network of community health centers in the Southeastern United States. A quasi-experimental design based upon pre- and postintervention measurement via chart reviews was utilized in the study. Both the pre- and postintervention chart reviews revealed high levels of inappropriate prescribing. Following intervention, no gross decrease in prescribing rates was noted. Qualitative differences were noted postintervention that included increased rates of prescriptions for delayed antibiotic therapy and decreased rates of reflexive prescription writing for farmers. Additionally, the results reflected the decreased use of broad-spectrum antibiotics after the intervention. Although the study utilized a limited sample, it shows promise for the use of quality assurance approaches in moderating inappropriate prescribing practices.