Multiscale simulations of human telomeric G-quadruplex DNA.
We present a coarse-grain (CG) model of human telomeric G-quadruplex, obtained using the inverse Monte Carlo (IMC) and iterative Boltzmann inversion (IBI) techniques implemented within the software package called MagiC. As a starting point, the 2HY9 human telomeric [3 + 1] hybrid, a 26-nucleobase sequence, was modeled performing a 1 μs long atomistic molecular dynamics (MD) simulation. The chosen quadruplex includes two kinds of loops and all possible combinations of relative orientations of guanine strands that can be found in quadruplexes. The effective CG potential for a one bead per nucleotide model has been developed from the radial distribution functions of this reference system. The obtained potentials take into account explicitly the interaction with counterions, while the effect of the solvent is included implicitly. The structural properties of the obtained CG model of the quadruplex provided a perfect match to those resulting from the reference atomistic MD simulation. The same set of interaction potentials was then used to simulate at the CG level another quadruplex topology (PDB id 1KF1 ) that can be formed by the human telomeric DNA sequence. This quadruplex differs from 2HY9 in the loop topology and G-strand relative orientation. The results of the CG MD simulations of 1KF1 are very encouraging and suggest that the CG model based on 2HY9 can be used to simulate quadruplexes with different topologies. The CG model was further applied to a higher order human telomeric quadruplex formed by the repetition, 20 times, of the 1KF1 quadruplex structure. In all cases, the developed model, which to the best of our knowledge is the first model of quadruplexes at the CG level presented in the literature, reproduces the main structural features remarkably well.


The prevalence and characteristics of incentive plans for clinical productivity among academic anesthesiology programs.
Performance-based compensation is encouraged in medical schools to improve faculty productivity. Medical specialties other than anesthesiology have used financial incentives for clinical work. The goal of this study was to determine the prevalence and the types of clinical incentive plans among academic anesthesiology departments. We performed an electronic survey of the members of the Society of Academic Anesthesiology Chairs and the Association of Anesthesiology Program Directors in the spring of 2003. The survey included questions about departmental size, presence of a clinical incentive plan, characteristics of existing incentive plans, primary quantifiers of productivity, and factors used to modify productivity measurements. An incentive plan was considered to be present if the department measured clinical productivity and varied compensation according to the measurements. The plans were grouped by the primary measure used into the following categories: None, Charges, Time, Shift, Late/Call (only late rooms and call), and Other. Eighty-eight (64%) of 138 programs responded to the survey, and 5 were excluded for incomplete data. Of the responding programs, 29% had no system, 30% used a Late/Call system, 20% used a Shift system, 11% used a Charges system, 6% used a Time system, and 3% fit in the Other category. Larger groups (>40 faculty members) had a significantly more frequent prevalence of incentive plans compared with smaller groups (<20 faculty members). Incentives were paid monthly or quarterly in 85% of the groups. In 90% of groups, incentive payments accounted for <25% of total compensation. Adjustments for operating room schedule supervisors, personally performed cases, day surgery preoperative clinics, pain-management services, and critical care services were included in less than half of the programs that reported incentive plans. Call and late room compensation was based on varied formulas. Sixty-nine percent of academic anesthesiology departments did not vary compensation according to clinical activity during regular hours. Most did vary payments on the basis of call and/or late rooms worked. Larger departments were more likely to use clinical incentive plans.


Aortic root sizing for transcatheter aortic valve implantation using a shape model parameterisation.
During a transcatheter aortic valve implantation, an axisymmetric implant is placed in an irregularly shaped aortic root. Implanting an incorrect size can cause complications such as leakage of blood alongside or through the implant. The aim of this study was to construct a method that determines the optimal size of the implant based on the three-dimensional shape of the aortic root. Based on the pre-interventional computed tomography scan of 89 patients, a statistical shape model of their aortic root was constructed. The weights associated with the principal components and the volume of calcification in the aortic valve were used as parameters in a classification algorithm. The classification algorithm was trained using the patients with no or mild leakage after their intervention. Subsequently, the algorithms were applied to the patients with moderate to severe leakage. Cross validation showed that a random forest classifier assigned the same size in 65 ± 7% of the training cases, while 57 ± 8% of the patients with moderate to severe leakage were assigned a different size. This initial study showed that this semi-automatic method has the potential to correctly assign an implant size. Further research is required to assess whether the different size implants would improve the outcome of those patients.


Cost considerations in therapeutic drug monitoring of aminoglycosides.
Aminoglycoside antibiotics are very important in the treatment of Gram-negative infections and as synergistic agents for the treatment of staphylococcal and streptococcal (group B streptococci and enterococci) infections. However, these agents have a narrow therapeutic index. Thus, a number of new antibiotics have been introduced in an attempt to reduce the number of patients treated with aminoglycosides. Unfortunately, these new antibiotics tend to be costly, and are often associated with development of resistance and treatment failure. Data suggest that a pharmacokinetic/pharmacodynamic relationship exists for some aspects of efficacy and toxicity of aminoglycosides. Serum drug concentrations and/or tissue accumulation are related to the development of nephrotoxicity, and individualised pharmacokinetic monitoring may decrease rates of nephrotoxicity. Peak serum drug concentrations and the ratio of peak serum drug concentration to minimum inhibitory concentration appear to correlate with clinical efficacy in the treatment of patients with bacteraemia or pneumonia. Therapeutic drug monitoring (TDM) has been used to optimise aminoglycoside therapy and reduce toxicity. Cost-effective approaches to drug selection and TDM are important considerations in the proper use of aminoglycosides.


Searching for Biosignatures in Exoplanetary Impact Ejecta.
With the number of confirmed rocky exoplanets increasing steadily, their characterization and the search for exoplanetary biospheres are becoming increasingly urgent issues in astrobiology. To date, most efforts have concentrated on the study of exoplanetary atmospheres. Instead, we aim to investigate the possibility of characterizing an exoplanet (in terms of habitability, geology, presence of life, etc.) by studying material ejected from the surface during an impact event. For a number of impact scenarios, we estimate the escaping mass and assess its subsequent collisional evolution in a circumstellar orbit, assuming a Sun-like host star. We calculate the fractional luminosity of the dust as a function of time after the impact event and study its detectability with current and future instrumentation. We consider the possibility to constrain the dust composition, giving information on the geology or the presence of a biosphere. As examples, we investigate whether calcite, silica, or ejected microorganisms could be detected. For a 20 km diameter impactor, we find that the dust mass escaping the exoplanet is roughly comparable to the zodiacal dust, depending on the exoplanet's size. The collisional evolution is best modeled by considering two independent dust populations, a spalled population consisting of nonmelted ejecta evolving on timescales of millions of years, and dust recondensed from melt or vapor evolving on much shorter timescales. While the presence of dust can potentially be inferred with current telescopes, studying its composition requires advanced instrumentation not yet available. The direct detection of biological matter turns out to be extremely challenging. Despite considerable difficulties (small dust masses, noise such as exozodiacal dust, etc.), studying dusty material ejected from an exoplanetary surface might become an interesting complement to atmospheric studies in the future. Key Words: Biosignatures-Exoplanets-Impacts-Interplanetary dust-Remote sensing. Astrobiology 17, 721-746.


Plasma extravasation induced by dietary supplemented histamine in histamine-free mice.
Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. To evaluate the role of histamine in skin allergic reaction, we used HDC gene knockout mice lacking histamine. No plasma extravasation reaction was observed in HDC-/- mice after passive cutaneous anaphylaxis (PCA) test. Compound 48/80, a mast cell granule depletor, produced plasma extravasation inHDC+/+ mice but no extravasation in HDC-/- mice. Interestingly, orally administered histamine was distributed in the skin in HDC-/- mice and in these histamine-supplemented mice the plasma extravasation reaction was observed after the injection of compound 48/80 and the PCA test. Cultured bone marrow-derived mast cells of HDC-/- mice took up histamine from the histamine-supplemented medium into the secretory granules. The absorbed histamine was released in response to the same antigen and antibody combination used as in PCA test. In contrast to the immediate-type response, the delayed-type hypersensitive response, observed as a thickening of the ear skin after trinitrochlorobenzene challenge (following sensitization), showed no differences between HDC+/+ and HDC-/- mice. Therefore, among the allergic skin reactions, histamine is revealed to be an important mediator especially for the plasma extravasation in an immediate-type allergy model.


Peptide immobilisation on porous silicon surface for metal ions detection.
In this work, a Glycyl-Histidyl-Glycyl-Histidine (GlyHisGlyHis) peptide is covalently anchored to the porous silicon PSi surface using a multi-step reaction scheme compatible with the mild conditions required for preserving the probe activity. In a first step, alkene precursors are grafted onto the hydrogenated PSi surface using the hydrosilylation route, allowing for the formation of a carboxyl-terminated monolayer which is activated by reaction with N-hydroxysuccinimide in the presence of a peptide-coupling carbodiimide N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide and subsequently reacted with the amino linker of the peptide to form a covalent amide bond. Infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy are used to investigate the different steps of functionalization.The property of peptides to form stable complexes with metal ions is exploited to achieve metal-ion recognition by the peptide-modified PSi-based biosensor. An electrochemical study of the GlyHisGlyHis-modified PSi electrode is achieved in the presence of copper ions. The recorded cyclic voltammograms show a quasi-irreversible process corresponding to the Cu(II)/Cu(I) couple. The kinetic factors (the heterogeneous rate constant and the transfer coefficient) and the stability constant of the complex formed on the porous silicon surface are determined. These results demonstrate the potential role of peptides grafted on porous silicon in developing strategies for simple and fast detection of metal ions in solution.


Novel adjuvants & delivery vehicles for vaccines development: a road ahead.
The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.


Cortical Remyelination Is Heterogeneous in Multiple Sclerosis.
Cortical lesions (CLs) are an important component of multiple sclerosis (MS) pathology; they correlate better with physical disability and cognitive impairment than white matter lesions (WMLs). Because remyelination can be extensive in CLs, we quantified remyelination in gray matter (GM) and white matter (WM), addressing oligodendrocyte (OGD) maturation state and clinical relevance of remyelination. Brain tissue samples from 21 chronic MS patients were immunohistochemically stained for myelin proteolipid protein, Olig2, which is strongly expressed in OGD precursor cells (OPCs), but weakly expressed in mature OGDs and other OGD markers. Sections were scored for the presence of normal-appearing WM and GM, de- and remyelination, and OPC and OGD cell counts. Remyelination was significantly more extensive in CLs than in WMLs with a trend toward more GM remyelination in primary progressive MS (PPMS) vs relapse-onset MS patients. More OPCs were found in remyelinated and nonremyelinated CLs vs remyelinated WMLs and nonremyelinated WMLs. Thus, there is more remyelination in the GM than in the WM in MS patient brains, with a trend toward more remyelination in those with PPMS. There does not seem to be a significant OPC recruitment failure in the GM, which casts new light on the process of remyelination failure.


Qualitative and quantitative prey requirements of two aphidophagous coccinellids, Adalia tetraspilota and Hippodamia variegata.
The suitability of two prey species, Aphis pomi De Geer (Hemiptera: Aphididae) and Brevicoryne brassicae (L.), for two generalist aphidophagous coccinellids, Adalia tetraspilota (Hope) (Coleoptera: Coccinellidae) and Hippodamia variegata (Goeze), at various abundance levels was investigated under laboratory conditions. While both A. pomi and B. brassicae were found to be suitable, the predators performed better when feeding upon B. brassicae. The prey densities affected the developmental parameters of the two predators appreciably. Optimal growth and development was noted in the prey density range of 40-80 aphids per day per predator. Both species and abundance levels of prey significantly affected the larval period of the two predators. Appreciable variation in survivorship of larvae, prepupal and pupal period, and adult weight was noted by varying the prey species and prey abundance. Longer reproductive period (oviposition period) and shorter non-reproductive periods (preoviposition and postoviposition periods) were noted for females that fed on B. brassicae as compared to those that fed on A. pomi. Reproductive output was appreciably higher for females that fed on B. brassicae, and the fecundity decreased drastically under food shortage.


A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania.
Considerable levels of resistance to sulfadoxine-pyrimethamine (SP) have been reported in Plasmodium falciparum in north-eastern Tanzania, and the identification of a suitable antimalarial to replace SP is now a high priority. We conducted a trial in July 2000 to determine the efficacy of proguanil (PG) plus dapsone (DS), compared with that of SP, for the treatment of asymptomatic falciparum infection. A total of 220 children with parasitaemia > or = 2000 per microL completed the study; 112 had received a single dose of SP (dosage calculated for pyrimethamine 1.25 mg/kg and sulfadoxine 25 mg/kg) and 108 had taken PG 10 mg/kg with DS 2.5 mg/kg each day for 3 days. Clearance of asexual parasites at day 7 was 14.3% with SP, but 93.5% with PG-DS. The remarkably high failure rate with SP was not associated with occurrence of leucine substitution at position 164 of the dhfr gene. Both treatment regimens were well tolerated. Compared with available data on another antifolate combination, chlorproguanil-dapsone ('Lapdap'), PG-DS was slightly but significantly inferior in achieving parasite clearance (99.5% versus 93.5%). The estimated cost of a 3-day course of PG-DS treatment for a child weighing 18 kg is US $0.15. With the rising incidence of SP-resistant P. falciparum infection, PG-DS could provide an effective, affordable and already available therapeutic alternative for malaria in East Africa at least until chlorproguanil-dapsone is registered.


The Role of UID for the Usage of Verb Phrase Ellipsis: Psycholinguistic Evidence From Length and Context Effects.
We investigate the underexplored question of when speakers make use of the omission phenomenon verb phrase ellipsis (VPE) in English given that the full form is also available to them. We base the interpretation of our results on the well-established information-theoretic Uniform Information Density (UID) hypothesis: Speakers tend to distribute processing effort uniformly across utterances and avoid regions of low information by omitting redundant material through, e.g., VPE. We investigate the length of the omittable VP and its predictability in context as sources of redundancy which lead to larger or deeper regions of low information and an increased pressure to use ellipsis. We use both naturalness rating and self-paced reading studies in order to link naturalness patterns to potential processing difficulties. For the length effects our rating and reading results support a UID account. Surprisingly, we do not find an effect of the context on the naturalness and the processing of VPE. We suggest that our manipulation might have been too weak or not effective to evidence such an effect.


Rapid nondestructive on-site screening of methylamphetamine seizures by attenuated total reflection fourier transform infrared spectroscopy.
The identification and quantification of illicit substances in the field is often desirable. Fourier transform infrared spectroscopy (FT-IR) has both qualitative and quantitative capabilities and field portable instruments are commercially available. Transmission infrared spectra of mixtures containing ephedrine hydrochloride, glucose, and caffeine and attenuated total reflection (ATR) infrared spectra of mixtures composed of methylamphetamine hydrochloride, glucose, and caffeine were used to develop principal component regression (PCR) calibration models. The root mean sum of errors of predictions (RMSEP) of all individual components in a mixture from a single measurement was <6% w/w, which reduced to approximately 3% w/w when triplicates were averaged. Sample mixing and grinding are essential to minimize the effect of heterogeneity, as deviations of up to 20% w/w were observed for single measurements of unground samples. Poor predictions of the components in a mixture occurred when samples were "contaminated" with substances not present in the calibration set, as would be expected. When only a single analyte (drug) was targeted, using a calibration set that contained both contaminated and uncontaminated samples, an RMSEP of approximately 4% w/w was achieved. The results demonstrate that ATR-FT-IR has the potential to quantify methylamphetamine samples, and possibly other licit or illicit substances, in at-seizure and on-site scenarios.


A randomized study of financial incentives to increase physical activity among sedentary older adults.
Less than half of all U.S. adults meet public health recommendations for physical activity, and even fewer older adults (aged 50 years and over) are sufficiently active. Because inactivity increases the risk of costly medical complications, successful efforts to increase physical activity among older adults may potentially be cost-effective. We sought to test if financial incentives for walking could increase physical activity among sedentary older adults. We conducted a 4-week randomized controlled study using pedometers. A total of 51 adults age 50+ from the Raleigh-Durham area of North Carolina participated in the study in April-May 2007. Individuals were randomized into one of two arms. The control group received a fixed payment of $75; the intervention group received a fixed payment of $50 plus up to $25 more per week depending on the number of weekly aerobic minutes, defined as 10+ minutes of continuous walking or jogging. The control group logged 2.3 h per week, on average. The intervention group logged 4.1 h per week and received an additional weekly payment of $17.50, on average. Modest financial incentives tied to aerobic minutes are an effective, and potentially cost-effective, approach for increasing physical activity among sedentary older adults.


Interleukin-1β-31C/T and -511T/C polymorphisms were associated with preeclampsia in Chinese Han population.
The purpose of our study is to investigate the relationship between IL-1β -31C/T (rs1143627) and -511T/C (rs16944) polymorphisms and the preeclampsia (PE), and analyze the Linkage disequilibrium (LD) and haplotype frequency of the two polymorphism loci. Polymorphisms at -31C/T and -511T/C of IL-1β were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP) in 232 PE and 447 control subjects. Genotype and allele frequencies between case-control groups were compared by chi-square(X2) tests. Two-point LD and haplotype frequency analyses were done with the software Haploview4.2. Significant statistical differences were found between PE and control groups regarding genotype and allele frequencies of the two polymorphisms of IL-1β (For IL-1β -31C/T: X2 = 11.478, P = 0.003; For IL-1β-511T/C: X2 = 9.687, P = 0.008). LD analysis revealed that the IL-1β -31C/T SNP was in high LD with the IL-1β-511C/T SNP(D' = 0.92, r2 = 0.79). Both CT and TC haplotypes showed significant differences between case and control groups. Only the plasma level of Prothrombin Time had a significantly statistical difference among TT, CT and CC groups of the preeclamptic two polymorphisms of IL-1β-31C/T and -511T/C (for IL-1β-31C/T, F = 1.644, P = 0.01; F = 1.587, P = 0.016). Our results revealed IL-1β was associated with the PE in Chinese Han population. The CT haplotype may increase the risk of PE, while haplotype TC could be considered as a protective haplotype of PE.


Utilisation and outcomes of cervical cancer prevention services among HIV-infected women in Cape Town.
An audit of outcomes of cervical cancer screening and prevention services for HIV-positive women in Cape Town, South Africa. Retrospective review of clinic registers, patient records and pathology databases at three HIV primary health clinics and a tertiary colposcopy referral centre. Women recently diagnosed with HIV at three primary health clinics between 2006 and 2008 (N=2 240); new patients seen for colposcopy at a tertiary referral centre between 2006 and 2009 (N=2 031). The proportion of women undergoing cervical cancer screening after HIV diagnosis at primary health clinics, demographic characteristics of women referred for colposcopy at a tertiary centre, and outcomes of therapy for precancerous lesions of the cervix. The proportion of women undergoing at least one Pap smear at HIV primary health clinics after HIV diagnosis was low (13.1%). Women referred for colposcopy tended to be HIV-positive and over the age of 30 years, and in most (70.2%) cytological examination revealed high-grade cervical dysplasia. HIV-positive women treated with excision for precancerous lesions of the cervix were significantly more likely than their HIV-negative counterparts to undergo incomplete excision, experience persistent cervical disease after treatment, and be lost to follow-up. Cervical cancer screening efforts must be scaled up for women with HIV. Treatment and surveillance guidelines for cervical intraepithelial neoplasia in HIV-positive women may need to be revised and new interventions developed to reduce incomplete treatment and patient default.


Urothelial ATP exocytosis: regulation of bladder compliance in the urine storage phase.
The bladder urothelium is more than just a barrier. When the bladder is distended, the urothelium functions as a sensor to initiate the voiding reflex, during which it releases ATP via multiple mechanisms. However, the mechanisms underlying this ATP release in response to the various stretch stimuli caused by bladder filling remain largely unknown. Therefore, the aim of this study was to elucidate these mechanisms. By comparing vesicular nucleotide transporter (VNUT)-deficient and wild-type male mice, we showed that ATP has a crucial role in urine storage through exocytosis via a VNUT-dependent mechanism. VNUT was abundantly expressed in the bladder urothelium, and when the urothelium was weakly stimulated (i.e. in the early filling stages), it released ATP by exocytosis. VNUT-deficient mice showed reduced bladder compliance from the early storage phase and displayed frequent urination in inappropriate places without a change in voiding function. We conclude that urothelial, VNUT-dependent ATP exocytosis is involved in urine storage mechanisms that promote the relaxation of the bladder during the early stages of filling.


Fundamental limits to learning closed-form mathematical models from data.
Given a finite and noisy dataset generated with a closed-form mathematical model, when is it possible to learn the true generating model from the data alone? This is the question we investigate here. We show that this model-learning problem displays a transition from a low-noise phase in which the true model can be learned, to a phase in which the observation noise is too high for the true model to be learned by any method. Both in the low-noise phase and in the high-noise phase, probabilistic model selection leads to optimal generalization to unseen data. This is in contrast to standard machine learning approaches, including artificial neural networks, which in this particular problem are limited, in the low-noise phase, by their ability to interpolate. In the transition region between the learnable and unlearnable phases, generalization is hard for all approaches including probabilistic model selection.


Risk assessment of unsuitable winter conditions for manure and nutrient application across Ontario.
Practical guidelines addressing the timing of manure and nutrient application must consider the concerns of the farm operators while ensuring the protection of the environment. An approach was developed and analyzed through case studies to determine the first recommended day in the spring, and the last in the fall, for manure and nutrient application based on probability analysis. Since most manure and nutrient application guidelines recommend avoiding adverse conditions, the three criteria established to perform a risk assessment were: (i) a frost depth greater than 0.05 m; (ii) a snow accumulation of greater than 0.05 m; and (iii) a soil volumetric water content greater than or equal to that of the plastic limit for the soil. Climatic data and typical soil information for seven locations in Ontario were used to model volumetric soil water contents, frost depths, and snow accumulation from the simultaneous heat and water (SHAW) model for a 48-yr period (1954-2001). Applying the three criteria to the modeled output, the average range between the least limiting probability (0.1, or one in ten year occurrence) and the greatest limiting probability (0.001, or one in one thousand year occurrence) analyzed among the locations was 16 d in the spring as compared to 29 d in the fall. Although geographical location affected the predicted spring start and fall end recommended manure and nutrient application dates, local climate and soil hydraulic properties also played an important part in the determination of these days. Overall the prediction method developed performed reasonably well and provided insight into the environmental factors influencing manure and nutrient application timing.


A thermally stable form of bacterial cocaine esterase: a potential therapeutic agent for treatment of cocaine abuse.
Rhodococcal cocaine esterase (CocE) is an attractive potential treatment for both cocaine overdose and cocaine addiction. CocE directly degrades cocaine into inactive products, whereas traditional small-molecule approaches require blockade of the inhibitory action of cocaine on a diverse array of monoamine transporters and ion channels. The usefulness of wild-type (wt) cocaine esterase is hampered by its inactivation at 37 degrees C. Herein, we characterize the most thermostable form of this enzyme to date, CocE-L169K/G173Q. In vitro kinetic analyses reveal that CocE-L169K/G173Q displays a half-life of 2.9 days at 37 degrees C, which represents a 340-fold improvement over wt and is 15-fold greater than previously reported mutants. Crystallographic analyses of CocE-L169K/G173Q, determined at 1.6-A resolution, suggest that stabilization involves enhanced domain-domain interactions involving van der Waals interactions and hydrogen bonding. In vivo rodent studies reveal that intravenous pretreatment with CocE-L169K/G173Q in mice provides protection from cocaine-induced lethality for longer time periods before cocaine administration than wt CocE. Furthermore, intravenous administration (pretreatment) of CocE-L169K/G173Q prevents self-administration of cocaine in a time-dependent manner. Termination of the in vivo effects of CoCE seems to be dependent on, but not proportional to, its clearance from plasma as its half-life is approximately 2.3 h and similar to that of wt CocE (2.2 h). Taken together these data suggest that CocE-L169K/G173Q possesses many of the properties of a biological therapeutic for treating cocaine abuse but requires additional development to improve its serum half-life.


Diagnostic value of T-Spot TB combined with INF-γ and IL-27 in tuberculous pleurisy.
The purpose of the present study was to investigate the diagnostic value of T cells spot test (T-Spot TB) combined with interferon-γ (INF-γ) and interleukin-27 (IL-27) in tuberculous pleurisy. Sixty patients with tuberculous pleurisy (observation group) and 60 patients with non-tuberculous pleurisy (control group) were enrolled in this study. T-Spot TB was performed to detect the pleural effusion of two groups of patients. Levels of IFN-γ and IL-27 in serum and pleural effusion were detected by enzyme-linked immunosorbent assay (ELISA). Relative expression of IFN-γ mRNA and IL-27 mRNA in peripheral blood mononuclear cells were detected by RT-PCR. Positive rate of T-Spot TB in observation group was 96.7% (58 cases), which was significantly higher than that in control group (p<0.05). Concentration of INF-γ in pleural effusion of observation group was 468.6±24.8 ng/l, which was significantly higher than that in control group (131.3±18.7 ng/l, p<0.05). Concentration of IL-27 in pleural effusion of observation group was 423.4±37.2 ng/l, which was significantly higher than that in control group (116.2±15.5 ng/l, p<0.05). Concentrations of INF-γ and IL-27 in serum of observation group were 48.2±13.4 and 41.7±10.6 ng/l, respectively, which were significantly higher than those in control group (38.6±11.2 and 35.3±8.4 ng/l, p<0.05). Relative expression levels of INF-γ mRNA and IL-27 mRNA in observation group were significantly higher than those in control group (p<0.05). Therefore, combination of T-Spot TB with INF-γ and IL-27 has significant application value in the clinical diagnosis of tuberculous pleurisy, and should be popularized.


Rabies virus matrix protein interplay with eIF3, new insights into rabies virus pathogenesis.
Viral proteins are frequently multifunctional to accommodate the high density of information encoded in viral genomes. Matrix (M) protein of negative-stranded RNA viruses such as Rhabdoviridae is one such example. Its primary function is virus assembly/budding but it is also involved in the switch from viral transcription to replication and the concomitant down regulation of host gene expression. In this study we undertook a search for potential rabies virus (RV) M protein's cellular partners. In a yeast two-hybrid screen the eIF3h subunit was identified as an M-interacting cellular factor, and the interaction was validated by co-immunoprecipitation and surface plasmon resonance assays. Upon expression in mammalian cell cultures, RV M protein was localized in early small ribosomal subunit fractions. Further, M protein added in trans inhibited in vitro translation on mRNA encompassing classical (Kozak-like) 5'-UTRs. Interestingly, translation of hepatitis C virus IRES-containing mRNA, which recruits eIF3 via a different noncanonical mechanism, was unaffected. Together, the data suggest that, as a complement to its functions in virus assembly/budding and regulation of viral transcription, RV M protein plays a role in inhibiting translation in virus-infected cells through a protein-protein interaction with the cellular translation machinery.


Epigenetics, epidemiology and mitochondrial DNA diseases.
Over the last two decades, the mutation of mitochondrial DNA (mtDNA) has emerged as a major cause of inherited human disease. The disorders present clinically in at least 1 in 10,000 adults, but pathogenic mutations are found in approximately 1 in 200 of the background population. Mitochondrial DNA is maternally inherited and there can be marked phenotypic variability within the same family. Heteroplasmy is a significant factor and environmental toxins also appear to modulate the phenotype. Although genetic and biochemical studies have provided part of the explanation, a comprehensive understanding of the incomplete penetrance of these diseases is lacking--both at the population and family levels. Here, we review the potential role of epigenetic factors in the pathogenesis of mtDNA diseases and the contribution that epidemiological approaches can make to improve our understanding in this area. Despite being previously dismissed, there is an emerging evidence that mitochondria contain the machinery required to epigenetically modify mtDNA expression. In addition, the increased production of reactive oxygen species seen in several mtDNA diseases could lead to the epigenetic modification of the nuclear genome, including chromatin remodelling and alterations to DNA methylation and microRNA expression, thus contributing to the diverse pathophysiology observed in this group of diseases. These observations open the door to future studies investigating the role of mtDNA methylation in human disease.


Is hypomagnesaemia a coronary risk factor among Indians with coronary artery disease?
Magnesium is an essential element that has numerous biological functions in the cardiovascular system. Hence, three hundred patients with known cardiovascular disease above the age of 25 years were studied to evaluate association between dietary and serum magnesium with cardiovascular risk factors. Patients were divided into three groups according to serum magnesium levels; ≤1.6 (Group 1), >1.6-2.6 (Group 2) and: >2.6 mg/dl (Group 3), and into two groups according to dietary magnesium intake; ≤350 mg/day (Group 1) and >350 mg/day (Group 2), respectively. Mean age of patients was 60.97 ± 12.5 years. Total cholesterol, triglycerides, VLDL, and LDL were significantly higher and HDL cholesterol significantly lower in group 1 when compared with group 2 and group 3. Diabetes, dyslipidemia, and hypertension were negatively correlated with serum magnesium levels; which were maintained even after adjustment with age, sex, and anthropometric parameters in multiple regression analysis. Similar observations were observed in dietary magnesium intake except LDL and total cholesterol. Dietary magnesium was positively correlated with serum magnesium. Hypomagnesaemia and low dietary intake of magnesium are strongly related to cardiovascular risk factors among known subjects with coronary artery disease. Hence, magnesium supplementation may help in reducing cardiovascular disease.


Contextual Feedback to Superficial Layers of V1.
Neuronal cortical circuitry comprises feedforward, lateral, and feedback projections, each of which terminates in distinct cortical layers [1-3]. In sensory systems, feedforward processing transmits signals from the external world into the cortex, whereas feedback pathways signal the brain's inference of the world [4-11]. However, the integration of feedforward, lateral, and feedback inputs within each cortical area impedes the investigation of feedback, and to date, no technique has isolated the feedback of visual scene information in distinct layers of healthy human cortex. We masked feedforward input to a region of V1 cortex and studied the remaining internal processing. Using high-resolution functional brain imaging (0.8 mm(3)) and multivoxel pattern information techniques, we demonstrate that during normal visual stimulation scene information peaks in mid-layers. Conversely, we found that contextual feedback information peaks in outer, superficial layers. Further, we found that shifting the position of the visual scene surrounding the mask parametrically modulates feedback in superficial layers of V1. Our results reveal the layered cortical organization of external versus internal visual processing streams during perception in healthy human subjects. We provide empirical support for theoretical feedback models such as predictive coding [10, 12] and coherent infomax [13] and reveal the potential of high-resolution fMRI to access internal processing in sub-millimeter human cortex.


Relationships between stereotyped movements and sensory processing disorders in children with and without developmental or sensory disorders.
Stereotyped movements (SM) are a defining characteristic of autism but are also present in children with a range of sensory and developmental disorders. We examined whether the severity of sensory processing disorders (SPD) was associated with the severity of SM and whether SPD accounted for between-group differences in SM. The Short Sensory Profile and the Stereotyped and Self-Injurious Movements Interview were administered to children with autism, intellectual disability, visual impairment, and hearing impairment and to typically developing children. SPD predicted the severity of SM in all samples and accounted for differences in SM between the groups. Other differences in the severity of SM were the result of diagnosis and the interaction between diagnosis and an intellectual disability. SPD may be a source of SM, but functional connections between these phenomena will need to be tested in future research. Implications for occupational performance are addressed.


Early life stage trimethyltin exposure induces ADP-ribosylation factor expression and perturbs the vascular system in zebrafish.
Trimethyltin chloride (TMT) is an organotin contaminant, widely detected in aqueous environments, posing potential human and environmental risks. In this study, we utilized the zebrafish model to investigate the impact of transient TMT exposure on developmental progression, angiogenesis, and cardiovascular development. Embryos were waterborne exposed to a wide TMT concentration range from 8 to 96 h post fertilization (hpf). The TMT concentration that led to mortality in 50% of the embryos (LC(50)) at 96 hpf was 8.2 μM; malformations in 50% of the embryos (EC(50)) was 2.8 μM. The predominant response observed in surviving embryos was pericardial edema. Additionally, using the Tg (fli1a: EGFP) y1 transgenic zebrafish line to non-invasively monitor vascular development, TMT exposure led to distinct disarrangements in the vascular system. The most susceptible developmental stage to TMT exposure was between 48 and 72 hpf. High density whole genome microarrays were used to identify the early transcriptional changes following TMT exposure from 48 to 60 hpf or 72 hpf. In total, 459 transcripts were differentially expressed at least 2-fold (P<0.05) by TMT compared to control. Using Ingenuity Pathway Analysis (IPA) tools, it was revealed that the transcripts misregulated by TMT exposure were clustered in numerous categories including metabolic and cardiovascular disease, cellular function, cell death, molecular transport, and physiological development. In situ localization of highly elevated transcripts revealed intense staining of ADP-ribosylation factors arf3 and arf5 in the head, trunk, and tail regions. When arf5 expression was blocked by morpholinos, the zebrafish did not display the prototypical TMT-induced vascular deficits, indicating that the induction of arf5 was necessary for TMT-induced vascular toxicity.


Multiscale Symmetry Detection in Scalar Fields by Clustering Contours.
The complexity in visualizing volumetric data often limits the scope of direct exploration of scalar fields. Isocontour extraction is a popular method for exploring scalar fields because of its simplicity in presenting features in the data. In this paper, we present a novel representation of contours with the aim of studying the similarity relationship between the contours. The representation maps contours to points in a high-dimensional transformation-invariant descriptor space. We leverage the power of this representation to design a clustering based algorithm for detecting symmetric regions in a scalar field. Symmetry detection is a challenging problem because it demands both segmentation of the data and identification of transformation invariant segments. While the former task can be addressed using topological analysis of scalar fields, the latter requires geometry based solutions. Our approach combines the two by utilizing the contour tree for segmenting the data and the descriptor space for determining transformation invariance. We discuss two applications, query driven exploration and asymmetry visualization, that demonstrate the effectiveness of the approach.


Impact of breast-feeding and high- and low-protein formula on the metabolism and growth of infants from overweight and obese mothers.
The combination of maternal obesity in early pregnancy and high protein intake in infant formula feeding might predispose to obesity risk in later life. This study assesses the impact of breast- or formula-feeding (differing in protein content by 1.65 or 2.7 g/100 kcal) on the metabolism of term infants from overweight and obese mothers. From birth to 3 mo of age, infants received exclusively either breast- or starter formula-feeding and until 6 mo, exclusively either a formula designed for this study or breast-feeding. From 6 to 12 mo, infants received complementary weaning food. Metabonomics was conducted on the infants' urine and stool samples collected at the age of 3, 6, and 12 mo. Infant formula-feeding resulted in higher protein-derived short-chain fatty acids and amino acids in stools. Urine metabonomics revealed a relationship between bacterial processing of dietary proteins and host protein metabolism stimulated with increasing protein content in the formula. Moreover, formula-fed infants were metabolically different from breast-fed infants, at the level of lipid and energy metabolism (carnitines, ketone bodies, and Krebs cycle). Noninvasive urine and stool metabolic monitoring of responses to early nutrition provides relevant readouts to assess nutritional requirements for infants' growth.


Intraoperative Bypass Graft Flow Measurement With Transit Time Flowmetry: A Clinical Assessment.
Guidelines advocate transit time flowmetry (TTFM) for intraoperative graft patency verification during coronary artery bypass graft surgery (CABG), but studies on accuracy and precision of the TTFM technique are few. In an observational study of CABG patients, we analyzed covariation of left internal mammary artery (LIMA) blood flow with TTFM and free flow measurements. Covariation of TTFM and free blood flows was evaluated in 60 patients undergoing CABG using the LIMA as one of the conduits. With LIMA flow measurements routinely performed before and after vasodilation, results are based on 120 paired intraoperative measurements. As demonstrated by a combined approach of regression and Bland-Altman analysis for the two flow situations, TTFM was higher than free flow in 64% of measurements, with an overestimation by TTFM of 7.1% ± 16.3% in the overall cohort (prevasodilation), statistically carried by measurements with 4-mm probes (overestimation by 13.3% ± 15.4%, both p < 0.01). In a multiregression analysis, oversizing of the TTFM probe (odds ratio 9.56, 95% confidence interval: 2.03 to 45.10, p = 0.004) and high flows (odds ratio 1.02, 95% confidence interval: 1.01 to 1.04, p < 0.001) were independent determinants of flow overestimation by TTFM, although in the Bland-Altman analysis no systematic overestimation was seen in the postvasodilation situation. In a receiver-operating characteristics analysis, optimal cutoff value as determined from Youden's index for assuming flow overestimation was 68 mL/min. Overall, with slight overall overestimation of 7.1%, TTFM is an accurate indicator of LIMA blood flow during CABG, with a clinically acceptable precision. Overestimation may be expected with flows greater than 68 mL/min, but most importantly, in situations with oversized TTFM probes.


Reliability of BOD POD Measurements Remains High After a Short-Duration Low-Carbohydrate Diet.
The purpose of the current study was to determine whether expected changes in body weight via a 3-day low-carbohydrate (LC) diet will disrupt the reliability of air displacement plethysmography measurements via BOD POD. Twenty-four subjects recorded their typical diets for 3 days before BOD POD and 7-site skinfold analyses. Subjects were matched for lean body mass and divided into low-CHO (LC) and control (CON) groups. The LC group was given instruction intended to prevent more than 50 grams/day of carbohydrate consumption for 3 consecutive days, and the CON group replicated their previously recorded diet. Body composition measurements were repeated after dietary intervention. Test-retest reliability measures were significant (p < .01) and high for body fat percentage in both the LC and the CON groups (rs = .993 and .965, respectively). Likewise, skinfold analysis for body fat percentage reliability was high in both groups (rs = .996 and .997, respectively). There were significant differences between 1st and 2nd BOD POD measurements for body mass (72.9 ± 13.3 vs. 72.1 ± 13.0 kg [M ± SD]) and body volume (69.0 ± 12.7-68.1 ± 12.2 L) in the LC group (p < .05). However, there were no differences (p > .05) in BOD POD-determined body fat percentage, lean body mass, or fat mass between the 1st and 2nd trial in either group. Body composition measures via BOD POD and 7-site skinfolds remain reliable after 3 days of an LC diet despite significant decreases in body mass.


Higher sensitivity towards light stress and ocean acidification in an Arctic sea-ice-associated diatom compared to a pelagic diatom.
Thalassiosira hyalina and Nitzschia frigida are important members of Arctic pelagic and sympagic (sea-ice-associated) diatom communities. We investigated the effects of light stress (shift from 20 to 380 µmol photons m-2 s-1 , resembling upwelling or ice break-up) under contemporary and future pCO2 (400 vs 1000 µatm). The responses in growth, elemental composition, pigmentation and photophysiology were followed over 120 h and are discussed together with underlying gene expression patterns. Stress response and subsequent re-acclimation were efficiently facilitated by T. hyalina, which showed only moderate changes in photophysiology and elemental composition, and thrived under high light after 120 h. In N. frigida, photochemical damage and oxidative stress appeared to outweigh cellular defenses, causing dysfunctional photophysiology and reduced growth. pCO2 alone did not specifically influence gene expression, but amplified the transcriptomic reactions to light stress, indicating that pCO2 affects metabolic equilibria rather than sensitive genes. Large differences in acclimation capacities towards high light and high pCO2 between T. hyalina and N. frigida indicate species-specific mechanisms in coping with the two stressors, which may reflect their respective ecological niches. This could potentially alter the balance between sympagic and pelagic primary production in a future Arctic.


Affine structure from motion.
A mobile observer samples sequences of narrow-field projections of configurations in ambient space. The so-called structure-from-motion problem is to infer the structure of these spatial configurations from the sequence of projections. For rigid transformations, a unique metrical reconstruction is known to be possible from three orthographic views of four points. However, human observers seem able to obtain much shape information from a mere pair of views, as is evident in the case of binocular stereo. Moreover, human observers seem to find little use for the information provided by additional views, even though some improvement certainly occurs. The rigidity requirement in its strict form is also relaxed. We indicate how solutions of the structure-from-motion problem can be stratified in such a way that one explicitly knows at which stages various a priori assumptions enter and specific geometrical expertise is required. An affine stage is identified at which only smooth deformation is assumed (thus no rigidity constraint is involved) and no metrical concepts are required. This stage allows one to find the spatial configuration (modulo an affinity) from two views. The addition of metrical methods allows one to find shape from two views, modulo a relief transformation (depth scaling and shear). The addition of a third view then merely serves to settle the calibration. Results of a numerical experiment are discussed.


Imatinib protects against human beta-cell death via inhibition of mitochondrial respiration and activation of AMPK.
The protein tyrosine kinase inhibitor imatinib is used in the treatment of various malignancies but may also promote beneficial effects in the treatment of diabetes. The aim of the present investigation was to characterize the mechanisms by which imatinib protects insulin producing cells. Treatment of non-obese diabetic (NOD) mice with imatinib resulted in increased beta-cell AMP-activated kinase (AMPK) phosphorylation. Imatinib activated AMPK also in vitro, resulting in decreased ribosomal protein S6 phosphorylation and protection against islet amyloid polypeptide (IAPP)-aggregation, thioredoxin interacting protein (TXNIP) up-regulation and beta-cell death. 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) mimicked and compound C counteracted the effect of imatinib on beta-cell survival. Imatinib-induced AMPK activation was preceded by reduced glucose/pyruvate-dependent respiration, increased glycolysis rates, and a lowered ATP/AMP ratio. Imatinib augmented the fractional oxidation of fatty acids/malate, possibly via a direct interaction with the beta-oxidation enzyme enoyl coenzyme A hydratase, short chain, 1, mitochondrial (ECHS1). In non-beta cells, imatinib reduced respiratory chain complex I and II-mediated respiration and acyl-CoA carboxylase (ACC) phosphorylation, suggesting that mitochondrial effects of imatinib are not beta-cell specific. In conclusion, tyrosine kinase inhibitors modestly inhibit mitochondrial respiration, leading to AMPK activation and TXNIP down-regulation, which in turn protects against beta-cell death.


Sex-related differences in D-dimer levels for venous thromboembolism screening.
D-dimer is generally considered positive above 0.5 mg/L irrespective of sex. However, women have been shown to be more likely to have a positive D-dimer after controlling for other factors. Thus, differences may exist between males and females for using D-dimer as a marker of venous thromboembolic (VTE) disease. We hypothesized that the accuracy of D-dimer tests may be enhanced by using appropriate cutoff values that reflect sex-related differences in D-dimer levels. This research is a secondary analysis of a multicenter, international, prospective, observational study of adult (18+ years) patients suspected of VTE, with low-to-intermediate pretest probability based on Wells criteria ≤ 6 for pulmonary embolism (PE) and ≤ 2 for deep vein thrombosis (DVT). VTE diagnoses were based on computed tomography, ventilation perfusion scanning, or venous ultrasound. D-dimer levels were tested for statistical difference across groups stratified by sex and diagnosis. Multivariable regression was used to investigate sex as a predictor of diagnosis. Sex-specific optimal D-dimer thresholds for PE and DVT were calculated from receiver operating characteristic analyses. A Youden threshold (D-dimer level coinciding with the maximum of sensitivity plus specificity) and a cutoff corresponding to 95% sensitivity were calculated. Statistical difference for cutoffs was tested via 95% confidence intervals from 2,000 bootstrapped samples. We included 3,586 subjects for analysis, of whom 61% were female. Race demographics were 63% White, 27% Black/African American, and 6% Hispanic. In the suspected PE cohort, 6% were diagnosed with PE, while in the suspected DVT cohort, 11% were diagnosed with DVT. D-dimer levels were significantly higher in males than females for the PE-positive group and the DVT-negative group, but males had significantly lower D-dimer levels than females in the PE-negative group. Regression models showed male sex as a significant positive predictor of DVT diagnosis, controlling for D-dimer levels. The Youden thresholds for PE patients were 0.97 (95% CI = 0.64 to 1.79) mg/L and 1.45 (95% CI = 1.36 to 1.95) mg/L for females and males, respectively; 95% sensitivity cutoffs for this group were 0.64 (95% CI = 0.20 to 0.89) and 0.55 (95% CI = 0.29 to 1.61). For DVT, the Youden thresholds were 0.98 (95% CI = 0.84 to 1.56) mg/L for females and 1.25 (95% CI = 0.65 to 3.33) mg/L for males with 95% sensitivity cutoffs of 0.33 (95% CI = 0.2 to 0.61) and 0.32 (95% CI = 0.18 to 0.7), respectively. Differences in D-dimer levels between males and females are diagnosis specific; however, there was no significant difference in optimal cutoff values for excluding PE and DVT between the sexes.


Heat shock protein 90: role in enterovirus 71 entry and assembly and potential target for therapy.
Although several factors participating in enterovirus 71 (EV71) entry and replication had been reported, the precise mechanisms associated with these events are far from clear. In the present study, we showed that heat shock protein 90 (HSP90) is a key element associated with EV71 entry and replication in a human rhabdomyosarcoma of RD cells. Inhibition of HSP90 by pretreating host cells with HSP90β siRNA or blocking HSP90 with a HSP90-specific antibody or geldanamycin (GA), a specific inhibitor of HSP90, as well as recombinant HSP90β resulted in inhibiting viral entry and subsequent viral replication. Co-immunprecipitation of EV71 with recombinant HSP90β and colocalization of EV71-HSP90 in the cells demonstrated that HSP90 was physically associated with EV71 particles. HSP90 seems to mediate EV71 replication by preventing proteosomal degradation of the newly synthesized capsid proteins, but does not facilitate viral gene expression at transcriptional level. This was evident by post-treatment of host cells with GA, which did not affect the expression of viral transcripts but accelerated the degradation of viral capsid proteins and interfered with the formation of assembled virions. In vivo studies were carried out using human SCARB2-transgenic mice to evaluate the protection conferred by HSP90 inhibitor, 17-allyamino-17-demethoxygeldanamycin (17-AAG), an analog of geldanamycin, that elicited similar activity but with less toxicity. The results showed that the administration of 17-AAG twice conferred the resistance to hSCARB2 mice challenged with C2, C4, and B4 genotypes of EV71. Our data supports HSP90 plays an important role in EV71 infection. Targeting of HSP90 with clinically available drugs might provide a feasible therapeutic approach to treat EV71 infection.


First Report of White Mold Caused by Sclerotinia sclerotiorum on Blue Marguerite (Felicia amelloides) in Italy.
Felicia amelloides (Asteraceae family), also known as blue marguerite, is cultivated as a potted plant in Italy and increasingly used for ornamental purposes. In winter 2002, plants grown outdoors in 14-cm-diameter pots (2 liters) in commercial farms near Albenga (northern Italy) showed leaf yellowing. At the soil level, soft and watery tissues covered with whitish mycelium were evident. Later, dark brown sclerotia differentiated from the mycelium. As necrosis progressed, infected plants wilted and died. Sclerotinia sclerotiorum (1) was consistently recovered from infected stem pieces of F. amelloides that were disinfested for 1 min in 1% NaOCl and plated on potato dextrose agar (PDA) amended with 100 ppm of streptomycin sulfate. Sclerotia produced on PDA were ellipsoid and measured 1.3 to 6.1 × 1.1 to 3.3 mm (average 2.9 × 2.3 mm) (2). Pathogenicity of three isolates (used as a mixture and obtained from infected plants from the same farm) was confirmed by inoculating 90-day-old plants grown in 14-cm-diameter pots. Inoculum that consisted of wheat kernels infested with mycelium and sclerotia of each isolate was placed on the soil surface around the base of each of 20 plants. Ten noninoculated plants served as controls. The inoculation trial was repeated. All plants were kept outdoors at temperatures ranging between 5 and 26°C and watered as needed. All inoculated plants developed symptoms of leaf yellowing, followed by the appearance of white mycelium within 15 days, and then eventually wilted. Control plants remained symptomless. White mycelium and sclerotia developed on infected tissues, and S. sclerotiorum was reisolated from inoculated plants. To our knowledge, this is the first report of white mold of F. amelloides caused by S. sclerotiorum in Italy as well as elsewhere in the world. References: (1) N. F. Buchwald. Den. Kgl. Veterin.er-og Landbohojskoles Aarsskrift, 32:75, 1949. (2) C. M. Messiaen et al. Les Maladies des Plantes Maraichères. INRA, Paris, 1991.


Modified procedure for the microscopic and macroscopic study of viral plaques.
A virus plaque method that consistently gives good visual contrast for macroscopic observation and also permits microscopic study is described. Cells are grown in plastic flasks and the gelled overlay medium can be of any desired agar concentration or volume. A fixing solution is used prior to removal of the agar overlay, and dye is added to the fixing solution or staining can follow fixation and agar removal. The bottom of the flask with the fixed monolayer is separated from the rest of the container and handled as a slide. A new mounting medium is described.


Scientific production of electronic health record research, 1991-2005.
The increasing numbers of publications on electronic health record (EHR) indicate its increasing importance in the world. This study attempted to quantify the scientific production of EHR research articles, and how they have changed over time, in an effort to investigate changes in the trends cited in these critical evaluations. The articles were based on the science citation index (SCI) from 1991 to 2005. A descriptive study was performed using the 1803 documents published in the SCI from 39 countries in America, Europe, Africa, Asia, and Oceania. The evaluation was based on parameters including document type, language, first author's country of origin, number of citations and citations per publication. Of all publications, 1455 (80.7%) were articles, followed by meeting abstracts which represented about one-tenth of all types of EHR publications. Numbers of published articles have significantly increased when compared by each 5-year period. Most articles were published in English (98%) and were from the region of America (57%). The top 10 of the 374 journals accounted for 41% of the number of published articles. The US dominates publication production (57%) with a cumulative impact factor (IF) of 2227 and followed by the UK (8.5%, with a cumulative IF of 257.0) and the Netherlands (7.8%, with a cumulative IF of 211.1). An analysis of the number of articles related to population revealed a high publication output for relative small countries like Switzerland, the Netherlands, and Norway. Research production in EHR showed a considerable increase during 1991-2005. The production was dominated by articles, those from the US, and those published in English. The production came from many countries, denoting the devotion to this field in different areas around the world.


Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.
Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.


Crude extract of Fusarium oxysporum induces apoptosis and structural alterations in the skin of healthy rats.
We evaluate the biological and physicochemical effects of a Fusarium oxysporum crude extract (CE) on the skin of healthy rats. The CE is topically applied and subsequently the skin is collected after 3, 6, 12, and 24 h. The samples are analyzed by Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) and histomorphometric analysis. Terminal dUTP nick end labeling (TUNEL assay) is performed to detect both the cells in apoptosis and proliferation. There is a thickening of the epidermis after 6, 12, and 24 h and dermis after 12 and 24 h of CE application. A reduction of the dermis thickness is observed at 3 and 6 h. The treated skin shows higher labeling intensity by TUNEL at 3 h, while a higher intensity by proliferating cell nuclear antigen occurs at 3 and 12 h. FTIR-PAS data support the histology observations showing an increase in the absorption peaks in the dermis after the application of the CE. F. oxysporum CE permeated through the epidermis and the dermis, reaching the subcutaneous tissue, inducing cell apoptosis, and causing physicochemical changes in the organic molecules located in the dermis. This is the first known study associating histopathological and physical chemistry changes on healthy skin after the application of F. oxysporum CE.


Application of the ESRI Geostatistical Analyst for determining the adequacy and sample size requirements of ozone distribution models in the Carpathian and Sierra Nevada Mountains.
Models of O3 distribution in two mountain ranges, the Carpathians in Central Europe and the Sierra Nevada in California were constructed using ArcGIS Geostatistical Analyst extension (ESRI, Redlands, CA) using kriging and cokriging methods. The adequacy of the spatially interpolated ozone (O3) concentrations and sample size requirements for ozone passive samplers was also examined. In case of the Carpathian Mountains, only a general surface of O3 distribution could be obtained, partially due to a weak correlation between O3 concentration and elevation, and partially due to small numbers of unevenly distributed sample sites. In the Sierra Nevada Mountains, the O3 monitoring network was much denser and more evenly distributed, and additional climatologic information was available. As a result the estimated surfaces were more precise and reliable than those created for the Carpathians. The final maps of O3 concentrations for Sierra Nevada were derived from cokriging algorithm based on two secondary variables--elevation and maximum temperature as well as the determined geographic trend. Evenly distributed and sufficient numbers of sample points are a key factor for model accuracy and reliability.


Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials.
To conduct a systematic review and meta-analysis of randomized trials that assessed the effect of testosterone use on cardiovascular events and risk factors in men with different degrees of androgen deficiency. Librarian-designed search strategies were used to search the MEDLINE (1966 to October 2004), EMBASE (1988 to October 2004), and Cochrane CENTRAL (inception to October 2004) databases. The database search was performed again in March 2005. We also reviewed reference lists from included studies and content expert files. Eligible studies were randomized trials that compared any formulation of commercially available testosterone with placebo and that assessed cardiovascular risk factors (lipid fractions, blood pressure, blood glucose), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, angina or claudication, revascularization, stroke), and cardiovascular surrogate end points (ie, laboratory tests indicative of cardiac or vascular disease). Using a standardized data extraction form, we collected data on participants, testosterone administration, and outcome measures. We assessed study quality with attention to allocation concealment, blinding, and loss to follow-up. The 30 trials included 1642 men, 808 of whom were treated with testosterone. Overall, the trials had limited reporting of methodological features that prevent biased results (only 6 trials reported allocation concealment), enrolled few patients, and were of brief duration (only 4 trials followed up patients for > 1 year). The median loss to follow-up across all 30 trials was 9%. Testosterone use in men with low testosterone levels led to inconsequential changes in blood pressure and glycemia and in all lipid fractions (total cholesterol: odds ratio [OR], -0.22; 95% confidence interval [CI], -0.71 to 0.27; high-density lipoprotein cholesterol: OR, -0.04; 95% CI, -0.39 to 0.30; low-density lipoprotein cholesterol: OR, 0.06; 95% CI, -0.30 to 0.42; and triglycerides: OR, -0.27; 95% CI, -0.61 to 0.08); results were similar in patients with low-normal to normal testosterone levels. The OR between testosterone use and any cardiovascular event pooled across trials that reported these events (n = 6) was 1.82 (95% CI, 0.78 to 4.23). Several trials failed to report data on measured outcomes. For reasons we could not explain statistically, the results were inconsistent across trials. Currently available evidence weakly supports the inference that testosterone use in men is not associated with important cardiovascular effects. Patients and clinicians need large randomized trials of men at risk for cardiovascular disease to better inform the safety of long-term testosterone use.


Comparison of a web-based food record tool and a food-frequency questionnaire and objective validation using the doubly labelled water technique in a Swedish middle-aged population.
Two web-based dietary assessment tools have been developed for use in large-scale studies: the Riksmaten method (4-d food record) and MiniMeal-Q (food-frequency method). The aim of the present study was to examine the ability of these methods to capture energy intake against objectively measured total energy expenditure (TEE) with the doubly labelled water technique (TEEDLW), and to compare reported energy and macronutrient intake. This study was conducted within the pilot study of the Swedish CArdioPulmonary bioImage Study (SCAPIS), which included 1111 randomly selected men and women aged 50-64 years from the Gothenburg general population. Of these, 200 were enrolled in the SCAPIS diet substudy. TEEDLW was measured in a subsample (n 40). Compared with TEEDLW, both methods underestimated energy intake: -2·5 (sd 2·9) MJ with the Riksmaten method; -2·3 (sd 3·6) MJ with MiniMeal-Q. Mean reporting accuracy was 80 and 82 %, respectively. The correlation between reported energy intake and TEEDLW was r 0·4 for the Riksmaten method (P < 0·05) and r 0·28 (non-significant) for MiniMeal-Q. Women reported similar average intake of energy and macronutrients in both methods whereas men reported higher intakes with the Riksmaten method. Energy-adjusted correlations ranged from 0·14 (polyunsaturated fat) to 0·77 (alcohol). Bland-Altman plots showed acceptable agreement for energy and energy-adjusted protein and carbohydrate intake, whereas the agreement for fat intake was poorer. According to energy intake data, both methods displayed similar precision on energy intake reporting. However, MiniMeal-Q was less successful in ranking individuals than the Riksmaten method. The development of methods to achieve limited under-reporting is a major challenge for future research.


The pathophysiologic role of incretins.
Many patients with type 2 diabetes mellitus (T2DM) are unable to achieve adequate glycemic control. Of the approximately 19 million individuals with T2DM in the United States, only about a third achieve the hemoglobin A(1c) (HbA(1c)0 goal set forth by the American Diabetes Association (HbA(1c) <7% [6% if it can be achieved safely]). The incretin mimetics are a new class of medications available for treating patients with T2DM. They mimic the action of incretins, which are peptide hormones that originate in the gastrointestinal tract. The two major incretins in humans are glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). These hormones are released during nutrient absorption, augmenting insulin secretion. However, incretins are susceptible to degradation by dipeptidyl peptidase IV (DPP-IV). Dipeptidyl peptidase IV inhibitors suppress the degradation of incretins, thus extending the activity of GLP-1 and GIP. The glycemic profiles of patients after administration of incretin mimetics and DPP-IV inhibitors show improvement in postprandial glucose levels and ultimately in HbA(1c). Therefore, incretin mimetics and DPP-IV inhibitors may play a clinically significant role in the treatment of patients with T2DM.


Formal thought disorder is characterised by impaired lexical access.
Recent studies have proposed that difficulty with accessing the lexical-semantic memory store may underpin some of the specific linguistic problems associated with formal thought disorder (FTD). We examined the consistency of name retrieval as an indicator of the ability to access lexical-semantic knowledge in patients with and without marked FTD to see if problems are specific to the former or common to schizophrenic patients in general. A graded naming test was administered on two separate occasions 8-16 weeks apart to 48 participants in three groups: 16 schizophrenic patients with high ratings of FTD, 16 schizophrenic patients with low ratings of FTD and 16 healthy controls. We compared the groups for naming consistency across time and the relationship between naming consistency and specific symptoms of FTD. Both patient groups had impaired naming and this was significantly greater in high than low FTD patients. The high FTD patients showed a profile that differed from both low FTD patients and healthy controls insofar as their naming was inconsistent across time, characteristic of an access disorder. Specifically, the FTD symptoms of derailment, tangentality and incoherence were related to the ability to access the lexical-semantic store. In conclusion, most patients with schizophrenia show an impaired semantic memory store. Nevertheless, FTD is associated with additional lexical-semantic difficulties that are quantitatively different to those seen in patients without FTD, and which may reflect disorganized semantic access.


Expression and Purification of Quinine Dihydro Pteridine Reductase from astrocytes and its significance in the astrocyte pathology.
Quinine dihydropteridinereductase (QDPR) is involved in the synthesis of tetradihydrobiopteridine (BH4) that serve as cofactor for many aromatic hydroxylases including induced nitric oxide synthase (NOS) leading to NO production. Increased activity of QDPR has been associated with decrease levels of TGF-β, a cytokine that regulates the immune response and that elevated levels of NO has been associated with neurodegenerative diseases. Thus, expression of QDPR in astrocytes is essential to study the pathological changes observed in many neurodegenerative disorders. We have expressed QDPR in astrocytes and generated stably expressing clones that overexpresses QDPR. We further verified the specificity of QDPR expression using immunofluorescence and immunoblotting. To further confirm, we purified QDPR using Ni-NTA column and subjected the purified fraction to immunoblotting using anti-QDPR antibody and identified two major protein products of QDPR resolving at 25 and 17 kDa as reported in the literature. In order to further assess the significance of QDPR expression, we verified the expression of iNOS in QDPR over expressing cells. We show for the first time statistically significant up regulation of iNOS in QDPR overexpressing astrocytes. Increased expression of iNOS associated with astrocyte pathology seen in many neurodegenerative disorders may have implications in autoimmune neurodegenerative disorders.


The host response to the probiotic Escherichia coli strain Nissle 1917: specific up-regulation of the proinflammatory chemokine MCP-1.
The use of live microorganisms to influence positively the course of intestinal disorders such as infectious diarrhea or chronic inflammatory conditions has recently gained increasing interest as a therapeutic alternative. In vitro and in vivo investigations have demonstrated that probiotic-host eukaryotic cell interactions evoke a large number of responses potentially responsible for the effects of probiotics. The aim of this study was to improve our understanding of the E. coli Nissle 1917-host interaction by analyzing the gene expression pattern initiated by this probiotic in human intestinal epithelial cells. Gene expression profiles of Caco-2 cells treated with E. coli Nissle 1917 were analyzed with microarrays. A second human intestinal cell line and also pieces of small intestine from BALB/c mice were used to confirm regulatory data of selected genes by real-time RT-PCR and cytometric bead array (CBA) to detect secretion of corresponding proteins. Whole genome expression analysis revealed 126 genes specifically regulated after treatment of confluent Caco-2 cells with E. coli Nissle 1917. Among others, expression of genes encoding the proinflammatory molecules monocyte chemoattractant protein-1 ligand 2 (MCP-1), macrophage inflammatory protein-2 alpha (MIP-2alpha) and macrophage inflammatory protein-2 beta (MIP-2beta) was increased up to 10 fold. Caco-2 cells cocultured with E. coli Nissle 1917 also secreted high amounts of MCP-1 protein. Elevated levels of MCP-1 and MIP-2alpha mRNA could be confirmed with Lovo cells. MCP-1 gene expression was also up-regulated in mouse intestinal tissue. Thus, probiotic E. coli Nissle 1917 specifically upregulates expression of proinflammatory genes and proteins in human and mouse intestinal epithelial cells.


Assessment of aggregative growth of MnZn ferrite nanoparticles.
MnZn ferrite (MnZnFe2O4, MZF) nanoparticles (NPs) represent an intriguing class of magnetic NPs in terms of composition-tunable magnetic properties, but the ability to control the size and morphology is essential to exploit such properties. This report describes the findings of an investigation of the size and morphology controllability in terms of growth kinetics of the NPs in a thermochemical synthesis process. MZF NPs of different sizes were synthesized at different temperatures. In addition to shape evolution, the overall size of the as-synthesized magnetic NPs is shown to increase with the reaction temperature and reaction time, revealing that the size growth process can be described by an aggregative growth mechanism. While the apparent rate constant decreases with the reaction temperature, the growth factor remains at 1-2, consistent with a low-dimensionality growth mode. Higher temperature and longer reaction time apparently favor the formation of cubic shapes. The dependence of the overall average particle size on the reaction temperature yields a diffusional activation energy in the order of 10-20 kJ mol-1, a value slightly smaller than those reported for aggregative growth of other types of NPs in solutions. The unravelling of the kinetic parameters provides some new insights into the development of strategies for synthesizing MZF NPs with controllable sizes and shapes.


Evaluation of cage designs and feeding regimes for honey bee (Hymenoptera: Apidae) laboratory experiments.
The aim of this study was to improve cage systems for maintaining adult honey bee (Apis mellifera L.) workers under in vitro laboratory conditions. To achieve this goal, we experimentally evaluated the impact of different cages, developed by scientists of the international research network COLOSS (Prevention of honey bee COlony LOSSes), on the physiology and survival of honey bees. We identified three cages that promoted good survival of honey bees. The bees from cages that exhibited greater survival had relatively lower titers of deformed wing virus, suggesting that deformed wing virus is a significant marker reflecting stress level and health status of the host. We also determined that a leak- and drip-proof feeder was an integral part of a cage system and a feeder modified from a 20-ml plastic syringe displayed the best result in providing steady food supply to bees. Finally, we also demonstrated that the addition of protein to the bees' diet could significantly increase the level ofvitellogenin gene expression and improve bees' survival. This international collaborative study represents a critical step toward improvement of cage designs and feeding regimes for honey bee laboratory experiments.


Transverse pattern modifications in a stable apertured laser resonator.
The effects of hard apertures on the transversal mode distribution and the output near and far field distributions are investigated both theoretically and experimentally. Wavefronts propagating in different directions inside a CO(2) laser cavity were measured at the same plane and found to have different transversal amplitude profiles. The influence of intracavity aperture's location and diameter on the near field distribution and far field beam quality were measured and calculated. Quantitative figures of merit are introduced to evaluate the departure of the transversal mode patterns from ideal Gaussians.


Traumatic brain injury does not alter cerebral artery contractility.
Previous studies have shown that traumatic brain injury (TBI) significantly reduces cerebral blood flow determined in vivo and reduces vascular reactivity in the pial circulation measured with cranial window preparations. We have now tested the hypothesis that TBI induces these changes by impairing intrinsic contractile activity of cerebral arteries. Anesthetized rats underwent moderate (2.2 atm) and severe (3.0 atm) midline fluid percussion TBI or sham injury following which posterior cerebral or middle cerebral arteries were isolated and isometric force generation was measured. Moderate (n = 5) and severe (n = 3) trauma had no effect on the magnitude of serotonin- or K+-induced force generation or sensitivity to serotonin in arteries isolated within 10 min of TBI. Functional disruption of the endothelium of posterior cerebral arteries isolated 10 min after moderate trauma or sham injury caused a reduction in the active tension response to serotonin that was similar in both groups. Blockade of cyclooxygenase with 5 microM indomethacin had no effect on serotonin-induced force generated by vessels with moderate trauma or in sham-treated rats. Acetylcholine induced an endothelium-dependent relaxation of posterior and middle cerebral arteries; the magnitude of the response was unaffected by moderate TBI. To determine whether prolonged in situ exposure of vessels to the traumatized cerebral milieu could reveal an alteration in intrinsic contractility, posterior cerebral arteries were isolated 30 min after TBI; again, no differences in the tension or relaxation responses were observed. It is concluded that midline fluid percussion TBI did not affect contraction or relaxation of proximal middle or posterior cerebral arteries in rats.


Development and evaluation of a new telerehabilitation system based on VR technology using multisensory feedback for patients with stroke.
[Purpose] The purpose of this study was to develop a new telerehabilitation system based on VR technology for training of paralyzed upper and lower extremities and poor balance in patients with stroke. Moreover, the effectiveness of the system was verified by analysis of the recovery of these patients. [Subjects] Five healthy persons and five people with motor paralysis, caused by cerebrovascular disease, participated. [Methods] The features of our system are as follows: (1) Our system can train upper and lower limbs and balancing with 3D images. (2) A Kinect(®) is used for user posture detection. (3) A vibrator is used for feedback to a sensory receptor in order to promote the learning effect of motion. Upper limb and balance training were conducted in this study. [Results] The time necessary for the upper limb and balance training tasks was shortened for the participants with disabilities. The joint angle for the participants with disabilities tended to equate to that of the healthy participants over time. Moreover, our system had no side effects. [Conclusion] These points suggest that our system is effective and safe. The user interface and assessment of the conditions of patients from a distance should be studied in the future.


Direct intermode selection for H.264 video coding using phase correlation.
The H.264 video coding standard exhibits higher performance compared to the other existing standards such as H.263, MPEG-X. This improved performance is achieved mainly due to the multiple-mode motion estimation and compensation. Recent research tried to reduce the computational time using the predictive motion estimation, early zero motion vector detection, fast motion estimation, and fast mode decision, etc. These approaches reduce the computational time substantially, at the expense of degrading image quality and/or increase bitrates to a certain extent. In this paper, we use phase correlation to capture the motion information between the current and reference blocks and then devise an algorithm for direct motion estimation mode prediction, without excessive motion estimation. A bigger amount of computational time is reduced by the direct mode decision and exploitation of available motion vector information from phase correlation. The experimental results show that the proposed scheme outperforms the existing relevant fast algorithms, in terms of both operating efficiency and video coding quality. To be more specific, 82 ~92% of encoding time is saved compared to the exhaustive mode selection (against 58 ~74% in the relevant state-of-the-art), and this is achieved without jeopardizing image quality (in fact, there is some improvement over the exhaustive mode selection at mid to high bit rates) and for a wide range of videos and bitrates (another advantages over the relevant state-of-the-art).


Differences in expression of serum protein in patients with psoriasis vulgaris and blood heat syndrome and healthy volunteers.
To explore the mechanism of psoriasis vulgaris (PV), serum protein expression profiles between PV patients with blood-heat syndrome and healthy volunteers were detected by isobaric tags for relative and absolute quantitation (iTRAQ). First, sera from 15 PV patients with blood-heat syndrome and 10 healthy volunteers were collected; then, serum proteins were separated and hydrolyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and a specific iTRAQ marker enzyme respectively after further purification and protein abundance treatment. Compared with the control group, differentially expressed proteins in PV patients with blood-heat syndrome were identified and analyzed by tandem mass spectrometry. A total of 787 proteins were identified and 718 proteins had a functional annotation with gene ontology (GO) by iTRAQ in the current study. Significant differences (P <0.05) and great differences (P <0.01) were found in 681 proteins and 536 proteins respectively between the patient group and healthy group. ). Different protein expression profiles in serum existed between PV patients with blood-heat syndrome and healthy volunteers; the differences largely involved immune-related proteins and lipoproteins. The proteins specific for PV with blood-heat syndrome deserves further investigation.


The spatial-temporal clustering of Plasmodium falciparum infection over eleven years in Gezira State, The Sudan.
Malaria infection and disease exhibit microgeographic heterogeneity which if predictable could have implications for designing small-area intervention. Here, the space-time clustering of Plasmodium falciparum infections using data from repeat cross-sectional surveys in Gezira State, a low transmission area in northern Sudan, is investigated. Data from cross-sectional surveys undertaken in January each year from 1999-2009 in 88 villages in the Gezira state were assembled. During each survey, about a 100 children between the ages two to ten years were sampled to examine the presence of P. falciparum parasites. In 2009, all the villages were mapped using global positioning systems. Cluster level data were analysed for spatial-only and space-time clustering using the Bernoulli model and the significance of clusters were tested using the Kulldorff scan statistic. Over the study period, 96,022 malaria slide examinations were undertaken and the P. falciparum prevalence was 8.6% in 1999 and by 2009 this had reduced to 1.6%. The cluster analysis showed the presence of one significant spatial-only cluster in each survey year and one significant space-time cluster over the whole study period. The primary spatial-only clusters in 10/11 years were either contained within or overlapped with the primary space-time cluster. The results of the study confirm the generally low malaria transmission in the state of Gezira and the presence of spatial and space-time clusters concentrated around a specific area in the south of the state. Improved surveillance data that allows for the analysis of seasonality, age and other risk factors need to be collected to design effective small area interventions as Gezira state targets malaria elimination.


Optimum modulation and demodulation matrices for solar polarimetry.
Both temporal and/or spatial modulation are mandatory in current solar polarimetry [Appl. Opt. 24, 3893 (1985); 26, 3838 (1987)]. The modulating and demodulating processes are mathematically described by matrices O and D, respectively, on whose structure the accuracy of Stokes parameter measurements depend. We demonstrate, based on the definition of polarimetric efficiency [Instituto de Astrofísica de Canarias Internal Report (1994); ASP Conf. Ser. 184, 3 (1999)], that the maximum efficiencies of an ideal polarimeter are unity for Stokes I and for (Q(2) + U(2) + V(2))(1/2) and that this occurs if and only if O(T)O is diagonal; given a general (possibly nonideal) modulation matrix O, the optimum demodulation matrix turns out to be D = (O(T)O)(-1)O(T); and the maximum efficiencies in the nonideal case are given by the rms value of the column elements of matrix O and are reached by modulation matrices such that O(T)O is diagonal. From these analytical results we distill two recipes useful in the practical design of polarimeters. Their usefulness is illustrated by discussing cases of currently available solar polarimeters. Although specifically devoted to solar polarimetry, the results here may be applied in practically all other branches of science for which polarimetric measurements are needed.


Galaxies as gravitational lenses.
Of all the galaxies in the visible part of the universe, 500 million are seen through intervening galaxies. In some instances the foreground galaxy will act as a gravitational lens and produce distorted and (in brightness) greatly amplified images of the galaxy behind it; such images may simulate starlike superluminous objects such as quasars (quasi-stellar objects). The number of gravitational lenses is several times greater than the number of quasars yet observed. In other instances the superposition of the image upon a visible foreground galaxy may simulate morphological configurations resembling N-type, dumbbell, spiral, or barred-spiral galaxies.


Fluid management in acute respiratory distress syndrome.
Fluid management is one of the most important measures shown to impact acute respiratory distress syndrome (ARDS) outcomes. This review summarizes the current strategies aimed at evaluating and modulating lung fluid balance. Multiple recent studies have shown that a conservative fluid management in ARDS patients had beneficial effects on morbidity and mortality. These findings were replicated also in different patient populations assumed to have potential deleterious effects from this approach. So far, only one retrospective study raised the possibility of impaired cognitive function in ARDS patients managed with a conservative fluid strategy. Thermodilution methods and serum biomarkers can be used to monitor lung fluid balance and guide therapy. Recent evidence has indicated significant detrimental effects associated with beta-2 agonists use in ARDS, despite a putative beneficial role in the resolution of alveolar edema seen in preliminary studies. Dynamic monitoring of lung fluid balance needs to be implemented to guide fluid therapy in ARDS patients. A conservative fluid strategy seems safe and yields overall good clinical outcomes, but its impact on cognitive function needs to be evaluated in further studies. The role of colloids and other pharmacological agents deserves further investigation.


Can an evidence-based book club intervention delivered via a tablet computer improve physical activity in middle-aged women?
Fewer than 50% of middle-aged women participate in regular physical activity (PA). Innovative approaches that engage women who may not otherwise participate in PA programs are warranted. The purpose of this study was to explore the acceptability and feasibility of a 12-week tablet-based book club for improving middle-aged women's PA. Thirty women (35-64 years of age) were randomized to the Fit Minded Tablet (n=15) and the Standard Fit Minded (i.e., face-to-face intervention) (n=15) groups. The Fit Minded Tablet was adapted from the Standard Fit Minded, a previously tested, theory-based book club intervention using books as a platform for discussion and group support to help women adopt regular PA. Both interventions met weekly for 3 months, for a total of 12 sessions. Tablet group participants accessed materials (e.g., e-books, workbook, live/recorded videoconferencing) via a tablet computer; Standard group participants received materials (e.g., printed books, workbook, live face-to-face meetings) in person. Feasibility (i.e., implementation and expansion) was assessed using process evaluation, qualitative interviews, satisfaction surveys, and quantitative outcome assessments. Women in the Tablet group attended fewer meetings (mean, 8.25) than women in the Standard group (mean, 9.9). Videoconferencing, digital literacy, and participant engagement limitations were observed in the Tablet group. Tablet participants enjoyed the e-books but thought technology barriers hindered their engagement during meetings. Women in both groups valued the support they received from other group members. Standard participants cited this support as a key contributor to their PA changes, whereas Tablet participants reported needing in-person contact to feel more connected. Given the popularity of tablet computers and the value that middle-aged women place on group interaction to support their PA behaviors, additional research is warranted to determine best strategies for optimizing social support, mitigating technology barriers, and improving engagement in online and mobile health promotion programs targeting middle-aged women.


Endoscopic ultrasound features of chronic pancreatitis: A pictorial review.
As endoscopic ultrasound (EUS) is the most sensitive imaging modality for diagnosing pancreatic disorders, it can demonstrate subtle alterations in the pancreatic parenchymal and ductal structure even before traditional imaging and functional testing demonstrate any abnormality. In spite of this fact and abundant literature, the exact role of EUS in the diagnosis of chronic pancreatitis (CP) is still not established. The EUS features to diagnose CP have evolved over a period from a pure qualitative approach to more advanced and complicated scoring systems incorporating multiple parenchymal and ductal EUS features. The rosemont criteria have attempted to define precisely each EUS criterion and thus have good inter-observer agreement. However, initial studies have failed to demonstrate any significant improvement in the inter-observer variability and further validation studies are needed to define the exact role of these criteria. The measurement of strain ratio using quantitative EUS elastography and thus allowing quantification of pancreatic fibrosis seems to be a promising new technique.


Herbal treatments for alleviating premenstrual symptoms: a systematic review.
Premenstrual syndrome (PMS) is a condition of cyclical and recurrent physical and psychological discomfort occurring 1 to 2 weeks before menstrual period. More severe psychological symptoms have been described for the premenstrual dysphoric disorder (PMDD). No single treatment is universally recognised as effective and many patients often turn to therapeutic approaches outside of conventional medicine. This systematic review is aimed at analysing the effects of herb remedies in the above conditions. Systematic literature searches were performed in electronic databases, covering the period January 1980 to September 2010. Randomised controlled clinical trials (RCTs) were included. Papers quality was evaluated with the Jadad' scale. A further evaluation of PMS/PMDD diagnostic criteria was also done. Of 102 articles identified, 17 RCTs were eligible and 10 of them were included. The heterogeneity of population included, study design and outcome presentation refrained from a meta-analysis. Vitex agnus castus was the more investigated remedy (four trials, about 500 women), and it was reported to consistently ameliorate PMS better than placebo. Single trials also support the use of either Gingko biloba or Crocus sativus. On the contrary, neither evening primrose oil nor St. John's Wort show an effect different than placebo. None of the herbs was associated with major health risks, although the reduced number of tested patients does not allow definitive conclusions on safety. Some herb remedies seem useful for the treatment of PMS. However, more RCTs are required to account for the heterogeneity of the syndrome.