An evaluation of morphine and oxymorphone administered via patient-controlled analgesia (PCA) or PCA plus basal infusion in postcesarean-delivery patients.
The analgesic efficacy and adverse effects of morphine and oxymorphone in 32 patients who received traditional patient-controlled analgesia (PCA) following cesarean delivery were compared with those in 32 other patients receiving the same agents via PCA plus basal opioid infusion (PCA + BI). All patients were operated upon during epidural anesthesia with 2% lidocaine and 1:200,000 epinephrine to achieve a T4 sensory level. Upon first complaint of pain in the recovery room, patients were given a titrated iv loading dose of the assigned opioid until comfortable and were then provided with a programmable PCA device. Group I (PCA) consisted of two subsets in which incremental boluses of morphine (1.8 mg, n = 16) or oxymorphone (0.3 mg, n = 16) could be self-administered via conventional PCA. Patients in group II (PCA + BI) received a basal infusion of morphine (0.6 mg/hour, n = 16) or oxymorphone (0.1 mg/hour, n = 16) in addition to self-administered boluses of 1.8 and 0.3 mg, respectively. Patients were evaluated for 24 h following initiation of analgesic therapy, and 10-cm visual analog scales (VAS) were utilized at selected intervals to assess pain at rest, pain during movement, and satisfaction with therapy. The level of sedation and incidence of nausea/vomiting and pruritus were also recorded. Patients utilizing PCA + BI noted significant reductions in resting pain scores with oxymorphone and decreased pain during movement with both opioids when compared with individuals using PCA alone (P less than 0.05). There were no significant differences between treatment groups in 24-h dose requirements or patient satisfaction with therapy (P = ns).(ABSTRACT TRUNCATED AT 250 WORDS)


Subseabed disposal of nuclear wastes.
Fine-grained clay formations within stable (predictable) deep-sea regions away from lithospheric plate boundaries and productive surface waters have properties that might serve to permanently isolate radioactive waste. The most important characteristics of such clays are their vertical and lateral unifomity, low permeability, very high cation retention capacity, and potential for self-healing when disturbed. The most attractive abyssal clay formation (oxidized red ciay)covers nearly 30 percent of the sea floor and hence 20 percent of the earth's surface.


Superfluid Filaments of Dipolar Bosons in Free Space.
We systematically investigate the zero temperature phase diagram of bosons interacting via dipolar interactions in three dimensions in free space via path integral Monte Carlo simulations with a few hundreds of particles and periodic boundary conditions based on the worm algorithm. Upon increasing the strength of the dipolar interaction and at sufficiently high densities we find a wide region where filaments are stabilized along the direction of the external field. Most interestingly by computing the superfluid fraction we conclude that the superfluidity is anisotropic and is greatly suppressed along the orthogonal plane. Finally, we perform simulations at finite temperature confirming the stability of the filaments against thermal fluctuations and provide an estimate of the superfluid fraction in the weak coupling limit in the framework of the Landau two-fluid model.


Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K(+)-channel Kv2.1.
The voltage-sensing domains of voltage-gated potassium channels Kv2.1 (drk1) contain four transmembrane segments in each subunit, termed S1 to S4. While S4 is known as the voltage sensor, the carboxyl terminus of S3 (S3C) bears a gradually broader interest concerning the site for gating modifier toxins like hanatoxin and thus the secondary structure arrangement as well as its surrounding environment. To further examine the putative three-dimensional (3-D) structure of S3C and to illustrate the residues required for hanatoxin binding (which may, in turn, show the influence on the S4 in terms of changes in channel gating), molecular simulations and dockings were performed. These were based on the solution structure of hanatoxin and the structural information from lysine-scanning results for S3C fragment. Our data suggest that several basic and acidic residues of hanatoxin are electrostatically and stereochemically mapped onto their partner residues on S3C helix, whereas some aromatic or hydrophobic residues located on the same helical fragment interact with the hydrophobic patch of the toxin upon binding. Therefore, a slight distortion of the S3C helix, in a direction toward the N-terminus of S4, may exist. Such conformational change of S3C upon toxin binding is presented as a possible explanation for the observed shift in hanatoxin binding-induced gating.


A visual approach to efficient analysis and quantification of ductile iron and reinforced sprayed concrete.
This paper describes advanced volume visualization and quantification for applications in non-destructive testing (NDT), which results in novel and highly effective interactive workflows for NDT practitioners. We employ a visual approach to explore and quantify the features of interest, based on transfer functions in the parameter spaces of specific application scenarios. Examples are the orientations of fibres or the roundness of particles. The applicability and effectiveness of our approach is illustrated using two specific scenarios of high practical relevance. First, we discuss the analysis of Steel Fibre Reinforced Sprayed Concrete (SFRSpC). We investigate the orientations of the enclosed steel fibres and their distribution, depending on the concrete's application direction. This is a crucial step in assessing the material's behavior under mechanical stress, which is still in its infancy and therefore a hot topic in the building industry. The second application scenario is the designation of the microstructure of ductile cast irons with respect to the contained graphite. This corresponds to the requirements of the ISO standard 945-1, which deals with 2D metallographic samples. We illustrate how the necessary analysis steps can be carried out much more efficiently using our system for 3D volumes. Overall, we show that a visual approach with custom transfer functions in specific application domains offers significant benefits and has the potential of greatly improving and optimizing the workflows of domain scientists and engineers.


Public involvement policies in health: exploring their conceptual basis.
Despite its obvious appeal, the concept of public involvement is poorly defined and its rationale and objectives are rarely specified when applied to current health policy contexts. This paper explores some of the underlying concepts, definitions, and issues underpinning public involvement policies and proposes a set of criteria and questions that need to be addressed to allow for the evaluation of public involvement strategies and their impact on the health policy process. It aims to further our understanding of the role that public involvement may play in contributing to health systems that are responsive to the needs and priorities of the public, and, ultimately, providing better health and health care services to the community at large.


Two novel nodal-related genes initiate early inductive events in Xenopus Nieuwkoop center.
In vertebrates, Nodal-related protein plays crucial roles in mesoderm and endoderm induction. Here we describe two novel Xenopus nodal-related genes, Xnr5 and Xnr6, which are first zygotically expressed at the mid-blastula transition, in the dorsal-vegetal region including the Nieuwkoop center. Xnr5 and Xnr6 were isolated by expression screening of a library enriched with immediate-early-type transcripts, and are strong inducers of both mesoderm and endoderm. They also induce the other nodal-related genes in the animal cap. In embryos, cerberus-short (nodal-specific inhibitor) can inhibit Xnr1 and Xnr2 express to the same extent goosecoid, but not Xnr5 and Xnr6 transcription. Xnr5 and Xnr6 are regulated completely cell autonomously, differently from other Xnrs in the cell-dissociated embryos. The expression of Xnr5 and Xnr6 is regulated by maternal VegT and (beta)-catenin, but does not require TGF-(beta) signaling. Therefore, expression of Xnr5 and Xnr6 is controlled by different mechanisms from other Xnr family genes.


Clinical and MRI predictors of no early recanalization within 1 hour after tissue-type plasminogen activator administration.
The aim of the present study was to investigate independent clinical and MRI factors associated with no early recanalization within 1 hour after tissue-type plasminogen activator (tPA) administration. Patients with acute stroke within 3 hours of onset who were treated with tPA were studied prospectively. Patients with internal carotid artery, M1, and M2 occlusion were enrolled, and independent clinical and MRI factors associated with no early recanalization within 1 hour after tPA administration were examined using multivariate logistic regression analysis. One hundred thirty-two patients (63 men; mean age, 76.4±10.2 years; internal carotid artery occlusion in 37 patients, M1 occlusion in 58, and M2 occlusion in 37) were enrolled. Follow-up MR angiography within 60 minutes after tPA infusion revealed early recanalization in 49 (37.1%) patients (complete in 16 patients, partial in 33) and no recanalization in 83 (62.9%). Using 8 variables (atrial fibrillation, time from stroke onset to treatment ≥140 minutes, use of warfarin, glucose ≥135 mg/dL, large artery diseases, internal carotid artery occlusion, M1 occlusion, and M1 susceptibility vessel sign on T2*) identified on univariate analysis at P<0.2, multivariate logistic regression analysis revealed that M1 susceptibility vessel sign was the only independent factor associated with no early recanalization (OR, 7.157; 95% CI, 1.756 to 29.172; P=0.006). The sensitivity, specificity, positive predictive value, and negative predictive value of M1 susceptibility vessel sign for predicting no early recanalization were 31.3%, 93.9%, 89.7%, and 44.7%, respectively. Of clinical and MRI factors before tPA infusion, M1 susceptibility vessel sign on T* is the only independent factor associated with no early recanalization within 1 hour after tPA administration.


The Evolution of Human Homosexual Behavior.
Homosexuality presents a paradox for evolutionists who explore the adaptedness of human behavior. If adaptedness is measured by reproductive success and if homosexual behavior is nonreproductive, how has it come about? Three adaptationist hypotheses are reviewed here and compared with the anthropological literature. There is little evidence that lineages gain reproductive advantage through offspring care provided by homosexual members. Therefore, there is little support for the hypothesis that homosexuality evolved by kin selection. Parents at times control children's reproductive decisions and at times encourage children in homosexual behavior. There is therefore more support for the hypothesis of parental manipulation. Support is strongest, however, for the hypothesis that homosexual behavior comes from individual selection for reciprocal altruism. Same-sex alliances have reproductive advantages, and sexual behavior at times maintains these alliances. Nonhuman primates, including the apes, use homosexual behavior in same-sex alliances, and such alliances appear to have been key in the expanded distribution of human ancestors during the Pleistocene. Homosexual emotion and behavior are, in part, emergent qualities of the human propensity for same-sex affiliation. Adaptationist explanations do not fully explain sexual behavior in humans, however; social and historical factors also play strong roles.


Synthesis and characterisation of biocompatible organic-inorganic core-shell nanocomposite particles based on ureasils.
Organic-inorganic core-shell nanocomposites have attracted increasing attention for applications in imaging, controlled release, biomedical scaffolds and self-healing materials. While tunable properties can readily be achieved through the selection of complementary building blocks, synergistic enhancement requires management of the core-shell interface. In this work, we report a one-pot method to fabricate hybrid core-shell nanocomposite particles (CSNPs) based on ureasils. The native structure of ureasils, which are poly(oxyalkylene)/siloxane hybrids, affords formation of an organic polymer core via nanoprecipitation, while the terminal siloxane groups act as a template for nucleation and growth of the silica shell via the Stöber process. Through optimisation of the reaction conditions, we demonstrate the reproducible synthesis of ureasil CSNPs, with a hydrodynamic diameter of ∼150 nm and polydispersity <0.2, which remain electrostatically stabilised in aqueous media for >50 days. Selective functionalisation, either through the physical entrapment of polarity-sensitive fluorescent probes (coumarin 153, pyrene) or covalent-grafting to the silica shell (fluorescein isothiocyanate) is also demonstrated and provides insight into the internal environment of the particles. Moreover, preliminary studies using a live/dead cell assay indicate that ureasil CSNPs do not display cytotoxicity. Given the simple fabrication method and the structural tunability and biocompatability of the ureasils, this approach presents an efficient route to multifunctional core-shell nanocomposite particles whose properties may be tailored for a targeted application.


Erythema migrans-like rash illness at a camp in North Carolina: a new tick-borne disease?
Borrelia burgdorferi, the causative agent of Lyme disease, has never been isolated from a patient thought to have acquired Lyme disease in any southeastern state. To investigate 14 cases of an erythema migrans (EM)-like rash illness that occurred during 2 summers at an outdoor camp in central North Carolina in an effort to determine the etiologic, epidemiological, and clinical aspects of this illness. Using active surveillance, we identified cases of clinically diagnosed EM in residents and staff of the camp. We collected clinical and demographic information; history of exposure to ticks; acute and convalescent serum antibodies to B. burgdorferi, Rickettsia rickettsii, and Ehrlichia chaffeensis; and cultures for spirochetes from biopsy specimens of skin lesions. Serum samples from a group of residents and staff who did not develop rashes were tested for the same antibodies. We speciated ticks removed from people and collected from vegetation. We identified 14 cases of EM-like rash illness during the 2 summers. Of the 14 case-patients, 10 had associated mild systemic symptoms and 1 had documented fever. All 14 case-patients had removed attached ticks, and 8 remembered having removed a tick from the site where the rash developed a median of 12 days earlier (range, 2-21 days). One tick removed from the site where a rash later developed was identified as Amblyomma americanum, the Lone Star tick; 97% of ticks collected from vegetation and 95% of ticks removed from people were A. americanum. No spirochetes were isolated from skin biopsy specimens. Paired serum samples from 13 case-patients did not show diagnostic antibody responses to B. burgdorferi or other tick-borne pathogens. This investigation suggests the existence of a new tick-associated rash illness. We suspect that the disease agent is carried by A. americanum ticks. In the southern United States, EM-like rash illness should no longer be considered definitive evidence of early Lyme disease.


Macrovascular disease in diabetics in Central Africa.
Six hundred African diabetics were examined for evidence of large vessel disease using a standardised technique based on the World Health Organisation Multinational Study, in which no country from Africa was represented. Twelve patients had electrocardiograms coded coronary probable using Minnesota coding. Seven patients had had strokes and 10 peripheral vascular disease. Despite the high prevalence of hypertension large vessel disease was uncommon, being comparable with Japan and Hong Kong, who had the lowest prevalence in the WHO study. Overall, only 49 patients had evidence of macrovascular disease.


Brain and CSF water and ions during dilutional and isosmotic hyponatremia in the rat.
Dilutional (DH) and isosmotic (IH) hyponatremia (plasma [Na+] = 103-109 meq/l) were produced in conscious rats over 3-6 h by intraperitoneal injection of water or mannitol Ringer solution. During DH, CSF [Na+], [Cl-], and osmolality decreased as predicted by passive dilution by the water load. During IH, these variables exhibited little change. Brain water was unchanged during IH despite significant reduction of brain Na+ and Cl- content suggesting that tissue ions lost were replaced by other osmoles. During DH, brain water increased but less than predicted by passive osmotic equilibration. Cell volume increased as predicted by passive swelling while the extracellular volume (Cl space) decreased. Tissue K+ content decreased by a small but significant amount. Tissue Na+ and Cl- decreased by 21 and 28%. This pattern of fluid compartmental and electrolyte changes suggests that brain volume regulation during acute DH occurs via reduction of extracellular volume as cells swell. This may result from bulk flow of extracellular fluid to CSF or from ion and water movement across the blood-brain barrier.


Respiratory effects of xanthines and adenosine analogs in rhesus monkeys.
This study examined the relative contributions of phosphodiesterase inhibition and adenosine receptor blockade in the respiratory-stimulant effects of selected xanthines. The respiratory effects of caffeine, theophylline, 8-phenyltheophylline (8-PT), 8-cyclopentyltheophylline (8-CPT), 3-isobutyl-1-methylxanthine and enprofylline, as well as the nonxanthine phosphodiesterase inhibitor, rolipram, and the adenosine analogs, N6-cyclopentyladenosine (CPA) and 5'-N-ethylcarboxamide adenosine (NECA), were studied in unanesthetized rhesus monkeys. Ventilation was measured continuously by enclosing the monkey's head in a fitted Lexan helmet while a pressure transducer measured differences in pressure produced by inspirations and expirations against a constant flow of air. Drugs were administered (i.m.) using cumulative-dosing procedures while the subjects breathed air or 5% CO2 mixed in air. All xanthines except 8-PT produced dose-related increases in respiratory frequency and less pronounced changes in tidal volume, both in air and in 5% CO2 mixed in air. 8-PT, an adenosine antagonist with little activity as a phosphodiesterase inhibitor, did not have respiratory effects over the range of doses studied. Enprofylline, a phosphodiesterase inhibitor with little activity as an adenosine antagonist, had effects that were comparable to those of caffeine. Rolipram also had effects on respiration that were similar to those of caffeine, and it was approximately 100 times more potent than caffeine. The adenosine A1/A2 agonist, NECA, produced dose-related increases in respiratory frequency, and both CPA (an A1-selective agonist) and NECA produced dose-related decreases in tidal volume; NECA was 30 to 100 times more potent than CPA.(ABSTRACT TRUNCATED AT 250 WORDS)


Modulation of immune responses after portal venous injection of antigen.
How the localization of antigen to the liver, through means such as oral ingestion, induces tolerance is poorly understood. To elucidate potential mechanisms we used an adoptive transfer system wherein ova-specific T cells were infused into a syngeneic host, and antigen-specific T-cell responses after delivery of soluble antigen into the liver were monitored. After infusion of antigen into the portal vein, the frequency of antigen-specific T cells in lymph nodes draining the liver was lower than the frequency in peripheral lymph nodes. These findings were the reverse of what is typically observed after subcutaneous injection of antigen with adjuvant. Infusion of antigen with adjuvant into the portal vein did not alter this pattern of antigen-specific T-cell localization; however, an increased frequency of T cells, compared with antigen alone, was observed in peripheral lymph nodes and spleen. After exposure to antigen via the portal vein, T cells isolated from lymph nodes draining the liver and challenged with antigen in vitro exhibited a diminished proliferative response compared with T cells isolated from nondraining lymph nodes. This hyporesponsiveness was not observed when the antigen was administered with adjuvant. Our findings suggest that the influence of the liver on immune responses might reflect two processes: (1) loss of antigen-specific T cells after primary antigen injection, and (2) hyporesponsiveness on reexposure to antigen. These mechanisms may contribute to the prevention of undesirable immune responses to foods and enteric bacteria in the gastrointestinal tract. Furthermore, these results underscore the importance of minimizing inflammation in circumstances such as islet transplantation, if endogenous mechanisms of tolerance induction are to be maximized.


Can We Predict Psychosis Outside the Clinical High-Risk State? A Systematic Review of Non-Psychotic Risk Syndromes for Mental Disorders.
Recent evidence has suggested that psychosis could develop not only in people at clinical high risk for psychosis (CHR-P) but also in those with clinical risk syndromes for emergent nonpsychotic mental disorders. The proportion of people with these clinical risk syndromes who will develop psychosis rather than to other nonpsychotic mental disorders is undetermined. Electronic databases were searched for studies reporting on clinical risk syndromes for the development of emergent nonpsychotic mental disorders. Incidence of emerging psychotic and nonpsychotic mental disorders defined on the ICD or DSM. Of a total of 9 studies relating to 3006 nonpsychotic at-risk individuals were included. Within prospective studies (n = 4, sample = 1051), the pooled incidence of new psychotic disorders across these clinical risk syndromes was of 12.9 per 1000 person-years (95% CI: 4.3 to 38.6) and that of nonpsychotic disorders (n = 3, sample = 538) was of 43.5 per 1000 person-years (95% CI: 30.9 to 61.3). Psychotic disorders may emerge outside the CHR-P paradigm, from clinical risk syndromes for incident nonpsychotic disorders, albeit at lower rates than in the CHR-P group. The clinical risk syndromes for emerging nonpsychotic disorders may exhibit a pluripotential risk of developing several types of mental disorders compared with CHR-P. If substantiated by future research, the current findings suggest that it may be useful to move beyond the current strategy of identifying individuals meeting CHR-P criteria only.


The Effects of the COVID-19 Economic Downturn on Medicaid Coverage for Podiatry Services.
As of 2016, Medicaid accounted for nearly 20% of state general fund budgets. Optional Medicaid services such as podiatry are often subject to cost-cutting measures in periods of economic downturn, as was the case in the wake of the 2007 financial crisis. Although the cuts were intended as a cost-saving measure, research indicates that they had the opposite effect. The restriction and limitation of these services during the Great Recession resulted in both poorer health outcomes for beneficiaries, and poorer financial outcomes for state Medicaid programs. With states citing record levels of unemployment as of April of 2020 and projecting significant declines in annual revenue in 2021, the economic conditions resulting from the coronavirus disease of 2019 pandemic are likely to rival those of the Great Recession. Given the historical precedent for restricting or eliminating optional Medicaid services as a cost-saving measure, it is likely that podiatric services will once again come under scrutiny. Previous efforts by state-level podiatric societies have proven successful in lobbying for the reinstatement of coverage under Medicaid by conveying evidence of the negative outcomes associated with elimination to stakeholders. The specialty must once again engage policymakers by drawing on evidence gleaned and lessons learned from past cuts of optional Medicaid services to avert counterproductive coverage restrictions intended to mitigate the financial impact of the coronavirus disease of 2019 pandemic.


Efficacy and safety of azelastine nasal spray for the treatment of allergic rhinitis.
Azelastine hydrochloride is a nasally administered antihistamine that is effective and safe for the treatment of perennial and seasonal allergic rhinitis. In addition to acting as a histamine H1-receptor antagonist, azelastine also inhibits the production or release of many chemical mediators of the allergic response such as leukotrienes, free radicals, and cytokines. After nasal administration, azelastine is systemically absorbed with a bioavailability of about 40%. The side effects of azelastine are drowsiness, headache, and bitter taste. Azelastine has a rapid onset of action with a benefit in about 2 hours and a prolonged duration of activity (12 to 24 hours). Studies have shown azelastine to be more effective than placebo in terms of reduction of the major and total symptom complexes of allergic rhinitis. Comparison studies have demonstrated that azelastine is as effective as ebastine, loratadine, cetirizine hydrochloride, and terfenadine at symptom reduction, with varying results when compared with the corticosteroids budesonide and beclomethasone. Although there are conflicting studies, some have demonstrated that azelastine reduces the nasal congestion of allergic rhinitis. This feature that distinguishes it from oral antihistamines is of great interest because corticosteroids are known to be quite effective for the relief of nasal congestion, whereas the antihistamines are effective for the sneezing, itchy eyes, itchy nose, and watery eyes, but not the congestion. Azelastine nasal spray seems to be an efficacious treatment for allergic rhinitis with a rapid onset and long duration of activity, but without the systemic adverse effects of traditional sedating antihistamines.


Selection of retroviral reverse transcription primer is coordinated with tRNA biogenesis.
Initiation of retrovirus reverse transcription requires the selection of a tRNA primer from the intracellular milieu. To investigate the features of primer selection, a human immunodeficiency virus type 1 (HIV-1) and a murine leukemia virus (MuLV) were created that require yeast tRNA(Phe) to be supplied in trans for infectivity. Wild-type yeast tRNA(Phe) expressed in mammalian cells was transported to the cytoplasm and aminoacylated. In contrast, tRNA(Phe) without the D loop (tRNA(Phe)D(-)) was retained within the nucleus and did not complement infectivity of either HIV-1 or MuLV; however, infectivity was restored when tRNA(Phe)D(-) was directly transfected into the cytoplasm of cells. A tRNA(Phe) mutant (tRNA(Phe)UUA) that did not have the capacity to be aminoacylated was transported to the cytoplasm and did complement infectivity of both HIV-1 and MuLV, albeit at a level less than that with wild-type tRNA(Phe). Collectively, our results demonstrate that the tRNA primer captured by HIV-1 and MuLV occurs after nuclear export of tRNA and supports a model in which primer selection for retroviruses is coordinated with tRNA biogenesis at the intracellular site of protein synthesis.


Seasonal changes in plasma steroid levels in relation to ovarian steroidogenic ultrastructural features and progesterone receptors in the house gecko, Hemidactylus flaviviridis, in Oman.
A comprehensive study of the annual ovarian cycle in the house gecko, Hemidactylus flaviviridis, was conducted in Oman. Circulating estradiol (E(2)), progesterone (P), and testosterone (T) were measured during the active and inactive phases of the cycle. The steroid levels were related to the steroidogenic ultrastructural features such as the abundance of smooth endoplasmic reticulum (SER), the presence of cisternal whorls, and close association of lipid droplets with swollen vesiculated mitochondria and SER. The steroids were measured using a sensitive detection technique HPLC-MS/MS. E(2) levels began to rise in January at the onset of vitellogenesis and continued to rise between February and May relative to ovulation, postovulation, gravidity and oviposition. Afterwards, E(2) remained low during the inactive phase (June-December). P levels increased significantly in March and peaked in April, which coincided with luteinization. P levels began to decline relative to luteolysis (May-June). Afterwards, it remained low throughout the inactive phase. T levels rose significantly in March-April coinciding with vitellogenesis, but decreased rapidly and significantly in May and remained low during the inactive phase. Progesterone receptors (PR), identified using immunohistochemistry, were strongly expressed during the breeding period, but were absent during the non-breeding period. The appearance of the steroidogenic ultrastructural features in the preovulatory and lutein granulosa cells was correlated with the significant rise in the three steroid levels and the PR. As the steroid levels declined, the granulosa cells underwent a general degeneration and disruption of the associated steroidogenic features.


Behavior and social competency in idiopathic and cryptogenic childhood epilepsy.
Behavioral and related disorders are frequently reported in association with childhood epilepsy but the reasons for this are unclear. In a long-term prospective, community-based study of newly-diagnosed childhood epilepsy, behavioral assessments (Child Behavior Checklist) were performed in children 8 to 9 years after the initial diagnosis of epilepsy to determine the impact of remission and medication status on behavioral problems. Children with epilepsy were also compared with sibling controls. A total of 226 children (108 females, 118 males; mean age 13y 1mo [SD 2y 8mo], range 8-17y) with idiopathic or cryptogenic epilepsy were included in the analyses. One hundred and twenty-eight matched pairs were included in analyses of case-sibling differences. Lack of remission and current medication use were associated with worse behavioral problem and competency scores. Lack of remission generally had a greater effect than medication use, except for attention problems; medication status had the more deleterious effect (p<0.001). Children with epilepsy had significantly worse behavioral problems and competency scores relative to sibling controls. Even in paris in which the patient was seizure-free and off medication, significant case-sibling differences persisted for most scales (p=0.05 to p=0.001). Lack of remission and continued use of antiepileptic drugs have a negative influence on behavioral problems in children with epilepsy but do not fully explain the worse scores relative to siblings. This suggests an independent effect associated with the epilepsy itself.


Long-term trends in the Oxford knee score following total knee replacement.
The Oxford knee score (OKS) is a validated and widely accepted disease-specific patient-reported outcome measure, but there is limited evidence regarding any long-term trends in the score. We reviewed 5600 individual OKS questionnaires (1547 patients) from a prospectively-collected knee replacement database, to determine the trends in OKS over a ten-year period following total knee replacement. The mean OKS pre-operatively was 19.5 (95% confidence interval (CI) 18.8 to 20.2). The maximum post-operative OKS was observed at two years (mean score 34.4 (95% CI 33.7 to 35.2)), following which a gradual but significant decline was observed through to the ten-year assessment (mean score 30.1 (95% CI 29.1 to 31.1)) (p < 0.001). A similar trend was observed for most of the individual OKS components (p < 0.001). Kneeling ability initially improved in the first year but was then followed by rapid deterioration (p < 0.001). Pain severity exhibited the greatest improvement, although residual pain was reported in over two-thirds of patients post-operatively, and peak improvement in the night pain component did not occur until year four. Post-operative OKS was lower for women (p < 0.001), those aged < 60 years (p < 0.003) and those with a body mass index > 35 kg/m(2) (p < 0.014), although similar changes in scores were observed. This information may assist surgeons in advising patients of their expected outcomes, as well as providing a comparative benchmark for evaluating longer-term outcomes following knee replacement.


A Distributed Approach Toward Discriminative Distance Metric Learning.
Distance metric learning (DML) is successful in discovering intrinsic relations in data. However, most algorithms are computationally demanding when the problem size becomes large. In this paper, we propose a discriminative metric learning algorithm, develop a distributed scheme learning metrics on moderate-sized subsets of data, and aggregate the results into a global solution. The technique leverages the power of parallel computation. The algorithm of the aggregated DML (ADML) scales well with the data size and can be controlled by the partition. We theoretically analyze and provide bounds for the error induced by the distributed treatment. We have conducted experimental evaluation of the ADML, both on specially designed tests and on practical image annotation tasks. Those tests have shown that the ADML achieves the state-of-the-art performance at only a fraction of the cost incurred by most existing methods.


The epidemiology and natural history of anal human papillomavirus infection in men who have sex with men.
Studies on the epidemiology and natural history of anal human papillomavirus (HPV) infection are essential to understand the significance of this virus in the aetiology of anal cancer in men who have sex with men (MSM). This paper presents a review of studies on anal HPV in MSM. For this review, a Medline search was performed to identify English-language articles published in peer-reviewed journals on the epidemiology, natural history and risk factors for anal HPV infection in MSM. Anal HPV prevalence is high in MSM and infection with multiple HPV types is common. The available prospective data suggest detection of new anal HPV infections may also be common. However, with limited epidemiological data available on infection dynamics and associated behavioural risk factors, it is difficult to draw conclusions on how persistent anal HPV infection is in this population.


Automated Sound Recognition Provides Insights into the Behavioral Ecology of a Tropical Bird.
Computer-assisted species recognition facilitates the analysis of relevant biological information in continuous audio recordings. In the present study, we assess the suitability of this approach for determining distinct life-cycle phases of the Southern Lapwing Vanellus chilensis lampronotus based on adult vocal activity. For this purpose we use passive 14-min and 30-min soundscape recordings (n = 33 201) collected in 24/7 mode between November 2012 and October 2013 in Brazil's Pantanal wetlands. Time-stamped detections of V. chilensis call events (n = 62 292) were obtained with a species-specific sound recognizer. We demonstrate that the breeding season fell in a three-month period from mid-May to early August 2013, between the end of the flood cycle and the height of the dry season. Several phases of the lapwing's life history were identified with presumed error margins of a few days: pre-breeding, territory establishment and egg-laying, incubation, hatching, parental defense of chicks, and post-breeding. Diurnal time budgets confirm high acoustic activity levels during midday hours in June and July, indicative of adults defending young. By August, activity patterns had reverted to nonbreeding mode, with peaks around dawn and dusk and low call frequency during midday heat. We assess the current technological limitations of the V. chilensis recognizer through a comprehensive performance assessment and scrutinize the usefulness of automated acoustic recognizers in studies on the distribution pattern, ecology, life history, and conservation status of sound-producing animal species.


Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2.
The effects of somatostatin analogues RC-160 and SMS-201-995 on tyrosine phosphatase and cell proliferation were investigated in COS-7 and NIH 3T3 cells expressing human somatostatin receptor subtype 1 or 2 (SSTR1 or SSTR2). Binding experiments were performed on membranes from COS-7 cells expressing human SSTR1 or SSTR2 using 125I-labeled [Tyr11]S-14 or [Tyr3]SMS-201-995, respectively. The somatostatin analogues RC-160 and SMS-201-995 exhibited low affinity for SSTR1 (IC50 of 0.43 and 1.5 microM, respectively) and high affinity for SSTR2 (IC50 of 0.27 and 0.19 nM). Addition of these analogues to cells expressing either SSTR1 or SSTR2 did not result in an inhibition of adenylate cyclase activity. In SSTR2-expressing cells, both analogues induced a rapid stimulation of a tyrosine phosphatase activity (EC50: RC-160, 2 pM; SMS-201-995, 6 pM) and an inhibition of serum-stimulated proliferation (EC50: RC-160, 6.3 pM; SMS-201-995, 12 pM). In SSTR1-expressing cells, only RC-160 induced stimulation of a tyrosine phosphatase activity. Both analogues caused an inhibition of cell proliferation at a concentration higher than 10 nM in accordance with their affinities for the SSTR1 receptor subtype. A good correlation between the affinities of RC-160 and SMS-201-995 for each receptor subtype and their potencies to inhibit cell proliferation suggests the involvement of these receptors in cell growth regulation. Tyrosine phosphatase was stimulated by both these analogues in SSTR2 and by RC-160 in SSTR1 at affinities similar to their ability to inhibit growth and bind to receptors, implicating tyrosine phosphatase as a transducer of the growth inhibition signal. We also found that mRNAs of receptor subtypes were variably expressed in different pancreatic and colon cancer cell lines, indicating the necessity of a precise analysis of receptor subtypes in target tissues before therapy with analogues.


Na+ leak in erythrocytes from essential hypertensive patients.
Ouabain- and bumetanide-resistant (OBR) Na+ efflux from human erythrocytes into a Mg2+-sucrose medium exhibits kinetic properties consistent with a transmembrane Na+ leak. In 52 essential hypertensive patients, the rate constant of Na+ leak (ke) was 15.0 +/- 2.9 X 10(-3) h-1 (mean +/- SD). This was significantly higher than the ke in 47 normotensive controls (13.2 +/- 1.6 X 10(-3) h-1; t = 3.81, P less than 0.001; Mann-Whitney U rank sum test P = 0.0014). The relatively small number of patients studied was insufficient to decide if the hypertensive population was bimodally distributed. Nevertheless, if the upper end of the normotensive population is used as a cut-off point, it appears that a subgroup of 12 hypertensive patients had an increased Na+ leak, ke = 19.5 +/- 1.9 X 10(-3) h-1 (mean +/- SD). The increased Na+ leak remained constant in repeated determinations over several months. Na+ movements catalysed by the Na+-K+ co-transport and Na+-Li+ countertransport systems were measured in the above 52 hypertensive patients. Seventeen hypertensive patients showed a low apparent affinity of the co-transport system for internal Na+ and 12 exhibited a high maximal rate of Na+-Li+ countertransport. None of these two abnormalities was found in the 12 hypertensive patients with increased ke. We propose to denote them as Leak-(+) hypertensive patients. Passive net Na+ entry was abnormally high in all Leak-(+) hypertensive patients. However, erythrocyte Na+ content was increased in only five of the 12 Leak-(+) hypertensive patients. A normal or even decreased Na+ content was associated with the presence of compensatory increases in the maximal rate of the Na+-K+ pump and the Na+-K+ co-transport system.


Persistent infection of a glioma cell line generates a Theiler's virus variant which fails to induce demyelinating disease in SJL/J mice.
Theiler's murine encephalomyelitis virus (TMEV) induces demyelinating disease which is associated with persistent virus infection of the central nervous system. To study the interaction between TMEV and host cells, we infected the G26-20 glioma cell line in vitro, and this resulted in a lytic infection in which most, but not all, cells were killed. Surviving cells divided and formed a viable monolayer in which a small proportion of cells displayed viral cytopathic effects. Levels of virus produced by these cultures over a 6 month period fluctuated between 6 and 8 log10 p.f.u./ml as measured by viral plaque assay. Similarly, the percentage of cells producing both viral antigen and viral RNA, as measured by a simultaneous immunoperoxidase/in situ hybridization technique, varied between 5 and 30%. Although persistently infected cultures were susceptible to challenge by both vesicular stomatitis virus and herpes simplex virus, they were resistant to infection by homologous viruses. Interferon activity was not identified. TMEV isolated from passage 12 produced smaller plaques than wild-type Daniels strain virus (wt-DAV) on L-2 cell monolayers. In contrast to demyelination induced in SJL/J mice after intracerebral inoculation with wt-DAV, mice infected with the small plaque variant virus failed to develop viral persistence or chronic demyelination. However, following immunosuppression by total body irradiation, SJL/J mice infected with the small plaque variant developed viral persistence but no demyelination. Characterization of the biochemical and molecular determinants of the variant will lead to a better understanding of determinants important in viral persistence.


Towards non-invasive characterisation of coronary stent re-endothelialisation - An in-vitro, electrical impedance study.
The permanent implantation of a stent has become the most common method for ameliorating coronary artery narrowing arising from atherosclerosis. Following the procedure, optimal arterial wall healing is characterised by the complete regrowth of an Endothelial Cell monolayer over the exposed stent surface and surrounding tissue, thereby reducing the risk of thrombosis. However, excessive proliferation of Smooth Muscle Cells, within the artery wall can lead to unwanted renarrowing of the vessel lumen. Current imaging techniques are unable to adequately identify re-endothelialisation, and it has previously been reported that the stent itself could be used as an electrode in combination with electrical impedance spectroscopic techniques to monitor the post-stenting recovery phase. The utility of such a device will be determined by its ability to characterise between vascular cell types. Here we present in-vitro impedance spectroscopy measurements of pulmonary artery porcine Endothelial Cells, Human Umbilical Vein Endothelial Cells and coronary artery porcine Smooth Muscle Cells grown to confluence over platinum black electrodes in clinically relevant populations. These measurements were obtained, using a bespoke impedance spectroscopy system that autonomously performed impedance sweeps in the 1kHz to 100kHz frequency range. Analysis of the reactance component of impedance revealed distinct frequency dependent profiles for each cell type with post confluence reactance declines in Endothelial Cell populations that have not been previously reported. Such profiles provide a means of non-invasively characterising between the cell types and give an indication that impedance spectroscopic techniques may enable the non-invasive characterisation of the arterial response to stent placement.


The role of Abrams percutaneous pleural biopsy in the investigation of exudative pleural effusions.
Blind percutaneous pleural biopsy has traditionally been performed to investigate the etiology of exudative pleural effusion in which the initial thoracentesis has been nondiagnostic. In view of the increasing use of image-guided and thoracoscopic pleural biopsies, this study examines the role of blind Abrams pleural biopsy in the investigation of pleural effusion in a large urban hospital. Patients undergoing blind Abrams needle biopsy between January 1997 and 2003 were identified from the hospital pathology database. The case notes and pathology records of these patients were analyzed retrospectively. All patients had presented to respiratory teams with an exudative pleural effusion and had initial nondiagnostic thoracentesis. Seventy-five patients undergoing blind biopsy were identified. Pleural tissue was obtained in 59 biopsies (79%), with no statistically significant difference in pleural yield between respiratory specialist registrars (equivalent to pulmonary fellows in training) and senior house officers/preregistration house officers (equivalent to junior residents and interns, respectively) performing the biopsy (chi(2) test, p = 0.43). When up to three samples were obtained per episode, sufficient pleural tissue was obtained in 18 of 25 patients (72%) compared to 80% (32 of 40 patients) in whom four to six samples were taken (chi(2) test, p = 0.55 [not significant]). For all diagnoses, blind biopsy had a sensitivity of 38%, which rose to 43% when reviewing patients in whom sufficient pleural tissue was obtained (for malignant diagnosis alone, sensitivity values were 43% and 51%, respectively; specificity, 100%; negative and positive predictive values, 51%). No fatalities were reported, and pneumothorax was seen in eight patients (11%), with only two patients requiring specific intervention. Blind Abrams needle biopsy obtaining pleural tissue was diagnostic in approximately 50% of patients presenting with malignant effusion in the sample, and can be performed safely by all grades of medical staff with due attention to technique and supervision. The data support the continued use of the Abrams needle in the investigation of malignant pleural disease.


ANGY: A Rule-Based Expert System for Automatic Segmentation of Coronary Vessels From Digital Subtracted Angiograms.
This paper details the design and implementation of ANGY, a rule-based expert system in the domain of medical image processing. Given a subtracted digital angiogram of the chest, ANGY identifies and isolates the coronary vessels, while ignoring any nonvessel structures which may have arisen from noise, variations in background contrast, imperfect subtraction, and irrelevent anatomical detail. The overall system is modularized into three stages: the preprocessing stage and the two stages embodied in the expert itself. In the preprocessing stage, low-level image processing routines written in C are used to create a segmented representation of the input image. These routines are applied sequentially. The expert system is rule-based and is written in OPS5 and LISP. It is separated into two stages: The low-level image processing stage embodies a domain-independent knowledge of segmentation, grouping, and shape analysis. Working with both edges and regions, it determines such relations as parallel and adjacent and attempts to refine the segmentation begun by the preprocessing. The high-level medical stage embodies a domain-dependent knowledge of cardiac anatomy and physiology. Applying this knowledge to the objects and relations determined in the preceding two stages, it identifies those objects which are vessels and eliminates all others.


Clustering of equine grass sickness cases in the United Kingdom: a study considering the effect of position-dependent reporting on the space-time K-function.
Equine grass sickness (EGS) is a largely fatal, pasture-associated dysautonomia. Although the aetiology of this disease is unknown, there is increasing evidence that Clostridium botulinum type C plays an important role in this condition. The disease is widespread in the United Kingdom, with the highest incidence believed to occur in Scotland. EGS also shows strong seasonal variation (most cases are reported between April and July). Data from histologically confirmed cases of EGS from England and Wales in 1999 and 2000 were collected from UK veterinary diagnostic centres. The data did not represent a complete census of cases, and the proportion of all cases reported to the centres would have varied in space and, independently, in time. We consider the variable reporting of this condition and the appropriateness of the space-time K-function when exploring the spatial-temporal properties of a 'thinned' point process. We conclude that such position-dependent under-reporting of EGS does not invalidate the Monte Carlo test for space-time interaction, and find strong evidence for space time clustering of EGS cases (P < 0.001). This may be attributed to contagious or other spatially and temporally localized processes such as local climate and/or pasture management practices.


The green synthesis, characterization and evaluation of the biological activities of silver nanoparticles synthesized from Iresine herbstii leaf aqueous extracts.
Silver has been used since time immemorial in different chemical form to treat burns, wounds and several infections caused by pathogenic bacteria. Advancement of biological process of nanoparticles synthesis is evolving into a key area of nanotechnology. The current study deals with the synthesis, characterization of silver nanoparticles using Iresine herbstii and evaluation of their antibacterial, antioxidant and cytotoxic activity. The reaction mixture turned to brownish gray color after 7 days of incubation and exhibits an absorbance peak around 460 nm characteristic of Ag nanoparticle. Scanning electron microscopy (SEM) and EDX analysis showed silver nanoparticles were pure and polydispersed and the size were ranging from 44 to 64 nm. X-ray diffraction (XRD) studies revealed that most of the nanoparticles were cubic and face centered cubic in shape. Fourier transform infrared spectroscopy (FTIR) showed nanoparticles were capped with plant compounds. Biosynthesized silver nanoparticles showed potent antibacterial activity against human pathogenic bacteria. Phytosynthesized nanoparticles exhibited strong antioxidant activity as well as cytotoxicity against HeLa cervical cell lines. The approach of green synthesis seems to be cost efficient, eco-friendly and easy alternative to conventional methods of silver nanoparticles synthesis. The powerful bioactivity demonstrated by the synthesized silver nanoparticles leads towards the clinical use as antibacterial, antioxidant as well as cytotoxic agent.


Pheochromocytoma with inferior vena cava thrombosis: An unusual association.
Pheochromocytomas have been described in association with vascular abnormalities like renal artery stenosis. A 48-year-old man was admitted to our hospital with the complaints of headache, sweating, anxiety, dizziness, nausea, vomiting and hypertension. For last several days, he was having a dull aching abdominal pain. Abdominal computed tomography (CT) revealed the presence of a left adrenal pheochromocytoma. An inferior vena cava (IVC) venogram via the right jugular vein demonstrated occlusion of the IVC inferior to the right atrium. Surgical removal of pheochromocytoma was done, followed by anticoagulant treatment for IVC thrombosis, initially with subcutaneous low molecular weight heparin, and then with oral warfarin, resulting in restoration of patency. To the best of our knowledge, the occurrence of pheochromocytoma in IVC thrombosis has not been reported so far from India. Possible mechanisms of such an involvement are discussed.


Export of submicron particulate organic matter to mesopelagic depth in an oligotrophic gyre.
Sixty percent of the world ocean by area is contained in oligotrophic gyres [Longhurst A (1995) Prog Oceanog 36:77-16], the biomass of which is dominated by picophytoplankton, including cyanobacteria and picoeukaryotic algae, as well as picoheterotrophs. Despite their recognized importance in carbon cycling in the surface ocean, the role of small cells and their detrital remains in the transfer of particulate organic matter (POM) to the deep ocean remains disputed. Because oligotrophic marine conditions are projected to expand under current climate trends, a better understanding of the role of small particles in the global carbon cycle is a timely goal. Here we use the lipid profiles, radiocarbon, and stable carbon isotopic signatures of lipids from the North Pacific Subtropical Gyre to show that in the surface ocean, lipids from submicron POM (here called extra-small POM) are distinct from larger classes of suspended POM. Remarkably, this distinct extra-small POM signature dominates the total lipids collected at mesopelagic depth, suggesting that the lipid component of mesopelagic POM primarily contains the exported remains of small particles. Transfer of submicron material to mesopelagic depths in this location is consistent with model results that claim the biological origin of exported carbon should be proportional to the distribution of cell types in the surface community, irrespective of cell size [Richardson TL, Jackson GA (2007) Science 315:838-840]. Our data suggest that the submicron component of exported POM is an important contributor to the global biological pump, especially in oligotrophic waters.


Mechanistic phenotypes: an aggregative phenotyping strategy to identify disease mechanisms using GWAS data.
A single mutation can alter cellular and global homeostatic mechanisms and give rise to multiple clinical diseases. We hypothesized that these disease mechanisms could be identified using low minor allele frequency (MAF<0.1) non-synonymous SNPs (nsSNPs) associated with "mechanistic phenotypes", comprised of collections of related diagnoses. We studied two mechanistic phenotypes: (1) thrombosis, evaluated in a population of 1,655 African Americans; and (2) four groupings of cancer diagnoses, evaluated in 3,009 white European Americans. We tested associations between nsSNPs represented on GWAS platforms and mechanistic phenotypes ascertained from electronic medical records (EMRs), and sought enrichment in functional ontologies across the top-ranked associations. We used a two-step analytic approach whereby nsSNPs were first sorted by the strength of their association with a phenotype. We tested associations using two reverse genetic models and standard additive and recessive models. In the second step, we employed a hypothesis-free ontological enrichment analysis using the sorted nsSNPs to identify functional mechanisms underlying the diagnoses comprising the mechanistic phenotypes. The thrombosis phenotype was solely associated with ontologies related to blood coagulation (Fisher's p = 0.0001, FDR p = 0.03), driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse genetics models were enriched in DNA repair functions (p = 2×10-5, FDR p = 0.03) (POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L) while the additive model showed enrichment related to chromatid segregation (p = 4×10-6, FDR p = 0.005) (KIF25, PINX1). We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms.


Subtyping of non-small cell lung cancer by cytology specimens: A proposal for resource-poor hospitals.
Cancer diagnosis and treatment depend on pathology reports but naming a cancer is sometimes impossible without specialized techniques. We aimed to evaluate the sensitivity of cytological sub-classification of non-small cell lung carcinoma, not otherwise specified group (NSCLC-NOS) into Adenocarcinoma (AC) and Squamous cell carcinoma (SqCC) without using immunohistochemistry. Endobronchial ultrasound guided fine-needle aspiration biopsies and cytology slides diagnosed as NSCLC-NOS between 2004- 2008 were reviewed retrospectively. The final diagnosis was reached by immunohistochemistry (TTF-1, p63) when necessary. One hundred-twenty nine cases were retrieved. The final diagnoses were as follows: SqCC: 30.3%; AC: 65.7%; combined tumor (3 adenosquamous and 1 small cell + SqCC): 4%. Cytological diagnoses rendered were as follow: Definitely SqCC: 10.1%; favor SqCC: 14.1%; definitely AC: 38.4%; favor AC: 35.4%; NSCLC-NOS: 2%. The sensitivity and specificity of cytology were 86.3 and 87.5% for AC diagnosis respectively. Positive and negative predictive value of cytology was 95.3% and it was even 100% for well to moderately differentiated tumors. There was a tendency to sub-classify poorly differentiated SqCC as AC. Papanicolaou stain increased the diagnostic accuracy of SqCC. The combined tumor rate was 4% and after recognizing a tumor component, the second component was missed if the slide examination was terminated prematurely.


Propofol Exposure in Early Life Induced Developmental Impairments in the Mouse Cerebellum.
Propofol is a widely used anesthetic in the clinic while several studies have demonstrated that propofol exposure may cause neurotoxicity in the developing brain. However, the effects of early propofol exposure on cerebellar development are not well understood. Propofol (30 or 60 mg/kg) was administered to mice on postnatal day (P)7; Purkinje cell dendritogenesis and Bergmann glial cell development were evaluated on P8, and granule neuron migration was analyzed on P10. The results indicated that exposure to propofol on P7 resulted in a significant reduction in calbindin-labeled Purkinje cells and their dendrite length. Furthermore, propofol induced impairments in Bergmann glia development, which might be involved in the delay of granule neuron migration from the external granular layer (EGL) to the internal granular layer (IGL) during P8 to P10 at the 60 mg/kg dosage, but not at the 30 mg/kg dosage. Several reports have suggested that the Notch signaling pathway plays instructive roles in the morphogenesis of Bergmann glia. Here, it was revealed that propofol treatment decreased Jagged1 and Notch1 protein levels in the cerebellum on P8. Taken together, exposure to propofol during the neonatal period impairs Bergmann glia development and may therefore lead to cerebellum development defects. Our results may aid in the understanding of the neurotoxic effects of propofol when administrated to infants.


Considerations in developing and delivering a non-pharmacological intervention for symptom management in lung cancer: the views of health care professionals.
A respiratory distress symptom cluster has recently been identified in lung cancer associated with breathlessness, cough and fatigue, and the study reported here is part of a wider body of work being undertaken to develop a novel non-pharmacological intervention (NPI) for the management of this symptom cluster. The current paper reports the views of health care professionals (HCPs) involved with cancer care regarding the most appropriate ways of developing and delivering such a novel intervention. Five focus groups, supplemented with additional telephone interviews, were conducted with a range of both community- and acute-based HCPs involved in symptom management for lung cancer patients. Participants included oncologists, palliative care consultants, specialist nurses, occupational therapists and physiotherapists. The focus groups were transcribed verbatim and analysed using NVIVO to support a framework analysis approach. The current delivery of NPIs was found to be ad hoc and varied between sites both in terms of what was delivered and by which health care professionals. The provision of NPIs within acute medical settings faced common problems concerning staffing time and space, and there was a recognition that the preference of most patients to make as few hospital visits as possible also complicated NPI teaching. Moreover, there may only be a small window of opportunity in which to effectively teach lung cancer patients a novel NPI as the period between diagnosis and the onset of severe symptoms is often short. The participants agreed that the novel symptom management NPI should be individually personalised to the needs of each patient and be available for patients when they become receptive to it. Moreover, they agreed that the intervention would be most effective if delivered to patients individually rather than in groups, outside acute medical settings where possible and closer to patient's homes, should be delivered by an HCP rather than a trained volunteer or lay person and should involve informal carers wherever practicable.


The automaticity of face perception is influenced by familiarity.
In this study, we explore the automaticity of encoding for different facial characteristics and ask whether it is influenced by face familiarity. We used a matching task in which participants had to report whether the gender, identity, race, or expression of two briefly presented faces was the same or different. The task was made challenging by allowing nonrelevant dimensions to vary across trials. To test for automaticity, we compared performance on trials in which the task instruction was given at the beginning of the trial, with trials in which the task instruction was given at the end of the trial. As a strong criterion for automatic processing, we reasoned that if perception of a given characteristic (gender, race, identity, or emotion) is fully automatic, the timing of the instruction should not influence performance. We compared automaticity for the perception of familiar and unfamiliar faces. Performance with unfamiliar faces was higher for all tasks when the instruction was given at the beginning of the trial. However, we found a significant interaction between instruction and task with familiar faces. Accuracy of gender and identity judgments to familiar faces was the same regardless of whether the instruction was given before or after the trial, suggesting automatic processing of these properties. In contrast, there was an effect of instruction for judgments of expression and race to familiar faces. These results show that familiarity enhances the automatic processing of some types of facial information more than others.


Innovation and the English National Health Service: a qualitative study of the independent sector treatment centre programme.
Over the past two decades, an international trend of exposing public health services to different forms of economic organisation has emerged. In the English National Health Service (NHS), care is currently provided through a quasi-market including 'diverse' providers from the private and third sector. The predominant scheme through which private sector companies have been awarded NHS contracts is the Independent Sector Treatment Centre (ISTC) programme. ISTCs were designed to produce innovative models of service delivery for elective care and stimulate innovation among incumbent NHS providers. This paper investigates these claims using qualitative data on the impact of an ISTC upon a local health economy (LHE) composed of NHS organisations in England. Using the case of elective orthopaedic surgery, we conducted semi-structured interviews with senior managers from incumbent NHS providers and an ISTC in 2009. We show that ISTCs exhibit a different relationship with frontline clinicians because they counteract the power of professional communities associated with the NHS. This has positive and negative consequences for innovation. ISTCs have introduced new routines unencumbered by the extant norms of professional communities, but they appear to represent weaker learning environments and do not reproduce cooperation across organisational boundaries to the same extent as incumbent NHS providers.


Human glucose-6-phosphate dehydrogenase: the crystal structure reveals a structural NADP(+) molecule and provides insights into enzyme deficiency.
Glucose-6-phosphate dehydrogenase (G6PD) catalyses the first committed step in the pentose phosphate pathway; the generation of NADPH by this enzyme is essential for protection against oxidative stress. The human enzyme is in a dimer<-->tetramer equilibrium and its stability is dependent on NADP(+) concentration. G6PD deficiency results from many different point mutations in the X-linked gene encoding G6PD and is the most common human enzymopathy. Severe deficiency causes chronic non-spherocytic haemolytic anaemia; the usual symptoms are neonatal jaundice, favism and haemolytic anaemia. We have determined the first crystal structure of a human G6PD (the mutant Canton, Arg459-->Leu) at 3 A resolution. The tetramer is a dimer of dimers. Despite very similar dimer topology, there are two major differences from G6PD of Leuconostoc mesenteroides: a structural NADP(+) molecule, close to the dimer interface but integral to the subunit, is visible in all subunits of the human enzyme; and an intrasubunit disulphide bond tethers the otherwise disordered N-terminal segment. The few dimer-dimer contacts making the tetramer are charge-charge interactions. The importance of NADP(+) for stability is explained by the structural NADP(+) site, which is not conserved in prokaryotes. The structure shows that point mutations causing severe deficiency predominate close to the structural NADP(+) and the dimer interface, primarily affecting the stability of the molecule. They also indicate that a stable dimer is essential to retain activity in vivo. As there is an absolute requirement for some G6PD activity, residues essential for coenzyme or substrate binding are rarely modified.


A RAPD-PCR-based genetic diversity analysis of Helicoverpa armigera and H. zea populations in Brazil.
Helicoverpa armigera is the most significant pest of agriculture in Asia, Europe, Africa, and Australasia, causing damage to crops greater than US$2 billion annually and until 2013 it was not detected in Brazil. Helicoverpa zea is restricted to the American continent and is important to corn and a secondary pest of cotton and tomatoes. The wide range of crops exploited by H. armigera (mainly cotton, soybeans, chickpea, and corn), the possible mating between these species can promote population shifts, that could be assessed by RAPD-PCR technique. Therefore, the aim of this study was to determine the genetic diversity of H. armigera and H. zea populations by RAPD-PCR analysis. The most important result was the clustering of one H. armigera population in a group predominantly formed by H. zea. It could indicate a possible occurrence of an interspecific cross between these species. This is a concern to Brazilian agriculture due to the possibility of selection of hybrids well adapted to the American environment, which would be inherited from H. zea. The other noxious fact is the possible development of new biotypes resistant to insectides or Bt toxins expressed in transgenic crops, came from H. armigera gene pool.


Effects of nitric oxide on notexin-induced muscle inflammatory responses.
Excessive inflammatory response may delay the regeneration and damage the normal muscle fibers upon myoinjury. It would be important to be able to attenuate the inflammatory response and decrease inflammatory cells infiltration in order to improve muscle regeneration formation, resulting in better muscle functional recovery after myoinjury. This study was undertaken to explore the role of Nitric oxide (NO) during skeletal muscle inflammatory process, using a mouse model of Notexin induced myoinjury. Intramuscular injection (tibialis anterior, TA) of Notexin was performed for preparing mice myoinjury. NO synthase inhibitor (L-NAME) or NO donor (SNP) was intraperitoneally injected into model mice. On day 4 and 7 post-injury, expression of muscle-autoantigens and toll-like receptors (TLRs) was evaluated from muscle tissue by qRT-PCR and Western Blot; the intramuscular infiltration of monocytes/macrophage (CD11b(+) or F4/80(+) cells), CD8(+) T cell (CD3ε(+)CD8α(+)), apoptotic cell (CD11b(+)caspase3(+)), and MHC-I molecule H-2K(b)-expressing myofibers in damaged muscle were assessed by imunoflourecence analysis; the mRNAs expression of cytokines and chemokines associated with the preferential biological role during the muscle damage-induced inflammation response, were assessed by qRT-PCR. We detected the reduced monocytes/macrophages infiltration, and increased apoptotic cells in the damaged muscle treated with SNP comparing to untreatment. As well, SNP treatment down-regulated mRNA and protein levels of muscle autoantigens, TLR3, and mRNA levels of TNF-α, IL-6, MCP-1, MCP-3, and MIP-1α in damaged muscle. On the contrary, L-NAME induced more severe intramuscular infiltration of inflammatory cells, and mRNA level elevation of the above inflammatory mediators. Notably, we observed an increased number of MHC-I (H2-K(b)) positive new myofibers, and of the infiltrated CD8(+) T cells in damaged muscle at the day 7 after L-NAME treatment. The result herein shows that, NO can act as an endogenous anti-inflammatory molecule during the ongoing muscle inflammation. Our finding may provide new insight to optimize NO-based therapies for improving muscle regeneration after myoinjury.


Speech breathing in children and adolescents.
An investigation was conducted to elucidate the nature of speech breathing in children and adolescents and to determine if sex and age influence performance. Eighty healthy boys and girls representing four age groups (7, 10, 13, and 16 years) were studied using helium dilution to obtain measures of subdivisions of the lung volume and using magnetometers to obtain measures of resting tidal breathing and speech breathing. Results for subdivisions of the lung volume and resting tidal breathing revealed sex- and age-related differences, most of which were attributable to differences in breathing apparatus size. Results for speech breathing indicated that sex was not an important variable, but that age was critical in determining speech breathing performance. The most substantial differences were between the 7-year-old group and older groups. These differences were characterized by larger lung volume, rib cage volume, and abdominal volume initiations and terminations for breath groups, larger lung volume excursions per breath group, fewer numbers of syllables per breath group, and larger lung volume expenditures per syllable for the 7-year-old group compared to older groups. In most respects, speech breathing appeared adultlike by the end of the first decade of life. Clinical implications regarding these findings are offered.


Influence of supramarginal resection on survival outcomes after gross-total resection of IDH-wild-type glioblastoma.
The authors' goal was to use a multicenter, observational cohort study to determine whether supramarginal resection (SMR) of FLAIR-hyperintense tumor beyond the contrast-enhanced (CE) area influences the overall survival (OS) of patients with isocitrate dehydrogenase-wild-type (IDH-wt) glioblastoma after gross-total resection (GTR). The medical records of 888 patients aged ≥ 18 years who underwent resection of GBM between January 2011 and December 2017 were reviewed. Volumetric measurements of the CE tumor and surrounding FLAIR-hyperintense tumor were performed, clinical variables were obtained, and associations with OS were analyzed. In total, 101 patients with newly diagnosed IDH-wt GBM who underwent GTR of the CE tumor met the inclusion criteria. In multivariate analysis, age ≥ 65 years (HR 1.97; 95% CI 1.01-2.56; p < 0.001) and contact with the lateral ventricles (HR 1.59; 95% CI 1.13-1.78; p = 0.025) were associated with shorter OS, but preoperative Karnofsky Performance Status ≥ 70 (HR 0.47; 95% CI 0.27-0.89; p = 0.006), MGMT promotor methylation (HR 0.63; 95% CI 0.52-0.99; p = 0.044), and increased percentage of SMR (HR 0.99; 95% CI 0.98-0.99; p = 0.02) were associated with longer OS. Finally, 20% SMR was the minimum percentage associated with beneficial OS (HR 0.56; 95% CI 0.35-0.89; p = 0.01), but > 60% SMR had no significant influence (HR 0.74; 95% CI 0.45-1.21; p = 0.234). SMR is associated with improved OS in patients with IDH-wt GBM who undergo GTR of CE tumor. At least 20% SMR of the CE tumor was associated with beneficial OS, but greater than 60% SMR had no significant influence on OS.


Supplementation of vitamin C reduces blood glucose and improves glycosylated hemoglobin in type 2 diabetes mellitus: a randomized, double-blind study.
No study has ever examined the effect of vitamin C with metformin on fasting (FBS) and postmeal blood glucose (PMBG) as well as glycosylated hemoglobin (HbA1c) in the treatment of type 2 diabetes mellitus (DM). The goal was to examine the effect of oral vitamin C with metformin on FBS, PMBG, HbA1c, and plasma ascorbic acid level (PAA) with type 2 DM. Seventy patients with type 2 DM participated in a prospective, double-blind, placebo-controlled, 12-week study. The patients with type 2 DM were divided randomly into placebo and vitamin C group of 35 each. Both groups received the treatment for twelve weeks. Decreased PAA levels were found in patients with type 2 diabetes mellitus. This level was reversed significantly after treatment with vitamin C along with metformin compared to placebo with metformin. FBS, PMBG, and HbA1c levels showed significant improvement after 12 weeks of treatment with vitamin C. In conclusion, oral supplementation of vitamin C with metformin reverses ascorbic acid levels, reduces FBS, PMBG, and improves HbA1c. Hence, both the drugs in combination may be used in the treatment of type 2 DM to maintain good glycemic control.


Home-Based Care Program Reduces Disability And Promotes Aging In Place.
The Community Aging in Place, Advancing Better Living for Elders (CAPABLE) program, funded by the Center for Medicare and Medicaid Innovation, aims to reduce the impact of disability among low-income older adults by addressing individual capacities and the home environment. The program, described in this innovation profile, uses an interprofessional team (an occupational therapist, a registered nurse, and a handyman) to help participants achieve goals they set. For example, it provides assistive devices and makes home repairs and modifications that enable participants to navigate their homes more easily and safely. In the period 2012-15, a demonstration project enrolled 281 adults ages sixty-five and older who were dually eligible for Medicare and Medicaid and who had difficulty performing activities of daily living (ADLs). After completing the five-month program, 75 percent of participants had improved their performance of ADLs. Participants had difficulty with an average of 3.9 out of 8.0 ADLs at baseline, compared to 2.0 after five months. Symptoms of depression and the ability to perform instrumental ADLs such as shopping and managing medications also improved. Health systems are testing CAPABLE on a larger scale. The program has the potential to improve older adults' ability to age in place.


How is rating of perceived capacity related to VO2max and what is VO2max at onset of training?
To evaluate how rating of perceived capacity (RPC) is related to maximal oxygen uptake (VO2max) and examine VO2max at onset of training in healthy adults. In total, 125 newly registered fitness centre members, equally men and women, answered the RPC scale and performed a treadmill test for measurement of VO2max. Eligible criteria were <4 weeks of fitness centre membership, physically inactive, ≥18 years and not pregnant. The RPC is a one-page scale (1-20) based on metabolic equivalent tasks, where the individual chooses the most strenuous activity that can be sustained for at least 30 min. The Bland-Altman plot demonstrated a tendency of overestimation, meaning that the participants ranked their own aerobic capacity 17.5% higher than objectively measured values of VO2max. The mean difference between the two methods were +4.92±1.96 and +6.35±1.96 mL/min/kg VO2 in men and women, respectively. The Pearson correlation coefficient was moderate, with r=0.426 (p<0.01). A linear regression analysis showed that both age and VO2max were significant predictors of RPC (p<0.01). Measured VO2max at onset of fitness centre membership was in men aged 38.7±11.7 and women aged 34.7±9.9, 40.5±7.2 and 35.0±6.0 mL/min/kg, respectively. Estimated VO2max from the RPC scale was 45.7±9.8 and 41.4±10.1 mL/min/kg in men and women, respectively. The RPC seems less accurate at the individual level and may overestimate VO2max. Still, it may be considered useful in large-scale studies.


Do children with autism fail to process information in context?
This research investigated the proposal that children with autism are impaired in processing information in its context. To date, this proposal rests almost exclusively on evidence from verbal tasks. Given evidence of visuo-spatial proficiency in autism in other areas of functioning, it is possible that the ability to use context is spared in the visual domain but impaired in the verbal domain. Fifteen children with autism and 16 age and IQ-matched typically developing children were tested on their ability to take account of visual context information (Experiment 1) and verbal context information (Experiment 2) using an adaptation of Palmer's (1975) visual context task. They were also given an adaptation of Tager-Flusberg's (1991) visual and verbal semantic memory task (Experiment 3) and Frith and Snowling's (1983) homograph task (Experiment 4). Experiment 1 showed that children with autism were facilitated by the provision of visual context information. Experiments 2 and 3 showed that the same children were also able to use both verbal context information when identifying words and semantic category information in a verbal task when naming and recalling words. However, in Experiment 4 these children had difficulties with a sentence-processing task when using sentence context to disambiguate homographs. These findings demonstrate that children with autism do not have a general difficulty in connecting context information and item information as predicted by weak central coherence theory. Instead the results suggest that there is specific difficulty with complex verbal stimuli and in particular with using sentence context to disambiguate meaning.


A dose escalation study of paclitaxel and carboplatin in untreated Japanese patients with advanced non-small cell lung cancer.
The combination of paclitaxel (225 mg/m(2), 3-h infusion) and carboplatin (area under the curve 6) is widely used for non-small cell lung cancer in the USA. In Japan, however, the recommended dose for single-use paclitaxel in 3-h infusion is 210 mg/m(2) and the optimal dose of this agent in combination with carboplatin has not been established. This dose escalation study was designed to determine the maximum tolerated dose of paclitaxel in 3-h infusion plus carboplatin at a fixed dose of area under the curve 6 for Japanese patients with advanced, untreated non-small cell lung cancer. Between October 1999 and May 2000, 19 patients were enrolled and 18 of these patients were evaluable for toxicity. Chemotherapy consisted of carboplatin area under the curve 6 and an escalated dose of paclitaxel on day 1 every 3-4 weeks. The initial dose of paclitaxel was 175 mg/m(2) and was increased by 25 mg/m(2) at each dose level. Neutropenia was the major toxicity observed, but was not dose related. Febrile neutropenia was not observed. No grade 3 or more peripheral neuropathy, myalgia or arthralgia was reported. The maximum tolerated dose was not determined even at the highest paclitaxel dose level (225 mg/m(2)) in this study. Partial responses were observed in six of the 19 patients (31.6%). We conclude that paclitaxel at 225 mg/m(2) in 3-h infusion and carboplatin area under the curve 6 can safely be given to Japanese patients with non-small cell lung cancer.


Non-clinical studies of progesterone.
Progesterone is a steroid hormone that is essential for the regulation of reproductive function. Progesterone has been approved for several indications including the treatment of anovulatory menstrual cycles, assisted reproductive technology, contraception during lactation and, when combined with estrogen, for the prevention of endometrial hyperplasia in postmenopausal hormonal therapy. In addition to its role in reproduction, progesterone regulates a number of biologically distinct processes in other tissues, particularly in the nervous system. This physiological hormone is poorly absorbed when administered in a crystalline form and is not active when given orally, unless in micronized form, or from different non-oral delivery systems that allow a more constant delivery rate. A limited number of preclinical studies have been conducted to document the toxicity, carcinogenicity and overall animal safety of progesterone delivered from different formulations, and these rather old studies showed no safety concern. More recently, it has been shown in animal experiments that progesterone, its metabolite allopregnanolone and structurally related progestins have positive effects on neuroregeneration and repair of brain damage, as well as myelin repair. These recent preclinical findings have the potential to accelerate therapeutic translation for multiple unmet neurological needs.


Reciprocal transplantation of the heterotrophic coral Tubastraea coccinea (Scleractinia: Dendrophylliidae) between distinct habitats did not alter its venom toxin composition.
Tubastraea coccinea is an azooxanthellate coral species recorded in the Indian and Atlantic oceans and is presently widespread in the southwestern Atlantic with an alien status for Brazil. T. coccinea outcompete other native coral species by using a varied repertoire of biological traits. For example, T. coccinea has evolved potent venom capable of immobilizing and digesting zooplankton prey. Diversification and modification of venom toxins can provide potential adaptive benefits to individual fitness, yet acquired alteration of venom composition in cnidarians is poorly understood as the adaptive flexibility affecting toxin composition in these ancient lineages has been largely ignored. We used quantitative high-throughput proteomics to detect changes in toxin expression in clonal fragments of specimens collected and interchanged from two environmentally distinct and geographically separate study sites. Unexpectedly, despite global changes in protein expression, there were no changes in the composition and abundance of toxins from coral fragments recovered from either site, and following clonal transplantation between sites. There were also no apparent changes to the cnidome (cnidae) and gross skeletal or soft tissue morphologies of the specimens. These results suggest that the conserved toxin complexity of T. coccinea co-evolved with innovation of the venom delivery system, and its morphological development and phenotypic expression are not modulated by habitat pressures over short periods of time. The adaptive response of the venom trait to specific predatory regimes, however, necessitates further consideration.


Novel pyrrolobenzodiazepine benzofused hybrid molecules inhibit NF-κB activity and synergise with bortezomib and ibrutinib in hematological cancers.
Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are incurable hematological malignancies that are pathologically linked with aberrant NF-κB activation. In this study, we identified a group of novel C8-linked benzofused Pyrrolo[2,1-c][1,4]benzodiazepines (PBD) monomeric hybrids capable of sequence-selective inhibition of NF-κB with low nanomolar LD50 values in CLL (n=46) and MM cell lines (n=5). The lead compound, DC-1-192, significantly inhibited NF-κB DNA binding after just 4h exposure and demonstrating inhibitory effects on both canonical and non-canonical NF-κB subunits. In primary CLL cells, sensitivity to DC-1-192 was inversely correlated with RelA subunit expression (r2=0.2) and samples with BIRC3 or NOTCH1 mutations showed increased sensitivity (P=0.001). RNA-sequencing and gene set enrichment analysis confirmed the over-representation of NF-κB regulated genes in the down-regulated gene list. Furthermore, In vivo efficacy studies in NOD/SCID mice, using a systemic RPMI 8226 human multiple myeloma xenograft model, showed that DC-1-192 significantly prolonged survival (P=0.017). In addition, DC1-192 showed synergy with bortezomib and ibrutinib; synergy with ibrutinib was enhanced when CLL cells were co-cultured on CD40L-expressing fibroblasts in order to mimic the cytoprotective lymph node microenvironment (P = 0.01). Given that NF-κB plays a role in both bortezomib and ibrutinib resistance mechanisms, these data provide a strong rationale for the use of DC-1-192 in the treatment of NF-κB-driven cancers, particularly in the context of relapsed/refractory disease.


Disentangling Alzheimer's disease neurodegeneration from typical brain ageing using machine learning.
Neuroimaging biomarkers that distinguish between changes due to typical brain ageing and Alzheimer's disease are valuable for determining how much each contributes to cognitive decline. Supervised machine learning models can derive multivariate patterns of brain change related to the two processes, including the Spatial Patterns of Atrophy for Recognition of Alzheimer's Disease (SPARE-AD) and of Brain Aging (SPARE-BA) scores investigated herein. However, the substantial overlap between brain regions affected in the two processes confounds measuring them independently. We present a methodology, and associated results, towards disentangling the two. T1-weighted MRI scans of 4054 participants (48-95 years) with Alzheimer's disease, mild cognitive impairment (MCI), or cognitively normal (CN) diagnoses from the Imaging-based coordinate SysTem for AGIng and NeurodeGenerative diseases (iSTAGING) consortium were analysed. Multiple sets of SPARE scores were investigated, in order to probe imaging signatures of certain clinically or molecularly defined sub-cohorts. First, a subset of clinical Alzheimer's disease patients (n = 718) and age- and sex-matched CN adults (n = 718) were selected based purely on clinical diagnoses to train SPARE-BA1 (regression of age using CN individuals) and SPARE-AD1 (classification of CN versus Alzheimer's disease) models. Second, analogous groups were selected based on clinical and molecular markers to train SPARE-BA2 and SPARE-AD2 models: amyloid-positive Alzheimer's disease continuum group (n = 718; consisting of amyloid-positive Alzheimer's disease, amyloid-positive MCI, amyloid- and tau-positive CN individuals) and amyloid-negative CN group (n = 718). Finally, the combined group of the Alzheimer's disease continuum and amyloid-negative CN individuals was used to train SPARE-BA3 model, with the intention to estimate brain age regardless of Alzheimer's disease-related brain changes. The disentangled SPARE models, SPARE-AD2 and SPARE-BA3, derived brain patterns that were more specific to the two types of brain changes. The correlation between the SPARE-BA Gap (SPARE-BA minus chronological age) and SPARE-AD was significantly reduced after the decoupling (r = 0.56-0.06). The correlation of disentangled SPARE-AD was non-inferior to amyloid- and tau-related measurements and to the number of APOE ε4 alleles but was lower to Alzheimer's disease-related psychometric test scores, suggesting the contribution of advanced brain ageing to the latter. The disentangled SPARE-BA was consistently less correlated with Alzheimer's disease-related clinical, molecular and genetic variables. By employing conservative molecular diagnoses and introducing Alzheimer's disease continuum cases to the SPARE-BA model training, we achieved more dissociable neuroanatomical biomarkers of typical brain ageing and Alzheimer's disease.


Wideband optical sensing using pulse interferometry.
Advances in fabrication of high-finesse optical resonators hold promise for the development of miniaturized, ultra-sensitive, wide-band optical sensors, based on resonance-shift detection. Many potential applications are foreseen for such sensors, among them highly sensitive detection in ultrasound and optoacoustic imaging. Traditionally, sensor interrogation is performed by tuning a narrow linewidth laser to the resonance wavelength. Despite the ubiquity of this method, its use has been mostly limited to lab conditions due to its vulnerability to environmental factors and the difficulty of multiplexing - a key factor in imaging applications. In this paper, we develop a new optical-resonator interrogation scheme based on wideband pulse interferometry, potentially capable of achieving high stability against environmental conditions without compromising sensitivity. Additionally, the method can enable multiplexing several sensors. The unique properties of the pulse-interferometry interrogation approach are studied theoretically and experimentally. Methods for noise reduction in the proposed scheme are presented and experimentally demonstrated, while the overall performance is validated for broadband optical detection of ultrasonic fields. The achieved sensitivity is equivalent to the theoretical limit of a 6 MHz narrow-line width laser, which is 40 times higher than what can be usually achieved by incoherent interferometry for the same optical resonator.


Manipulation of the potassium channel Kv1.1 and its effect on neuronal excitability in rat sensory neurons.
Potassium channels play a critical role in regulating many aspects of action potential (AP) firing. To establish the contribution of the voltage-dependent potassium channel Kv1.1 in regulating excitability, we used the selective blocker dendrotoxin-K (DTX-K) and small interfering RNA (siRNA) targeted to Kv1.1 to determine their effects on AP firing in small-diameter capsaicin-sensitive sensory neurons. A 5-min exposure to 10 nM DTX-K suppressed the total potassium current (I(K)) measured at +40 mV by about 33%. DTX-K produced a twofold increase in the number of APs evoked by a ramp of depolarizing current. Associated with increased firing was a decrease in firing threshold and rheobase. DTX-K did not alter the resting membrane potential or the AP duration. A 48-h treatment with siRNA targeted to Kv1.1 reduced the expression of this channel protein by about 60% as measured in Western blots. After treatment with siRNA, I(K) was no longer sensitive to DTX-K, indicating a loss of functional protein. Similarly, after siRNA treatment exposure to DTX-K had no effect on the number of evoked APs, firing threshold, or rheobase. However, after siRNA treatment, the firing threshold had values similar to those obtained after acute exposure to DTX-K, suggesting that the loss of Kv1.1 plays a critical role in setting this parameter of excitability. These results demonstrate that Kv1.1 plays an important role in limiting AP firing and that siRNA may be a useful approach to establish the role of specific ion channels in the absence of selective antagonists.


A Randomized, Placebo-Controlled Trial of Ibuprofen Plus Metaxalone, Tizanidine, or Baclofen for Acute Low Back Pain.
Patients with low back pain are often treated with nonsteroidal anti-inflammatory drugs and skeletal muscle relaxants. We compare functional outcomes and pain among patients with acute low back pain who were randomized to a 1-week course of ibuprofen plus placebo versus ibuprofen plus 1 of 3 skeletal muscle relaxants: baclofen, metaxalone, and tizanidine. This was a randomized, double-blind, parallel-group, 4-arm study conducted in 2 urban emergency departments (EDs). Patients with nonradicular low back pain for less than or equal to 2 weeks were eligible if they had a score greater than 5 on the Roland-Morris Disability Questionnaire, a 24-item inventory of functional impairment caused by low back pain. All participants received 21 tablets of ibuprofen 600 mg, to be taken 3 times a day as needed. Additionally, they were randomized to baclofen 10 mg, metaxalone 400 mg, tizanidine 2 mg, or placebo. Participants were instructed to take 1 or 2 of these capsules 3 times a day as needed. All participants received a 10-minute educational session. The primary outcome was improvement on the Roland-Morris Disability Questionnaire between ED discharge and 1week later. Secondary outcomes included pain intensity 1 week after ED discharge (severe, moderate, mild, or none). Three hundred twenty patients were randomized. One week later, the mean Roland-Morris Disability Questionnaire score of patients randomized to placebo improved by 11.1 points (95% confidence interval [CI] 9.0 to 13.3), baclofen by 10.6 points (95% CI 8.6 to 12.7), metaxalone by 10.1 points (95% CI 8.0 to 12.3), and tizanidine by 11.2 points (95% CI 9.2 to 13.2). At 1-week follow-up, 30% of placebo patients (95% CI 21% to 41%) reported moderate to severe low back pain versus 33% of baclofen patients (95% CI 24% to 44%), 37% of metaxalone patients (95% CI 27% to 48%), and 33% of tizanidine patients (95% CI 23% to 44%). Adding baclofen, metaxalone, or tizanidine to ibuprofen does not appear to improve functioning or pain any more than placebo plus ibuprofen by 1 week after an ED visit for acute low back pain.


Optical absorption and magnetic circular dichroism spectra of thiouracils: a quantum mechanical study in solution.
The excited electronic states of 2-thiouracil, 4-thiouracil and 2,4-dithiouracil, the analogues of uracil where the carbonyl oxygens are substituted by sulphur atoms, have been investigated by computing the magnetic circular dichroism (MCD) and one-photon absorption (OPA) spectra at the time-dependent density functional theory level. Special attention has been paid to solvent effects, included by a mixed discrete/continuum model, and to determining how our results depend on the adopted DFT functional (CAM-B3LYP and B3LYP). Whereas including solvent effects does not dramatically impact the MCD and OPA spectra, though improving the agreement with the experimental spectra, the performances of CAM-B3LYP and B3LYP are remarkably different. CAM-B3LYP captures well the effect of thionation on the uracil excited states and provides spectra in good agreement with the experiments, whereas B3LYP shows some deficiency in describing 2-TU and 2,4-DTU spectra, despite being more accurate than CAM-B3LYP for 4-TU.


Characterization of lipoteichoic acid binding to polymorphonuclear leukocytes of human blood.
Human polymorphonuclear leukocytes (PMN) were shown to possess specific binding sites for lipoteichoic acid (LTA). LTA binding was reversible and time and temperature dependent. Scatchard plot analysis revealed an apparently single population of 6.6 X 10(6) LTA binding sites per PMN with a dissociation constant of 5.6 microM. Attachment of an avirulent, unencapsulated, M-negative strain of group A streptococci to PMN was inhibited by LTA, but not by other bacterial somatic antigens tested. Occupation of 30% of the LTA binding sites resulted in greater than 70% inhibition of streptococcal attachment to PMN. In contrast, LTA failed to block attachment of Escherichia coli or antibody-coated streptococci, indicating that binding sites for E. coli and the Fc portion of immunoglobulin G are distinct from those for LTA. Immunofluorescent studies demonstrated that LTA remained uniformly bound to PMN membranes for as long as 2 h at 37 degrees C. Cross-linking of PMN-bound LTA with anti-LTA resulted in rapid capping of LTA receptor sites. The results suggest that LTA is a monovalent ligand interacting with mobile receptors in the plasma membrane of PMN.


A comprehensive database of quality-rated fossil ages for Sahul's Quaternary vertebrates.
The study of palaeo-chronologies using fossil data provides evidence for past ecological and evolutionary processes, and is therefore useful for predicting patterns and impacts of future environmental change. However, the robustness of inferences made from fossil ages relies heavily on both the quantity and quality of available data. We compiled Quaternary non-human vertebrate fossil ages from Sahul published up to 2013. This, the FosSahul database, includes 9,302 fossil records from 363 deposits, for a total of 478 species within 215 genera, of which 27 are from extinct and extant megafaunal species (2,559 records). We also provide a rating of reliability of individual absolute age based on the dating protocols and association between the dated materials and the fossil remains. Our proposed rating system identified 2,422 records with high-quality ages (i.e., a reduction of 74%). There are many applications of the database, including disentangling the confounding influences of hypothetical extinction drivers, better spatial distribution estimates of species relative to palaeo-climates, and potentially identifying new areas for fossil discovery.


Tuberculosis of pancreas, the first case reported from Qatar.
Despite the high prevalence of tuberculosis (TB) in developing countries, primary pancreatic TB is a rare entity. We present a case of pancreatic TB in an immunocompetent patient who was found to have pancreatic mass resembling malignancy. A 40-year-old Indian male presented to the medical emergency room with complaints of abdominal pain and fever for 2 weeks' duration. He had a history of unintentional weight loss of about 20 pounds in the past 2 months. There was no significant history of exposure to TB patient. Family history was unremarkable for any malignancy. On examination, the significant finding was epigastric tenderness. He was thoroughly investigated, his purified protein derivative and QuantiFERON were negative. Chest X-ray was unremarkable. Computed tomography scan abdomen was performed that revealed large heterogenous necrotic mass in the lesser sac likely arising from pancreatic body with possible infiltration of the stomach, left lobe of the liver and encasing celiac vessels and portal vein with multiple peripancreatic and retroperitoneal necrotic lymph nodes. Endoscopic ultrasound with fine-needle aspiration of pancreatic mass was done, biopsy specimen revealed the presence of inflammation with no evidence of malignancy. TB polymerase chain reaction and culture came positive for Mycobacterium tuberculosis. He was started on antituberculosis treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol with a plan to continue for total 6 months. However, follow-up of the patient could not be done as he traveled back to his home country.