Interocular suppression in normal and amblyopic vision:spatio-temporal properties

We measured the properties of interocular suppression in strabismic amblyopes and compared these to dichoptic masking in binocularly normal observers. We used a dichoptic version of the well-established probed-sinewave paradigm that measured sensitivity to a brief target stimulus (one of four letters to be discriminated) in the amblyopic eye at different times relative to a suppression-inducing mask in the fixing eye. This was done using both sinusoidal steady state and transient approaches. The suppression-inducing masks were either modulations of luminance or contrast (full field, just overlaying the target, or just surrounding the target). Our results were interpreted using a descriptive model that included contrast gain control and spatio-temporal filtering prior to excitatory binocular combination. The suppression we measured, other than in magnitude, was not fundamentally different from normal dichoptic masking: lowpass spatio-temporal properties with similar contributions from both surround and overlay suppression

A Selberg integral for the Lie algebra A_n

A new q-binomial theorem for Macdonald polynomials is employed to prove an A_n analogue of the celebrated Selberg integral. This confirms the g=A_n case of a conjecture by Mukhin and Varchenko concerning the existence of a Selberg integral for every simple Lie algebra g.Comment: 32 page

Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS): literature review and case series report

Background: “Neuroleptic malignant syndrome” (NMS) is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. <p/>Aims: To identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. <p/>Methodology: A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. <p/>Results: 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7mg/day during days 1-15 to 346.9mg/day during days 16-30) and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. <p/>Conclusions: Rapid dose escalation occurred in less than half of this case series (n=5, 38.5%), although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS

Mapping Health Literacy Research in the European Union: A Bibliometric Analysis

Background: To examine and compare the research productivity on selected fields related to health literacy of the curren

Early and Middle Holocene Hunter-Gatherer Occupations in Western Amazonia: The Hidden Shell Middens

We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region's past and offers a new context within which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged. © 2013 Lombardo et al

Discovery of 4,6-bis(2-((E)-benzylidene)hydrazinyl)pyrimidin-2-Amine with antibiotic activity

Robenidine (E)-N'-((E)-1-(4-chlorophenyl)ethylidene)-2-(1-(4-chlorophenyl)ethylidene)hydrazine-1-carboximidhydrazide displays methicillin-resistant Staphyoccoccus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) MICs of 2 μg mL-1. Herein we describe the structure-activity relationship development of a novel series of guanidine to 2-aminopyrimidine isosteres that ameliorate the low levels of mammalian cytotoxicity in the lead compound while retaining good antibiotic activity. Removal of the 2-NH2 pyrimidine moiety renders these analogues inactive. Introduction of a central 2-NH2 triazine moiety saw a 10-fold activity reduction. Phenyl to cyclohexyl isosteres were inactive. The 4-BrPh and 4-CH3Ph with MIC values of 2 and 4 μg mL-1, against MRSA and VRE respectively, are promising candidates for future development.Cecilia C. Russe, Andrew Stevens, Kelly A. Young, Jennifer R. Baker ... Manouchehr Khazandi ... Abiodun Ogunniyi ... et al

Stakeholder perspectives on the importance of water quality and other constraints for sustainable mariculture

Aquaculture, including marine aquaculture (mariculture), is the fastest growing food production sector globally and is expected to play a key role in delivering future food security. A potential factor limiting growth of the aquaculture industry, however, is the maintenance of good water quality, on which all forms of aquaculture depend. This is particularly challenging in ‘open’ coastal and estuarine systems and requires engagement with a wide range of stakeholders that can influence water quality. We applied a semi-quantitative method (Q-method) to capture and evaluate perspectives across diverse stakeholders in order to address the overarching question: “How do stakeholders rank water quality issues and management options versus other issues and actions for ensuring the sustainability of shellfish mariculture in South West England?” Results from this regional case study were used to highlight key issues and knowledge gaps that have national and international relevance. Stakeholders were found to hold distinct perspectives (P1−3), but there was general consensus that good water quality is essential for sustainable aquaculture, and that there is a need for better understanding of spatial and temporal variations in land use throughout catchments to ensure effective water quality management. Stakeholder engagement highlighted the importance of managing anthropogenic and environmental (climatic) pressures on land and water through agri-environment and urban planning policy in order to ensure sustainable food production, including from mariculture

In vitro activity of robenidine Analog NCL195 in combination with outer membrane permeabilizers against gram-negative bacterial pathogens and impact on systemic gram-positive bacterial infection in mice

Multidrug-resistant (MDR) pathogens, particularly the ESKAPE group (Enterococcus faecalis/faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter spp.), have become a public health threat worldwide. Development of new antimicrobial classes and the use of drugs in combination are potential strategies to treat MDR ESKAPE pathogen infections and promote optimal antimicrobial stewardship. Here, the in vitro antimicrobial activity of robenidine analog NCL195 alone or in combination with different concentrations of three outer membrane permeabilizers [ethylenediaminetetraacetic acid (EDTA), polymyxin B nonapeptide (PMBN), and polymyxin B (PMB)] was further evaluated against clinical isolates and reference strains of key Gram-negative bacteria. NCL195 alone was bactericidal against Neisseria meningitidis and Neisseria gonorrhoeae (MIC/MBC = 32 μg/mL) and demonstrated synergistic activity against P. aeruginosa, E. coli, K. pneumoniae, and Enterobacter spp. strains in the presence of subinhibitory concentrations of EDTA, PMBN, or PMB. The additive and/or synergistic effects of NCL195 in combination with EDTA, PMBN, or PMB are promising developments for a new chemical class scaffold to treat Gram-negative infections. Tokuyasu cryo ultramicrotomy was used to visualize the effect of NCL195 on bioluminescent S. aureus membrane morphology. Additionally, NCL195's favorable pharmacokinetic and pharmacodynamic profile was further explored in in vivo safety studies in mice and preliminary efficacy studies against Gram-positive bacteria. Mice administered two doses of NCL195 (50 mg/kg) by the intraperitoneal (IP) route 4 h apart showed no adverse clinical effects and no observable histological effects in major organs. In bioluminescent Streptococcus pneumoniae and S. aureus murine sepsis challenge models, mice that received two 50 mg/kg doses of NCL195 4 or 6 h apart exhibited significantly reduced bacterial loads and longer survival times than untreated mice. However, further medicinal chemistry and pharmaceutical development to improve potency, solubility, and selectivity is required before efficacy testing in Gram-negative infection models.Hongfei Pi, Hang Thi Nguyen, Henrietta Venter, Alexandra R. Boileau, Lucy Woolford, Sanjay Garg ... et al

Weight loss for individuals with type 2 diabetes following a very-low-calorie diet in a community-based setting with trained facilitators for 12 weeks.

Approximately 80% of people with type 2 diabetes mellitus (T2DM) are overweight or obese, and obesity compounds the cardiovascular risk of T2DM. The aim of this retrospective study was twofold: first to investigate whether a twelve-week, community-based VLCD programme can result in important weight loss; and second to investigate any potential difference in the weight loss achieved using this community based approach in individuals with and without T2DM. Three hundred and fifty five participants with T2DM were matched for age, BMI and gender to participants without T2DM. The total cohort comprised 204 males: 506 females; age (years) 54.0 ± 9.1; BMI (kg/m2) 41.6 ± 8.1; weight (kg) 116.1 ± 25.1). The programme included a daily intake of 550kcal in addition to group support and behaviour therapy provided by trained facilitators within a community-based setting. After twelve weeks, there was significant weight loss within each group when compared to baseline (T2DM: 115.0 ± 24.4 kg vs 96.7 ± 21.4 kg, p < 0.0001; non-T2DM: 117.2 ± 25.8 kg vs 97.3 ± 22.2 kg, p < 0.0001). At twelve weeks, both weight change (-18.3 ± 7.3 kg vs -19.9 ± 7.0 kg, p = 0.012) and BMI change (-6.7 ± 2.9 kg/m2 vs -7.1 ± 2.1 kg/m2, p = 0.011) were significantly less in the T2DM group when compared to the non-T2DM group. Our results suggest that the use of VLCD approaches for weight management in T2DM can achieve more than 90% of the weight loss seen in obese individuals without T2DM

Observation of the Ωc0\Omega_{c}^{0} Charmed Baryon at CLEO

The CLEO experiment at the CESR collider has used 13.7 fb$^{-1}$ of data to search for the production of the $\Omega_c^0$ (css-ground state) in $e^{+}e^{-}$ collisions at $\sqrt{s} \simeq 10.6$ {\rm GeV}. The modes used to study the $\Omega_c^0$ are $\Omega^- \pi^+$, $\Omega^- \pi^+ \pi^0$, $\Xi^- K^- pi^+ \pi^+$, $\Xi^0 K^- pi^+$, and $\Omega^- \pi^+ \pi^- \pi^+$. We observe a signal of 40.4$\pm$9.0(stat) events at a mass of 2694.6$\pm$2.6(stat)$\pm$1.9(syst) {\rm MeV/$c^2$}, for all modes combined.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN