Nesting Behavior of Palila, as Assessed from Video Recordings

We quantified nesting behavior of Palila (Loxioides bailleui), an endangered Hawaiian honeycreeper, by recording at nests during three breeding seasons using a black-and-white video camera connected to a videocassette recorder. A total of seven nests was observed. We measured the following factors for daylight hours: percentage of time the female was on the nest (attendance), length of attendance bouts by the female, length of nest recesses, and adult provisioning rates. Comparisons were made between three stages of the 40-day nesting cycle: incubation (day 1–day 16), early nestling stage (day 17–day 30 [i.e., nestlings ≤ 14 days old]), and late nestling stage (day 31–day 40 [i.e., nestlings \u3e 14 days old]). Of seven nests observed, four fledged at least one nestling and three failed. One of these failed nests was filmed being depredated by a feral cat (Felis catus). Female nest attendance was near 82% during the incubation stage and decreased to 21% as nestlings aged. We did not detect a difference in attendance bout length between stages of the nesting cycle. Mean length of nest recesses increased from 4.5 min during the incubation stage to over 45 min during the late nestling stage. Mean number of nest recesses per hour ranged from 1.6 to 2.0. Food was delivered to nestlings by adults an average of 1.8 times per hour for the early nestling stage and 1.5 times per hour during the late nestling stage and did not change over time. Characterization of parental behavior by video had similarities to but also key differences from findings taken from blind observations. Results from this study will facilitate greater understanding of Palila reproductive strategies

Short-Lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing in a Patient with Varicella-Zoster Virus Encephalomyelitis

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome (SUNCT) is a type of trigeminal autonomic cephalalgia. Its etiology is generally idiopathic, though rarely it has been associated with viral infections. We describe the fourth case reported in the literature of SUNCT in association with viral meningoencephalitis

Psychedelics Promote Structural and Functional Neural Plasticity.

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders

Prevalence, determinants, and clinical associations of high-sensitivity cardiac troponin in patients attending emergency departments

Background: High-sensitivity cardiac troponin assays may improve the diagnosis of myocardial infarction but increase the detection of elevated cardiac troponin in patients without acute coronary syndrome. Methods: In a prospective cohort study, we evaluated the prevalence, determinants, and outcome of patients with elevated cardiac troponin attending the emergency department without suspected acute coronary syndrome. We measured high-sensitivity cardiac troponin in 918 consecutive patients attending the emergency department without suspected acute coronary syndrome who had blood sampling performed by the attending clinician. Elevated high-sensitivity cardiac troponin I was defined as concentrations above the sex-specific 99th percentile threshold. Clinical demographics, physiological measures, and all-cause mortality at 1 year associated with elevated high-sensitivity cardiac troponin concentrations were recorded. Results: Elevated cardiac troponin concentration occurred in 114 (12.4%) patients, of whom 2 (0.2%), 3 (0.3%), and 109 (11.9%) were adjudicated as type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively. Elevated troponin concentrations were associated with increasing age, worsening renal function, multimorbidity, and adverse physiology. Across a total of 912 patient-years follow-up, cardiac troponin concentration was a strong predictor of death (hazard ratio [HR] 1.26 per 2-fold increase, 95% confidence interval [CI] 1.06 to 1.49) independent of age, sex, multimorbidity, and adverse physiology. Conclusions: High-sensitivity cardiac troponin concentrations were elevated in 1 in 8 consecutive patients without suspected acute coronary syndrome attending the emergency department and were associated with increasing age, multimorbidity, adverse physiology, and death. Elevated cardiac troponin in unselected patients predominantly reflects myocardial injury rather than myocardial infarction

A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study

PURPOSE: Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer. PATIENTS AND METHODS: Eligible patients had recurrent or persistent endometrial cancer after receiving one or two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group (GOG) performance status of ≤2 (≤1 if two prior cytotoxic regimens given). Cediranib 30mg orally daily for a 28daycycle was administered until disease progression or prohibitive toxicity. Microvessel density (MVD) was measured in tumor tissue from initial hysterectomy specimens and correlated with clinical outcome. Primary endpoints were tumor response and surviving progression-free for six months without subsequent therapy (6-month event-free survival [EFS]). RESULTS: Of 53 patients enrolled, 48 were evaluable for cediranib efficacy and toxicity. Median age was 65.5 years, 52% of patients had received prior radiation, and 73% of patients received only one prior chemotherapy regimen. A partial response was observed in 12.5%. Fourteen patients (29%) had six-month EFS. Median progression-free survival (PFS) was 3.65 months and median overall survival (OS) 12.5 months. No grade 4 or 5 toxicities were observed. A trend towards improved PFS was found in patients whose tumors expressed high MVD. CONCLUSION: Cediranib as a monotherapy treatment for recurrent or persistent endometrial cancer is well tolerated and met protocol set objectives for sufficient activity to warrant further investigation. MVD may be a useful biomarker for activity

Identifying conservation priorities for an understudied species in decline: Golden cats (Catopuma temminckii) in mainland Tropical Asia

Abstract Identifying conservation priorities for an understudied species can be challenging, as the amount and type of data available to work with are often limited. Here, we demonstrate a flexible workflow for identifying priorities for such data-limited species, focusing on the little-studied Asian golden cat (Catopuma temminckii) in mainland Tropical Asia. Using recent occurrence records, we modeled the golden cat's expected area of occurrence and identified remaining habitat strongholds (i.e., large intact areas with moderate-to-high expected occurrence). We then classified these strongholds by recent camera-trap survey status (from a literature review) and near-future threat status (based on publicly available forest loss projections and Bayesian Belief Network derived estimates of hunting-induced extirpation risk) to identify conservation priorities. Finally, we projected the species' expected area of occurrence in the year 2000, approximately three generations prior to today, to define past declines and better evaluate the species' current conservation status. Lower levels of hunting-induced extirpation risk and higher levels of closed-canopy forest cover were the strongest predictors of recent camera-trap records. Our projections suggest a 68% decline in area with moderate-to-high expected occurrence between 2000 and 2020, with a further 18% decline predicted over the next 20 years. Past and near-future declines were primarily driven by cumulatively increasing levels of hunting-induced extirpation risk, suggesting assessments of conservation status based solely on declines in habitat may underestimate actual population declines. Of the 40 remaining habitat strongholds, 77.5% were seriously threatened by forest loss and hunting. Only 52% of threatened strongholds had at least one site surveyed, compared to 100% of low-to-moderate threat strongholds, thus highlighting an important knowledge gap concerning the species' current distribution and population status. Our results suggest the golden cat has experienced, and will likely continue to experience, considerable population declines and should be considered for up-listing to a threatened category (i.e., VU/EN) under criteria A2c of the IUCN Red List

Phase 1/2a Study of the Malaria Vaccine Candidate Apical Membrane Antigen-1 (AMA-1) Administered in Adjuvant System AS01B or AS02A

Contains fulltext : 79496.pdf (publisher's version ) (Open Access)BACKGROUND: This Phase 1/2a study evaluated the safety, immunogenicity, and efficacy of an experimental malaria vaccine comprised of the recombinant Plasmodium falciparum protein apical membrane antigen-1 (AMA-1) representing the 3D7 allele formulated with either the AS01B or AS02A Adjuvant Systems. METHODOLOGY/PRINCIPAL FINDINGS: After a preliminary safety evaluation of low dose AMA-1/AS01B (10 microg/0.5 mL) in 5 adults, 30 malaria-naive adults were randomly allocated to receive full dose (50 microg/0.5 mL) of AMA-1/AS01B (n = 15) or AMA-1/AS02A (n = 15), followed by a malaria challenge. All vaccinations were administered intramuscularly on a 0-, 1-, 2-month schedule. All volunteers experienced transient injection site erythema, swelling and pain. Two weeks post-third vaccination, anti-AMA-1 Geometric Mean Antibody Concentrations (GMCs) with 95% Confidence Intervals (CIs) were high: low dose AMA-1/AS01B 196 microg/mL (103-371 microg/mL), full dose AMA-1/AS01B 279 microg/mL (210-369 microg/mL) and full dose AMA-1/AS02A 216 microg/mL (169-276 microg/mL) with no significant difference among the 3 groups. The three vaccine formulations elicited equivalent functional antibody responses, as measured by growth inhibition assay (GIA), against homologous but not against heterologous (FVO) parasites as well as demonstrable interferon-gamma (IFN-gamma) responses. To assess efficacy, volunteers were challenged with P. falciparum-infected mosquitoes, and all became parasitemic, with no significant difference in the prepatent period by either light microscopy or quantitative polymerase chain reaction (qPCR). However, a small but significant reduction of parasitemia in the AMA-1/AS02A group was seen with a statistical model employing qPCR measurements. SIGNIFICANCE: All three vaccine formulations were found to be safe and highly immunogenic. These immune responses did not translate into significant vaccine efficacy in malaria-naive adults employing a primary sporozoite challenge model, but encouragingly, estimation of parasite growth rates from qPCR data may suggest a partial biological effect of the vaccine. Further evaluation of the immunogenicity and efficacy of the AMA-1/AS02A formulation is ongoing in a malaria-experienced pediatric population in Mali. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00385047

Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways

One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization