Baited remote underwater video stations (BRUVS) are increasingly being used to evaluate and monitor reef communities. Many BRUVS studies compare multiple sites sampled at single time points that may ...differ from the sampling time of another site. As BRUVS use grows in its application to provide data relevant to sustainable management, marine protected area success, and overall reef health, understanding repeatability of sampling results is vital. We examined the repeatability of BRUVS results for the elasmobranch community both within and between seasons and years, and explored environmental factors affecting abundances at two sites in Indonesia. On 956 BRUVS, 1139 elasmobranchs (69% rays, 31% sharks) were observed. We found consistent results in species composition and abundances within a season and across years. However, elasmobranch abundances were significantly higher in the wet season. The elasmobranch community was significantly different between the two sites sampled, one site being more coastal and easily accessed by fishermen. Our results demonstrate that while BRUVS are a reliable and repeatable method for surveying elasmobranchs, care must be taken in the timing of sampling between different regions to ensure that any differences observed are due to inherent differences amongst sampling areas as opposed to seasonal dissimilarities.
Three open-label, multicenter trials were conducted to evaluate the efficacy and safety of single-agent Mylotarg (gemtuzumab ozogamicin; CMA-676; Wyeth Laboratories, Philadelphia, PA), an ...antibody-targeted chemotherapy agent, in patients with CD33-positive acute myeloid leukemia (AML) in untreated first relapse.
The study population comprised 142 patients with AML in first relapse with no history of an antecedent hematologic disorder and a median age of 61 years. All patients received Mylotarg as a 2-hour intravenous infusion, at a dose of 9 mg/m(2), at 2-week intervals for two doses. Patients were evaluated for remission, survival, and treatment-emergent adverse events.
Thirty percent of patients treated with Mylotarg obtained remission as characterized by 5% or less blasts in the marrow, recovery of neutrophils to at least 1,500/microL, and RBC and platelet transfusion independence. Although patients treated with Mylotarg had relatively high incidences of myelosuppression, grade 3 or 4 hyperbilirubinemia (23%), and elevated hepatic transaminase levels (17%), the incidences of grade 3 or 4 mucositis (4%) and infections (28%) were relatively low. There was a low incidence of severe nausea and vomiting (11%) and no treatment-related cardiotoxicity, cerebellar toxicity, or alopecia. Many patients received Mylotarg on an outpatient basis (38% and 41% of patients for the first and second doses, respectively). Among the 142 patients, the median total duration of hospitalization was 24 days; 16% of patients required 7 days of hospitalization or less.
Administration of the antibody-targeted chemotherapy agent Mylotarg to patients with CD33-positive AML in first relapse induces complete remissions with what appears to be a favorable safety profile.
The effects of ACE‐011 on safety, pharmacokinetics, and bone biomarkers were evaluated in healthy, postmenopausal women. Our data indicate that ACE‐011 results in a sustained increase in biomarkers ...of bone formation and reduction in markers of bone resorption. The activin type IIA receptor (ActRIIA) is the high‐affinity receptor for activin. ACE‐011 is a dimeric fusion protein consisting of the extracellular domain of the human ActRIIA linked to the Fc portion of human IgG1. ACE‐011 binds to activin, preventing activin from binding endogenous receptors. A randomized, double‐blind, placebo‐controlled study was conducted to evaluate the safety and tolerability of ACE‐011. Forty‐eight healthy, postmenopausal women were randomized to receive either a single dose of ACE‐011 or placebo and were followed for 4 mo. Dose levels ranged from 0.01 to 3.0 mg/kg intravenously and from 0.03 to 0.1 mg/kg subcutaneously. Safety and pharmacokinetic (PK) analyses and the biological activity of ACE‐011, as assessed by markers of bone turnover, and follicle stimulating hormone (FSH) levels were measured. No serious adverse events (AEs) were reported. AEs were generally mild and transient. The PK of ACE‐011 was linear over the dose range studied, with a mean half‐life of 24–32 days. The absorption after subcutaneous dosing was essentially complete. ACE‐011 caused a rapid and sustained dose‐dependent increase in serum levels of bone‐specific alkaline phosphatase (BSALP) and a dose‐dependent decrease in C‐terminal type 1 collagen telopeptide (CTX) and TRACP‐5b levels. There was also a dose‐dependent decrease in serum FSH levels consistent with inhibition of activin. ACE‐011 is a novel agent with biological evidence of both an increase in bone formation and a decrease in bone resorption. ACE‐011 may be an effective therapy in a variety of diseases involving bone loss.
Background & Aims The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on ...the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. Methods We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET—a prospective observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, there were 836 patients with HCV genotype 1 infection who began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most patients had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as the level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment—a 2-week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias. Results The overall SVR rate was 84% (675 of 802 patients, 95% confidence interval, 81%–87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively. Conclusions In a large prospective observational cohort study, a 12-week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation. ClinicalTrials.gov : NCT01474811.
Several common alleles in the oxytocin receptor gene (OXTR) are associated with altered brain function in reward circuitry in neurotypical adults and may increase risk for autism spectrum disorders ...(ASD). Yet, it is currently unknown how variation in the OXTR relates to brain functioning in individuals with ASD, and, critically, whether neural endophenotypes vary as a function of aggregate genetic risk. Here, for we believe the first time, we use a multi-locus approach to examine how genetic variation across several OXTR single-nucleotide polymorphisms (SNPs) affect functional connectivity of the brain's reward network. Using data from 41 children with ASD and 41 neurotypical children, we examined functional connectivity of the nucleus accumbens (NAcc) - a hub of the reward network - focusing on how connectivity varies with OXTR risk-allele dosage. Youth with ASD showed reduced NAcc connectivity with other areas in the reward circuit as a function of increased OXTR risk-allele dosage, as well as a positive association between risk-allele dosage and symptom severity, whereas neurotypical youth showed increased NAcc connectivity with frontal brain regions involved in mentalizing. In addition, we found that increased NAcc-frontal cortex connectivity in typically developing youth was related to better scores on a standardized measure of social functioning. Our results indicate that cumulative genetic variation on the OXTR impacts reward system connectivity in both youth with ASD and neurotypical controls. By showing differential genetic effects on neuroendophenotypes, these pathways elucidate mechanisms of vulnerability versus resilience in carriers of disease-associated risk alleles.
Background
There are currently no validated methods for energy intake assessment in adolescents with intellectual and developmental disabilities (IDD). The purpose of this study was to determine the ...feasibility of collecting 3‐day image‐assisted food records (IARs) and doubly labelled water (TDEEDLW) data in adolescents with IDD and to obtain preliminary estimates of validity and reliability for energy intake estimated by IAR.
Methods
Adolescents with IDD completed a 14‐day assessment of mean daily energy expenditure using doubly labelled water. Participants were asked to complete 3‐day IARs twice during the 14‐day period. To complete the IAR, participants were asked to fill out a hard copy food record over three consecutive days (two weekdays/one weekend day) and to take before and after digital images of all foods and beverages consumed using an iPad tablet provided by the study. Energy intake from the IAR was calculated using Nutrition Data System for Research. Mean differences, intraclass correlations and Bland–Altman limits of agreement were performed.
Results
Nineteen adolescents with IDD, mean age 15.1 years, n = 6 (31.6%) female and n = 6 (31.6%) ethnic/racial minorities, enrolled in the trial. Participants successfully completed their 3‐day food records and self‐collected doubly labelled water urine samples for 100% of required days. Images were captured for 67.4 ± 30.1% of all meals recorded at assessment 1 and 72.3 ± 29.5% at assessment 2. The energy intake measured by IAR demonstrated acceptable test–retest reliability (intraclass correlation = 0.70). On average, IAR underestimated total energy intake by −299 ± 633 kcal/day (mean per cent error = −9.6 ± 22.2%); however, there was a large amount of individual variability in differences between the IAR and TDEEDLW (range = −1703 to 430).
Conclusions
The collection of IAR and TDEEDLW is feasible in adolescents with IDD. While future validation studies are needed, the preliminary estimates obtained by this study suggest that in adolescents with IDD, the IAR method has acceptable reliability and may underestimate energy intake by ~9%.
Background The utility and safety of endoscopic biliary orifice balloon dilation (EBD) for bile duct stone removal (with use of large-diameter balloons) after biliary endoscopic sphincterotomy (BES) ...is currently not well established. Objective Our purpose was to evaluate the efficacy and complications of BES followed by ≥12 mm diameter EBD for bile duct stone removal. Design Retrospective, multicenter series. Setting Five ERCP referral centers in the United States. Patients and Interventions Patients who underwent attempted removal of bile duct stones by BES followed by EBD with ≥12 mm diameter dilating balloons were identified by searching the prospectively recorded endoscopic databases from 1999 to 2007. Clinical parameters, endoscopic data, and outcomes were collected and analyzed. Results One hundred three patients, mean age 70 ± 17 years (range 23-98 years), with 56 (54%) women, underwent 107 procedures. Eleven patients (11%) had a prior history of acute pancreatitis. Pancreatogram was performed in 15 (14%) patients. Median stone size and median balloon diameter used was 13 mm. Complete stone removal in the first session of EBD was accomplished in 102 (95%) procedures, and mechanical lithotripsy was required in 29 (27%). Six patients (5.4%) had documented procedure-related complications including one patient with severe bleeding and one with severe cystic duct perforation. No acute pancreatitis occurred. Conclusion EBD with a large-diameter balloon in conjunction with BES for bile duct stone removal is effective and relatively safe. This technique appears to be a reasonable alternative option when standard BES and basket or balloon sweep are inadequate to remove bile duct stones.
As the organ shortage continues to grow, the creation of social media communities by transplant hospitals and the public is rapidly expanding to increase the number of living donors. Social media ...communities are arranged in myriad ways and without standardization, raising concerns about transplant candidates’ and potential donors’ autonomy and quality of care. Social media communities magnify and modify extant ethical issues in deceased and living donation related to privacy, confidentiality, professionalism, and informed consent, and increase the potential for undue influence and coercion for potential donors and transplant candidates. Currently, no national ethical guidelines have been developed in the United States regarding the use of social media to foster organ transplantation. We provide an ethical framework to guide transplant stakeholders in using social media for public and patient communication about transplantation and living donation, and offer recommendations for transplant clinical practice and future research.
In an effort to guide transplant stakeholders in using social media for public and patient communication about transplantation and living donation, this article provides an ethical framework and offers recommendations for transplant clinical practice and future research.
Endoscopic sphincterotomy is commonly used to remove bile-duct stones and to treat other problems. We prospectively investigated risk factors for complications of this procedure and their outcomes.
...We studied complications that occurred within 30 days of endoscopic biliary sphincterotomy in consecutive patients treated at 17 institutions in the United States and Canada from 1992 through 1994.
Of 2347 patients, 229 (9.8 percent) had a complication, including pancreatitis in 127 (5.4 percent) and hemorrhage in 48 (2.0 Percent). There were 55 deaths from all causes within 30 days; death was directly or indirectly related to the procedure in 10 cases. Of five significant risk factors for complications identified in a multivariate analysis, two were characteristics of the patients (suspected dysfunction of the sphincter of Oddi as an indication for the procedure and the presence of cirrhosis) and three were related to the endoscopic technique (difficulty in cannulating the bile duct achievement of access to the bile duct by "precut" sphincterotomy, and use of a combined percutaneous-endoscopic procedure). The overall risk of complications was not related to the patient's age, the number of coexisting illnesses, or the diameter of the bile duct. The rate of complications was highest when the indication for the procedure was suspected dysfunction of the sphincter of Oddi (21.7 percent) and lowest when the indication was removal of bile-duct stones within 30 days of laparoscopic cholecystectomy (4.9 percent). As compared with those who performed fewer procedures, endoscopists who performed more than one sphincterotomy per week had lower rates of all complications (8.4 percent vs. 11.1 percent, P=0.03) and severe complications (0.9 percent vs. 2.3 percent, P=0.01).
The rate of complications after endoscopic biliary sphincterotomy can vary widely in different circumstances and is primarily related to the indication for the procedure and to endoscopic technique, rather than to the age or general medical condition of the patients.
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