Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) ...and overall survival (OS), we carried out a meta-analysis using individual patient level trial data.
Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated.
OS data were available for 912 patients. The median PFS was 3.3months (95% CI 2.9–3.6) and 6-month PFS rate was 27% (95% CI 24–30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3cm versus <3cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2months (95% CI 9.5–11.0) and 1year OS was 43% (95% CI 40–47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS.
Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.
Tissue-based burdens of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) were integrated with ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) ...enzyme activity in bull (Carcharhinus leucas), blacktip (Carcharhinus limbatus), and bonnethead (Sphyrna tiburo) sharks from Galveston Bay, TX. The potential toxicity of these burdens was evaluated by calculation of toxic equivalents (TEQs). Concentrations of total PAHs (∑PAHs) were significantly greater in blacktip and bonnethead sharks than bull sharks in liver, but did not exhibit differences in muscle among species. Hepatic concentrations of ∑PAHs in these sharks (range of means: 1560–2200 ng/g wet wt.) were greater than concentrations previously reported in oysters from Galveston Bay (range of means: 134–333 ng/g dry wt.), which suggests that trophic dilution of PAHs may not be reflected in sharks. Total PCBs (∑PCBs) were significantly greatest in bull sharks and lowest in bonnetheads, while blacktips were intermediate to these species. EROD activity was greater in bonnetheads than the other species, whereas GST activity was significantly higher in blacktips and bonnetheads than in bull sharks. Integration of hepatic burdens with biomarker activity via constrained multivariate analysis found correlations for only a small number of individual PAH/PCB congeners. Hepatic TEQ measurements suggest potential physiological effects of these burdens compared to established TEQ thresholds for other taxa, although the likelihood of similar effects in sharks requires further study and the inclusion of toxic endpoints. Our findings indicate that sharks may be prone to the accumulation of PAHs and PCBs, which may result in negative health outcomes for these cartilaginous fishes.
Display omitted
•PAH/PCB burdens and biomarker activity were quantified in three shark species.•Potential toxicity was evaluated by measuring TEQs.•Sharks accumulated higher than expected PAH burdens.•Multivariate analyses found correlations among some congeners and biomarkers.•Comparison with toxicity benchmarks suggests potential physiological impacts.
•83% of overdoses involved an opioid and another substance.•Black race, homelessness associated with opioid overdose death with stimulant use.•Of the 808 deaths with stimulants, 695 involved cocaine ...alone.
While prescribed and illicit opioid use are primary drivers of the national surges in overdose deaths, opioid overdose deaths in which stimulants are also present are increasing in the U.S. We determined the social determinants and sociodemographic factors associated with opioid-only versus polysubstance opioid overdose deaths in Massachusetts. Particular attention was focused on the role of stimulants in opioid overdose deaths.
We analyzed all opioid-related overdose deaths from 2014 to 2015 in an individually-linked population database in Massachusetts. We used linked postmortem toxicology data to identify drugs present at the time of death. We constructed a multinomial logistic regression model to identify factors associated with three mutually exclusive overdose death groups based on toxicological results: opioid-related deaths with (1) opioids only present, (2) opioids and other substances not including stimulants, and (3) opioids and stimulants with or without other substances.
Between 2014 and 2015, there were 2,244 opioid-related overdose deaths in Massachusetts that had accompanying toxicology results. Toxicology reports indicated that 17% had opioids only, 36% had opioids plus stimulants, and 46% had opioids plus another non-stimulant substance. Persons older than 24 years, non-rural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone.
Polysubstance opioid overdose is increasingly common in the US. Addressing modifiable social determinants of health, including barriers to mental health services and homelessness, is important to reduce polysubstance use and overdose deaths.
ABSTRACT
Tooth morphology is often used to inform the feeding ecology of an organism as these structures are important to procure and process dietary resources. In sharks, differences in morphology ...may facilitate the capture and handling of prey with different physical properties. However, few studies have investigated differences in tooth morphology over ontogeny, throughout the jaws of a single species, or among species at multiple tooth positions. Bull (Carcharhinus leucas), blacktip (Carcharhinus limbatus), and bonnethead sharks (Sphyrna tiburo) are coastal predators that exhibit ontogenetic dietary shifts, but differ in their feeding ecologies. This study measured tooth morphology at six positions along the upper and lower jaws of each species using elliptic Fourier analysis to make comparisons within and among species over their ontogeny. Significant ontogenetic differences were detected at four of the six tooth positions in bull sharks, but only the posterior position on the lower jaw appeared to exhibit a functionally relevant shift in morphology. No ontogenetic changes in morphology were detected in blacktip or bonnethead sharks. Intraspecific comparisons found that most tooth positions significantly differed from one another across all species, but heterodonty was greatest in bull sharks. Additionally, interspecific comparisons found differences among all species at each tooth position except between bull and blacktip sharks at two positions. These morphological patterns within and among species may have implications for prey handling efficiency, as well as in providing insight for paleoichthyology studies and reevaluating heterodonty in sharks.
Ontogenetic changes in morphology are limited in bull sharks and do not occur in blacktip and bonnethead sharks. Heterodonty is ubiquitous within the jaws of each species. Significant interspecific differences were found at all six tooth positions.
There has been an increase in the incidence of acute pancreatitis reported worldwide. Despite improvements in access to care, imaging and interventional techniques, acute pancreatitis continues to be ...associated with significant morbidity and mortality. Despite the availability of clinical practice guidelines for the management of acute pancreatitis, recent studies auditing the clinical management of the condition have shown important areas of noncompliance with evidence-based recommendations. This underscores the importance of creating understandable and implementable recommendations for the diagnosis and management of acute pancreatitis. The purpose of the present guideline is to provide evidence-based recommendations for the management of both mild and severe acute pancreatitis as well as the management of complications of acute pancreatitis and of gall stone–induced pancreatitis. Une hausse de l’incidence de pancréatite aiguë a été constatée à l’échelle mondiale. Malgré l’amélioration de l’accès aux soins et aux techniques d’imagerie et d’intervention, la pancréatite aiguë est toujours associée à une morbidité et une mortalité importantes. Bien qu’il existe des guides de pratique clinique pour la prise en charge de la pancréatite aiguë, des études récentes sur la vérification de la prise en charge clinique de cette affection révèlent des lacunes importantes dans la conformité aux recommandations fondées sur des données probantes. Ces résultats mettent en relief l’importance de formuler des recommandations compréhensibles et applicables pour le diagnostic et la prise en charge de la pancréatite aiguë. La présente ligne directrice vise à fournir des recommandations fondées sur des données probantes pour la prise en charge de la pancréatite aiguë, qu’elle soit bénigne ou grave, ainsi que de ses complications et de celles de la pancréatite causée par un calcul biliaire.
This paper describes the design, industrial application, and field testing of a technique for autonomous wheeled‐vehicle path following that uses iterative learning control (ILC) in a feedback ...linearized space. One advantage of this approach is that ILC is used without having to employ approximate linearization at every time step. The main contribution of this paper is the unique field experiments that used two large industrial‐scale center‐articulated underground mining vehicles. The described field work not only tested the underlying technique on commercial vehicles, but also presents a method for parallel speed learning, wherein the speed is adjusted over subsequent learning trials to improve cycle productivity. Finally, presented are field results for an approach to prelearning through simulation before deployment in the field to reduce the initial path‐following errors.
This paper presents the development and field validation of an iterative learning-based admittance control algorithm for autonomous excavation in fragmented rock using robotic wheel loaders. An ...admittance control strategy is augmented with iterative learning, which automatically updates control parameters based on the error between a target bucket fill weight and the measured fill weight at the end of each excavation pass. The algorithm was validated through full-scale autonomous excavation experiments with a 14-tonne capacity load-haul-dump (LHD) machine and two different types of excavation materials: fragmented rock and gravel. In both excavation scenarios, the iterative learning algorithm is able to update the admittance control parameters for a specified target bucket fill weight, eliminating the need to manually re-tune control parameters as material characteristics change. These results have practical significance for increasing the autonomy of robotic wheel loaders used in mining and construction.
This paper proposes a high‐performance path following algorithm that combines Gaussian processes (GP) based learning and feedback linearization (FBL) with model predictive control (MPC) for ground ...mobile robots operating in off‐road terrains, referred to as GP‐FBLMPC. The algorithm uses a nominal kinematic model and learns unmodeled dynamics as GP models by using observation data collected during field experiments. Extensive outdoor experiments using a Clearpath Husky A200 mobile robot show that the proposed GP‐FBLMPC algorithm's performance is comparable to existing GP learning‐based nonlinear MPC (GP‐NMPC) methods with respect to the path following errors. The advantage of GP‐FBLMPC is that it is generalizable in reducing path following errors for different paths that are not included in the GP models training process, while GP‐NMPC methods only work well on exactly the same path on which GP models are trained. GP‐FBLMPC is also computationally more efficient than the GP‐NMPC because it does not conduct iterative optimization and requires fewer GP models to make predictions over the MPC prediction horizon loop at every time step. Field tests show the effectiveness and generalization of reducing path following errors of the GP‐FBLMPC algorithm. It requires little training data to perform GP modeling before it can be used to reduce path‐following errors for new, more complex paths on the same terrain (see video at https://youtu.be/tC09jJQ0OXM).
•A UAV that rotates as it falls is capable of generating a point cloud of a cavity.•This solution could offer a cheaper and more accurate method of cavity surveying.•The prototype UAV did maintain ...its integrity during all four drop tests.•The prototype UAV did not exhibit autorotation during test trials.
This paper presents the conceptual design, construction, and preliminary testing of a novel auto-rotating platform for cavity surveying. Cavity surveying involves generating a 3D model of an opening from acquired point cloud data. 3D models are used for volume estimation, stope reconciliation, dilution control, convergence monitoring, and rock mass stability analysis. In contrast to conventional cavity monitoring systems (CMS), which employ a rotating light detection and ranging (LiDAR) sensor attached to a stationary boom, the presented novel platform consists of a single point LiDAR sensor attached to an auto-rotating body as a unique solution to the cavity surveying problem. A proof of concept device consisting of a four-blade rotor and a data acquisition system was constructed and dropped from a five-metre overhang. Although auto-rotation was not reached, the set of indoor drop tests provide preliminary results that illustrate the design concept and describes the impact of design parameters. .
Background Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, ...the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. Objectives Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. Results The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. Conclusions Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.
PDF
