During the lifetime of an organism, every individual encounters many combinations of diverse changes in the somatic genome, epigenome and microbiome. This gives rise to many novel combinations of internal failures which are unique to each individual. How any individual can tolerate this high load of new, individual-specific scenarios of failure is not clear. While stress-induced plasticity and hidden variation have been proposed as potential mechanisms of tolerance, the main conceptual problem remains unaddressed, namely: how largely non-beneficial random variation can be rapidly and safely organized into net benefits to every individual.
Active learning methods have been shown to be superior to traditional lecture in terms of student achievement, and our findings on the use of Peer-Led Team Learning (PLTL) concur. Students in our introductory biology course performed significantly better if they engaged in PLTL. There was also a drastic reduction in the failure rate for underrepresented minority (URM) students with PLTL, which further resulted in closing the achievement gap between URM and non-URM students. With such compelling findings, we strongly encourage the adoption of Peer-Led Team Learning in undergraduate Science, Technology, Engineering, and Mathematics (STEM) courses.
Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality.
- Proceedings of the National Academy of Sciences of the United States of America
- Published 9 months ago
A continuing debate in studies of social development in both humans and other animals is the extent to which early life experiences affect adult behavior. Also unclear are the relative contributions of cognitive skills (“intelligence”) and temperament for successful outcomes. Guide dogs are particularly suited to research on these questions. To succeed as a guide dog, individuals must accomplish complex navigation and decision making without succumbing to distractions and unforeseen obstacles. Faced with these rigorous demands, only ∼70% of dogs that enter training ultimately achieve success. What predicts success as a guide dog? To address these questions, we followed 98 puppies from birth to adulthood. We found that high levels of overall maternal behavior were linked with a higher likelihood of program failure. Furthermore, mothers whose nursing style required greater effort by puppies were more likely to produce successful offspring, whereas mothers whose nursing style required less effort were more likely to produce offspring that failed. In young adults, an inability to solve a multistep task quickly, compounded with high levels of perseveration during the task, was associated with failure. Young adults that were released from the program also appeared more anxious, as indicated by a short latency to vocalize when faced with a novel object task. Our results suggest that both maternal nursing behavior and individual traits of cognition and temperament are associated with guide dog success.
Background Treatment with nasal high-flow therapy has efficacy similar to that of nasal continuous positive airway pressure (CPAP) when used as postextubation support in neonates. The efficacy of high-flow therapy as the primary means of respiratory support for preterm infants with respiratory distress has not been proved. Methods In this international, multicenter, randomized, noninferiority trial, we assigned 564 preterm infants (gestational age, ≥28 weeks 0 days) with early respiratory distress who had not received surfactant replacement to treatment with either nasal high-flow therapy or nasal CPAP. The primary outcome was treatment failure within 72 hours after randomization. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the chosen margin of noninferiority was 10 percentage points. Infants in whom high-flow therapy failed could receive rescue CPAP; infants in whom CPAP failed were intubated and mechanically ventilated. Results Trial recruitment stopped early at the recommendation of the independent data and safety monitoring committee because of a significant difference in the primary outcome between treatment groups. Treatment failure occurred in 71 of 278 infants (25.5%) in the high-flow group and in 38 of 286 infants (13.3%) in the CPAP group (risk difference, 12.3 percentage points; 95% confidence interval [CI], 5.8 to 18.7; P<0.001). The rate of intubation within 72 hours did not differ significantly between the high-flow and CPAP groups (15.5% and 11.5%, respectively; risk difference, 3.9 percentage points; 95% CI, -1.7 to 9.6; P=0.17), nor did the rate of adverse events. Conclusions When used as primary support for preterm infants with respiratory distress, high-flow therapy resulted in a significantly higher rate of treatment failure than did CPAP. (Funded by the National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12613000303741 .).
Earthquakes normally occur as frictional stick-slip instabilities resulting in catastrophic failure and seismic rupture. Tectonic faults also fail in slow earthquakes with rupture durations of months or more, yet their origin is poorly understood. Here, we present laboratory observations of repetitive, slow stick-slip in serpentinite fault zones and mechanical evidence for their origin. We document a transition from unstable to stable frictional behavior with increasing slip velocity, providing a mechanism to limit the speed of slow earthquakes. We also document reduction of P-wave speed within the active shear zone prior to stick-slip events. If similar mechanisms operate in nature, our results suggest that higher-resolution studies of elastic properties in tectonic fault zones may aid in the search for reliable earthquake precursors.
Object Ventriculoperitoneal (VP) shunt placement remains the mainstay treatment for pediatric hydrocephalus. These devices have a relatively high complication and failure rate, often requiring multiple revisions. The authors present a single institution’s experience of pediatric patients treated with VP shunts. With an average follow-up time of 20 years, this study is among the longest reports of VP shunt revision in the literature to date. Hydrocephalus origins, shunt revision rates, and causes of shunt failure are described. Patients who underwent their first shunt revision more than 10 years after initial shunt placement were also explored. Methods A retrospective chart review was performed on all pediatric patients who underwent VP shunt placement from January 1990 through November 1996 at the University of Rochester Medical Center. Only patients who had at least 15 years of follow-up since their initial shunting procedure were included. Results A total of 234 procedures were performed on 64 patients, with a mean follow-up of 19.9 years. Patients ranged from a few days to 17.2 years old when they received their original shunt, with a median age of 4 months; 84.5% of the patients required 1 or more shunt revisions and 4.7% required 10 or more. Congenital defects, Chiari Type II malformations, tumors, and intraventricular hemorrhage were the most common causes of hydrocephalus. Overall, patients averaged 2.66 revisions, with proximal (27%) and distal (15%) catheter occlusion, disconnection (11%), and infection (9%) comprising the most common reasons for shunt malfunction. Notably, 12.5% of patients did not require their first shunt revision until more than 10 years after initial device placement, a previously undescribed finding due to the short follow-up duration in previous studies. Conclusions This long-term retrospective analysis of pediatric VP shunt placement revealed a relatively high rate of complications with need for shunt revision as late as 17 years after initial placement. Catheter occlusion represented a significant percentage of shunt failures. Cerebrospinal fluid shunting has a propensity for mechanical failure and patients with VP shunts should receive follow-up through the transition to adulthood.
Practical relevance: Flea allergic dermatitis is one of the most common skin diseases of cats presented for veterinary attention. It is therefore important for the practitioner to be able to design an appropriate flea management plan for their patients. Clinical challenges: There is no ‘one size fits all’ flea control programme for cats. Successful flea management requires an understanding of flea biology and knowledge of the mode of action of commercial flea products, of which there is a wide range available. Management of owner expectations can often present a challenge. Cat owners generally attribute a persistence of fleas after the administration of routine flea control to be a reflection of product failure. Owners may also be sceptical that fleas are responsible for the clinical signs of overgrooming in their cat and perceive a lack of response to flea adulticide treatment to be evidence of this fact. Evidence base: This article reviews an extensive body of published literature to update some concepts in flea control and discuss how judicious use of traditional and newer flea products can contribute to an integrated flea control strategy for cats.
BACKGROUND: Transnasal cannulation of the natural ostium in patients with an intact uncinate process is complicated by the lack of direct visualizationof the ostium. Accuracy of transnasal dilation of the maxillary ostium was evaluated for a malleable-tipped balloon device that was bent to specific angles for avoiding the fontanelle during cannulation.METHODS: Transnasal cannulation and dilation of 42 cadaver maxillary sinus ostia was attempted by 6 surgeons including 3 with very limited clinicalexperience using the study device. All physicians received procedure training including the technique to shape the balloon device into the recommended 135 degree maxillary configuration. Tissue dissection was prohibited. Canine fossa trephination and transantral endoscopy were used to evaluate cannulation and dilation outcomes. Physician operators were blinded to transantral images and results were documented by two observers.RESULTS: Appropriate transnasal cannulation and dilation of natural maxillary sinus ostia occurred in 92.9% (39/42) of attempts. Two failures emanated from procedural deviations. In one deviation, the bend angle was changed to 90 degrees and the device tip did not cannulate the ostium. In the second, the device was passed through a preexisting hole in the uncinate and cannulated the natural ostium. A third failure occurred when the device was passed through the fontanelle creating a false lumen.CONCLUSION: Using recommended procedural techniques and a malleable-tipped balloon device, newly trained and experienced physicians alike can perform uncinate-preserving transnasal cannulation and dilation of the maxillary ostium with a high rate of success.
BACKGROUND: Our goal was to analyze reported instances of the da Vinci robotic surgical system instrument failures using the FDA’s MAUDE (Manufacturer and User Facility Device Experience) database. From these data we identified some root causes of failures as well as trends that may assist surgeons and users of the robotic technology. METHODS: We conducted a survey of the MAUDE database and tallied robotic instrument failures that occurred between January 2009 and December 2010. We categorized failures into five main groups (cautery, shaft, wrist or tool tip, cable, and control housing) based on technical differences in instrument design and function. RESULTS: A total of 565 instrument failures were documented through 528 reports. The majority of failures (285) were of the instrument’s wrist or tool tip. Cautery problems comprised 174 failures, 76 were shaft failures, 29 were cable failures, and 7 were control housing failures. Of the reports, 10 had no discernible failure mode and 49 exhibited multiple failures. CONCLUSIONS: The data show that a number of robotic instrument failures occurred in a short period of time. In reality, many instrument failures may go unreported, thus a true failure rate cannot be determined from these data. However, education of hospital administrators, operating room staff, surgeons, and patients should be incorporated into discussions regarding the introduction and utilization of robotic technology. We recommend institutions incorporate standard failure reporting policies so that the community of robotic surgery companies and surgeons can improve on existing technologies for optimal patient safety and outcomes.