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Concept: Failure

150

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.

Concepts: Immune system, DNA, Genetics, Evolution, Randomness, Failure, Organization, Toleration

44

Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality.

Concepts: Clinical trial, Myocardial infarction, Medical statistics, Cardiology, Heart failure, Ejection fraction, Failure, Reliability engineering

43

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.

Concepts: Education, Science, Engineering, Learning, Failure, Student, Course, Active learning

36

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.

Concepts: Psychology, Decision making, Cognition, Failure, Labrador Retriever, Dog, Success, Adult

35

Research suggests that temporary abstinence from alcohol may convey physiological benefits and enhance well-being. The aim of this study was to address a lack of information about: (a) correlates of successful completion of a planned period of abstinence, and (b) how success or failure in planned abstinence affects subsequent alcohol consumption.

Concepts: Alcohol, Failure, Alcoholic beverage, Success, Seventh-day Adventist Church, Dry county, Prohibition in the United States

32

The ability to control desires, whether for food, sex, or drugs, enables people to function successfully within society. Yet, in tempting situations, strong impulses often result in self-control failure. Although many triggers of self-control failure have been identified, the question remains as to why some individuals are more likely than others to give in to temptation. In this study, we combined functional neuroimaging and experience sampling to determine if there are brain markers that predict whether people act on their food desires in daily life. We examined food-cue-related activity in the nucleus accumbens (NAcc), as well as activity associated with response inhibition in the inferior frontal gyrus (IFG). Greater NAcc activity was associated with greater likelihood of self-control failures, whereas IFG activity supported successful resistance to temptations. These findings demonstrate an important role for the neural mechanisms underlying desire and self-control in people’s real-world experiences of temptations.

Concepts: Central nervous system, Neuroanatomy, Brain, Neuroimaging, Cerebrum, Failure, Inferior frontal gyrus, Dopamine

31

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 .).

Concepts: Infant, Clinical trial, Pulmonology, Fetus, Respiratory system, Positive airway pressure, Failure, Gestational age

31

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.

Concepts: Failure, Earthquake, Earthquake engineering, Seismology, Fault, Shear, Structural geology, Love wave

30

We previously reported modest clinical 3-year benefit for topical imiquimod compared with surgery for superficial or nodular basal cell carcinoma at low-risk sites in our noninferiority randomized controlled SINS trial. Here we report 5-year data. Participants were randomized to imiquimod 5% cream once daily (superficial basal cell carcinoma, 6 weeks; nodular basal cell carcinoma, 12 weeks) or excisional surgery (4-mm margin). The primary outcome was clinical absence of initial failure or signs of recurrence at the 3-year dermatology review. Five-year success was defined as 3-year success plus absence of recurrences identified through hospital, histopathology, and general practitioner records. Of 501 participants randomized, 401 contributed to the modified intention-to-treat analyses at year 3 (primary outcome), 383 (96%) of whom had data at year 5. Five-year success rates for imiquimod were 82.5% (170/206) compared with 97.7% (173/177) for surgery (relative risk of imiquimod success = 0.84, 95% confidence interval = 0.77-0.91, P < 0.001). These were comparable to year 3 success rates of 83.6% (178/213) and 98.4% (185/188) for imiquimod and surgery, respectively. Most imiquimod treatment failures occurred in year 1. Although surgery is clearly superior to imiquimod, this study shows sustained benefit for lesions that respond early to topical imiquimod.

Concepts: Cohort study, Clinical trial, Medical statistics, Anatomical pathology, Squamous cell carcinoma, Failure, Basal cell carcinoma, Epidermal nevi, neoplasms, cysts

28

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.

Concepts: Intracranial pressure, Cerebrospinal fluid, Failure, Congenital disorder, Hydrocephalus, Congenital disorders, Arnold-Chiari malformation, Cerebral shunt