Clinical trials that end prematurely (or "terminate") raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for ...termination have not been well characterized.
A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial.
Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
More than a decade ago, the International Committee of Medical Journal Editors established a policy requiring trial registration. This article reviews the current state of this endeavor.
Laws and ...policies to establish a global trial reporting system have greatly increased the transparency and accountability of the clinical research enterprise. The three components of the trial reporting system are trial registration, reporting of aggregate results, and sharing of individual participant data.
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Trial registration is foundational to our understanding and interpretation of trial results, because it requires that information be provided about all relevant clinical trials (to put results in a broad context) and their prespecified protocol details (to ensure adherence to the scientific plan).
In this article, we describe the current trial registration landscape and summarize evidence of . . .
The loss of protein homeostasis (proteostasis) is a primary driver of age-related tissue dysfunction. Recent studies have revealed that the failure of proteostasis with age is triggered by ...developmental and reproductive cues that repress the activity of proteostasis-related pathways in early adulthood. In Caenorhabditis elegans, reduced mitochondrial electron transport chain (ETC) function during development can override signals that promote proteostasis collapse in aged tissues. However, it is unclear precisely how these beneficial effects are mediated. Here, we reveal that in response to ETC impairment, the PP2A complex generates a dephosphorylated, mitochondrial stress-specific variant of the transcription factor HSF-1. This results in the selective induction of small heat shock proteins in adulthood, thereby protecting against age-related proteostasis collapse. We propose that mitochondrial signals early in life can protect the aging cytosolic proteome by tailoring HSF-1 activity to preferentially drive the expression of non-ATP-dependent chaperones.
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•Mitochondrial stress promotes HSF-1 dephosphorylation through the PP2A complex•Hypo-phosphorylated HSF-1 drives a stress response that is enriched for small HSPs•Mitochondria protect against cytosolic protein aggregation through small HSPs•Overexpressing the PP2A catalytic subunit suppresses proteostasis collapse
Using the worm Caenorhabditis elegans as a model system, Williams et al. demonstrate that in response to developmental electron transport chain impairment, HSF-1 activity is re-modeled in adulthood by the PP2A complex. This results in the preferential up-regulation of small heat shock proteins, thereby protecting the cytosol against proteostasis collapse.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To describe electronic cigarette (e-cigarette) use and cigarette use among adolescents and determine whether established risk factors for smoking discriminate user categories.
School-based survey of ...1941 high school students (mean age 14.6 years) in Hawaii; data collected in 2013. The survey assessed e-cigarette use and cigarette use, alcohol and marijuana use, and psychosocial risk and protective variables (eg, parental support, academic involvement, smoking expectancies, peer smoking, sensation seeking). Analysis of variance and multinomial regression examined variation in risk and protective variables across the following categories of ever-use: e-cigarette only, cigarette only, dual use (use of both products), and nonuser (never used either product).
Prevalence for the categories was 17% (e-cigarettes only), 12% (dual use), 3% (cigarettes only), and 68% (nonusers). Dual users and cigarette-only users were highest on risk status (elevated on risk factors and lower on protective factors) compared with other groups. E-cigarette only users were higher on risk status than nonusers but lower than dual users. E-cigarette only users and dual users more often perceived e-cigarettes as healthier than cigarettes compared with nonusers.
This study reports a US adolescent sample with one of the largest prevalence rates of e-cigarette only use in the existing literature. Dual use also had a substantial prevalence. The fact that e-cigarette only users were intermediate in risk status between nonusers and dual users raises the possibility that e-cigarettes are recruiting medium-risk adolescents, who otherwise would be less susceptible to tobacco product use.
•Few data are available on the association of e-cigarette use with health indices.•We found e-cigarette use associated with asthma and chronic respiratory disorder.•Results were independent of ...cigarette smoking, physical and psychosocial covariates.•Associations with respiratory disorder were significant primarily among nonsmokers.
Little evidence is available on the association of e-cigarettes with health indices. We investigated the association of e-cigarette use with diagnosed respiratory disorder among adults in data from the Behavioral Risk Factor Surveillance Survey (BRFSS).
The 2016 Hawaii BRFSS, a cross-sectional random-dial telephone survey, had 8087 participants; mean age was 55 years. Items asked about e-cigarette use, cigarette smoking, and being diagnosed by a health professional with (a) asthma or (b) chronic obstructive pulmonary disease. Multivariable analyses tested associations of e-cigarette use with the respiratory variables controlling for smoking and for demographic, physical, and psychosocial variables.
Controlling for the covariates and smoking there was a significant association of e-cigarette use with chronic pulmonary disorder in the total sample (AOR = 2.58, CI 1.36–4.89, p < 0.01) and a significant association with asthma among nonsmokers (AOR = 1.33, CI 1.00–1.77, p < 0.05). The associations were stronger among nonsmokers than among smokers. Results were similar for analyses based on relative risk and absolute risk. There was also a greater likelihood of respiratory disorder for smokers, females, and persons with overweight, financial stress, and secondhand smoke exposure.
This is the first study to show a significant independent association of e-cigarette use with chronic respiratory disorder. Several aspects of the data are inconsistent with the possibility that e-cigarettes were being used for smoking cessation by persons with existing respiratory disorder. Theoretical mechanisms that might link e-cigarettes use and respiratory symptoms are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The role of law and policy in encouraging a sustainable global diet is often underestimated. I argue that targeted laws and environmental policy are key to bring the agricultural sector on the path ...towards sustainability.
A subset of the sinuous ridges (SRs) in the Aeolis/Zephyria Plana (AZP) region of Mars has been previously hypothesized to be inverted fluvial features, although the precise induration and erosion ...mechanisms were not specified. Morphological observations and thermal inertia data presented here support this hypothesis. A variety of mechanisms can cause inversion, and identification of the specific events that lead to fluvial SR formation can provide insights into the sedimentological, geochemical, and climatic processes of the region. Reconnaissance of two terrestrial lava‐capped ridges suggests some criteria that may be used to identify inverted fluvial features formed by lava infill on Mars, but these criteria are not satisfied by the majority of the AZP fluvial SRs. Armoring also appears inconsistent with terrestrial analogs. Layering and surface textures of fluvial SRs indicate that the most likely induration mechanism was geochemical cementation of fluvial sediments, and that the primary erosional mechanism that exposed the fluvial SRs was aeolian abrasion. This analysis of formation mechanism provides a foundation for estimating paleodischarge using an empirical form‐discharge approach, to which we have applied scaling, for Martian gravity. For those fluvial SRs meeting a set of criteria for accurate paleodischarge estimates, paleodischarge values generally range between 101 and 103 m3 s−1. The largest of these initial estimates are comparable to paleodischarge estimates for some late‐stage Noachian fluvial channels on Mars, and provide a constraint on the atmospheric conditions at this equatorial location during the late Hesperian to early Amazonian time frame.
ObjectiveUse of electronic cigarettes (e-cigarettes) is prevalent among adolescents, but there is little knowledge about the consequences of their use. We examined, longitudinally, how e-cigarette ...use among adolescents is related to subsequent smoking behaviour.MethodsLongitudinal school-based survey with a baseline sample of 2338 students (9th and 10th graders, mean age 14.7 years) in Hawaii surveyed in 2013 (time 1, T1) and followed up 1 year later (time 2, T2). We assessed e-cigarette use, tobacco cigarette use, and psychosocial covariates (demographics, parental support and monitoring, and sensation seeking and rebelliousness). Regression analyses including the covariates tested whether e-cigarette use was related to the onset of smoking among youth who had never smoked cigarettes, and to change in smoking frequency among youth who had previously smoked cigarettes.ResultsAmong T1 never-smokers, those who had used e-cigarettes at T1 were more likely to have smoked cigarettes at T2; for a complete-case analysis, adjusted OR=2.87, 95% CI 2.03 to 4.05, p<0.0001. Among ever-smokers at T1, using e-cigarettes was not related to significant change in their frequency of smoking at T2. Uptake of e-cigarette use among T1 never-users of either product was predicted by age, Caucasian or Native Hawaiian (vs Asian-American) ethnicity, lower parental education and parental support, higher rebelliousness, and perception of e-cigarettes as healthier.ConclusionsAdolescents who use e-cigarettes are more likely to start smoking cigarettes. This result together with other findings suggests that policies restricting adolescents’ access to e-cigarettes may have a rationale from a public health standpoint.
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BFBNIB, CEKLJ, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
A decade after ClinicalTrials.gov launched a database for reporting results of clinical trials, the database includes results of approximately 36,000 trials. The authors discuss laws, regulations, ...and policies relevant to results reporting, trends over time in the frequency of reporting, and adherence to requirements for the completeness and quality of the results reported.
The landing site for the Curiosity rover is located at the distal end of the Peace Vallis fan in Gale Crater. Peace Vallis fan covers 80 km2 and is fed by a 730 km2 catchment, which drains an upland ...plains area through a 15 km wide gap in the crater rim. Valley incision into accumulated debris delivered sediment through a relatively low density valley network to a main stem channel to the fan. An estimated total fan volume of 0.9 km3 matches the calculated volume of removal due to valley incision (0.8 km3) and indicates a mean thickness of 9 m. The fan profile is weakly concave up with a mean slope of 1.5% for the lower portion. Numerous inverted channels outcrop on the western surface of the fan, but on the eastern portion such channels are rare suggesting a change in process from distributary channel domination on the west to sheet flow on the eastern portion of the fan. Runoff (discharge/watershed area) to produce the fan is estimated to be more than 600 m, perhaps as much as 6000 m, indicating a hydrologic cycle that likely lasted at least thousands of years. Atmospheric precipitation (possibly snow) not seepage produced the runoff. Based on topographic data, Peace Vallis fan likely onlapped Bradbury Rise and spilled into a topographic low to the east of the rise. This argues that the light‐toned fractured terrain within this topographic low corresponds to the distal deposits of Peace Vallis fan, and in such a setting, lacustrine deposits are expected.
Key Points
Distal end of Peace Vallis fan was near MSL landing
Sediment in the fan was derived from valley incision into colluvium
Fan morphology consistent with fluvial processes
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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