Concerns about a lack of reproducibility of statistically significant results have recently been raised in many fields, and it has been argued that this lack comes at substantial economic costs. We here report the results from prediction markets set up to quantify the reproducibility of 44 studies published in prominent psychology journals and replicated in the Reproducibility Project: Psychology. The prediction markets predict the outcomes of the replications well and outperform a survey of market participants' individual forecasts. This shows that prediction markets are a promising tool for assessing the reproducibility of published scientific results. The prediction markets also allow us to estimate probabilities for the hypotheses being true at different testing stages, which provides valuable information regarding the temporal dynamics of scientific discovery. We find that the hypotheses being tested in psychology typically have low prior probabilities of being true (median, 9%) and that a "statistically significant" finding needs to be confirmed in a well-powered replication to have a high probability of being true. We argue that prediction markets could be used to obtain speedy information about reproducibility at low cost and could potentially even be used to determine which studies to replicate to optimally allocate limited resources into replications.reproducibility | replications | prediction markets T he process of scientific discovery centers on empirical testing of research hypotheses. A standard tool to interpret results in statistical hypothesis testing is the P value. A result associated with a P value below a predefined significance level (typically 0.05) is considered "statistically significant" and interpreted as evidence in favor of a hypothesis. However, concerns about the reproducibility of statistically significant results have recently been raised in many fields including medicine (1-3), neuroscience (4), genetics (5, 6), psychology (7-11), and economics (12, 13). For example, an industrial laboratory could only reproduce 6 out of 53 key findings from "landmark" studies in preclinical oncology (2) and it has been argued that the costs associated with irreproducible preclinical research alone are about US$28 billion a year in the United States (3). The mismatch between the interpretation of statistically significant findings and a lack of reproducibility threatens to undermine the validity of statistical hypothesis testing as it is currently practiced in many research fields (14).The problem with inference based on P values is that a P value provides only partial information about the probability of a tested hypothesis being true (14,15). This probability also depends on the statistical power to detect a true positive effect and the prior probability that the hypothesis is true (14). Lower statistical power increases the probability that a statistically significant effect is a false positive (4, 14). Statistically significant results from small studies are therefore more likely to be fals...

Purpose To determine the change in intraocular pressure (IOP) after cataract extraction in the Observation Group of the Ocular Hypertension Treatment Study (OHTS). Design Comparative case series Participants Forty-two participants (63 eyes) who underwent cataract surgery in at least one eye during the study and a control group of 743 participants (743 eyes) who did not undergo cataract surgery Methods We defined the “split date” as the study visit date that cataract surgery was reported in the cataract surgery group, and a corresponding date in the control group. Preoperative IOP was defined as the mean IOP of up to 3 visits prior to split date. Postoperative IOP was the mean IOP of up to 3 visits including the split date (0, 6, and 12 months with ‘0 months’ equaling the split date). In both groups, we censored data after initiation of ocular hypotensive medication, or glaucoma surgery of any kind. Main outcome measures Difference in preoperative and postoperative IOP. Results In the cataract group, postoperative IOP was significantly lower than the preoperative IOP (19.8 ± 3.2 mmHg vs. 23.9 ± 3.2 p<0.001). The postoperative IOP remained lower than preoperative IOP for at least 36 months. The average decrease in postoperative IOP from preoperative IOP was 16.5%, and 39.7% of eyes had postoperative IOP ≥ 20% below preoperative IOP. A greater reduction in postoperative IOP occurred in the eyes with the highest preoperative IOP. In the control group, the corresponding mean IOP’s were 23.8 ± 3.6 prior to the split date and 23.4 ± 3.9 after the split date. Conclusion Cataract surgery decreases IOP in ocular hypertensive patients over a long period of time.

Some SDAT subjects retain "safe" driving skills. The greater the dementia severity, the greater the likelihood of poor driving ability. Performance-based (road test) evaluations are necessary to properly determine driving skills at present, but attention and other cognitive screening measures should be developed.

Prednisone has been shown to improve strength in Duchenne dystrophy. Azathioprine often benefits corticosteroid-responsive diseases and can reduce the dose of prednisone needed. The present study reports a randomized, controlled trial of prednisone and azathioprine designed to assess the longer-term effects of prednisone and to determine whether azathioprine alone, or in combination with prednisone, improves strength. Ninety-nine boys (aged five to 15 years) with Duchenne dystrophy were randomized to one of three groups: (I) placebo; (II) prednisone 0.3 mg/kg/d; or (III) prednisone 0.75 mg/kg/d. After 6 months, azathioprine 2 to 2.5 mg/kg/d was added in groups I and II and placebo added in group III. The study showed that the beneficial effect of prednisone (0.75 mg/kg/d) is maintained for at least 18 months and is associated with a 36% increase in muscle mass. There was weight gain, growth retardation, and other side effects. Azathioprine did not have a beneficial effect. This study suggests that prednisone's beneficial effect is not due to immunosuppression.

Two successive, 6-month, randomized, double-blind, controlled trials of prednisone showed that 0.75 mg/kg/d was the optimal dose to improve strength in boys with Duchenne muscular dystrophy (DMD). We attempted to maintain 93 boys on that dose for an additional 2 years. During the 3 years of observation, the decline in average muscle strength scores of all boys taking prednisone was 0.072 units/yr, as compared with an expected decline of 0.341 units/yr from natural history controls. The occurrence of side effects in some boys prevented maintenance of the full dose, which may have lessened the response. At the time of last visit, dosages ranged from 0.15 mg/kg to 0.75 mg/kg. In addition to maintaining their strength, several of the boys actually improved their performance in lifting kilogram weights and in some timed function tests. Treatment of DMD with prednisone significantly slows the progression of weakness and loss of function for at least 3 years.

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Nonspecific airway hyperresponsiveness (AHR) is a hallmark of human asthma. Both airway eosinophilia and high serum levels of total and antigen-specific immunoglobulin E (IgE) are associated with AHR. It is unclear, however, whether either eosinophilia or increased IgE levels contribute directly to, or predict, the development of AHR. Investigations conducted with various murine models of asthma and different mouse strains have resulted in conflicting evidence about the roles that IgE and airway eosinophilia play in the manifestation of AHR. We show that systemic priming with ovalbumin (OVA) in alum, followed by a single day of OVA aerosol challenge, is sufficient to induce AHR, as measured by increased pulmonary resistance in response to intravenously delivered methacholine in BALB/c, but not C57BL/6 or B6D2F1, mice. This was observed despite the fact that OVA-challenged BALB/c mice had less airway eosinophilia and smaller increases in total IgE than either C57BL/6 or B6D2F1 mice, and had less pulmonary inflammation and OVA-specific IgE than B6D2F1 mice. We conclude that airway eosinophilia, pulmonary inflammation, and high serum levels of total or OVA-specific IgE are all insufficient to induce AHR in C57BL/6 and B6D2F1 mice, whereas BALB/c mice demonstrate AHR in the absence of airway eosinophilia. These data confirm that the development of AHR is genetically determined, not only in naive mice, but also in actively immunized ones, and cannot be predicted by levels of airway eosinophilia, pulmonary inflammation, total IgE, or antigen-specific IgE.