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A Framework for Learning From Null Results
A substantial number of randomized trials of educational interventions that have been conducted over the past two decades have produced null results, with either no impact or an unreliable estimate of impact on student achievement or other outcomes of interest. The investment of time and money spent implementing such trials warrants more useful information than simply \"this didn't work.\" In this article, we propose a framework for defining null results and interpreting them and then propose a method for systematically examining a set of potential reasons for a study's findings. The article builds on prior work on the topic and synthesizes it into a common framework designed to help the field improve both the design and interpretation of randomized trials.
Journal Article
Evaluation of cold ironing and speed reduction policies to reduce ship emissions near and at ports
Different port operating policies have the potential to reduce emissions from shipping; however, their efficacy varies for different ports. This article extends existing literature to present a consistent and transferable methodology that examines emissions reduction port policies based on ship-call data. Carbon dioxide (CO
2
); sulphur dioxide (SO
2
); nitrogen oxides (NO
x
); and black carbon (BC) emissions from near-port containership activities are estimated. Two emissions reduction policies are considered for typical container terminals. Participation of all calling vessels with a speed reduction scheme can lead to reductions of 8–20 per cent, 9–40 per cent and 9–17 per cent for CO
2
, SO
2
and NO
x
, respectively. However, speed reduction policies may increase BC emissions by up to 10 per cent. Provision of Alternative Marine Power (AMP) for all berthing vessels can reduce in-port emissions by 48–70 per cent, 3–60 per cent, 40–60 per cent and 57–70 per cent for CO
2
, SO
2
, NO
x
and BC, respectively. The analysis shows that emissions depend on visiting fleet, berthing durations, baseline operating pattern of calling ships, sulphur reduction policies in force and the emissions intensity of electricity supply. The potential of emissions reduction policies varies considerably across ports making imperative the evaluation and prioritization of such policies based on the unique characteristics of each port and each vessel.
Journal Article
The Potential for School-Based Interventions That Target Executive Function to Improve Academic Achievement: A Review
This article systematically reviews what is known empirically about the association between executive function and student achievement in both reading and math and critically assesses the evidence for a causal association between the two. Using meta-analytic techniques, the review finds that there is a moderate unconditional association between executive function and achievement that does not differ by executive function construct, age, or measurement type but finds no compelling evidence that a causal association between the two exists.
Journal Article
Exploring the Causal Impact of the McREL Balanced Leadership Program on Leadership, Principal Efficacy, Instructional Climate, Educator Turnover, and Student Achievement
This study uses a randomized design to assess the impact of the Balanced Leadership program on principal leadership, instructional climate, principal efficacy, staff turnover, and student achievement in a sample of rural northern Michigan schools. Participating principals report feeling more efficacious, using more effective leadership practices, and having a better instructional climate than control group principals. However, teacher reports indicate that the instructional climate of the schools did not change. Furthermore, we find no impact of the program on student achievement. There was an impact of the program on staff turnover, with principals and teachers in treatment schools significantly more likely to remain in the same school over the 3 years of the study than staff in control schools.
Journal Article
Consumer Perceptions of Meat Redness Were Strongly Influenced by Storage and Display Times
Lamb (n = 79) meat colour was scored by 879 untrained consumers using a scale of 0 (brown) to 100 (red). This consumer colour score (CCS) was obtained on m. longissimus lumborum (loin) and m. semimembranosus (topside), stored for short (5–7 days), medium (33–35 days), and long periods (110–112 days) and a retail display time of up to 4 days. Consumers perceived topside to be less red initially and changed from red to brown more rapidly when stored for the long-storage period (p < 0.01). Whereas, the initial CCS of loin samples were similar across the storage periods (p > 0.05). CCS and the instrument measure oxy/met (reflectance of light at wavelengths 630 nm and 580 nm) had a low correlation coefficient of 0.33 (p < 0.01). The propensity for lamb growth and leanness indicated by sire breeding values for lamb weight, eye muscle depth, eye muscle fat depth, and loin intramuscular fat had varied and inconsistent effects on CCS. Therefore, even the selection on CCS.
Journal Article
Distribution of symptomatic cerebral vasospasm following subarachnoid hemorrhage assessed using cone-beam CT angiography
Background and purposeCone-beam CT angiography (CB-CTA) provides a three-dimensional spatial resolution which is, so far, unmatched in clinical practice compared with other conventional techniques such as two-dimensional digital subtracted angiography. We aimed to assess the distribution of symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) using CB-CTA.Methods30 consecutive patients with aSAH undergoing vasospasm percutaneous balloon angioplasty (PBA) were recruited and underwent CB-CTA in this single-center prospective cohort series. Intracranial arteries were systematically analyzed by two independent observers from the large trunks to the distal cortical branches and perforators using a high-resolution reconstruction protocol. Intermediate and severe cerebral vasospasm was defined as 30–50% and >50% narrowing in the diameter of the vessel, respectively.Results35 arterial cervical artery territories were analyzed, of which 80% were associated with clinical or radiological signs of delayed cerebral ischemia. The median spatial resolution was 150 µm (range 100–250 µm). Intermediate or severe vasospasm was observed in the proximal (86%, 95% CI 74% to 97%), middle (89%, 95% CI 78% to 99%), and distal (60%, 95% CI 44% to 76%) segments of the large trunks, as well as the cortical branches (11%, 95% CI 1% to 22%). No vasospasm was observed in basal ganglia or cortical perforators, or in arteries smaller than 900 µm. Vasospasm was more severe in middle or distal segments compared with proximal segments in 43% (95% CI 26% to 59%) of cases.ConclusionsOur study demonstrated that symptomatic cerebral vasospasm following aSAH did not involve arteries smaller than 900 µm, and frequently predominated in middle or distal segments. These results offer new insights into the potential management options for vasospasm using PBA.
Journal Article
Genetic correlations between meat quality traits and growth and carcass traits in Merino sheep
Genetic correlations between 16 meat quality and nutritional value traits and live weight at various ages, live ultrasound fat and muscle depth, carcass measures, and carcass dissection traits were estimated for Merino sheep in the Information Nucleus (IN). Genetic correlations between live weight at various ages and the carcass traits are also reported. The IN comprised 8 genetically linked flocks managed across a range of Australian sheep environments. Meat quality traits included between 1,200 and 1,300 records for progeny from over 170 sires for intramuscular fat (IMF), lean meat yield (LMY), shear force (SF5), pH, meat color, and meat nutritional value traits including iron and zinc levels and long-chain omega-3 and omega-6 polyunsaturated fatty acid levels. The genetic correlations indicated that selection of Merino sheep to either reduce fat or increase muscle using ultrasound assessments will result in little change in IMF and SF5. Myoglobin levels would tend to be reduced following selection for reduced ultrasound fat depth (0.35 ± 0.21, 0.43 ± 0.14), whereas increases in myoglobin levels would occur due to selection for increased ultrasound muscle depth (0.25 ± 0.24, 0.38 ± 0.15). Selection for increased live weight will result in favorable correlated responses in hot carcass weight (0.76 to 0.97), dressing percentage (0.13 to 0.47), and carcass muscle (0.37 to 0.95), but unfavorable responses of increases in carcass fatness (0.13 to 0.65) and possible small reductions in muscle oxidative activity (−0.13 ± 0.14 to −0.73 ± 0.33) and iron content (−0.14 ± 0.15 to −0.38 ± 0.16), and a possible deterioration of shear force from selection at later ages (0.15 ± 0.26, 0.27 ± 0.24). Negligible changes are generally expected for LMY and meat color traits following selection for increased live weight (most genetic correlations less than 0.20 in size). Selection for increased LMY would tend to result in unfavorable changes in several aspects of meat quality, including reduced IMF (−0.27 ± 0.18), meat tenderness (0.53 ± 0.26), and meat redness (−0.69 ± 0.40), as well as reduced iron levels (−0.25 ± 0.22). These genetic correlations are a first step in assisting the development of breeding values for new traits to be incorporated into genetic evaluation programs to improve meat production from Merino sheep and other dual-purpose sheep breeds.
Journal Article
Next generation sequencing of PD-L1 for predicting response to immune checkpoint inhibitors
Background
PD-L1 immunohistochemistry (IHC) has been traditionally used for predicting clinical responses to immune checkpoint inhibitors (ICIs). However, there are at least 4 different assays and antibodies used for PD-L1 IHC, each developed with a different ICI. We set to test if next generation RNA sequencing (RNA-seq) is a robust method to determine
PD-L1
mRNA expression levels and furthermore, efficacy of predicting response to ICIs as compared to routinely used, standardized IHC procedures.
Methods
A total of 209 cancer patients treated on-label by FDA-approved ICIs, with evaluable responses were assessed for PD-L1 expression by RNA-seq and IHC, based on tumor proportion score (TPS) and immune cell staining (ICS). A subset of serially diluted cases was evaluated for RNA-seq assay performance across a broad range of PD-L1 expression levels.
Results
Assessment of
PD-L1
mRNA levels by RNA-seq demonstrated robust linearity across high and low expression ranges.
PD-L1
mRNA levels assessed by RNA-seq and IHC (TPS and ICS) were highly correlated (
p
< 2e-16). Sub-analyses showed sustained correlation when IHC results were classified as high or low by clinically accepted cut-offs (
p
< 0.01), and results did not differ by tumor type or anti-PD-L1 antibody used. Overall, a combined positive PD-L1 result (≥1% IHC TPS and high
PD-L1
expression by RNA-Seq) was associated with a 2-to-5-fold higher overall response rate (ORR) compared to a double negative result. Standard assessments of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) showed that a
PD-L1
positive assessment for melanoma samples by RNA-seq had the lowest sensitivity (25%) but the highest PPV (72.7%). Among the three tumor types analyzed in this study, the only non-overlapping confidence interval for predicting response was for “RNA-seq low vs high” in melanoma.
Conclusions
Measurement of
PD-L1
mRNA expression by RNA-seq is comparable to PD-L1 expression by IHC both analytically and clinically in predicting ICI response. RNA-seq has the added advantages of being amenable to standardization and avoidance of interpretation bias.
PD-L1
by RNA-seq needs to be validated in future prospective ICI clinical studies across multiple histologies.
Journal Article
Overcoming the legal and regulatory barriers to drug repurposing
Drug repurposing has been proposed as a strategy to develop new therapies that has fewer risks, lower costs and shorter timelines than developing completely new drugs. However, the potential of this strategy has not been as widely realized as hoped, in part owing to legal and regulatory barriers. Here, we highlight these barriers and consider how they could be overcome.
Journal Article