Organising evidence for environmental management decisions: a '4S' hierarchy.

Making decisions informed by the best-available science is an objective for many organisations managing the environment or natural resources. Yet, available science is still not widely used in environmental policy and practice. We describe a '4S' hierarchy for organising relevant science to inform decisions. This hierarchy has already revolutionised clinical practice. It is beginning to emerge for environmental management, although all four levels need substantial development before environmental decision-makers can reliably and efficiently find the evidence they need. We expose common bypass routes that currently lead to poor or biased representation of scientific knowledge. We argue that the least developed level of the hierarchy is that closest to decision-makers, placing synthesised scientific knowledge into environmental decision support systems.L.V.D. is funded by the Natural Environment Research Council (Grant code NE/K015419/1). J.C.W. is funded by the UK Commonwealth Scholarship Commission and the Cambridge Commonwealth, European and International Trust. W.J.S. is funded by Arcadia.This is the final version of the article. It first appeared from Cell Press/Elsevier via http://dx.doi.org/10.1016/j.tree.2014.09.00

Conservation practice could benefit from routine testing and publication of management outcomes

Effective conservation requires a step change in the way practitioners can contribute to science and can have access to research outputs. The journal Conservation Evidence was established in 2004 to help practitioners surmount several obstacles they face when attempting to document the effects of their conservation actions scientifically. It is easily and freely accessible online. It is free to publish in and it enables global communication of the effects of practical trials and experiments, which are virtually impossible to get published in most scientific journals. The driving force behind Conservation Evidence is the need to generate and share scientific information about the effects of interventions

Kaneohe Bay Sewage Diversion Experiment: Perspectives on Ecosystem Responses to Nutritional Perturbation

Kaneohe Bay, Hawaii, received increasing amounts of sewage from the 1950s through 1977. Most sewage was diverted from the bay in 1977 and early 1978. This investigation, begun in January 1976 and continued through August 1979, described the bay over that period, with particular reference to the responses of the ecosystem to sewage diversion. The sewage was a nutritional subsidy. All of the inorganic nitrogen and most of the inorganic phosphorus introduced into the ecosystem were taken up biologically before being advected from the bay. The major uptake was by phytoplankton, and the internal water-column cycle between dissolved nutrients, phytoplankton, zooplankton, microheterotrophs, and detritus supported a rate of productivity far exceeding the rate of nutrient loading. These water-column particles were partly washed out of the ecosystem and partly sedimented and became available to the benthos. The primary benthic response to nutrient loading was a large buildup of detritivorous heterotrophic biomass. Cycling of nutrients among heterotrophs, autotrophs, detritus, and inorganic nutrients was important. With sewage diversion, the biomass of both plankton and benthos decreased rapidly. Benthic biological composition has not yet returned to presewage conditions, partly because some key organisms are long-lived and partly because the bay substratum has been perturbed by both the sewage and other human influences

Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children

BACKGROUND Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited PK data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. OBJECTIVES To describe the pharmacokinetics of LAmB in children aged 1-17 years with suspected or documented IFD. METHODS Thirty-five children were treated with LAmB at dosages of 2.5-10 mg kg(-1) daily. Samples were taken at baseline and at 0.5-2.0 hourly intervals for twenty-four hours after receipt of the first dose (n=35 patients) and on the final day of therapy (n=25 patients). LAmB was measured using high performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. RESULTS An evolution in PK was observed during the course of therapy resulting in a proportion of patients (n=13) having significantly higher maximum serum concentration (Cmax) and area under the concentration time curve (AUC0-24) later in the course of therapy, without evidence of drug accumulation (Cmin accumulation ratio, AR < 1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC0-24 and probability of nephrotoxicity (OR 2.37; 95% CI 1.84-3.22, p=0.004). CONCLUSIONS LAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation or observed clinical factors

Observations of Radar Backscatter at Ku and C Bands in the Presence of Large Waves during the Surface Wave Dynamics Experiment

Ocean radar backscatter in the presence of large waves is investigated using data acquired with the Jet Propulsion Laboratory NUSCAT radar at Ku band for horizontal and vertical polarizations and the University of Massachusetts CSCAT radar at C band for vertical polarization during the Surface Wave Dynamics Experiment. Off-nadir backscatter data of ocean surfaces were obtained in the presence of large waves with significant wave height up to 5.6 m. In moderate-wind cases, effects of large waves are not detectable within the measurement uncertainty and no noticeable correlation between backscatter coefficients and wave height is found. Under high-wave light-wind conditions, backscatter is enhanced significantly at large incidence angles with a weaker effect at small incidence angles. Backscatter coefficients in the wind speed range under consideration are compared with SASS-2 (Ku band), CMOD3-H1 (C band), and Plant's model results which confirm the experimental observations. Variations of the friction velocity, which can give rise to the observed backscatter behaviors in the presence of large waves, are presented

Public Benefits of Undeveloped Lands on Urban Outskirts: Non-Market Valuation Studies and their Role in Land Use Plans

Over the past three decades, the economics profession has developed methods for estimating the public benefits of green spaces, providing an opportunity to incorporate such information into land-use planning. While federal regulations routinely require such estimates for major regulations, the extent to which they are used in local land use plans is not clear. This paper reviews the literature on public values for lands on urban outskirts, not just to survey their methods or empirical findings, but to evaluate the role they have played--or have the potential to play-- in actual land use plans. Based on interviews with authors and representatives of funding agencies and local land trusts, it appears that academic work has had a mixed reception in the policy world. Reasons for this include a lack of interest in making academic work accessible to policy makers, emphasizing revealed preference methods which are inconsistent with policy priorities related to nonuse values, and emphasis on benefit-cost analyses. Nevertheless, there are examples of success stories that illustrate how such information can play a vital role in the design of conservation policies. Working Paper 07-2

What Can State Medical Boards Do to Effectively Address Serious Ethical Violations?

State Medical Boards (SMBs) can take severe disciplinary actions (e.g., license revocation or suspension) against physicians who commit egregious wrongdoing in order to protect the public. However, there is noteworthy variability in the extent to which SMBs impose severe disciplinary action. In this manuscript, we present and synthesize a subset of 11 recommendations based on findings from our team’s larger consensus-building project that identified a list of 56 policies and legal provisions SMBs can use to better protect patients from egregious wrongdoing by physicians

What can state medical boards do to effectively address serious ethical violations?

State Medical Boards (SMBs) can take severe disciplinary actions (e.g., license revocation or suspension) against physicians who commit egregious wrongdoing in order to protect the public. However, there is noteworthy variability in the extent to which SMBs impose severe disciplinary action. In this manuscript, we present and synthesize a subset of 11 recommendations based on findings from our team\u27s larger consensus-building project that identified a list of 56 policies and legal provisions SMBs can use to better protect patients from egregious wrongdoing by physicians

Sample matching by inferred agonal stress in gene expression analyses of the brain

<p>Abstract</p> <p>Background</p> <p>Gene expression patterns in the brain are strongly influenced by the severity and duration of physiological stress at the time of death. This agonal effect, if not well controlled, can lead to spurious findings and diminished statistical power in case-control comparisons. While some recent studies match samples by tissue pH and clinically recorded agonal conditions, we found that these indicators were sometimes at odds with observed stress-related gene expression patterns, and that matching by these criteria still sometimes results in identifying case-control differences that are primarily driven by residual agonal effects. This problem is analogous to the one encountered in genetic association studies, where self-reported race and ethnicity are often imprecise proxies for an individual's actual genetic ancestry.</p> <p>Results</p> <p>We developed an Agonal Stress Rating (ASR) system that evaluates each sample's degree of stress based on gene expression data, and used ASRs in <it>post hoc </it>sample matching or covariate analysis. While gene expression patterns are generally correlated across different brain regions, we found strong region-region differences in empirical ASRs in many subjects that likely reflect inter-individual variabilities in local structure or function, resulting in region-specific vulnerability to agonal stress.</p> <p>Conclusion</p> <p>Variation of agonal stress across different brain regions differs between individuals, revealing a new level of complexity for gene expression studies of brain tissues. The Agonal Stress Ratings quantitatively assess each sample's extent of regulatory response to agonal stress, and allow a strong control of this important confounder.</p

Surgical Outcomes After Neoadjuvant Nivolumab or Nivolumab With Ipilimumab in Patients With Non-Small Cell Lung Cancer

BACKGROUND: Surgical outcomes for non-small cell lung cancer after neoadjuvant immune checkpoint inhibitors continue to be debated. We assessed perioperative outcomes of patients treated with Nivolumab or Nivolumab plus Ipilimumab (NEOSTAR) and compared them with patients treated with chemotherapy or previously untreated patients with stage I-IIIA non-small cell lung cancer. METHODS: Forty-four patients with stage I to IIIA non-small cell lung cancer (American Joint Committee on Cancer Staging Manual, seventh edition) were randomized to nivolumab (N; 3 mg/kg intravenously on days 1, 15, and 29; n = 23) or nivolumab with ipilimumab (NI; I, 1 mg/kg intravenously on day 1; n = 21). Curative-intent operations were planned between 3 and 6 weeks after the last dose of neoadjuvant N. Patients who completed resection upfront or after chemotherapy from the same time period were used as comparison. RESULTS: In the N arm, 21 (91%) were resected on-trial, 1 underwent surgery off-trial, and one was not resected (toxicity-related). In the NI arm, 16 (76%) resections were performed on-trial, one off-trial, and 4 were not resected (none toxicity-related). Median time to operation was 31 days, and consisted of 2 (5%) pneumonectomies, 33 (89%) lobectomies, and 1 (3%) each of segmentectomy and wedge resection. The approach was 27 (73%) thoracotomy, 7 (19%) thoracoscopy, and 3 (8%) robotic-assisted. Conversion occurred in 17% (n = 2/12) of minimally invasive cases. All 37 achieved R0 resection. Pulmonary, cardiac, enteric, neurologic, and wound complications occurred in 9 (24%), 4 (11%), 2 (5%), 1 (3%), and 1 (3%) patient, respectively. The 30- and 90-day mortality rate was 0% and 2.7% (n = 1), respectively. Postoperative complication rates were comparable with lung resection upfront or after chemotherapy. CONCLUSIONS: Operating after neoadjuvant N or NI is overall safe and effective and yields perioperative outcomes similar to those achieved after chemotherapy or upfront resection