Are You "Tilting at Windmills" or Undertaking a Valid Clinical Trial?

In this review, several aspects surrounding the choice of a therapeutic intervention and the conduct of clinical trials are discussed. Some of the background for why human studies have evolved to their current state is also included. Specifically, the following questions have been addressed: 1) What criteria should be used to determine whether a scientific discovery or invention is worthy of translation to human application? 2) What recent scientific advance warrants a deeper understanding of clinical trials by everyone? 3) What are the different types and phases of a clinical trial? 4) What characteristics of a human disorder should be noted, tracked, or stratified for a clinical trial and what inclusion /exclusion criteria are important to enrolling appropriate trial subjects? 5) What are the different study designs that can be used in a clinical trial program? 6) What confounding factors can alter the accurate interpretation of clinical trial outcomes? 7) What are the success rates of clinical trials and what can we learn from previous clinical trials? 8) What are the essential principles for the conduct of valid clinical trials

The importance of seahorses and pipefishes in the diet of marine animals

A review of 135 accounts of predation on seahorses and pipefishes identified 82 predator species, with nine species of seahorses and 25 of pipefishes recorded as prey. These cryptic fishes were generally depredated in low numbers. Where syngnathids formed a high proportion of predator diets, predation occurred on (1) a single abundant species during a population boom or large die-off, (2) concentrations of individuals utilising floating marine vegetation, or (3) juveniles when abundant during the breeding season. Predation coinciding with high syngnathid densities suggests their predators are foraging opportunistically rather than targeting syngnathids as prey. Invertebrates, fishes, sea turtles, waterbirds and marine mammals were all syngnathid predators: these included taxa that do not frequent the demersal habitat generally occupied by seahorses and pipefishes. Thus, seahorses and pipefishes may be moving in the open ocean more than suspected, perhaps using floating mats of marine vegetation. If so, this behaviour could act as a hitherto unknown vector for syngnathid movement and dispersal. Information on syngnathid abundance in predator diet (measured as percent number, volume, or mass) was available in 45 reviewed accounts; in 27% (n = 12) of these studies seahorses or pipefishes comprised ≥20% of predator diet (range 0.005–100%). Frequency of occurrence (percent stomachs, seabird bill-loads, or regurgitations in which a prey item occurred) was provided in 39 accounts, with 15% (n = 6) of these recording a frequency of ≥20% (range 0.003–65%)

Outcome measures for acute/subacute cervical sensorimotor complete (AIS-A) spinal cord injury during a phase 2 clinical trial

Effective treatment after cervical spinal cord injury (SCI) is imperative as so many activities of daily living (ADLs) are dependent on functional recovery of arm and hand actions. We focus on defining and comparing neurological and functional endpoints that might be used during acute or subacute Phase 2 clinical trials involving subjects with cervical sensorimotor complete SCI (ASIA Impairment Scale [AIS-A]). For the purposes of this review, the trial would examine the effects of a pharmaceutical small molecule, drug, biologic, or cell transplant on spinal tissue. Thus, neurological improvement is the intended consequence and is most directly measured by assessing neurological impairment (eg, motor aspects of the International Standards Neurological Classification of Spinal Cord Injury [ISNCSCI]). However, changes in neurological function, even if statistically significant, may not be associated with a clear functional impact (ie, a meaningful improvement in individual activity, such as independent self-care ADLs). The challenge is to measure improvement as precisely as possible (change in impairment), but to define a clinically meaningful response in the context of functional improvement (impact on activity limitations). The principal comparisons focused on elements of the ISNCSCI assessment, including upper extremity motor score and motor level. Personal activity capabilities were also examined at various time points. The data suggest that an improvement of 2 or more motor levels after cervical sensorimotor complete SCI may be a clinically meaningful endpoint threshold that could be used for acute and subacute Phase 2 trials with subjects having sensorimotor complete cervical SCI

Fishing for data in the Ross Sea

The public perceives a certification by the Marine Stewardship Council (MSC) to mean an environmentally friendly fishery, not one characterized by the \u201cdearth of key data\u201d. Significant data deficiencies lead to conclude that an eco-friendly label for the fishery of Ross Sea Antarctic toothfish (Dissostichus mawsoni) is scientifically indefensible. Credible life history data are missing: spawning areas, eggs, and larvae have never been found, spawning intervals are unknown, and most density-dependent aspects of ecological relationships are undetermined. Stock assessment is problematic because severe Antarctic pack ice conditions for more than 9 months a year prevent scientists from effectively using standard models, which require random tagging over time, space, and age classes. The number of fish harvested by illegal, unregulated, and unreported fisheries is likely substantial. Finally, ecosystem effects of removing 50% of spawning biomass of this slow-to-mature species are unlikely to be neutral. The large, adult toothfish targeted by the fishery are a key structural link in the food web of the Ross Sea, currently the most pristine marine area on Earth. Instead of a certification that lacks proper data, a moratorium should be placed on further Ross Sea fishing until the quality of science at least equals that of certified fisheries elsewhere

Impacts of anthropogenic noise on marine life: Publication patterns, new discoveries, and future directions in research and management

Anthropogenic underwater noise is now recognized as a world-wide problem, and recent studies have shown a broad range of negative effects in a variety of taxa. Underwater noise from shipping is increasingly recognized as a significant and pervasive pollutant with the potential to impact marine ecosystems on a global scale. We reviewed six regional case studies as examples of recent research and management activities relating to ocean noise in a variety of taxonomic groups, locations, and approaches. However, as no six projects could ever cover all taxa, sites and noise sources, a brief bibliometric analysis places these case studies into the broader historical and topical context of the peer-reviewed ocean noise literature as a whole. The case studies highlighted emerging knowledge of impacts, including the ways that non-injurious effects can still accumulate at the population level, and detailed approaches to guide ocean noise management. They build a compelling case that a number of anthropogenic noise types can affect a variety of marine taxa. Meanwhile, the bibliometric analyses revealed an increasing diversity of ocean noise topics covered and journal outlets since the 1940s. This could be seen in terms of both the expansion of the literature from more physical interests to ecological impacts of noise, management and policy, and consideration of a widening range of taxa. However, if our scientific knowledge base is ever to get ahead of the curve of rapid industrialization of the ocean, we are going to have to identify naïve populations and relatively pristine seas, and construct mechanistic models, so that we can predict impacts before they occur, and guide effective mitigation for the most vulnerable populations