Patient participation in the clinical encounter and clinical practice guidelines: The case of patients’ participation in a GRADEd world

It is widely acknowledged that the patient's perspective should be considered when making decisions about how her care will be managed. Patient participation in the decision making process may play an important role in bringing to light and incorporating her perspective. The GRADE framework is touted as an evidence-based process for determining recommendations for clinical practice; i.e. determining how care ought to be managed. GRADE recommendations are categorized as “strong” or “weak” based on several factors, including the “values and preferences” of a “typical” patient. The strength of the recommendation also provides instruction to the clinician about when and how patients should participate in the clinical encounter, and thus whether an individual patient's values and preferences will be heard in her clinical encounter. That is, a “strong” recommendation encourages “paternalism” and a “weak” recommendation encourages shared decision making. We argue that adoption of the GRADE framework is problematic to patient participation and may result in care that is not respectful of the individual patient's values and preferences. We argue that the root of the problem is the conception of “values and preferences” in GRADE – the framework favours population thinking (e.g. “typical” patient “values and preferences”), despite the fact that “values and preferences” are individual in the sense that they are deeply personal. We also show that tying the strength of a recommendation to a model of decision making (paternalism or shared decision making) constrains patient participation and is not justified (theoretically and/or empirically) in the GRADE literature.     

Narrative constructs in modern clinical case reporting

Modern clinical case reporting takes the form of problem-solution narratives that redescribe symptoms in terms of disease categories. Authored almost always by those who have played a part in the medical assessment of the patient, reports historicise the salient details of an individual's illness as a complex effect of identifiable antecedent causes. Candidate hypotheses linking illness to pathological mechanisms are suggested by the patient’s experience, and by data that emerge from clinical examination and investigation. Observational and interpretive statements from these considerations are fitted into a temporally inflected account of the patient’s medical condition, configured from the vantage point of hindsight. Drawing on established forms of deferred telling, readers are invited to follow a story that drip-feeds a mixture of contingent and non-incidental information into the account, which engenders and frustrates curiosity, creates expectations, and challenges powers of reasoning and pattern recognition. Whereas case reporting once favoured memoir, the sentimental tale and eccentric biography as the means by which its historical narrative was cast, the preferred genres of contemporary case reporting include detective fiction, and puzzle and riddle narratives, formats that conceptualise the medical consultation in narrow problem-solution terms.     

Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.     

Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli

Primary cilia with a diameter of ~200 nm have been implicated in development and disease. Calcium signaling within a primary cilium has never been directly visualized and has therefore remained a speculation. Fluid-shear stress and dopamine receptor type-5 (DR5) agonist are among the few stimuli that require cilia for intracellular calcium signal transduction. However, it is not known if these stimuli initiate calcium signaling within the cilium or if the calcium signal originates in the cytoplasm. Using an integrated single-cell imaging technique, we demonstrate for the first time that calcium signaling triggered by fluid-shear stress initiates in the primary cilium and can be distinguished from the subsequent cytosolic calcium response through the ryanodine receptor. Importantly, this flow-induced calcium signaling depends on the ciliary polycystin-2 calcium channel. While DR5-specific agonist induces calcium signaling mainly in the cilioplasm via ciliary CaV1.2, thrombin specifically induces cytosolic calcium signaling through the IP₃ receptor. Furthermore, a non-specific calcium ionophore triggers both ciliary and cytosolic calcium responses. We suggest that cilia not only act as sensory organelles but also function as calcium signaling compartments. Cilium-dependent signaling can spread to the cytoplasm or be contained within the cilioplasm. Our study thus provides the first model to understand signaling within the cilioplasm of a living cell.     

Zoogeographic patterns and faunal change of South Dakota fishes

We summarized historic and recent fish distributions in South Dakota and analyzed fish faunal similarity at 2 spatial scales (geomorphic province and river drainage) for both historic (native) and recent (post-1990) faunas. We quantified zoogeographic patterns between geomorphic provinces and among neighboring river drainages for historic and recent faunas. We also quantified faunal change (species losses and additions) between provinces and among drainages. Ninety-seven fishes were native to South Dakota, but 111 fishes were present in recent collections because 8 native species were missing, and 22 nonnatives were present. There was high β diversity among historic and recent river drainage fish faunas, but there was between 22% and 56% faunal change between periods. Recent faunas were homogenized compared to historic faunas at both provincial and river drainage spatial scales. Patterns of nonnative species establishment were geographically distinct from patterns of native species loss. Most nonnative species additions were in cold-water or human-made habitats of the Great Plains. Most native species declines stemmed from warm water streams of the Central Lowlands and Missouri River valley. Conservation of rare and declining native species and containment of nonnatives are both necessary to preserve historical patterns of fish biodiversity in South Dakota.     

Fishtail Mesa: a vegetation resurvey of relict area in Grand Canyon National Park, Arizona

Relict sites are geographically isolated areas that are undisturbed by direct and indirect human influences. These sites facilitate long-term ecological monitoring by providing a reference for gauging impacts occurring elsewhere. Knowledge gained through comparing vegetation change on matched relict and proximal disturbed areas can help partition the causes of change into natural and human-produced components. Fishtail Mesa in Grand Canyon National Park is a 439-ha relict site that is inaccessible to domestic livestock. Human visitation is infrequent and irregular, and fires have never been suppressed or managed. In 1958, U.S. Forest Service range scientists conducted a survey of Fishtail Mesa to gather reference data on vegetation, wildlife, and soils. Vegetation sampling was conducted using a method called the ";";elb.";"; We returned to Fishtail Mesa in May 1996 to perform a general vegetation and floristic survey, assess the extent of vegetation change after 38 years, and evaluate the suitability of the site as a location for long-term surveillance of ecological change. Fishtail Mesas vegetation consists primarily of a Pinus edulis (pinyon) and Juniperus osteosperma (Utah juniper) woodland with an Artemisia tridentata (sagebrush) understory, or tree-type (310.9 ha), and an Artemisia and Poa fendleriana (mutton grass) steppe, or shrub-type (127.5 ha). Since 1958 vegetation changes in both shrub- and tree-types have been limited to only a few species. In the shrub-type we detected slight increases from 1958 to 1996 in both Pinus and Juniperus , and reexamination of 1958 photo sites confirmed that Pinus and Juniperus are reoccupying the shrub-type. Artemisia cover declined from 1958 to 1996, whereas Poa increased from near trace amounts in 1958 to moderate cover in 1996. In the tree-type, Poa has increased from 1958 to 1996, while Artemisia , Juniperus , and Pinus showed no apparent change. Other species such as Ephedra torreyana (Torrey joint-fir), Opuntia polyacantha (prickly pear), and Gutierrezia sarothrae (snakeweed) have decreased. Vegetation analysis aided by TWINSPAN revealed that the shrub-type is defined more on the basis of absence of Pinus and Juniperus rather than any special association of differential species with a high preference for this type. We interpret the ";";invasion";"; of the shrub-type by Pinus and Juniperus as a ";";reoccupation.";"; Indirect ordination using DECORANA inferred 2 environmental gradients, a moisture gradient and perhaps a substrate texture gradient, that appeared to influence vegetation distribution on Fishtail Mesa. Fishtail Mesa is a valuable relict area for studying the effects of livestock grazing and prescribed fire. It should be designated a Federal Research Natural Area based on its vegetation communities, size, and protection afforded by its location in Grand Canyon National Park.     

Methods and materials for capturing and monitoring flammulated owls

Techniques for locating, capturing, and monitoring activities and movements of Flammulated Owls were developed during four years of study. Adults responded to imitated territorial song throughout the nesting season. Nests were found by noting vocalizations and behaviors associated with courtship-feeding and food transfers between the sexes. After fledging, broods were difficult to follow, unless the young or adults were radio-tagged. Adults and young were captured with noose poles, hoop nets, and mist nets. Backpack harnesses and tail-mounted transmitters were used on adults and backpacks on fledglings. Transmitter life was 30–40 nights.         

Science and philosophy in early modern Europe: The historiographical significance of the work of Charles B. Schmitt

In his many contributions to the history of science and the history of philosophy, the late Charles Schmitt demonstrated the interdependence of these two spheres of thought in early modern Europe. Schmitt was particularly insistent on a large and positive role for Aristotelian philosophy in the development of early modern science.