Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened ...long-term postoperative cognitive trajectory is the Alzheimer's disease (AD) genetic risk factor APOE4. APOE4 is thought to elevate AD risk partly by increasing neuroinflammation, which is also a theorized mechanism for PND. Yet, it is unclear whether modulating apoE4 protein signaling in older surgical patients would reduce PND risk or severity.
MARBLE is a randomized, blinded, placebo-controlled phase II sequential dose escalation trial designed to evaluate perioperative administration of an apoE mimetic peptide drug, CN-105, in older adults (age≥60 years). The primary aim is evaluating the safety of CN-105 administration, as measured by adverse event rates in CN-105 versus placebo-treated patients. Secondary aims include assessing perioperative CN-105 administration feasibility and its efficacy for reducing postoperative neuroinflammation and PND severity.
201 patients undergoing non-cardiac, non-neurological surgery will be randomized to control or CN-105 treatment groups and receive placebo or drug before and every six hours after surgery, for up to three days after surgery. Chart reviews, pre- and postoperative cognitive testing, delirium screening, and blood and CSF analyses will be performed to examine effects of CN-105 on perioperative adverse event rates, cognition, and neuroinflammation. Trial results will be disseminated by presentations at conferences and peer-reviewed publications.
MARBLE is a transdisciplinary study designed to measure CN-105 safety and efficacy for preventing PND in older adults and to provide insight into the pathogenesis of these geriatric syndromes.
A new family of AC-DC converters is derived which integrate the functions of low-harmonic rectification, low-frequency energy storage, and wide-bandwidth output voltage control into a single ...converter containing one, two, or four active switches. These converters utilize a discontinuous conduction mode input inductor, an internal energy storage capacitor, and transformer secondary circuits which resemble the bridge, forward, flyback, or Cuk DC-DC converters. A large-signal equivalent circuit model for this family is presented, which uses the "loss-free resistor" concept. Design strategies and experimental results are given. High-performance regulation with satisfactory line-current harmonics is demonstrated with conventional duty-ratio control. Further improvements in line current are possible by simultaneous duty-ratio and switching-frequency control.
Vasopressin is an indicating biomarker for blood pressure in the human body and low vasopressin levels can be indicative of late-phase hemorrhagic shock or other traumatic injuries. In this paper we ...have developed an aptamer-based label-free microfluidic biosensor for the electrochemical detection of vasopressin. The detection area consists of aptamers immobilized on carbon nanotubes which specifically capture the vasopressin molecules in solution resulting in changes in conductivity across the sensor. We report a limit of detection of 43pM in standard solutions and demonstrate high detection specificity toward vasopressin when different interferents are present. The miniaturized microfluidic biosensor offers continuous monitoring of different vasopressin levels with good potential for portability. Ultimately such a system could serve as a point-of-care diagnostics tool for patients with excessive bleeding when standard medical infrastructure is not available.
Species richness (S) increases with area (A) as shown in the well-known power function proposed by Arrhenius: S=cAz. We show that the exponent of the species-area curves, z, was negatively correlated ...with aboveground annual production (biomass) but the coefficient of the curves, c, was positively correlated with production in two communities dominated by grasses and sedges in beaver meadows in northern Minnesota. The parameters of the species-area power function were not correlated with water table depth nor with soil nutrient availabilities. We then show that the often-reported unimodal relationship between richness and productivity can be derived from the negative correlation of z and the positive correlation of c with productivity. We also show that the productivity corresponding to maximum richness declines with increasing area sampled. All other correlations of c and z with productivity yield either monotonically increasing or decreasing richness with increasing productivity. The relationships between richness and productivity depend on the area censused and the correlations of the coefficient and exponent of the species-area curve with productivity. Interpretations of diversity-productivity relationships are sensitive to plot size and require specification of the species-area relationship for the community in question.
Hurricane activity is predicted to increase over the mid‐Atlantic as global temperatures rise. Nitrous oxide (N2O), a greenhouse gas with a substantial source from tropical soils, may increase after ...hurricanes yet this effect has been insufficiently documented. On September 21, 1998, Hurricane Georges crossed Puerto Rico causing extensive defoliation. We used a before–after design to assess the effect of Georges on N2O emissions, and factors likely influencing N2O fluxes including soil inorganic nitrogen pools and soil water content in a humid tropical forest at El Verde, Puerto Rico. Emissions of N2O up to 7 months post‐Georges ranged from 5.92 to 4.26 ng cm−2 h−1 and averaged five times greater than fluxes previously measured at the site. N2O emissions 27 months after the hurricane remained over two times greater than previously measured fluxes. Soil ammonium pools decreased after Georges and remained low. The first year after the hurricane, nitrate pools increased, but not significantly when compared against a single measurement made before the hurricane. Soil moisture and temperature did not differ significantly in the two sampling periods. These results suggest that hurricanes increase N2O fluxes in these forests by altering soil N transformations and the relative availabilities of inorganic nitrogen.
Thalidomide, the drug that caused a worldwide epidemic of serious birth defects in the late 1950s and early 1960s, was recently approved by the US Food and Drug Administration (FDA) for use in ...treating the skin disease erythema nodosum leprosum, a complication of leprosy. The drug has also shown promise in the treatment of other serious diseases. If thalidomide is eventually approved for use in the US and other countries for treatment of diseases more prevalent than erythema nodosum leprosum, or if use of the drug for non-approved indications becomes widespread, hundreds of thousands of women with childbearing ability could be treated. If this should happen, can we prevent another epidemic of birth defects? In an effort to prevent fetal exposures to thalidomide, the FDA mandated a comprehensive programme to regulate prescription, dispensing and use of the drug. The programme is designed to require registration of all participating prescribers, pharmacies and patients. It also requires use of effective methods of contraception and periodic pregnancy testing of all patients with childbearing ability during treatment. Prescribers are directed to counsel both female and male patients on the risks, benefits and proper use of the drug, as well as on the proper use of contraceptives during treatment. The patient is required to sign an informed consent form before beginning treatment. Prescription and dispensing of thalidomide will be tightly controlled. Athalidomide registry will monitor prescription. dispensing and use of the drug, and will investigate all reported fetal exposures. This mandatory, but untested, programme promises to be effective at preventing fetal exposures to thalidomide, provided that patients, prescribers and pharmacists comply with all of its provisions. However, even if the programme proves to be successful in the US, there is concern that thalidomide may eventually be widely used in countries that may not require such stringent controls. In Brazil, where thalidomide is commercially available for treatment of leprosy patients, 33 cases of thalidomide embryopathy have already been reported in the literature. Even in countries that may tightly regulate the distribution and use of thalidomide, some patients may obtain the drug through black market sources. Should these events occur, many cases of thalidomide-induced birth defects could appear. Therefore, there is a need to develop nonteratogenic analogues of thalidomide that can provide effective treatment for erythema nodosum leprosum and other serious conditions without increasing the potential for another epidemic of thalidomide-related birth defects.
BACKGROUND
Two new prostate cancer markers, free‐prostate specific antigen (f‐PSA) and prostate specific membrane antigen (PSMA) were recently introduced. This report summarizes a prospective ...two‐year multicenter test of their diagnostic or prognostic capabilities. Total PSA was also measured.
METHODS
There were four clinical groups studied: (1) 226 individuals from a screening project undergoing ultrasound and biopsy evaluation had markers obtained: (2) 68 patients suspected of having prostate cancer and undergoing 2 or more biopsies had the markers obtained on multiple occasions: (3) 100 patients undergoing radical prostatectomy had markers obtained pre‐ and post‐operatively: and (4) 31 patients with metastatic prostate cancer each had multiple samples for marker assay obtained over a 2‐year period. In all, 465 patients had one or more samples obtained and studied.
RESULTS
Free‐PSA affords little additional diagnostic advantage compared with total PSA in the screening population. The reciever operating characteristic curves for diagnostic accuracy were ranked: (1) PSA density; (2) total PSA; (3) f‐PSA; and (4) PSMA. PSMA showed the best correlation with stage of the primary tumor in the screened group. In the multiple negative biopsy group, f‐PSA varied from 12 to 21%. PSMA values were evaluated in all histologic categories. PSA density was; ce0.15 in all categories. In the prostatectomy cases PSA values postoperatively were quite low in Stage II; f‐PSA was of no value. Later, f‐PSA was increased in association with elevated total PSA values. Mean PSMA values were above normal in all postoperative time periods except in Stage III patients at 6 months to 1 year postoperatively. PSA densities were all; ce0.15. In patients with metastatic carcinoma, elevated PSMA values correlated best with a poor prognosis (clinical progression), as has been described.
CONCLUSIONS
These data suggest that f‐PSA values do not provide additional diagnostic benefit compared with total PSA in screening populations, in the presence of suspected cancer, postprostatectomy, or in metastatic disease. PSMA is of prognostic significance, especially in the presence of metastatic disease, and correlates well with the stage of disease in cancers detected in a screened population. Cancer 1996;78:809‐18.
Hydrocarbons of worker honeybees of known pedigree were extracted and analyzed using gas chromatography and mass spectrometry. Variability in hydrocarbon extracts of individual workers is determined ...at least in part genetically. Correlations in hydrocarbon composition of extracts were highest among more closely related individuals. Individuals maintained in groups exchange hydrocarbons but still maintain enough self-produced compounds to retain genetically determined individual characteristics. These results demonstrate that extractable hydrocarbons of bees provide sufficiently reliable genetic information to function as labels for use during kin recognition
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