Extracellular enzyme activities (EEAs) are indicators of both soil microbial activity and nutrient availability for plants. However, it is unclear how EEAs change over the growing season in desert ...grasslands. We examined whether EEAs changed in response to the size and frequency of rain events during the summer monsoon in the northern Chihuahuan Desert, and if the response varied between plant and interspace associated soils. Potential EEAs were measured within a rainfall manipulation experiment at the Sevilleta National Wildlife Refuge in central New Mexico, USA. Rainfall treatments included either three 10-mm events or one 30-mm rain event per month throughout the three month summer monsoon (July-September). EEAs were measured immediately before and within hours after experimental rain events under plants and in unvegetated interspaces. Throughout the season hydrolase activities were higher under vegetation than in interspace soils. Potential activities of hydrolytic enzymes were similar for the two rainfall regimes. Activities increased following early season rain, showed little response to mid-season rain, and decreased following late-season rain. Although enzyme activities did not differ between rainfall treatments, ratios between enzymes varied, indicating different nutrient limitations imposed by rain event size and frequency. Larger nitrogen and phosphorus limitations occurred in interspace soils that experienced large, frequent rain events. Many factors, including location relative to plants, seasonality, and rainfall size and frequency, influenced enzyme activities and nutrient availability in these Chihuahuan Desert soils throughout the monsoon season.
Based on measured four-noise parameters and two-port noise theory, considerations for noise optimization of integrated low-noise amplifier (LNA) designs are presented. If arbitrary values of source ...impedance are allowed, optimal noise performance of the LNA is obtained by adjusting the source degeneration inductance. Even for a fixed source impedance, the integrated LNA can achieve near NF/sub min/ by choosing an appropriate device geometry along with an optimal bias condition. An 800 MHz LNA has been implemented in a standard 0.24 /spl mu/m CMOS technology. The amplifier possesses a 0.9 dB noise figure with a 7.1 dBm third-order input intercept point, while drawing 7.5 mW from a 2.0 V power supply, demonstrating that the proposed methodology can accurately predict noise performance of integrated LNA designs.
Therapeutic monoclonal immunoglobulins (mAbs) are used to treat patients with a wide range of disorders including autoimmune diseases. As pharmaceutical companies bring more fully humanized ...therapeutic mAb drugs to the healthcare market analytical platforms that perform therapeutic drug monitoring (TDM) without relying on mAb specific reagents will be needed. In this study we demonstrate that liquid-chromatography–mass spectrometry (LC–MS) can be used to perform TDM of mAbs in the same manner as smaller nonbiologic drugs. The assay uses commercially available reagents combined with heavy and light chain disulfide bond reduction followed by light chain analysis by microflow-LC–electrospray ionization-quadrupole-time-of-flight mass spectrometry (ESI-Q-TOF MS). Quantification is performed using the peak areas from multiply charged mAb light chain ions using an in-house developed software package developed for TDM of mAbs. The data presented here demonstrate the ability of an LC–MS assay to quantify a therapeutic mAb in a large cohort of patients in a clinical trial. The ability to quantify any mAb in serum via the reduced light chain without the need for reagents specific for each mAb demonstrates the unique capabilities of LC–MS. This fact, coupled with the ability to phenotype a patient’s polyclonal repertoire in the same analysis further shows the potential of this approach to mAb analysis.
•Mass spectrometry can identify bands of the same isotype as monoclonal or biclonal.•IgA M−proteins were most commonly found as monomers and dimers of a single clone.•IgG and IgM isotypes had a ...higher frequency of biclonal M−proteins.•Characterization by mass spectrometry can improve reporting accuracy.
Plasma cell disorders (PCDs) are typically characterized by excessive production of a single immunoglobulin, defined as a monoclonal protein (M−protein). Some patients have more than one identifiable M−protein, termed biclonal. Traditional immunofixation electrophoresis (IFE) cannot distinguish if two bands of the same isotype represent biclonal proteins or M−proteins with some other feature. A novel assay using immunoenrichment coupled to matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (Mass-Fix) was applied to determine whether two bands of the same isotype represented (1) monomers and dimers of a single M−protein, (2) an M−protein plus a therapeutic monoclonal antibody (t-mAb), (3) an M−protein with light chain glycosylation, or (4) two distinct biclonal M−proteins.
Patient samples with two bands of the same isotype identified by IFE were enriched using nanobodies against IgG, IgA, IgM, or κ and λ light chains then analyzed by Mass-Fix. Light chain masses were used to differentiate IgGκ M−proteins from t-mAbs. Mass differences between peaks were calculated to identify N-glycosylation or matrix adducts. High-resolution mass spectrometry was used as a comparator method in a subset of samples.
Eighty-one residual samples were collected. For IgA, 93% (n = 25) were identified as monoclonal. For IgG, 67% (n = 24) were monoclonal, and 33% (n = 12) were truly biclonal. Among the monoclonal IgGs, the second band represented a glycosylated form for 21% (n = 5), while 33% (n = 8) had masses consistent with a t-mAb. 44% (n = 8) of IgM samples were biclonal, and 56% (n = 10) were monoclonal, of which one was glycosylated.
We demonstrate the utility of mass spectrometry in the characterization of multiple IFE bands of the same isotype. Improved reporting accuracy of M−proteins is useful for monitoring of patients with PCDs.
•Utilization potential of Spray Dryer Absorber Material (SDAM) as an additive in concrete was determined.•A 20 wt% replacement of OPC with SDAM yielded a concrete that met the desirable 28-day ...performance criteria.•The results provide evidence against the stigma of poor durability when using SDAM in concrete.
The objective of this study was to determine the utilization potential of Spray Dryer Absorber Material (SDAM) as an additive in concrete made with portland cement. Utilizing SDAM for beneficial use such as portland cement replacement reduces the CO2 impact for every cubic meter of concrete placed, and provides a means for utilities to avoid the impacts of landfilling. The utilization of SDAM in concrete is often avoided due to delay in setting time, i.e. early-age strength-gain, and expansion related durability issues. The study included SDAM collected from five different coal combustion utilities. A series of laboratory experiments were conducted on the fresh and hardened concrete made by replacing 20 wt% of the portland cement. The findings of this research demonstrates that despite slow strength gain at early ages, a 20 wt% replacement of portland cement yielded a concrete that met the desirable 28-day performance criteria. Additionally, the incorporation of SDAM containing elevated levels of fly ash content improved the resistance to chloride permeability, and autoclave expansion resistance of concrete. These results provide evidence against the stigma of poor durability when using SDAM in concrete.
Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is ...genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
Abstract Context As endorsed by the palliative care “Measuring What Matters” initiative, capturing patients' direct assessment of their care is essential for ongoing quality reporting and ...improvement. Fostering an environment where seriously ill patients feel heard and understood is of crucial importance to modern health care. Objectives To describe the development and performance of a self-report field measure for seriously ill patients to report how well they feel heard and understood in the hospital environment. Methods As part of a larger ongoing cohort study of inpatient palliative care, we developed and administered the following point-of-care item: “Over the past two days, how much have you felt heard and understood by the doctors, nurses and hospital staff?” (completely, quite a bit, moderately, slightly, not at all). Participants completed the measure before and the day after palliative care consultation. For the postconsultation version, we changed the time frame from “past two days” to “today.” Results One hundred sixty patients with advanced cancer completed the preconsultation assessment, and 87% of them completed the postconsultation version. Responses encompassed full use of the ordinal scale, did not exhibit ceiling or floor effects, and showed improvement from preassessment to postassessment. The item was quick to administer and easy for patients to complete. Conclusion The “Heard & Understood” item is a promising self-report quality measure for the inpatient palliative care setting.
Purpose To predict the development of glaucomatous visual field (VF) defects using Fourier-domain optical coherence tomography (FD OCT) measurements at baseline visit. Design Multicenter longitudinal ...observational study. Glaucoma suspects and preperimetric glaucoma participants in the Advanced Imaging for Glaucoma Study. Methods The optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) were imaged with FD OCT. VF was assessed every 6 months. Conversion to perimetric glaucoma was defined by VF pattern standard deviation (PSD) or glaucoma hemifield test (GHT) outside normal limits on 3 consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. Predictive accuracy was measured by the area under the receiver operating characteristic curve (AUC). Results Of 513 eyes (309 participants), 55 eyes (46 participants) experienced VF conversion during 41 ± 23 months of follow-up. Significant ( P < .05, Cox regression) FD OCT risk factors included all GCC, NFL, and disc variables, except for horizontal cup-to-disc ratio. GCC focal loss volume (FLV) was the best single predictor of conversion (AUC = 0.753, P < .001 for test against AUC = 0.5). Those with borderline or abnormal GCC-FLV had a 4-fold increase in conversion risk after 6 years (Kaplan-Meier). Optimal prediction of conversion was obtained using the glaucoma composite conversion index (GCCI) based on a multivariate Cox regression model that included GCC-FLV, inferior NFL quadrant thickness, age, and VF PSD. GCCI significantly improved predictive accuracy (AUC = 0.783) over any single variable ( P = .04). Conclusions Reductions in NFL and GCC thickness can predict the development of glaucomatous VF loss in glaucoma suspects and preperimetric glaucoma patients.
Maximizing value in palliative care requires continued development and standardization of communication quality indicators.
To describe the basic epidemiology of a newly adopted patient-centered ...communication quality indicator for hospitalized palliative care patients with advanced cancer.
Cross-sectional analysis of 207 advanced cancer patients who received palliative care consultation at two medical centers in the U.S. Participants completed the Heard & Understood quality indicator immediately before and the day after the initial palliative care consultation: Over the past two days “24 hours” for the post-consultation version, how much have you felt heard and understood by the doctors, nurses, and hospital staff?—completely/quite a bit/moderately/slightly/not at all. We categorized completely as indicating ideal quality.
Approximately one-third indicated ideal Heard & Understood quality before palliative care consultation. Age, financial security, emotional distress, preferences for comfort-longevity tradeoffs at the end of life, and prognosis expectations were associated with preconsultation quality. Among those with less-than-ideal quality at baseline, 56% rated feeling more Heard & Understood the day after palliative care consultation. The greatest prepost improvement was among people who had unformed end-of-life treatment preferences or who reported having no idea about their prognosis at baseline.
Most patients felt incompletely heard and understood at the time of referral to palliative care consultation, and more than half of the patients improved after consultation. Feeling heard and understood is an important quality indicator sensitive to interventions to improve care and key variations in the patient experience.
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