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Native ion mobility-mass spectrometry (IM-MS) typically introduces protein ions into the gas phase through nano-electrospray ionization (nESI). Many nESI setups have mobile stages for tuning the ion signal and extent of co-solute and salt adduction. However, tuning the position of the emitter capillary in nESI can have unintended downstream consequences for collision-induced unfolding or collision-induced dissociation (CIU/D) experiments. Here, we show that relatively small variations in the nESI emitter position can shift the midpoint (commonly called the "CID50" or "CIU50") potential of CID breakdown curves and CIU transitions by as much as 8 V on commercial instruments. A spatial "map" of the shift in CID50 for the loss of heme from holomyoglobin onto the emitter position on a Waters Synapt G2-S i mass spectrometer shows that emitter positions closer to the instrument inlet can result in significantly greater in-source activation, whereas different effects are found on an Agilent 6545XT instrument for the ions studied. A similar effect is observed for CID of the singly protonated leucine enkephalin peptide and Shiga toxin 1 subunit B homopentamer on the Waters Synapt G2-S i instrument. In-source activation effects on a Waters Synapt G2-S i are also investigated by examining the RMSD between CIU fingerprints acquired at different emitter positions and the shifts in CIU50 for structural transitions of bovine serum albumin and NIST monoclonal antibody.

The decline of biodiversity from anthropogenic landscape modification is among the most pressing conservation problems worldwide. In North America, long-term population declines have elevated the recovery of the grassland avifauna to among the highest conservationpriorities. Because the vast majority of grasslands of the Great Plains are privately owned, the recovery of these ecosystems and bird populations within them depend on landscape-scale conservation strategies that integrate social, economic, and biodiversity objectives. The Conservation Reserve Program (CRP) is a voluntary program for private agricultural producers administered by the United States Department of Agriculture that provides financial incentives to take cropland out of production and restore perennial grassland. We investigated spatial patterns of grassland availability and restoration to inform landscape-scale conservation for a comprehensive community of grassland birds in the Great Plains. The research objectives were to (1) determine how apparent habitat loss has affected spatial patterns of grassland bird biodiversity, (2) evaluate the effectiveness of CRP for offsetting the biodiversity declines of grassland birds, and (3) develop spatially explicit predictions to estimate the biodiversity benefit of adding CRP to landscapes impacted by habitat loss. We used the Integrated Monitoring in Bird Conservation Regions program to evaluate hypotheses for the effects of habitat loss and restoration on both the occupancy and species richness of grassland specialists within a continuum-modeling framework. We found the odds of community occupancy declined by 37% for every 1 SD decrease in grassland availability [log e (km 2 )] and increased by 20% for every 1 SD increase in CRP land cover [log e (km 2 )]. There was 17% turnover in species composition between intact grasslands and CRP landscapes, suggesting that grasslands restored by CRP retained considerable, but incomplete, representation of biodiversity in agricultural landscapes. Spatially explicit predictions indicated that absolute conservation outcomes were greatest at high latitudes in regions with high biodiversity, whereas the relative outcomes were greater at low latitudes in highly modified landscapes. By evaluating community-wide responses to landscape modification and CRP restoration at bioregional scales, our study fills key information gaps for developing collaborative strategies, and for balancing conservation of avian biodiversity and social well-being in the agricultural production landscapes of the Great Plains., (© 2022 The Ecological Society of America.)

Distribution models are increasingly being used to understand how landscape and climatic changes are affecting the processes driving spatial and temporal distributions of plants and animals. However, many modeling efforts ignore the dynamic processes that drive distributional patterns at different scales, which may result in misleading inference about the factors influencing species distributions. Current occupancy models allow estimation of occupancy at different scales and, separately, estimation of immigration and emigration. However, joint estimation of local extinction, colonization, and occupancy within a multi-scale model is currently unpublished. We extended multi-scale models to account for the dynamic processes governing species distributions, while concurrently modeling local-scale availability. We fit the model to data for lark buntings and chestnut-collared longspurs in the Great Plains, USA, collected under the Integrated Monitoring in Bird Conservation Regions program. We investigate how the amount of grassland and shrubland and annual vegetation conditions affect bird occupancy dynamics and local vegetation structure affects fine-scale occupancy. Buntings were prevalent and longspurs rare in our study area, but both species were locally prevalent when present. Buntings colonized sites with preferred habitat configurations, longspurs colonized a wider range of landscape conditions, and site persistence of both was higher at sites with greener vegetation. Turnover rates were high for both species, quantifying the nomadic behavior of the species. Our model allows researchers to jointly investigate temporal dynamics of species distributions and hierarchical habitat use. Our results indicate that grassland birds respond to different covariates at landscape and local scales suggesting different conservation goals at each scale. High turnover rates of these species highlight the need to account for the dynamics of nomadic species, and our model can help inform how to coordinate management efforts to provide appropriate habitat configurations at the landscape scale and provide habitat targets for local managers.

Adaptive management provides a useful framework for managing natural resources in the face of uncertainty. An important component of adaptive management is identifying clear, measurable conservation objectives that reflect the desired outcomes of stakeholders. A common objective is to have a sustainable population, or metapopulation, but it can be difficult to quantify a threshold above which such a population is likely to persist. We performed a Bayesian metapopulation viability analysis (BMPVA) using a dynamic occupancy model to quantify the characteristics of two wood frog (Lithobates sylvatica) metapopulations resulting in sustainable populations, and we demonstrate how the results could be used to define meaningful objectives that serve as the basis of adaptive management. We explored scenarios involving metapopulations with different numbers of patches (pools) using estimates of breeding occurrence and successful metamorphosis from two study areas to estimate the probability of quasi-extinction and calculate the proportion of vernal pools producing metamorphs. Our results suggest that ≥50 pools are required to ensure long-term persistence with approximately 16% of pools producing metamorphs in stable metapopulations. We demonstrate one way to incorporate the BMPVA results into a utility function that balances the trade-offs between ecological and financial objectives, which can be used in an adaptive management framework to make optimal, transparent decisions. Our approach provides a framework for using a standard method (i.e., PVA) and available information to inform a formal decision process to determine optimal and timely management policies.

Background: Spinal cord stimulation (SCS) is an established treatment option for chronic pain. Prior to permanent implantation, temporary trials are performed to evaluate the SCS treatment. During the trial period, it is common for the patients to experience changes in paresthesias. However, it is unclear what the role of lead migration is, if any, in the changes in paresthesia., Objective: To evaluate the role of lead migration on the effect of postural stimulation changes during SCS trials., Study Design: Case series., Setting: University pain management center., Methods: X-rays of the patients with successful trials, in sitting and standing position, were obtained at the end of a 7 day SCS trial. Data were collected based on the need for adjustment of the stimulation settings due to changes in paresthesias with postural change of sitting versus standing., Results: The average lead migration was 3.05 mm inferiorly from a standing to sitting position for all subjects. The average migration was 2.85 mm in subjects requiring adjustment of the SCS setting due to change in paresthesia compared to 3.24 mm for those who did not require adjustment regardless of position. The results were insignificant based on P = 0.17., Limitations: Small sample size, case series., Conclusions: This case series demonstrates continued support for the role of the width of the cerebral spinal fluid space as the significant factor on paresthesia changes in SCS with respect to postural changes, even during the trial period.

Observations of star formation and kinematics in early galaxies at high spatial and spectral resolution have shown that two-thirds are massive rotating disk galaxies, with the remainder being less massive non-rotating objects. The line-of-sight-averaged velocity dispersions are typically five times higher than in today's disk galaxies. This suggests that gravitationally unstable, gas-rich disks in the early Universe are fuelled by cold, dense accreting gas flowing along cosmic filaments and penetrating hot galactic gas halos. These accreting flows, however, have not been observed, and cosmic accretion cannot power the observed level of turbulence. Here we report observations of a sample of rare, high-velocity-dispersion disk galaxies in the nearby Universe where cold accretion is unlikely to drive their high star formation rates. We find that their velocity dispersions are correlated with their star formation rates, but not their masses or gas fractions, which suggests that star formation is the energetic driver of galaxy disk turbulence at all cosmic epochs.

Objective: To demonstrate that including the patient's perspective of disease control (patient-reported symptoms) in asthma treatment and management decisions improves patient outcomes and reduces healthcare resource utilization., Study Design: Two study phases gathered patients' assessments of disease control. Phase 1 used a retrospective physician questionnaire. Phase 2 used a patient questionnaire at each office visit. Physicians and patients were members of the Independent Health Association, a health insurer in upstate New York., Methods: Phase 1 gathered patients' assessment of asthma control retrospectively using a physician questionnaire. Physicians received a list of pediatric patients in their practice who had intermittent and persistent asthma as their primary diagnosis. They reviewed a sample of these actively managed patients and answered 10 questions about them. Phase 2 was designed to include the patient's perspective. The Asthma Control Test was sent to every patient with asthma to complete and to bring to each physician visit., Results: In phase 1, emergency department visits and hospitalizations for asthma decreased during the program. Emergency department visits decreased from 3.71 to 2.92 per year (P < .01), and hospitalizations decreased from 0.83 to 0.81 per year (not statistically significant). Results for phase 2 are not yet available., Conclusions: Although not a controlled program, for the participating practices the Independent Health Association health plan seems to have improved patient outcomes when they included retrospective, documented, patient-reported symptoms in their asthma management decisions. Emergency department visits and hospitalizations decreased. Managed care organizations should consider adding the patient's perspective of disease control to their asthma management decisions.

The lysosomal aspartyl protease, cathepsin D, has been suggested to play a role in the metastatic potential of several types of cancer. Cathepsin D is secreted by malignant cells, and is believed to be involved in the breakdown of the extracellular matrix. High levels of active cathepsin D have been found in colon cancer, prostate cancer, uterine cancer and ovarian cancer. Also cathepsin D has recently been associated with the development of Alzheimer's disease. Hydroxyethyl isosteres with cyclic tertiary amine have proven to be clinically useful as inhibitors of aspartyl proteases similar to cathepsin D in activity, such as the HIV-1 aspartyl protease. In the present study twenty-eight compounds containing (hydroxyethyl)amine isosteres with cyclic tertiary amines have been synthesized. These compounds show significant activity as cathepsin D inhibitors, many with IC(50) values in the nanomolar range. For example, the compounds that contain hydroxyethylamines where the amine is formed from N-piperazine-2-carboxylic acid methyl ester, 4y-bb, show IC(50) values ranging from 2.5 to 15 nM.

Odontogenic causes are the most common source for spreading maxillo-facial infections. These infections can develop into life threatening events. However a fatal outcome is fortunately rare and is generally associated with an immunocompromised status. This case report highlights a spreading maxillo-facial infection, which resulted in massive haemorrhage from the subclavian vein into the pleural cavity and subsequent death of a young fit male patient.

New technology involving the use of high-frequency inductive power distribution (HID) has recently been developed for use in materials handling and personnel transfer. Sinusoidal magnetic fields at a frequency of 10 kHz with field intensities of approximately 0.2 mT are generated directly between the current-carrying coils of this equipment. Effects of 10 kHz magnetic fields on cell division, migration, and differentiation have never been previously investigated. To evaluate potential effects on these parameters, a rodent reproductive study was undertaken using Wistar rats. Exposures were at 0.095, 0.24, and 0.95 mT with a background exposure of 5-10 microT. Three sets of parental rats were exposed continuously for 20-23.5 h/day to the fields: maternal rats during gestation, paternal rats for at least 45 days prior to mating and maternal rats 1 month prior to mating. Exposure phases thus covered spermatogenesis, maturation of the ovum and ovulation, fertilization, implantation, embryogenesis, organogenesis, and maturation of the fetus immediately prior to parturition. In all experiments pregnancy outcome was assessed. These studies failed to demonstrate any reproductive toxicity resulting from maternal or fetal exposure during gestation or following paternal or maternal exposure for several weeks prior to mating. No quantitative or qualitative effects on spermatogenesis occurred after exposure, and no effects on the estrous cycle or ovulation could be demonstrably linked to the 10 kHz magnetic field exposure at 0.095, 0.25, or 0.95 mT. Where possible, parental clinical chemistry and hematology were also examined. As in mouse toxicology studies previously reported, minor differences were observed between control and treated groups. These were regarded as statistically, but not biologically, significant and could not categorically be attributed to magnetic field exposure.

A new methodology is presented to improve the design and tuning of a fuzzy logic controller (FLC) using variable structure control (VSC) theory. A VSC-type rule base is constructed and the fundamentals of FLC explored quantitatively by VSC theory. A very concise mathematical expression for the FLC is presented, in which the Lyapunov stability criterion can be applied to guide the design and tuning. This results in a simpler and more systematic procedure. Application of the method to higher order systems is made straight forward by applying a hierarchical technique. The validity of the design methodology is demonstrated by simulation.

Triamcinolone acetonide (TAA) aerosol nasal inhaler has been shown to effectively relieve the symptoms of seasonal allergic rhinitis in adults and adolescents. We conducted a study to evaluate the efficacy and safety of once-daily administration of TAA aerosol nasal inhaler in pediatric patients aged 6 to 11 years with grass seasonal allergic rhinitis. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled 116 children who were treated with either TAA aerosol nasal inhaler (220 micrograms/d) or placebo once daily for 2 weeks. Patients evaluated the severity of rhinitis symptoms (nasal stuffiness, discharge, sneezing, and itching) daily according to a four-point scale (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Patients' and physicians' global evaluations of overall treatment efficacy were assessed at the end of the 2-week treatment period. Patients treated with TAA aerosol nasal inhaler had significantly greater reductions in all nasal symptom scores overall and in virtually all symptoms at the end of week 1 and week 2 compared with those in the placebo group. Both patients' and physicians' global evaluations of efficacy favored TAA aerosol nasal inhaler over placebo. This study demonstrated that once-daily administration of 220 micrograms of TAA aerosol nasal inhaler was well tolerated and effectively reduced the symptoms of seasonal allergic rhinitis in pediatric patients.

A high-frequency inductive power distribution (HID) technology has been developed that generates sinusoidal magnetic fields at a frequency of 10 kHz. In typical industrial applications, field intensities in the order of 0.2 mT can be expected between the current-carrying coils. Because the possible health effects of 10 kHz sinusoidal magnetic fields of this type had never been investigated, a broad evaluation of possible effects on animal health was made in a preliminary 14 day acute study and in a 90 day subchronic study using male and female B6C3F1 mice. Exposures were at 0.08, 0.28, and 1.0 mT vs. a background exposure of 3.7 microT and were essentially continuous. These studies failed to demonstrate any health effects that can be clearly related to the magnetic field exposure. No changes in animal behaviour or indications of morbidity were detected during the initial exposure to the fields. There were no significant differences in body weight between exposed and unexposed (control) mice at any time in the study, and the clinical chemistry and hematology parameters were essentially unchanged. Although minor differences in some clinical chemistry and hematology parameters were seen between control and exposure groups, the lack of exposure dependence, the lack of consistency between sexes, and the lack of correspondence with the results of the two studies all suggest that these were chance associations. Even if the changes were real, the magnitude of the changes was very small and does not indicate serious biological effects. Finally, all organs were macroscopically and microscopically normal except for isolated, generally mild, histological lesions and lesions that were ascribed to fighting among males. There was no obvious association with field intensity.

The pharmacokinetics of theophylline and methylprednisolone were examined before and during cimetidine treatment in an asthmatic woman who required long-term administration of these drugs. Cimetidine reduced theophylline plasma clearance by 30 percent, and measurement of urinary metabolites showed that 3-methylxanthine formation was inhibited more strongly than that of the methylated uric acid metabolites. Assessment of methylprednisolone disposition following oral and intravenous doses revealed no effect of cimetidine on the bioavailability (74 to 81 percent absorption) or plasma clearance (22 to 24 liters per hour) of the steroid. Thus, cimetidine exhibits variable and selective effects on the biotransformation pathways of drugs important in asthma therapy.

During the summer of 1978, 22 patients who had large local reactions following insect stings were evaluated for the development of potential systemic sensitivity. Approximately half the patients had venom IgE antibodies, detected by either the immediate skin test or radioallergosorbent test (RAST). A control group of 26 patients experiencing normal sting reactions had only a 15% incidence of venom-specific IgE. No correlations could be found between the presence of venom-specific IgE and age, sex, sting location, atopic history, or prior stings. IgE antibodies were found in 13 of 17 patients who had experienced local reactions lasting more than 48 hr. Serum venom-specific IgG was detected in only three of 19 patients. These results suggest that following large local reactions from insect stings patients must be individually assessed for the presence of venom-specific IgE and consideration for specific immunotherapy.

The mean and standard deviation over 24 h for 3 groups of animals - active, intermediate and inactive - in physical activity units were 10948 +/- 3360, 2611 +/- 1973 and 484 +/- 316 respectively. The differences were significant (P = 0.004), demonstrating the ability of the method to distinguish between groups that can be visibly differentiated. The small within-animal physical activity standard deviation (18.85 PAU) obtained in another group, suggests that it also yields reliable physical activity measurements for non-human primates. The monitoring device used can discriminate between individual nonhuman primates physical activity levels in a free-living environment and does not alter daily behaviour. This makes possible the study of the relationship between physical activity and atherosclerosis in nonhuman primates.

Troleandomoycin (TAO), a macrolide antibiotic, has an apparent "steroid-sparing" effect when used in the treatment of severe steroid-dependent asthma. This study was designed to investigate the effect of TAO on methylprednisolone elimination. Pharmacokinetic studies were performed before and 1 wk after starting TAO in 10 severe steroid-dependent asthmatics. Baseline total body clearance of methylprednisolone was 406 +/- 139 (mean +/- SD) ml/min/1.73 m2 and decreased significantly (p < 0.001) to 146 +/- 57 ml/min/1.73 m2 1 wk after TAO therapy was initiated. Methylprednisolone half-life was 2.46 +/- 0.75 hr before TAO and increased significantly (p < 0.01) to 4.63 +/- 1.35 hr after 1 wk on TAO therapy. A follow-up evaluation of methylprednisolone pharmacokinetics in three patients after at least 1 mo on TAO therapy demonstrated continuation of the reduced methylprednisolone elimination. TAO inhibition of methylprednisolone clearance may contribute to the beneficial effects observed initially with combined methylprednisolone-troleandomycin therapy in severe steroid-dependent asthma.

One hundred thirty-two asthmatic patients with bronchial asthma were studied by 20 independent investigators during this 49-day study. One hundred sixty-four patients entered into this study, and up to 132 were judged evaluable for statistical purposes. Criteria for entry included current q 12-hour therapy with an available theophylline product (eg, Theo-Dur, Slo-Bid, etc). Use of beta-agonist aerosols PRN was permitted, as was use of steroid aerosols for short periods of time. Chronic treatment with oral corticosteroids or other oral bronchodilators was prohibited. Baseline peak and trough serum theophylline concentrations (STCs) and performance of pulmonary function tests (PFTs) were determined during q 12-hour treatment. Patients were then switched within one dosing interval to an equivalent single daily dose of Theo-24 and maintained on this therapy for the duration of the study. STC and PFT measurements were repeated on days 8, 21, and 49 of the Theo-24 study period. Throughout the 49-day study, patients measured their peak expiratory flow rate at home, at 8 AM, and at 8 PM using a Mini-Wright Peak Flow Meter. These data, along with asthma symptomatology and frequency of inhaled bronchodilator aerosol usage, were recorded daily in diary form. Three days after the start of Theo-24 treatment, the mean peak STC (11.18 micrograms/mL) was not significantly different from the mean peak STC with q 12-hour treatment (11.4 micrograms/mL) in 121 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Melanotic hamster malignant melanoma (MM1) is a transplantable, locally invasive tumor which metastasizes widely in syngeneic hosts. We have established three clones, HM1, HM3, and HM4 of the original MM1 line in culture. Inoculation (s.c.) into 4- to 5-week-old male athymic mice produced highly vascular, melanotic, locally invasive tumors in 100% of mice inoculated with a latency of 4-7 days. Karyotype analysis of HM cells revealed modal chromosome numbers of 39-41 (43% HM1), 43 (22% HM3), and 44-47 (61% HM4). Sixty-one % of HM1 cells were hypodiploid, 4% diploid, and 5% hyperdiploid. HM1, -3, and -4 cells also exhibited aneuploidy, endoreduplication, translocational exchanges, additions, deletions, dicentromeric and ring chromosomes, and double minutes although not all cells exhibited all abnormalities. Initial metastasis was to regional lymph nodes with eventual progression to lung and liver. Mice inoculated with HM1, -3, and -4 cells were dead with metastatic disease within 57, 63, and 64 days, respectively, following s.c. inoculation (5 X 10(5) cells) when the mice were 90-100 days old. Mortality rate was highest in line HM3 with 50% of the mice dead within 33 days postinoculation. Metastatic potential of HM1 and HM3 cells rose significantly when successive generations of HM1 and HM3 cells cultured from isolated lung metastasis were reinoculated. Metastasis to lymph nodes and liver was not observed with increasing passage generations of lung metastasis. Our observations provide evidence that hamster melanomas are clonally heterogenous, locally invasive, and exhibit rapid growth and metastasis following s.c. inoculation into adult athymic mice. Transplantable melanotic hamster melanoma cells also exhibit a significant preferential metastasis to lung following culture and sequential reinoculation of lung metastasis in athymic mice. As such, they appear to provide a reproducible model of metastasis in an immunocompromised host.