Degree of Dietary Specialization on Furanocoumarin-Containing Hostplants in a Newly Invasive Web Building Caterpillar.

The genus Depressaria (Lepidoptera: Depressariidae) mostly comprises specialist herbivores with varying capacity for detoxification of defensive phytochemistry. Depressaria depressana, a Eurasian moth recently introduced into North America, is a family-level specialist of the Apiaceae, whose hosts include more than a dozen species in multiple tribes; Depressaria radiella is a super-specialist of Eurasian origin that feeds exclusively on species in the genera Pastinaca and Heracleum throughout its native and introduced range. In eastern North America, it feeds upon Pastinaca sativa, an invasive European species, and Heracleum maximum, a native species. We determined whether differences in furanocoumarin metabolism exist between D. depressana and two isolated populations of D. radiella, feeding exclusively on either P. sativa or H. maximum. We also compared gravimetric estimates of feeding efficiency to assess D. depressana larval performance on different diets. Both populations of D. radiella metabolized furanocoumarins at a greater rate than D. depressana. Although there was no difference in rates of metabolism of linear furanocoumarins in the two populations of D. radiella, individuals collected from H. maximum metabolized angular furanocoumarins more rapidly. The gravimetric assessments of feeding efficiencies revealed that D. depressana exhibited highest efficiencies consuming Daucus carota; moreover, this species survived to pupation consuming fruits of Zizia aurea, an apiaceous species native to North America. Our preliminary phylogenetic analysis, building on an earlier morphological analysis, incorporates mitochondrial cytochrome oxidase subunit 1 data from the BOLD database and revealed that the presence or absence of furanocoumarins is not a strong predictor of species-level evolution in Depressaria.

Experimental comparison of fiber optic parametric, Raman and erbium amplifiers for burst traffic for extended reach PONs.

We experimentally compare the performance of a polarization-independent fiber optic parametric amplifier (FOPA), a discrete Raman amplifier and a commercial erbium doped fiber amplifier (EDFA) for burst traffic amplification in extended reach passive optical networks (PON). We demonstrate that EDFA and Raman amplifiers suffer from severe transient effects, causing penalty on receiver sensitivity >5 dB for traffic bursts of 10 Gbps on-off keying signal shorter than 10 µs. On the other hand, we demonstrate that FOPA does not introduce a penalty on receiver sensitivity when amplifying signal bursts as short as 5 µs as compared to a non-burst signal. Therefore, FOPA used as a drop-in replacement for an EDFA or Raman amplifier allows us to improve receiver sensitivity by >3 dB for short signal bursts. We conclude that FOPA allows substantially increased power budget for an extended reach PON transmitting variable duration bursts. In addition, we identify the maximum burst duration tolerated by each examined amplifier.

Well-Posed Formulation of Scalar-Tensor Effective Field Theory.

Effective field theory provides a way of parametrizing strong-field deviations from general relativity that might be observable in the gravitational waves emitted in a black hole merger. To perform numerical simulations of mergers in such theories it is necessary that the equations be written in a form that admits a well-posed initial value formulation. We study gravity coupled to a scalar field including the leading (four-derivative) effective field theory corrections. We introduce a new class of "modified harmonic" gauges and gauge-fixed equations of motion, such that, at weak coupling, the equations are strongly hyperbolic and therefore admit a well-posed initial value formulation.

ß-Phenylethylamine and various monomethylated and para-halogenated analogs. Acute toxicity studies in mice.

Phenylethylamine's acute toxic effects in a population of adult (10 to 12 weeks old; ∼30 g) Swiss male albino mice are significantly increased by para-position aromatic ring halogenation. LDLO, LD50, and LD100 values (mg/kg; x ± SEM) for p-F- (116.7 ± 3.3, 136.7 ± 1.7, and 160.0 ± 2.9), p-Br- (126.7 ± 3.3, 145.0 ± 2.9, and 163.3 ± 3.3), p-Cl- (133.3 ± 3.3, 146.7 ± 1.7, and 165.0 ± 2.9), and p-I-PEA (133.3 ± 3.3, 153.3 ± 1.7, and 168.3 ± 1.7), compared to PEA 203.3 ± 3.3, 226.7 ± 4.4, and 258.3 ± 8.8). Like PEA, the difference between LDLO and LD50, and LD50 and LD100 for individual amines were similar and in the range (10 to 20%). Toxicity variation between the various p-halogenatedPEAs also fell within a relatively narrow range (as a group: LDLO 116.7 ± 3.3 to 133.3 ± 3.3, LD50 136.7 ± 1.7 to 153.3 ± 1.7, and LD100 160.0 ± 2.9 to 168.3 ± 1.7 mg/kg). PEA methylation, (exception of its α-methyl derivative), results in relatively modest changes in acute toxicity. LDLO, LD50, and LD100 values (mg/kg; x ± SEM) for N-Me- (176.6 ± 3.3, 200.0 ± 2.9, and 221.7 ± 3.3), p-Me- (183.3 ± 3.3, 206.7 ± 3.3, and 225.0 ± 2.9), o-Me- (210.0 ± 5.8, 233.3 ± 3.3, and 258.3 ± 1.7), and ß-MePEA (220.0 ± 5.8, 243.3 ± 4.4, and 278.3 ± 44). Similar to PEA, and the p-HPEAs, the difference between LDLO and LD50 and LD50 and LD100 values for individual amines fell within a relatively narrow range (10 to 20%). Variation in toxicity among the methylatedPEAs also fell within a limited range (as a group: LDLO 176 ± 3.3 to 220 ± 5.8, LD50 200.0 ± 2.9 to 243.3 ± 4.4 and LD100 221.7 ± 3.3 to 278.3 ± 4.4 mg/kg). With the exception of PEA's methyl derivative (amphetamine) all the amines studied are rapidly metabolized by monoamine oxidase. This pharmacokinetics difference would help to explain the markedly higher amphetamine toxicity [(LDLO, LD50 and LD100 (mg/kg; x ± SEM) of 21.3 ± 0.9, 25.0 ± 0.6, and 29.3 ± 0.7, respectively)].

Behavioral effects of ß-phenylethylamine and various monomethylated and monohalogenated analogs in mice are mediated by catecholaminergic mechanisms.

The effects of the administration [intraperitoneally, 15 and 75 mg/kg, except α-MePEA (amphetamine, AMPH) at 5 and 10 mg/kg] of ß-phenylethylamine (PEA), its methylated (o-Me-, p-Me-, α-Me-, ß-Me-, N-Me-, p-OMe-, N,N-di-Me-, and 3,4-diOH-N-Me-), para-halogenated (Br-, Cl-, F-, and I-), and other derivatives for example, p-OHPEA (p-tyramine), on Swiss male albino mice caged behavior fall into 3 broad categories. (1) N,N-diMe-, 3,4-diOH-N-Me-, and o-MePEA tend to reduce the behavioral activity, (2) p-OH and p-IPEA were without noticeable effects, and (3) the remaining compounds increased locomotor activity, produced hyperexcitability and fighting, jumping and vocalization, and convulsion in a graded manner (listed in increasing order p-OMe-, ß-Me-, p-Cl-, p-Br-, p-F-, p-Me-, and N-MePEA, PEA itself and α-MePEA). The latter compound (amphetamine) being the most potent among them; equieffective but with lower potency were p-MePEA, N-MePEA, and PEA itself. The effects of PEAs upon group cage behavior were increased by pretreatment with pargyline (1.5 hours; 15 mg/kg) and decreased after reserpine or haloperidol [4 hours and/or 24 hours (2.5 and/or 2.5 mg/kg) and 1 hour (1 mg/kg), respectively], reaching full suppression with the double-dose regimen of reserpine and single dose of haloperidol. As expected, none of these substances by themselves were noticeable changed group mice activity or stereotypic behavior. The effects of test amines and catecholamine-modulating agents on stereotypy were assessed by rating the sequentially occurring behaviors: increased exploratory behavior with increased sniffing; occasional side-to-side head weaving; paw-licking and other grooming; gnawing, fighting and continuous side-to-side head weaving, and periodic episodes of "popcorn" behavior, during which all mice in the cage ran, jumped, and vocalized. In general, rank efficacy in eliciting stereotype aligned with rank efficacy in affecting group cage behavior. Our results show that a number of as yet little studied monomethylated and monohalogenated PEA analogs share a similar behavioral profile with PEA and AMPH. Behavioral changes observed appear to be, at least in part, mediated by catecholaminergic mechanism as they are modulated by drugs known to influence catecholamine activity. PEA analogs provide a large number of clinically useful drugs; whether further studies on these novel amines will lead to the rational design of newer, safer, and effective PEA-class drugs remains to be seen.

Analgesic effects of ß-phenylethylamine and various methylated derivatives in mice.

Administration of ß-phenylethylamine (PEA), the simplest endogenous neuroamine, and various methylated PEA derivatives including α-methyl PEA (amphetamine, AMP) elicits analgesia in mice. Five or 20 min after intraperitoneal PEA injection of as little as 6 mg/kg resulted in an increased latency response time (from 2.4 ± 0.4 to 8.5 ± 2.3 or 7.0 ± 3.0 s, respectively) to the thermal stimulus (hot-plate test), which reached statistical significance at the 15 mg/kg (20 min; 13.1 ± 0.4 s) or 25 mg/kg dose (5 min; 15.3 ± 4.1 s). This PEA effect, was dose-dependent (albeit non-linear: 6, 12, 15, 25, 50 and 100 mg/kg), reached the cut-off time of 45 s at the upper PEA dose (5 min), and it was consistently enhanced by pretreatment with the monoamine oxidase inhibitor pargyline (P). Methylated PEA derivatives (15 and 100 mg/kg dose) produced various degrees of analgesia (in decreasing order p-Me PEA > PEA > N,N-diMe PEA > N-Me PEA) which, likewise to PEA itself, were consistently increased by P and declined over time (mice tested 5, 20 and 60 min after amine injection); small but statistically significant o- and ß-Me PEA antinociceptive effects (5 min) were observed only at the higher dose (in the presence of P for ß-Me PEA). A small analgesic effect was observed after the administration of AMP (5 or 10 mg/kg) which failed, even after P, to reach statistically significance. Independent of the amine and concentration tested, individual compound's antinociceptive properties were reliably increased by P (exception of AMP), decreased by reserpine (R) or haloperidol (H), and remained essentially unchanged after naloxone (N) administration suggesting the involvement of catecholamines, but not opioid peptides, in their observed analgesic effects. Injection of P + N produced results similar to those seen after P alone. Under the experimental conditions described neither P, R, H or N had any effects by themselves. These findings suggest additional understanding of the mechanism of action responsible for the analgesic effects of these amines would be of interest, leading further to controlled studies on their alleged usefulness as weight reducing agents and sport performance enhancers.

Comparison of soil eDNA to camera traps for assessing mammal and bird community composition and site use.

Species detections often vary depending on the survey methods employed. Some species may go undetected when using only one approach in community-level inventory and monitoring programs, which has management and conservation implications. We conducted a comparative study of terrestrial mammal and bird detections in the spring and summer of 2021 by placing camera traps at 30 locations across a large military installation in northern Michigan, USA and testing replicate soil samples from these sites for environmental DNA (eDNA) using an established vertebrate metabarcoding assay. We detected a total of 48 taxa from both survey methods: 26 mammalian taxa (excluding humans, 24 to species and two to genus) and 22 avian taxa (21 to species and one to genus). We detected a relatively even distribution of mammalian taxa on cameras (17) and via eDNA analysis (15), with seven taxa detected from both methods. Most medium-to-large carnivores were detected only on cameras, whereas semi-fossorial small mammals were detected only via eDNA analysis. We detected higher bird diversity with camera traps (18 taxa) compared to eDNA analysis (eight taxa; four taxa were detected with both methods), but cameras alone were most effective at detecting smaller birds that frequently occupy arboreal environments. We also used Bayesian spatial occupancy models for two widely distributed game species (white-tailed deer, Odocoileus virginianus, and ruffed grouse, Bonasa umbellus) that were moderately detected with both survey methods and found species-specific site use (occupancy) estimates were similar between cameras and eDNA analysis. Concordant with similar studies, our findings suggest that a combination of camera trap and eDNA surveys could be most useful for assessing the composition of terrestrial mammal communities. Camera traps may be most efficient for assessing bird diversity but can be complemented with eDNA analysis, particularly for species that spend considerable time on the ground.

Rat brain-uptake index for phenylethylamine and various monomethylated derivatives.

Phenylethylamine and its monomethylated derivatives p-methylphenylethylamine, α-methylphenylethylamine, phenylethylamine itself, N-methylphenylethylamine, o-methylphenylethylamine, and ß-methylphenylethylamine, readily cross the blood-brain barrier showing a brain-uptake index (%) ± SD (water considered 100 %), of 108 ± 11, 98 ± 14, 83 ± 6, 78 ± 11, 62 ± 7 and 56 ± 6, respectively (injection of tritiated water and 100 µg standard amine, which was measured by gas-liquid chromatography). Similar brain-uptake index values (determined by double isotope counting) were obtained for phenylethylamine and α-methylphenylethylamine (amphetamine) after the injection of tritiated water and C(14)-labeled amine (either 3 µg or when added 100 µg standard compound), suggesting that they entered the brain via passive diffusion. Accordingly, both amines distributed rather evenly in the various rat brain areas examined: uptake index (%) ± SD (double isotope counting; non-, and diluted labeled amine) for phenylethylamine (89 ± 8 and 78 ± 7, 83 ± 9 and 86 ± 9, 96 ± 6 and 84 ± 7) and for α-methylphenylethylamine (88 ± 11 and 87 ± 9, 93 ± 14 and 87 ± 11, 97 ± 12 and 87 ± 9) for the cerebellum, frontal cortex, and striatum, respectively. These results will aid a greater understanding of the pharmacological and behavioral effects observed after the administration of phenylethylamine and methylphenylethylamine derivatives.

Changes in plasma methionine-enkephalin levels associated with a cluster headache episode.

Eighteen male cluster headache (CH) inpatients within a CH series participated in this research. Blood samples were drawn from patients at least 6-hour pain-free after the last acute CH episode and then shortly prior (SP), during, and soon after (SA) a new acute CH attack. Three healthy male, age-comparable drug-free volunteers served as controls; 5 samples were obtained from each of these individual over a 24-hour period. Individual patient's methionine-enkephalin (MET) plasma concentration showed significant changes, and in some subjects, dramatic changes, during the different phases of a single CH episode. Peptide levels followed a general pattern of higher plasma concentration SP to an acute CH attack, followed by decreased levels during the attack itself, and falling even further SA the acute episode. Consistently, 16 of the 18 patients tested showed pre-CH peptide levels significantly higher (arbitrarily the authors considered values 20% or more as "significant") than their own values obtained during the acute CH pain phase, with observed differences reaching 80% or more in 7 of these individuals. For about half of these patients, peptide concentration during the acute CH episode was significantly above the control's range (68.2-87.6 pg MET/mL; control's circulating MET concentration remaining essentially unchanged during a 24-hour period). MET levels were further decreased in essentially all of the post-CH samples, with values falling within (n = 6) or even further below than those in the control's range (n = 11). Neither age, time of CH occurrence, nor patient's use of a number of medications known for failing to influence plasma MET degradation kinetics seemed to significantly influence MET levels. These results might help in the biochemical characterization of the actual phases of a CH episode. Developing drugs modulating MET bioavailability could lead to novel antinociceptive agents useful for the treatment of CH's associated pain.

A review of the etiology, associated comorbidities, and treatment of orthostatic hypotension.

The magnitude of increase in systolic blood pressure in response to the shift from supine to upright posture is considered to reflect the adequacy of orthostatic regulation. Orthostatic integrity is largely maintained by the interaction between the skeletal muscle pump, neurovascular compensation, neurohumoral effects, and cerebral blood flow regulation. Various physiological states and disease conditions may disrupt these mechanisms as seen in vasovagal syncope, dysautonomic orthostatic intolerance, and postural orthostatic tachycardia syndrome. Orthostatic hypotension (OH) and decreased cerebral blood flow are strongly related. Even subclinical OH has been associated to different degrees with impaired cognitive function, decreased effort, reduced motivation, increased hopelessness, and signs of attention-deficit hyperactivity disorder and dementia, diabetes mellitus, and Parkinson disease. Furthermore, subclinical levels of inadequate blood pressure regulation in response to orthostasis have been linked to increased depression and anxiety and intergenerational behavioral sequelae between mother and child. Identifying causes of subclinical and clinical OH is critical in improving quality of life for both children and older adults. A better understanding of the underlying causes responsible for the etiology of OH could lead to a rational design of novel effective therapeutic regimens for the treatment of this condition and associated comorbidities.

Decreased plasma methionine-enkephalin levels in cluster headache patients.

Results from a longitudinal study (blood drawn at days 29, 64, 89,124, 142, and 182 of the protocol) shows that the concentration of platelet-poor plasma (PPP) methionine(5)-enkephalin (MET) in healthy, drug-free, white male individuals (n = 5) remains within a relatively narrow range, well within the experimental error of the analytical procedures used. Interindividual differences fail to reach statistical significance [x ± SD and range (MET picograms per mL of PPP) of 91.2 ± 15.1, 67.1-113.5; 69.6 ± 7.5, 66.1-90.1; 76.6 ± 12.6, 58.5-93.1; 86.8 ± 10.9, 76.3-107.4; and 84.5 ± 11.4, 68.9-103.4; for subjects 1-5, respectively]. MET levels were similar to those recorded from single samples obtained from a group of 24 white male, age-comparable, drug-free healthy volunteers [x ± SD and range (picograms of MET per mL of PPP) of 83.3 ± 15.1 and 57.4-119.1]. The controls' range for all the subjects (n = 29) was 57.4-119.1 pgMET/mL PPP. Compared with the controls, individual patients with cluster headache (CH) show a much wider variation in PPP MET levels (blood drawn at different time intervals, at least 10 samples per patient, over a period of 221-298 days), with many (slightly over half) of single values below the controls range; no single MET level was above the controls range [x ± SD and range (picograms of MET per mL of PPP) of 56.4 ± 27.7, 6.1-100.5; 72.6 ± 20.5, 43.0-113.0; 46.0 ± 28.5, 10.0-92.6; 53.6 ± 27.5, 13.0-101.0; 52.0 ± 26.1, 17.5-83.6; 63.5 ± 22.3, 21.7-91.3 for individuals A-F, respectively]. Although interindividual differences within the patients' group were not statistically significant, their peptide levels were significantly lower than those of controls. Neither the presence of unspecified "headaches between clinic visits" and "daily headaches" (patients E and F, respectively), nor the use of a number of drugs known to lack inhibitory activity upon the aminopeptidase-MET degradation reaction, seemed to significantly influence MET concentration. The results could lead to a better understanding of the etiology of the pain associated with CH, with the relative changes in plasma peptide perhaps reflecting the patients' vulnerability to such a condition. Pharmacological modulation of MET function may prove useful in the treatment of CH-associated pain, whether the development of such drugs could find useful pharmacological applications remains to be explored.

A review of orthostatic blood pressure regulation and its association with mood and cognition.

AIMS: This paper will review literature that examines the psychological and neuropsychological correlates of orthostatic blood pressure regulation. RESULTS: The pattern of change in systolic blood pressure in response to the shift from supine to upright posture reflects the adequacy of orthostatic regulation. Orthostatic integrity involves the skeletal muscle pump, neurovascular compensation, neurohumoral effects and cerebral flow regulation. Various physiological states and disease conditions may disrupt these mechanisms. Clinical and subclinical orthostatic hypotension has been associated with impaired cognitive function, decreased effort, reduced motivation and increased hopelessness as well as dementia, diabetes mellitus, and Parkinson's disease. Furthermore, inadequate blood pressure regulation in response to orthostasis has been linked to increased depression and anxiety as well as to intergenerational behavioral sequalae. CONCLUSIONS: Identifying possible causes and consequences of subclinical and clinical OH are critical in improving quality of life for both children and older adults.

Genetic Structure and Colonization of North America by Depressaria depressana (Fabricius 1775) (Lepidoptera: Depressariidae) over 15 Years; Contrasts with Westward Expansion of Depressaria radiella (Goeze, 1783) over 160 Years.

Depressaria depressana, the purple carrot seed moth, is a Eurasian species first reported in North America in 2008 and currently undergoing range expansion. This invasion follows that of its Eurasion congener Depressaria radiella (parsnip webworm), first documented in North America 160 years ago. Unlike D. depressana, which utilizes hostplants across multiple tribes of Apiaceae, Depressaria radiella is a "superspecialist" effectively restricted in its native and non-indigenous ranges to two closely related apiaceous genera. We investigated the genetic structure of D. depressana populations across latitudinal and longitudinal gradients in the eastern United States by constructing COI haplotype networks and then comparing these with haplotype networks constructed from available COI sequence data from contemporary European D. depressana populations and from European and North American D. radiella populations. Haplotype data revealed higher genetic diversity in D. depressana, indicating high dispersal capacity, multiple introductions, and/or a genetically diverse founding population. Museum and literature records of D. radiella date back to 1862 and indicate that range expansion to the West Coast required more than 50 years. Higher levels of genetic diversity observed in D. depressana compared to its congener may indicate a greater propensity for dispersal, colonization and establishment in its non-indigenous range.

Degradation kinetics of methionine5-enkephalin by cerebrospinal fluid: in vitro studies.

Changes in the levels or biochemistry of cerebrospinal fluid (CSF) neuropeptides with opioid-like properties have been suggested to reflect alterations in specific biological processes. We have determined various kinetic parameters for methionine-enkephalin (MET) degradation by CSF samples from nonneurological patients. Study subjects included 9 males (51-67 years of age) and 5 females (47-61 years of age). Aliquots, removed from an incubation vessel containing buffer, CSF, and peptide [tyr-3',5'-H(N)MET], were analyzed for tyrosine and other degradation products. Essentially all of the labeled tyrosine from the added MET was recovered as free amino acid after 60 minutes of incubation (1:2 ratio, vol:vol; optimum pH 7.4; and temperature 37°C); other possible peptide metabolites (>3%) were not detected. Irrespective of age or gender, the peptide's degradation half-life and initial velocity values were in a limited range; t1/2 26.2 ± 5.5 and 20.8-33.8 minutes, and Iv 0.03 ±0.01 and 0.02-0.03 pg of peptide per milligram protein per minute. Km and Vmax values were 0.19 ± 0.02 and 0.17-0.21 mM, and 9.8 ± 2.2 and 7.6-12.0 µmol·L·min, respectively. Neither CSF sample storage time (up to a year) nor repeated freezing and thawing (up to 3 times over a year) altered the kinetics or products of this reaction. These preliminary findings might serve as reference values when conducting similar studies using CSF from patients diagnosed with specific neurological conditions; significant alterations in MET degradation profile in such a population could provide valuable biological markers for diagnostic and treatment purposes.

Biodegradable implants for sustained drug release in the eye.

The safety and effectiveness of systemic and topical medical therapies for ocular disorders are limited due to poor ocular drug uptake, nonspecificity to target tissues, systemic side effects, and poor adherence to therapy. Intravitreal injections can enhance ocular drug delivery, but the need for frequent retreatment and potential injection-related side effects limit the utility of this technique. Sustained-release drug delivery systems have been developed to overcome these limitations; such systems can achieve prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure and side effects and improving patient adherence to therapy. A critical factor in the development of safe and effective drug delivery systems has been the development of biocompatible polymers, which offer the versatility to tailor drug release kinetics for specific drugs and ocular diseases. Ocular implants include nonbiodegradable and biodegradable designs, with the latter offering several advantages. The polymers most commonly used in biodegradable delivery systems are synthetic aliphatic polyesters of the poly-α-hydroxy acid family including polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid. The characteristics of these polymers for medical applications as well as the pharmacological properties, safety, and clinical effectiveness of biodegradable drug implants for the treatment of ocular diseases are reviewed herein.

Etiology and risk factors for developing orthostatic hypotension.

Orthostatic hypotension (OH) is regarded as a decrease primarily in systolic blood pressure on changing position from supine to erect. Based on clinical criteria, it is characterized by a decrease in systolic pressure of 20 mmHg and diastolic pressure of 10 mmHg within 1 to 3 minutes of standing after being supine. It is most prevalent in, although not limited to, the elderly population and is characterized by a variety of problems, including diminished cognition and disturbed emotion along with gate problems, falls, and brain and cardiovascular difficulties. Although often seen as an age-related condition, occurrence of OH is also associated with a number of autonomic nervous system neurodegenerative disorders. Medications may play a direct role in the risk of triggering OH; these drugs include, but are not limited to, agents used in the treatment of hypertension, myocardial ischemia, psychosis and schizophrenia, depression, Alzheimer and Parkinson disease as well as a vaccine approved for the prevention of cervical cancer. Most of these agents increase the risk for triggering OH through varying vasodilative mechanisms or through sympathetic nervous system interruption; for other drugs, no mechanism of action has been identified. These factors should be considered when diagnosing OH and when prescribing remedies for both patients with OH and those without OH; medication's contributions to the severity and/or risk of developing OH could limit their use. However, their effects could be attenuated or even eliminated by modifying drug dosages.

Evaluation and comparison of store-and-forward teledermatology applications.

OBJECTIVE: Store-and-forward (S&F) teledermatology has been used to increase patient access to dermatologic care. A major challenge to implementing S&F teledermatology is selecting secure and cost-saving applications for data capture and transmission. Detailed analyses and comparison of the major S&F teledermatology applications do not exist in the current peer-reviewed literature. The objectives of this study were to identify, evaluate, and compare the major S&F teledermatology applications in the United States to help referral and consultant sites select applications responsive to their needs. MATERIALS AND METHODS: We identified four major, commercially available S&F teledermatology applications after surveying the members of the American Telemedicine Association Teledermatology Special Interest Group and the Telemedicine Task Force of the American Academy of Dermatology. A multidisciplinary team of dermatologists, primary care physicians, and information technologists established a set of criteria used to evaluate the applications. We performed a comparative analysis of the four major S&F teledermatology applications based on the predetermined evaluation criteria. RESULTS: The four major, commercially available S&F teledermatology applications evaluated in this study were Alaska Federal Health Care Access Network, Medweb, TeleDerm Solutions, and Second Opinion. All four teledermatology applications were mature and capable of addressing the basic needs of S&F teledermatology referrals and consultations. Each application adopts different approaches to organize medical information and facilitate consultations. Areas in need of improvement common to these major applications include (1) increased compatibility and integration with established electronic medical record systems, (2) development of fully integrated billing capability, (3) simplifying user interface and allowing user-designed templates to communicate recommendations and patient education, and (4) reducing the cost of the applications. CONCLUSION: The four major S&F teledermatology applications in the United States are versatile applications capable of facilitating communication between referral and consultant sites. Continued efforts in making these applications more secure, robust, user-friendly, and affordable will contribute to wider implementation of S&F teledermatology.

Inferring Evolutionary Timescales without Independent Timing Information: An Assessment of "Universal" Insect Rates to Calibrate a Collembola (Hexapoda) Molecular Clock.

Previous estimates of nucleotide substitution rates are routinely applied as secondary or "universal" molecular clock calibrations for estimating evolutionary timescales in groups that lack independent timing information. A major limitation of this approach is that rates can vary considerably among taxonomic groups, but the assumption of rate constancy is rarely evaluated prior to using secondary rate calibrations. Here I evaluate whether an insect mitochondrial DNA clock is appropriate for estimating timescales in Collembola-a group of insect-like arthropods characterized by high levels of cryptic diversity. Relative rates of substitution in cytochrome oxidase subunit 1 (COI) were inferred via Bayesian analysis across a topologically constrained Hexapod phylogeny using a relaxed molecular clock model. Rates for Collembola did not differ significantly from the average rate or from the rates estimated for most other groups (25 of 30), suggesting that (1) their apparent cryptic diversity cannot be explained by accelerated rates of molecular evolution and (2) clocks calibrated using "universal" insect rates may be appropriate for estimating evolutionary timescales in this group. However, of the 31 groups investigated, 10 had rates that deviated significantly from the average (6 higher, 4 lower), underscoring the need for caution and careful consideration when applying secondary insect rate calibrations. Lastly, this study exemplifies a relatively simple approach for evaluating rate constancy within a taxonomic group to determine whether the use of secondary rates are appropriate for molecular clock calibrations.