First light from a kilometer-baseline Scintillation Auroral GPS Array.

We introduce and analyze the first data from an array of closely spaced Global Positioning System (GPS) scintillation receivers established in the auroral zone in late 2013 to measure spatial and temporal variations in L band signals at 100-1000 m and subsecond scales. The seven receivers of the Scintillation Auroral GPS Array (SAGA) are sited at Poker Flat Research Range, Alaska. The receivers produce 100 s scintillation indices and 100 Hz carrier phase and raw in-phase and quadrature-phase samples. SAGA is the largest existing array with baseline lengths of the ionospheric diffractive Fresnel scale at L band. With an initial array of five receivers, we identify a period of simultaneous amplitude and phase scintillation. We compare SAGA power and phase data with collocated 630.0 nm all-sky images of an auroral arc and incoherent scatter radar electron precipitation measurements, to illustrate how SAGA can be used in multi-instrument observations for subkilometer-scale studies. KEY POINTS: A seven-receiver Scintillation Auroral GPS Array (SAGA) is now at Poker Flat, Alaska SAGA is the largest subkilometer array to enable phase/irregularities studies Simultaneous scintillation, auroral arc, and electron precipitation are observed.

Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.

The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.

Rates of movement of threatened bird species between IUCN red list categories and toward extinction.

In recent centuries bird species have been deteriorating in status and becoming extinct at a rate that may be 2-3 orders of magnitude higher than in prehuman times. We examined extinction rates of bird species designated critically endangered in 1994 and the rate at which species have moved through the IUCN (World Conservation Union) Red List categories of extinction risk globally for the period 1988-2004 and regionally in Australia from 1750 to 2000. For Australia we drew on historical accounts of the extent and condition of species habitats, spread of invasive species, and changes in sighting frequencies. These data sets permitted comparison of observed rates of movement through the IUCN Red List categories with novel predictions based on the IUCN Red List criterion E, which relates to explicit extinction probabilities determined, for example, by population viability analysis. The comparison also tested whether species listed on the basis of other criteria face a similar probability of moving to a higher threat category as those listed under criterion E. For the rate at which species moved from vulnerable to endangered, there was a good match between observations and predictions, both worldwide and in Australia. Nevertheless, species have become extinct at a rate that, although historically high, is 2 (Australia) to 10 (globally) times lower than predicted. Although the extinction probability associated with the critically endangered category may be too high, the shortfall in realized extinctions can also be attributed to the beneficial impact of conservation intervention. These efforts may have reduced the number of global extinctions from 19 to 3 and substantially slowed the extinction trajectory of 33 additional critically endangered species. Our results suggest that current conservation action benefits species on the brink of extinction, but is less targeted at or has less effect on moderately threatened species.

The Ionospheric Connection Explorer Mission: Mission Goals and Design.

The Ionospheric Connection Explorer, or ICON, is a new NASA Explorer mission that will explore the boundary between Earth and space to understand the physical connection between our world and our space environment. This connection is made in the ionosphere, which has long been known to exhibit variability associated with the sun and solar wind. However, it has been recognized in the 21st century that equally significant changes in ionospheric conditions are apparently associated with energy and momentum propagating upward from our own atmosphere. ICON's goal is to weigh the competing impacts of these two drivers as they influence our space environment. Here we describe the specific science objectives that address this goal, as well as the means by which they will be achieved. The instruments selected, the overall performance requirements of the science payload and the operational requirements are also described. ICON's development began in 2013 and the mission is on track for launch in 2017. ICON is developed and managed by the Space Sciences Laboratory at the University of California, Berkeley, with key contributions from several partner institutions.

SAMI3 ICON: MODEL OF THE IONOSPHERE/PLASMASPHERE SYSTEM.

The NRL ionosphere/plasmasphere model SAMI3 has been modified to support the NASA ICON mission. Specifically, SAMI3 ICON has been modified to import the thermospheric composition, temperature, and winds from TIEGCM-ICON and the high-latitude potential from AMIE data. The codes will be run on a daily basis during the ICON mission to provide ionosphere and thermosphere properties to the science community. SAMI3 ICON will provide ionospheric and plasmaspheric parameters such as the electron and ion densities, temperatures, and velocities, as well as the total electron content (TEC), peak ionospheric electron density (NmF2) and height of the F layer at NmF2 (hmF2).

Progesterone and 5alpha-pregnane-3,20-dione in peripheral blood of normal young women: Daily measurements throughout the menstrual cycle.

The peripheral plasma concentrations of progesterone and 5alpha-pregnane-3,20-dione were measured daily throughout the ovarian cycle of five presumptively ovulatory women. The concentrations of progesterone and 5alpha-pregnane-3,20-dione during the follicular phase were 0.11 +/- 0.02 ng/ml (mean +/- SE) and 0.16 +/- 0.01 ng/ml, respectively. In four of these women the concentrations of both progesterone and 5alpha-pregnane-3,20-dione began to rise immediately after the luteinizing hormone (LH) peak and reached maximal concentrations five to eight days later (progesterone: 8.6 to 19.9 ng/ml; 5alpha-pregnane-3,20-dione: 1.4 to 2.8 ng/ml). The luteal phases in these women, measured from the day of the LH peak to the onset of the next menses, varied from 13 to 18 days. In the other woman with a late LH surge (day 27 of the cycle) the peak concentrations of progesterone and 5alpha-pregnane-3,20-dione were reached four days after the LH peak (8.9 ng/ml and 0.8 ng/ml, respectively). The luteal phase in this woman was 11 days. From the results of this study, it appears that the concentrations of 5alpha-pregnane-3,20-dione in peripheral blood during the luteal phase are proportional to the availability of progesterone as substrate for the 5alpha-reductase enzyme system.

Free triiodothyronine (T3) and thyroxine (T4) in a group of unipolar depressed patients and normal subjects.

We examined levels of free triiodothyronine (fT3) and free thyroxine (fT4) in serum from a group of 32 patients with unipolar major depression and 46 normal control subjects using the Amerlex (Amersham, Arlington Heights, IL) RIA procedures for these hormones. Free T3 levels were significantly lower (p less than 0.004) in the depressed patients as a group (5.02 +/- 1.01 pmol/L, mean +/- SD) than in the normal control subjects (5.74 +/- 1.23 pmol/L). Free T3 levels were lower (p less than 0.01) in depressed men (5.25 +/- 1.43 pmol/L) when compared with male control subjects (6.46 +/- 1.01 pmol/L). Depressed women (4.78 +/- 0.60 pmol/L) also had lower T3 levels than did the female control subjects (5.09 +/- 1.06 pmol/L), but the difference was not statistically significant. Lower fT3 levels were also observed in melancholic depressed patients when compared with nonmelancholic depressed patients or when compared with normal control subjects. No differences in fT4 were observed between groups in this study.

The dexamethasone suppression test in patients with mood disorders.

BACKGROUND: This study was undertaken to (1) determine whether the endogenous/nonendogenous mood disorder dichotomy is validated by the dexamethasone suppression test (DST); (2) determine whether other subtyping schemes (unipolar/bipolar, DSM-III melancholic/nonmelancholic, Winokur's family history subtypes) relate to the DST; (3) evaluate the relative contributions of symptom severity, weight loss, and other factors to DST status; and (4) assess the relative sensitivity of various post-dexamethasone cortisol determinations in the detection of dexamethasone nonsuppression. METHOD: 487 consecutive adult inpatients (N = 131) and outpatients (N = 356) with unipolar (N = 422) or bipolar disorder (N = 65) underwent the 1.0-mg DST. Nonsuppression was defined as at least one post-dexamethasone cortisol measurement > 4.0 micrograms/dL. RESULTS: Nonsuppression occurred in 27% of all patients with major depression and 43% of all bipolar depressed phase patients. For outpatients, dexamethasone nonsuppression occurred in 35.2% of subjects with endogenous (unipolar + bipolar; N = 145) and 9.0% of those with nonendogenous (unipolar only; N = 211) depressions (single 4 p.m. post-dexamethasone cortisol). For inpatients, dexamethasone nonsuppression was found in 61.5% of subjects with endogenous (N = 104) and 18.5% of those with nonendogenous (N = 27) depressions (three post-dexamethasone cortisol determinations). For the inpatient and outpatient sample together, the DST had a sensitivity of 46.2% and a specificity of 89.9% in differentiating endogenous from nonendogenous major depressive episodes. Weight loss, gender, and symptom severity added little to the endogenous/nonendogenous dichotomy. The Research Diagnostic Criteria (RDC) primary/secondary and Winokur and colleagues' family history subtypes for unipolar depression were not strongly validated by the DST. The 4 p.m. and 11 p.m. samples together detected 91.0% of those inpatients with abnormal three-sample DST results. The 8 a.m. sample alone detected 30% of those, the 4 p.m. sample alone detected 67%, and the 11 p.m. sample alone detected 62%. CONCLUSION: The RDC endogenous/nonendogenous dichotomy was validated by the DST.

Two-year trends in physical performance following supervised exercise among community-dwelling older veterans.

The extent to which exercise can delay the normal decline in physical performance associated with aging is unknown. We examined the impact of 2 years of supervised exercise on cardiovascular fitness, flexibility, and strength in a group of elderly (age 65-74) veterans. Seventy-five patients exercised 3 days/week for 90-minute sessions emphasizing aerobic, flexibility, and strength development. Thirty-six (47%) completed 2 years of a voluntary supervised exercise program (n = 25 with complete data). Over a 2-year follow-up period, cardiovascular outcome variables improved significantly: metabolic equivalents increased 20% (7.4 +/- 2.2 to 9.0 +/- 2.4, P less than 0.001) and submaximal heart rate decreased 7% (68.5 +/- 8.0 to 63.6 +/- 8.4 beats/minute, P = 0.02). Resting heart rate decreased 8% (131.4 +/- 14.8 to 121.0 +/- 18.5 beats/minute, P = 0.06), but this difference did not reach statistical significance. Flexibility, measured by hamstring length, improved 11% (57.5 +/- 15.1 to 64.0 +/- 11.1 degrees, P = 0.02). Strength variables did not improve. The study indicates that improvements in cardiovascular function and flexibility achieved by the elderly in the early stages of an exercise program can be maintained for at least 2 years.

Two-year trends in physical performance following supervised exercise among community-dwelling older veterans.

The extent to which exercise can delay the normal decline in physical performance associated with aging is unknown. We examined the impact of 2 years of supervised exercise on cardiovascular fitness, flexibility, and strength in a group of elderly (age 65-74) veterans. Seventy-five patients exercised 3 days/week for 90-minute sessions emphasizing aerobic, flexibility, and strength development. Thirty-six (47%) completed 2 years of a voluntary supervised exercise program (n = 16-25 with complete data). Over a 2-year follow-up period, cardiovascular outcome variables improved significantly: metabolic equivalents increased 20% (7.4 +/- 2.2 to 9.0 +/- 2.4, P less than 0.001) and submaximal heart rate decreased 7% (131.4 +/- 14.8 to 121.0 +/- 18.5 beats/minute, P = 0.06). Resting heart rate decreased 8% (68.5 +/- 8.0 to 63.6 +/- 8.4 beats/minute, P = 0.02) but this difference did not reach statistical significance. Flexibility, measured by hamstring length, improved 11% (57.5 +/- 15.1 to 64.0 +/- 11.1 degrees, P = 0.02). Strength variables did not improve. The study indicates that improvements in cardiovascular function and flexibility achieved by the elderly in the early stages of an exercise program can be maintained for at least 2 years.

Five-year performance trends for older exercisers: a hierarchical model of endurance, strength, and flexibility.

OBJECTIVE: To examine 5-year trends in measures of physical performance, and the impact of disease upon performance, in three domains: cardiovascular fitness, musculo-skeletal strength, and flexibility among older adults participating in a medically supervised exercise program. DESIGN: Longitudinal analyses of data obtained in an observational cohort study. SETTING: Department of Veterans Affairs Medical Center in Durham, North Carolina. PARTICIPANTS: Seventy-three community-dwelling veterans between 64 and 90 years of age. INTERVENTION: Voluntary participation in a medically supervised outpatient exercise program meeting 3 days per week for 90 minutes per session. MAIN OUTCOME MEASURES: Changes over time in cardiovascular fitness, musculoskeletal strength, and flexibility. RESULTS: Forty-nine percent of the original study participants remained in the program for a full 5 years. They had lower baseline rates of cardiorespiratory and musculoskeletal diseases than did the dropouts. Dropouts were significantly more impaired in baseline measures of cardiovascular fitness (P = .038) and strength (P = .007). Changes over time for cardiovascular fitness and strength were similar. Only linear (P < .05) and quadratic time (P < .001) were significant. Only linear time was significant for measures of flexibility (P < .05). Baseline cardiorespiratory disease, baseline musculoskeletal disease, and interaction terms were not significant. Overall, measures of physical performance demonstrated gradual improvement for 2 to 3 years, followed by a gradual decline in performance irrespective of baseline disease status. CONCLUSION: Older adults who exercise regularly, including those with multiple chronic diseases, can achieve significant gains in measures of physical performance, and these gains can be sustained for 2 to 3 years.

Evaluation of a supervised exercise program in a geriatric population.

Most studies that assess the effects of exercise in the elderly involve subjects who are in good health. The objective of this prospective longitudinal study was to examine the impact of exercise on cardiovascular fitness, flexibility, and strength in an elderly population that included chronically ill individuals. Patients were recruited initially from a population of veterans over 64 years of age who use a VA outpatient clinic as their regular source of care. The exercise intervention consisted of 90 minutes of exercise 3 days per week at 70% of the patient's maximal capacity. Activities included stationary cycling, stretching, weight training, and walking. Of 69 patients who began the program, 49 (71%) reached 4-month follow-up. Most patients completing follow-up (76%) had at least one chronic disease, such as arthritis, hypertension, or heart disease. Patients who dropped out were more likely to have multiple chronic illnesses than those who remained in the program. Average weekly attendance was 65% and was stable over time. Improvements in cardiovascular fitness at 4-month follow-up were significant: Metabolic equivalents increased from 7.1 +/- 2.3 to 8.3 +/- 2.6 (P less than .001), treadmill time increased from 8.5 +/- 3.8 to 11.2 +/- 4.2 minutes (P less than .001), submaximal heart rate decreased from 123.7 +/- 18.8 to 118.8 +/- 19.4 beats per minute (P less than .001) and resting heart rate decreased from 68.1 +/- 10.6 to 63.3 +/- 11.6 beats per minute (P = .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Spinal-flexibility-plus-aerobic versus aerobic-only training: effect of a randomized clinical trial on function in at-risk older adults.

BACKGROUND: As exercise is associated with favorable health outcomes, impaired older adults may benefit from specialized exercise interventions to achieve gains in function. The purpose of this study was to determine the added benefit of a spinal flexibility-plus-aerobic exercise intervention versus aerobic-only exercise on function among community-dwelling elders. METHODS: We employed a randomized clinical trial consisting of 3 months of supervised exercise followed by 6 months of home-based exercise with telephone follow-up. A total of 210 impaired males and females over age 64 enrolled in this study. Of these, 134 were randomly assigned to either spinal flexibility-plus-aerobic exercise or aerobic-only exercise, with 116 individuals completing the study. Primary outcomes obtained at baseline, after 3 months of supervised exercise, and after 6 months of home-based exercise included: axial rotation, maximal oxygen uptake (VO2max); functional reach, timed-bed-mobility; and the Physical Function Scale (PhysFunction) of the Medical Outcomes Study SF-36. RESULTS: Differences between the two interventions were minimal. Overall change scores for both groups combined indicated significant improvement for: axial rotation (p=.001), VO2max (p=.0001), and PhysFunction (p=.0016). Secondary improvements were noted for overall health (p=.0025) and reduced symptoms (p=.0008). Differences between groups were significant only for VO2max (p=.0014) at 3 months with the aerobic-only group improving twice as much in aerobic capacity as the spinal flexibility-plus-aerobic group. Repeated measures indicated both groups improved during the supervised portion of the intervention but tended to return toward baseline following the home-based portion of the trial. CONCLUSIONS: Gains in physical functioning and perceived overall health are obtained with moderate aerobic exercise. No differential improvements were noted for the spinal flexibility-plus-aerobic intervention.

The effect of dosage on the dexamethasone suppression test in normal controls.

A sample of 23 drug-free, normal adult subjects, aged 23 to 50 years, received 1 mg dexamethasone p.o. at midnight. Serum cortisols were obtained at 0800h, 1600h, and 2330h pre- and postdexamethasone. Only 1 of these 23 subjects (4.3%) evidenced nonsuppression, as defined by any postdexamethasone serum cortisol value of greater than 4.0 micrograms/dl. A dose of 0.75 mg dexamethasone was administered to 23 drug-free, normal adult subjects, 20 of whom participated in the above 1 mg trial. Six of these 23 (26.1%) showed nonsuppression at a threshold of 4.0 micrograms/dl. Another 11 normal adults who were taking various prescription medications (e.g., sympathomimetics, nasal decongestants, birth control pills, thyroid hormones) or who were suffering from untreated upper respiratory infections, venereal infections, or allergies were tested with 1 mg of dexamethasone. In this sample, 7 of 13 (53.8%) showed nonsuppression. These findings suggest that: (1) 1 mg of dexamethasone is the lowest effective dose that can be used in diagnostic testing for melancholic depression; (2) a false-positive response to the dexamethasone suppression test (DST) may occur with infections, allergies, or possibly with certain prescription medications. Further studies of the effects of illness and/or medications on DST responses are needed.

TRH-induced prolactin release is blunted in females with endogenous unipolar major depression.

Twenty-five women with unipolar primary major depressive disorder (20 endogenous, 5 nonendogenous) and 20 female control subjects were studied with the thyrotropin-releasing hormone stimulation test (TRH-ST). Prolactin (PRL) levels were measured before and after TRH administration for patients and control subjects. For patients, thyrotropin (thyroid-stimulating hormone; TSH) levels were measured from the same serum specimens as PRL levels, and the 1 mg dexamethasone suppression test (DST) was performed. Patients with endogenous depression (ED) had significantly lower maximal serum PRL levels (max PRL) following TRH, and a significantly reduced increase over basal serum PRL (delta max PRL) compared to normal controls (NC). Nonendogenous depressed (NED) patients did not differ significantly from the ED or NC groups on either of these measures. For the ED group, delta max PRL was inversely correlated with severity of depressive symptomatology. Basal PRL levels did not differentiate the depressed subgroups (ED, NED) from each other or from the NC group. Depressed patients with blunted delta max PRL values tended to have blunted delta max TSH values and vice versa. Almost all patients with blunting of either delta max PRL or delta max TSH were also DST nonsuppressors; conversely, only about half (7 of 12) of patients who were DST nonsuppressors had either blunted delta max PRL or delta max TSH. Patients with clinical diagnoses of melancholia or psychotic features were significantly more likely to have blunted delta max PRL values than patients without these diagnoses. A disturbance of central noradrenergic function could explain these findings.

The impact of supervised exercise on the psychological well-being and health status of older veterans.

This study examined the impact of supervised exercise on the health status (measured by the Sickness Impact Profile [SIP]) and well-being (measured by the Psychological General Well-Being Index [PGWB]) of a sample of 43 elderly veterans. The intervention consisted of 90 minutes of exercise, 3 days per week at 70% of maximal capacity. Twenty-three (53%) participants completed a 1-year follow-up. The mean PGWB score increased significantly from 83.0 +/- 15.8 to 89.4 +/- 8.9 (p = .01). Cardiovascular fitness (measured by treadmill performance) increased significantly (p = .004). Baseline SIP scores were low (little dysfunction) and changed little. The study suggests that small but significant improvements in well-being accompany physiological benefits that the elderly experience with exercise.

Effects of cooling the legs on performance in a standard Wingate anaerobic power test.

The possibility that peripheral hypothermia may impair muscular performance in various sports led us to assess the usefulness of the Wingate anaerobic power test in subjects with normal and cooled leg muscles. Using this test without modification, peak power, average power output, and cumulated work to the point of fatigue were all decreased by cooling, although the fatigue index (the declining rate of change of power output) was less. It is concluded that this test could usefully be employed in field studies to assess the possibility that muscle chilling may influence a person's potential for producing maximal bursts of muscular work.