Time course of repetitive heterosynaptic facilitation in Aplysia californica

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33356/1/0000754.pd

Activity recorded from the statocyst nerve of Pleurobranchaea californica during rotation and at different tilts

1. 1. The statocysts of Pleurobranchaea californica lie lateral to the pedal ganglia. The thirteen receptor cells communicate with the cerebro-pleural ganglion via the thirteen axons of the statocyst nerve.2. 2. Each unit in the statocyst nerve of Pleurobranchaea responds over a limited range of positions.3. 3. Receptor adaptation is slow. Each position in the active range of a unit is coded by the same steady-state firing rate. Initial frequencies upon reaching a particular position differ, depending upon the direction of approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34013/1/0000288.pd

Facilitation of excitatory post-synaptic potentials in the giant cell in the left pleural ganglion of Aplysia californica

1. 1. Heterosynaptic facilitation (HSF) was found to begin to develop after a latency of between 1900 and 2000 msec after which the amplitude of HSF increased as a function of the prime test interval.2. 2. Changes in the amplitude of the HSF could last as long as 42 hr.3. 3. The HSF in the pleural giant cell was of greater amplitude than that in the abdominal giant cell.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34181/1/0000470.pd

The gravity reference response, the rotation sensation, and other illusory sensations experienced in aircraft and space flight

An analysis of the gravitational and inertial forces which act during aircraft flight upon the vestibular systems of the aircraft occupants reveals that in the absence of a visual horizon, certain illusory sensations are predictable for various acceleration environments. Horizontal forward applied acceleration results in a climbing (backward tilting) sensation; conversely, horizontal rearward applied acceleration results in a diving (forward tilting) sensation. During any attempt to achieve weightlessness in aircraft parabolic flight, special care has to be taken to avoid unintended longitudinal ( x -axis) accelerations. Recent flight tests established that the ‘rotation sensation’ (Dzendolet, 1971; Gerathewohl, 1956) during entry into parabolic flight can be attributed to the existence of unintended longitudinal accelerations. However, the ‘inversion illusion’ (Graybiel and Kellogg, 1966) felt by some human subjects at 0 g seems to be different from the rotation sensation and could be caused by the diminished pressure forces of the otoliths on the maculae. The ‘inversion illusion’ of man correlates well with the blind fish diving behavior observed during aircraft parabolic flight (von Baumgarten et al. , 1969, 1972). It is suggested that the fish low g diving response and the human inversion illusion are due to the substitution of a predominately shearing force of low magnitude as a vestibular reference in place of a normal, predominately pressure force. This hypothesis indicates that vestibular senses alone cannot provide meaningful postural orientation to simulated or actual gravity of a magnitude below that of Earth's gravity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43353/1/11084_2004_Article_BF00930350.pd

Sugar receptor specificity in the fleshfly, Sarcophaga bullata

Various carbohydrates were tested for stimulating activity of the sweet receptor of Sarcophaga bullata. Efficacy appears to be highest in -pyranosides having equatorial substituents at C-2, C-3, C-4 and C-5, with the exception of the C-1 position where equatorial substituents detract. Similarly, myo-inositol, having 5 equatorial and 1 axial hydroxyl, is the most stimulatory of the cyclitols tested. The anomalous action of several compounds remains unexplained. -Glucose is stimulatory, while its [alpha]- and [beta]-pyranosides are not. Similarly, free fructose, an extremely potent sugar, is completely inactive as its [alpha]- or [beta]-furanoside or its [alpha]- or [beta]-pyranoside. This finding is discussed in relation to the stimulatory action of sucrose.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33504/1/0000001.pd

Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma

Purpose: In this phase II study (NCT00942747), temsirolimus was tested in patients with relapsed or refractory primary CNS lymphoma (PCNSL). Patients and Methods: Immunocompetent adults with histologically confirmed PCNSL after experiencing high-dose methotrexate-based chemotherapy failure who were not eligible for or had experienced high-dose chemotherapy with autologous stem-cell transplant failure were included. The first cohort (n = 6) received 25 mg temsirolimus intravenously once per week. All consecutive patients received 75 mg intravenously once per week. Results: Thirty-seven eligible patients (median age, 70 years) were included whose median time since their last treatment was 3.9 months (range, 0.1 to 14.6 months). Complete response was seen in five patients (13.5%), complete response unconfirmed in three (8%), and partial response in 12 (32.4%) for an overall response rate of 54%. Median progression-free survival was 2.1 months (95% CI, 1.1 to 3.0 months). The most frequent Common Toxicity Criteria ≥ 3° adverse event was hyperglycemia in 11 (29.7%) patients, thrombocytopenia in eight (21.6%), infection in seven (19%), anemia in four (10.8%), and rash in three (8.1%). Fourteen blood/CSF pairs were collected in nine patients (10 pairs in five patients in the 25-mg cohort and four pairs in four patients in the 75-mg cohort). The mean maximum blood concentration was 292 ng/mL for temsirolimus and 37.2 ng/mL for its metabolite sirolimus in the 25-mg cohort and 484 ng/mL and 91.1 ng/mL, respectively, in the 75-mg cohort. Temsirolimus CSF concentration was 2 ng/mL in one patient in the 75-mg cohort; in all others, no drug was found in their CSF. Conclusion: Single-agent temsirolimus at a weekly dose of 75 mg was found to be active in relapsed/refractory patients with PCNSL; however, responses were usually short lived

Behavioral responses to short periods of lowered gravitational force in blind goldfish

(1) The movements of blind goldfish flown in an aircraft through vertical flight patterns show a consistent correlation with the varying g loads as recorded by a g meter.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43344/1/11084_2004_Article_BF00924246.pd

Outcomes for depression and anxiety in primary care and details of treatment: a naturalistic longitudinal study

<p>Abstract</p> <p>Background</p> <p>There is little evidence as to whether or not guideline concordant care in general practice results in better clinical outcomes for people with anxiety and depression. This study aims to determine possible associations between guideline concordant care and clinical outcomes in general practice patients with depression and anxiety, and identify patient and treatment characteristics associated with clinical improvement.</p> <p>Methods</p> <p>This study forms part of the Netherlands Study of Depression and Anxiety (NESDA).</p> <p>Adult patients, recruited in general practice (67 GPs), were interviewed to assess DSM-IV diagnoses during baseline assessment of NESDA, and also completed questionnaires measuring symptom severity, received care, socio-demographic variables and social support both at baseline and 12 months later. The definition of guideline adherence was based on an algorithm on care received. Information on guideline adherence was obtained from GP medical records.</p> <p>Results</p> <p>721 patients with a current (6-month recency) anxiety or depressive disorder participated. While patients who received guideline concordant care (N = 281) suffered from more severe symptoms than patients who received non-guideline concordant care (N = 440), both groups showed equal improvement in their depressive or anxiety symptoms after 12 months. Patients who (still) had moderate or severe symptoms at follow-up, were more often unemployed, had smaller personal networks and more severe depressive symptoms at baseline than patients with mild symptoms at follow-up. The particular type of treatment followed made no difference to clinical outcomes.</p> <p>Conclusion</p> <p>The added value of guideline concordant care could not be demonstrated in this study. Symptom severity, employment status, social support and comorbidity of anxiety and depression all play a role in poor clinical outcomes.</p

Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated

PURPOSE: Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression for individual patients is of pivotal importance. However, only biomarkers for highly aggressive tumors are established (CDKN2A/B and TERT), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma. METHODS: DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases. RESULTS: Both CNV- and methylation family-based subgrouping independently resulted in increased prediction accuracy of risk of recurrence compared with the WHO classification (c-indexes WHO 2016, CNV, and methylation family 0.699, 0.706, and 0.721, respectively). Merging all risk stratification approaches into an integrated molecular-morphologic score resulted in further substantial increase in accuracy (c-index 0.744). This integrated score consistently provided superior accuracy in all three cohorts, significantly outperforming WHO grading (c-index difference P = .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34 [1.28-8.72] retrospective and prospective validation cohorts, respectively). CONCLUSION: Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction