Statistical assessment of time-varying dependency between two neurons

The joint peristimulus time histogram (JPSTH) provides a visual representation of the dynamics of correlated activity for a pair of neurons. There are many ways to adjust the JPSTH for the time-varying firing-rate modulation of each neuron, and then to define a suitable measure of time-varying correlated activity. Our approach is to introduce a statistical model for the time-varying joint spiking activity so that the joint firing rate can be estimated more efficiently. We have applied an adaptive smoothing method, which has been shown to be effective in capturing sudden changes in firing rate, to the ratio of joint firing probability to the probability of firing predicted by independence. A bootstrap procedure, applicable to both Poisson and non-Poisson data, was used to define a statistical significance test of whether a large ratio could be attributable to chance alone. A numerical simulation showed that the bootstrap-based significance test has very nearly the correct rejection probability, and can have markedly better power to detect departures from independence than does an approach based on testing contiguous bins in the JPSTH. In a companion paper, we show how this formulation can accommodate latency and time-varying excitability effects, which can confound spike timing effects.     

Esterases in acute leukemias: a cytochemical and electrophoretic study.

Specific and nonspecific esterases were extracted from various typical cytologic types of leukemic blasts and subjected to electrophoresis in polyacrylamide gel. Preparations rich in normal granulocytes and normal monocytes were analyzed in a similar manner. The results indicated the presence of specific esterase activity in normal monocytes and in myelomonocytic and histiomonocytic leukemia, and a lack of consistent differences in the electrophoretic patterns of both specific and nonspecific esterases in these leukemias. The results support the viewpoint that distinctions between myelomonocytic and histiomonocytic leukemias cannot be made with certainty, and that they may represent variants within a broad spectrum of monocytic leukemias rather than separate and distinct entities.     

Systemic factors in patients with low-tension glaucoma.

Nineteen patients (38 eyes) with low-tension glaucoma were compared with 53 subjects (106 eyes) with ocular hypertension. Comparable for age and sex, the 2 groups were assessed with respect to haematological and biochemical criteria, physical activity, and medical history. Statistical analyses of the differences between the 2 groups highlighted the importance of diastolic ophthalmodynamometry levels, prediagnosis exercise habits, cardiovascular disease status, and possibly systolic blood pressure. Patients with low-tension glaucoma suffered a higher prevalence of multiple abnormalities of these systemic factors than did their ocular hypertensive counterparts. There were no significant differences between the 2 groups with respect to the many other factors examined.     

Successful treatment of pure red cell aplasia associated with systemic lupus erythematosus with oral danazol and steroid

We describe a middle-aged Chinese systemic lupus erythematosus (SLE) patient developing steroid refractory and transfusion dependent red cell aplasia. Oral danazol 200 mg twice per day was started together with low-dose prednisolone therapy. There was no further recurrence of anemia 1 month after this combined therapy.     

Ventricular arterial stiffening: integrating the pathophysiology

Vascular stiffening of the large arteries is a common feature of aging and is exacerbated by many common disorders such as hypertension, diabetes, and renal disease. This change influences the phasic mechanical stresses imposed on the blood vessels that in turn is important to regulating smooth muscle tone, endothelial function, and vascular health. In addition, the heart typically adapts to confront higher and later systolic loads by both hypertrophy and ventricular systolic stiffening. This creates altered coupling between heart and vessel that importantly affects cardiovascular reserve function. In this overview, I discuss the notion of a coupling disease in which stiffness of both heart and arteries interact to limit performance and generate clinical symptoms. This involves changes in the mechanical interaction of both systems, changes in signaling within the arteries themselves, and alterations in coronary flow regulation. Lastly, I briefly review recent development in de-stiffening strategies that may pave the way to treat this syndrome and its clinical manifestations.     

Regulatory actions of the A-kinase anchoring protein Yotiao on a heart potassium channel downstream of PKA phosphorylation

A-kinase anchoring proteins (AKAPs) are thought to be passive members of protein complexes that coordinate the association of cAMP-dependent protein kinase A (PKA) with cellular substrates to facilitate targeted PKA protein phosphorylation. I(Ks), the slow heart potassium current, is carried by the I(Ks) potassium channel, a substrate for PKA phosphorylation in response to sympathetic nerve stimulation, is a macromolecular complex that includes the KCNQ1 alpha subunit, the KCNE1 regulatory subunit, and the AKAP Yotiao. Disruption of this regulation by mutation in the long QT syndrome is associated with elevated risk of sudden death. Here, we have studied the effects of the AKAP Yotiao on the function of the I(Ks) channel that had been mutated to simulate channel phosphorylation, and we report direct AKAP-mediated alteration of channel function distinct from its role in the coordination of channel phosphorylation by PKA. These data reveal previously undescribed actions of Yotiao that occur subsequent to channel phosphorylation and provide evidence that this adaptor protein also may serve as an effector in regulating this important ion channel.     

Computer-aided detection in diagnostic mammography: detection of clinically unsuspected cancers

OBJECTIVE: We had two objectives: to determine the percentage of women presenting with clinical findings whose diagnostic mammogram led to detection of a breast cancer at a site distant from the original clinical complaint and to assess the performance of computer-aided detection (CAD) on diagnostic mammography. MATERIALS AND METHODS: Three institutions contributed consecutive cases in which a mammogram was obtained to evaluate a clinical finding, after which a histologic diagnosis of breast cancer was made. Clinical data and the mammograms were reviewed to determine the nature of the clinical findings and to document the location and characteristics of 212 biopsy-proven cancers in 197 patients who met the study criteria. Standard four-view breast mammograms were then analyzed by a CAD system. RESULTS: The most common clinical finding was a palpable mass (90%, 177/197), with nipple discharge (5%, 9/197), focal tenderness or pain (2%, 5/197), and miscellaneous complaints (3%, 6/197) also noted. Two separate cancers were found in 7.6% (15/197) of the cases. In another 7.6% (15/197) of the cases, the single diagnosed cancer was not at the location of the specific clinical finding. The CAD system correctly marked 87% (26/30) of those cancers that were clinically unsuspected (i.e., not at the location of the clinical finding). CONCLUSION: Breast cancers occurred at locations other than the site of the presenting clinical finding in 15% (30/197) of patients undergoing diagnostic mammography in whom a cancer was detected. CAD identified 87% of these incidentally detected cancers and may therefore be useful as a detection aid to the radiologist when interpreting diagnostic mammograms.