Onset Of Association Research Articles

Actigraphy sleep patterns in presymptomatic Alzheimer’s Disease: the potential role of neuroinflammation

AbstractBackgroundBoth short and long sleep duration have been associated with increased risk of developing Alzheimer’s Disease (AD). While short sleep has been hypothesized to be a risk factor promoting neurodegenerative processes. Long sleep has been viewed as a marker of ongoing neurodegeneration, potentially as a result of neuroinflammation. The objective of the study is to evaluate sleep patterns measured with actigraphy close to expected symptom onset in association with neuroinflammatory biomarkers. We leveraged the PREVENT‐AD cohort in which participants with a parental history of sporadic AD are studied before clinical onset.Method203 participants (age: 68.5±5.4 years, 151 women) free of dementia were tested with a week of actigraphy. Nighttime sleep duration, time in bed, sleep latency, sleep efficiency, and number of sleep bouts were calculated using the Actiware scoring algorithm (medium threshold). The standard deviation of these characteristics was calculated across actigraphy days to assess day‐to‐day variability. Years to expected onset was calculated by the number of years remaining before the age of clinical onset of a parent, or the earliest age of clinical onset if both parents developed AD. A subset of 100 participants underwent a lumbar puncture, and IL‐6 and MCP‐1 levels were assessed using OLINK technology in cerebrospinal fluid (CSF). The association between sleep characteristics, years to expected onset and inflammatory markers was assessed using linear regressions adjusted for age, sex, and time interval between measurements.ResultBeing closer to expected onset was associated with longer nighttime sleep duration (b = ‐0.19, p = 0.015) and lower sleep bouts day‐to‐day variability (b = 0.17, p = 0.027). Higher CSF IL‐6 was associated with longer sleep duration and time in bed (b = 0.30, p = 0.006; b = 0.24, p = 0.028), whereas higher MCP‐1 was associated with longer nighttime sleep duration (b = 0.25, p = 0.019). Higher CSF MCP‐1 levels were associated with lower sleep bouts day‐to‐day variability and shorter sleep onset latency only in those within 10 years of expected onset (interaction p = 0.012 and 0.061; b = ‐0.31, p = 0.043; b = ‐0.31, p = 0.047).ConclusionProximity to parental onset of sporadic AD onset was associated with a longer sleep profile that is more consolidated and stable, which may be due to proinflammatory processes.

Rapid recovery of post-stroke cardiac autonomic dysfunction - causes to be considered.

Acute stroke frequently causes cardiovascular-autonomic dysfunction (CAD). Studies of CAD-recovery are inconclusive while post-stroke arrhythmias may wane within 72 hours. We evaluated whether post-stroke CAD recovers within 72 hours upon stroke-onset in association with neurological improvement or increased use of cardiovascular medication. In 50 ischemic-stroke patients (68±13 years) who - prior to hospital-admission - had no known diseases nor took medication affecting autonomic modulation, we assessed NIHSS-scores, RR-intervals (RRI), systolic, diastolic blood-pressures (BP), respiration-rate, parameters reflecting total autonomic modulation [RRI-standard-deviation, RRI-total-powers], sympathetic [RRI-low-frequency-powers, BPsys-low-frequency-powers] and parasympathetic modulation [RMSSD, RRI-high-frequency-powers], and baroreflex-sensitivity within 24 hours (assessment-1) and 72 hours after stroke-onset (assessment-2) and compared data to those of 31 healthy-controls (64±10 years). We correlated delta-NIHSS-values (assessment-1 - assessment-2) with delta-values of autonomic parameters (Spearman-Rank-correlation tests; significance: P<0.05). At assessment-1, patients were not yet on vasoactive medication and had higher systolic blood pressure, respiration-rate, heart rate, i.e. lower RRIs, but lower RRI-Standard-Deviation, RRI-coefficient-of-variance, RRI-low-frequency-powers, RRI-high-frequency-powers, RRI-total-powers, RMSSDs, and baroreflex-sensitivity. At assessment-2, patients were on antihypertensives, had higher RRI-Standard-Deviation, RRI-coefficient-of-variance, RRI-low-frequency-powers, RRI-high-frequency-powers, RRI-total-powers, RMSSDs, and baroreflex-sensitivity but lower systolic blood pressure and NIHSS-values than at assessment-1; values no longer differed between patients and controls except for lower RRIs and higher respiration-rate in patients. Delta-NIHSS-scores correlated inversely with delta-values of RRI-Standard-Deviation, RRI-coefficient-of-variance, RMSSDs, RRI-low-frequency-powers, RRI-high-frequency-powers, RRI-total-powers, and baroreflex-sensitivity. In our patients, CAD-recovery was almost complete within 72 hours after stroke-onset and correlated with neurological improvement. Most likely, early initiation of cardiovascular medication and probably attenuating stress supported rapid CAD-recovery.

Vesiculo-bullous Darier disease late onset in association with polycythemia vera

Vesiculo-bullous lesions as well as the late onset are extremely rare features of Darier disease (DD) making positive diagnosis more difficult. Its association with polycythemia vera prompts to look for signs suggestive of malignant hematological transformation. We report a case of a 62-year-old patient, followed in internal medicine since the age of 58 for polycythemia vera. She presented for pruriginous vesiculo-bullous dermatosis evolving for 4 years. On clinical examination, papulo-vesicular plaques were found involving all the folds: inguinal, axillary, inter-gluteal, neck and body with palmo-plantar blisters and pustules. Examination of the toe nails showed alternating red and white longitudinal bands. Abdominal examination showed moderate splenomegaly. Skin biopsy revealed focal acantholysis with supra-basal clefts, dyskeratosis with the presence of round bodies and grains compatible with Darier's disease. A paraneoplastic assessment was made including a thoraco-abdomino-pelvic CT scan, a breast ultrasound and mammography with cervico-vaginal smear, a CT scan of the cavum and a pancreatic MRI, which did not show any progressive malignant process. The patient was put on oral retinoids at a rate of 0.5 mg/kg per day and topical calcipotriol associated with bloodletting to reduce the hematocrit level. The evolution was marked by clinical improvement. The patient was followed in the hematology department and showed no acute leukemia or myelofibrosis or other neoplasms after a 2-year follow-up. We report a case of late DD in a woman followed for polycythemia vera, characterized by a rare vesiculo-bullous presentation and whose causal link remains to be determined.

OR14-4 Acute sleep disruption does not diminish pulsatile growth hormone secretion in pubertal children

Abstract Context: Growth hormone (GH) plays a critical role in glucose homeostasis and linear growth during childhood. GH secretion is controlled by multiple neurotransmitters and hormones. Sleep is also a powerful stimulus for GH secretion. In children, GH pulses occur after sleep onset in association with slow-wave sleep (SWS), but it is unclear if undisrupted sleep is required for normal GH secretion. Given the rising incidence of pediatric sleep disorders such as obstructive sleep apnea (OSA) that cause sleep fragmentation, it is critical to determine whether sleep fragmentation during childhood may dysregulate the somatotropic axis. Objective To quantify how undisrupted vs fragmented sleep affects GH secretion in children. Methods Pubertal subjects (10 M, 9 F; 9.1-14.4 yrs) were randomized to two overnight polysomnographic studies with frequent blood sampling (q10min) to measure GH: fourteen were healthy subjects studied with or without SWS disruption via auditory stimuli (3 sec, 1500 Hz tones, 40-100 dB followed by 18 sec of a 75 dB noise simulating a knock on the door) and five were subjects with OSA studied with or without prescribed continuous positive airway pressure (CPAP); the latter condition was expected to have sleep fragmentation due to untreated OSA. GH pulses were identified using sparse deconvolution. Studies without auditory stimuli or when using CPAP were combined and analyzed as 'undisrupted sleep'. The relationship between GH pulse rate per hour and sleep stage was evaluated using Poisson generalized estimating equations. Results In SWS disruption studies, an average of 77.51 ± 13.61 (range 23-190) auditory stimuli were delivered, causing a 40.02 ± 7.78% decrease in SWS in favor of lighter sleep stages. In subjects with OSA, CPAP withdrawal caused a slight increase in the apnea hypopnea index (1.08 ± 0.10 vs. 2.20 ± 1.70 events/hour of sleep, p=0.07) with no change in sleep stage durations. During undisrupted sleep, subjects had an average of 0.91 ± 0.067 GH pulses/hour with a mean pulse amplitude of 10.03 ± 1.00 ng/mL and mean basal secretion rate of 0.26 ± 0.10 ng/ml per min. GH pulses occurred more frequently during SWS (2.3 pulses/hour SWS, amplitude 9.92 ± 2.59 ng/mL) than during any other sleep stage (P &amp;lt; 0.001). Neither form of sleep disruption affected the distribution of GH pulses across sleep stages, GH pulse amplitude and frequency, nor basal GH secretion. Conclusion In children, nocturnal GH pulses are temporally associated with SWS. However, neither acute fragmentation of SWS nor nocturnal arousals from OSA altered basal or pulsatile GH secretion, indicating that somatotrophic axis activity is preserved in the face of acute sleep disruption in children. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

Imagetic and affective measures of memory reverberation diverge at sleep onset in association with theta rhythm

The ‘day residue’ - the presence of waking memories into dreams - is a century-old concept that remains controversial in neuroscience. Even at the psychological level, it remains unclear how waking imagery cedes into dreams. Are visual and affective residues enhanced, modified, or erased at sleep onset? Are they linked, or dissociated? What are the neural correlates of these transformations? To address these questions we combined quantitative semantics, sleep EEG markers, visual stimulation, and multiple awakenings to investigate visual and affect residues in hypnagogic imagery at sleep onset. Healthy adults were repeatedly stimulated with an affective image, allowed to sleep and awoken seconds to minutes later, during waking (WK), N1 or N2 sleep stages. ‘Image Residue’ was objectively defined as the formal semantic similarity between oral reports describing the last image visualized before closing the eyes (‘ground image’), and oral reports of subsequent visual imagery (‘hypnagogic imagery). Similarly, ‘Affect Residue’ measured the proximity of affective valences between ‘ground image’ and ‘hypnagogic imagery’. We then compared these grounded measures of two distinct aspects of the ‘day residue’, calculated within participants, to randomly generated values calculated across participants. The results show that Image Residue persisted throughout the transition to sleep, increasing during N1 in proportion to the time spent in this stage. In contrast, the Affect Residue was gradually neutralized as sleep progressed, decreasing in proportion to the time spent in N1 and reaching a minimum during N2. EEG power in the theta band (4.5-6.5 Hz) was inversely correlated with the Image Residue during N1. The results show that the visual and affective aspects of the ‘day residue’ in hypnagogic imagery diverge at sleep onset, possibly decoupling visual contents from strong negative emotions, in association with increased theta rhythm.

Acute Sleep Disruption Does Not Diminish Pulsatile Growth Hormone Secretion in Pubertal Children.

In children, growth hormone (GH) pulses occur after sleep onset in association with slow-wave sleep (SWS). There have been no studies in children to quantify the effect of disrupted sleep on GH secretion. This study aimed to investigate the effect of acute sleep disruption on GH secretion in pubertal children. Fourteen healthy individuals (aged 11.3-14.1 years) were randomly assigned to 2 overnight polysomnographic studies, 1 with and 1 without SWS disruption via auditory stimuli, with frequent blood sampling to measure GH. Auditory stimuli delivered during the disrupted sleep night caused a 40.0 ± 7.8% decrease in SWS. On SWS-disrupted sleep nights, the rate of GH pulses during N2 sleep was significantly lower than during SWS (IRR = 0.56; 95% CI, 0.32-0.97). There were no differences in GH pulse rates during the various sleep stages or wakefulness in disrupted compared with undisrupted sleep nights. SWS disruption had no effect on GH pulse amplitude and frequency or basal GH secretion. In pubertal children, GH pulses were temporally associated with episodes of SWS. Acute disruption of sleep via auditory tones during SWS did not alter GH secretion. These results indicate that SWS may not be a direct stimulus of GH secretion.

Incidence, Risk Factors, and Outcomes of Cancer in Systemic Sclerosis.

To quantify the burden of cancer in systemic sclerosis (SSc). Standardized incidence ratios (SIRs) and standardized mortality ratios relative to the general Australian population were derived. Cox proportional hazards regression was used to estimate survival in patients with SSc with cancer compared to patients without. Determinants of cancer were identified using logistic regression. Health care cost was quantified through cross-jurisdictional data linkage. This SSc cohort of 1,727 had a cancer incidence of 1.3% per year and a prevalence of 14.2%, with a SIR of 2.15 (95% confidence interval [95% CI] 1.84-2.49). The most common cancers were breast, melanoma, hematologic, and lung. Anti-RNA polymerase III (RNAP) antibody was associated with an increased risk of cancer (odds ratio [OR] 2.9, P = 0.044), diagnosed within 5 years of SSc disease onset. Calcium channel blockers were associated with a higher risk of overall cancer (OR 1.47, P = 0.016), breast cancer (OR 1.61, P = 0.051), and melanoma (OR 2.01, P = 0.042). Interstitial lung disease (ILD) was associated with lung cancer (OR 2.83, P = 0.031). Incident SSc cancer patients had >2-fold increased mortality compared to patients with SSc without cancer (hazard ratio 2.85 [95% CI 1.51-5.37], P = 0.001). Patients with SSc and cancer utilized more health care than those without cancer, with an excess annual health care cost of $1,496 Australian (P < 0.001). SSc carries an increased risk of developing cancer, particularly lung cancer associated with ILD, and breast cancer and melanoma occurring close to SSc disease onset in association with RNAP antibodies. Compared to those patients without cancer, patients with SSc and cancer had higher mortality and an increased health care cost, with an annual excess per patient cost of $1,496 Australian (P < 0.001).

Decadal Changes in Interannual Dependence of the Bay of Bengal Summer Monsoon Onset on ENSO Modulated by the Pacific Decadal Oscillation

Interannual variations of the Bay of Bengal summer monsoon (BOBSM) onset in association with El Nino-Southern Oscillation (ENSO) are reexamined using NCEP1, JRA-55 and ERA20C atmospheric and Hadley sea surface temperature (SST) reanalysis datasets over the period 1900–2017. Decadal changes exist in the dependence of the BOBSM onset on ENSO, varying with the Pacific Decadal Oscillation (PDO). A higher correlation between the BOBSM onset and ENSO arises during the warm PDO epochs, with distinct late (early) onsets following El Nino (La Nina) events. In contrast, less significant correlations occur during the cold PDO epochs. The mechanism for the PDO modulating the ENSO-BOBSM onset relationship is through the variations in SST anomaly (SSTA) patterns. During the warm PDO epochs, the superimpositions of the PDO-related and ENSO-related SSTAs lead to the SSTA distribution of an El Nino (La Nina) event exhibiting significant positive (negative) SSTAs over the tropical central-eastern Pacific and Indian Ocean along with negative (positive) SSTAs, especially over the tropical western Pacific (TWP), forming a strong zonal interoceanic SSTA gradient between the TWP and tropical Indian Ocean. Significant anomalous lower tropospheric easterlies (westerlies) together with upper-tropospheric westerlies (easterlies) are thus induced over the BOB, favoring an abnormally late (early) BOBSM onset. During the cold PDO epochs, however, the superimpositions of PDO-related SSTAs with El Nino-related (La Nina-related) SSTAs lead to insignificant SSTAs over the TWP and a weak zonal SSTA gradient, without distinct circulation anomalies over the BOB favoring early or late BOBSM onsets.

Mortality in intra-aortic balloon pump therapy in patients with ST elevation myocardial infarction and cardiogenic shock: Data from nationwide inpatient sample

treatment is required. LVHT in the presentedpatient is a strong argument for metabolicmyopathysince ithasneverbeen reported inassociationwithALS. This case shows that metabolic myopathy may mimic ALS, that ptosis, the absence of fasciculations, LVHT, family history, and the multisystem nature rule out ALS, and that previous traumatic brain injury and chronic DEET exposure may delay the correct diagnosis. Bulbar symptoms at onset in association with ptosis should raise the suspicion of a metabolic myopathy.

Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients

ObjectiveWeight regain is associated with the promotion of insulin resistance. The newly discovered myokine irisin, which was proposed to be involved in the management of insulin sensitivity, could play a role in this process. This study aimed to investigate the association between irisin and reduced insulin sensitivity induced by weight regain. Materials/MethodsInsulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) in 136 obese patients who followed an eight-week hypocaloric diet (30% reduced energy expenditure) to lose weight and was re-evaluated four or six months after treatment. Irisin plasma levels, as well as the levels of leptin, adiponectin, ghrelin and TNF-α, were quantified in a sub-cohort (n=73) from the initially studied patients at baseline (T0), at the diet endpoint (T1) and after the follow-up period (T2). ResultsAfter a successful dietary intervention to lose weight, 50% of the patients who regained the lost weight during the follow-up period were categorized as insulin resistant (HOMA-IR≥2.5) compared with only 25% of patients who maintained the weight loss (p=0.018). Importantly, in addition to the well-studied hormones leptin and adiponectin, irisin plasma levels were statistically associated with several risk factors for insulin resistance. Indeed, the increased risk of insulin resistance during the follow-up period was related to high irisin levels at baseline (odds ratio=4.2; p=0.039). ConclusionsCirculating irisin predicts the insulin resistance onset in association with weight regain. Therefore, irisin could be secreted as an adaptive response to counteract the deleterious effect of excess adiposity on glucose homeostasis.

Report From the Jerusalem Workshop on Lynch Syndrome-Hereditary Nonpolyposis Colorectal Cancer

A Workshop was held in Jerusalem, Israel, on October 26 and 27, 2009 to discuss the management of Lynch syndrome-hereditary nonpolyposis colorectal cancer (CRC), with the primary goal to develop consensus for the optimal management of this disease. A second goal was to identify areas of research with the potential to advance the clinical management of Lynch syndrome. The perspectives and recommendations from the workshop are meant to be a platform for discussion and deliberation. The Workshop was organized by Moshe Shike (Memorial Sloan Kettering Cancer Center, New York) and sponsored by The Colon Cancer Foundation. More details of each presentation are available in an on-line supplement.

Mass and energy transport in the near and middistant magnetotail around substorm onsets: Geotail observations

We have studied mass and energy transport in the magnetotail around substorm onsets by analyzing GEOTAIL data. We selected substorm events from Pi2 pulsations and applied a superposed epoch analysis. We found that particles (ions) are gradually provided from the upstream lobe to the downstream plasma sheet before onset. Energy is transported from the lobe to the plasma sheet in the form of the Poynting flux, which is particularly large and has a large Y component around X ∼ −10 RE continuously before and after onset. The Poynting flux as well as the mass flux toward the plasma sheet starts to increase first around (X, Y) ∼ (−20, 7) RE about 0 ∼ 2 min before onset and then successively increases in the surrounding regions. In the downstream plasma sheet the dominant energy flux is the thermal flux. It is directed duskward before onset as well as the mass flux. However, very large tailward mass and thermal fluxes develop in the region of −23 &gt; X &gt; −30 RE of the premidnight tail after onset in association with the plasmoid. They have a large duskward component in the premidnight sector. Earthward of X ∼ −20 RE, there are not only earthward mass and thermal fluxes but also large duskward fluxes in the plasma sheet after onset. The kinetic energy flux is much smaller than the Poynting and thermal fluxes in any regions before and after onset. These observational results would provide us with significant clues to an understanding of substorm processes, such as the magnetic reconnection and the dipolarization, and their relationship.

Water-Soluble Polymers. 78. Viscosity and NRET Fluorescence Studies of pH-Responsive Twin-Tailed Associative Terpolymers Based on Acrylic Acid and Methacrylamide

A series of terpolymers containing acrylic acid (AA), methacrylamide (MAM), and a twin-tailed hydrophobic monomer (DiC6AM, DiC8AM, or DiC10AM) were synthesized using micellar polymerization methods. These polymer systems were characterized using light scattering, viscometry, and fluorescence methods. Viscosity studies indicate that increasing the nonpolar character of the hydrophobic monomer (longer chain length or twin tailed vs single tailed) results in enhanced viscosity in aqueous solutions. The terpolymer with the highest hydrophobicity (MAM/AA/DiC10AM terpolymer) exhibited the most pronounced viscosity increase with polymer concentration and thus the best associative thickening. Fluorescence nonradiative energy transfer measurements performed on this terpolymer indicate the onset of association (c*) at a concentration of ∼0.1 g/dL. Also, changes in the energy transfer efficiency and viscosity behavior as a function of pH are consistent with a concentration-dependent transition from closed to open associations.

The Natural History of Alcoholic Chronic Pancreatitis.

An improved knowledge of the natural history is the indispensible basis for a rational concept in regard to the diagnosis, classification, understanding and management of pain in chronic pancreatitis. Unfortunately, data on the natural history of CP are scarce and conflicting. Some relevant observations of our prospective long-term study of a mixed medical-surgical cohort comprising 207 patients with alcoholic CP (mean follow-up 17 years from onset) are summarized. In early-stage CP, episodes of recurrent pancreatitis were predominant. Severe persistent pain was typically associated with local complications (mainly postnecrotic cysts in 54%; symptomatic cholestasis in 24%) relieved definitely by a drainage procedure. Lasting pain remission was documented in >80% of the whole cohort within 10 years from onset in association with marked pancreatic dysfunction. From our experience, the relief of "chronic" pain regularly follows selective surgery tailored to the presumptive pain cause or it occurs spontaneously in uncomplicated advanced CP (excluding narcotic addiction).

Acute Subdural Hematoma due to Ruptured Cerebral Aneurysm

The authors report three cases of subdural hematoma of acute onset in association with the rupture of intracranial aneurysms. Although all were in critical condition, two patients recovered after emergency surgery, which entailed removal of the hematoma and aneurysmal neck clipping. Acute subdural hematoma most often results from the tearing of bridging and cortical veins. Much less frequently, subdural bleeding may be secondary to the rupture of an intracranial aneurysm. In these instances, the subdural clot may be massive and immediately life-threatening. Currently, computed tomography (CT) is the examination of choice for the diagnosis of acute subdural hematoma. However, CT does not reliably depict blood vessels and so is of little value in ruling out such vascular abnormalities as aneurysms. The dilemma is whether or not to perform angiography prior to surgery in the presence of dire neurological signs. The authors conclude that, if the patient's condition allows, angiography should be performed, for the following reasons: 1) rebleeding from the aneurysm can be adequately controlled; 2) in skillful hands, angiography can be accomplished within the time required for other preoperative examinations; and 3) the aneurysm can be treated after evacuation of the hematoma, thereby such complications as vasospasm can be adequately managed.

Gpp(NH)p promotes the formation of a low affinity state for the δ opioid agonist-receptor complex

We previously demonstrated an association time-dependent dissociation of the δ opioid agonist, DADL, from its receptor that suggested multi-step formation of a high affinity complex. We have now examined the effect of the GTP analog, Gpp(NH)p, on the dissociation of [ 3H]DADL from these same sites on bovine hippocampal synaptic membranes. Gpp(NH)p accelerates dissociation of this complex in a dose-dependent manner resulting in the transformation of a high affinity form to a lower affinity state. The Gpp(NH)p effect was more pronounced when it was added at the time of initiation of dissociation. Under these conditions Gpp(NH)p engendered biphasic off-rates that were no longer association time-dependent. The addition of Gpp(NH)p at the onset of association did not prevent (but retarded) the formation of the high affinity state. Steady state homologous displacement binding curves demonstrated single site [ 3H]DADL binding in the absence of Gpp(NH)p but in its presence an improved fit for a two site model was obtained. In summary, on the basis of both kinetic and equilibrium binding data Gpp(NH)p appears to transform the δ opioid agonist-receptor complex into a low affinity state.

Nonionic polymer surfactants

AbstractNonionic water‐soluble polymeric surfactants have been prepared by addition of long‐chain n‐alkyl epoxides to nonionic cellulose ethers. The polymers exhibit properties which can be explained by interchain association. The relationship between hydrocarbon‐modifier carbon number and the onset of association follows a linear relation analogous to those observed for monomeric nonionic surfactants.

Estimates of current changes in the geomagnetotail associated with a substorm

Magnetic field variations in the near‐earth magnetotail during a weak magnetospheric substorm are studied by two approximate methods to estimate quantitatively the changes in the cross‐tail current. Analysis of the event indicates that the magnetic field variations can be interpreted as a tailward retreat of the cross‐tail current sheet location by ∼0.4‐3.5 RE and an overall reduction of the current density by ∼5‐25%. These changes are accompanied by enhancement of magnetic field‐aligned currents and earthward flowing plasma. The general features of the observations are consistent with the idea that the cross‐tail currents is being diverted into the ionosphere at the substorm onset in association with earthward drainage of plasma in the plasma sheet.