Determination of the

We report the first measurement of the parity-violating elastic electron scattering asymmetry on ^{27}Al. The ^{27}Al elastic asymmetry is A_{PV}=2.16±0.11(stat)±0.16(syst) ppm, and was measured at ⟨Q^{2}⟩=0.02357±0.00010 GeV^{2}, ⟨θ_{lab}⟩=7.61°±0.02°, and ⟨E_{lab}⟩=1.157 GeV with the Q_{weak} apparatus at Jefferson Lab. Predictions using a simple Born approximation as well as more sophisticated distorted-wave calculations are in good agreement with this result. From this asymmetry the ^{27}Al neutron radius R_{n}=2.89±0.12 fm was determined using a many-models correlation technique. The corresponding neutron skin thickness R_{n}-R_{p}=-0.04±0.12 fm is small, as expected for a light nucleus with a neutron excess of only 1. This result thus serves as a successful benchmark for electroweak determinations of neutron radii on heavier nuclei. A tree-level approach was used to extract the ^{27}Al weak radius R_{w}=3.00±0.15 fm, and the weak skin thickness R_{wk}-R_{ch}=-0.04±0.15 fm. The weak form factor at this Q^{2} is F_{wk}=0.39±0.04.

Precision Measurement of the Beam-Normal Single-Spin Asymmetry in Forward-Angle Elastic Electron-Proton Scattering.

A beam-normal single-spin asymmetry generated in the scattering of transversely polarized electrons from unpolarized nucleons is an observable related to the imaginary part of the two-photon exchange process. We report a 2% precision measurement of the beam-normal single-spin asymmetry in elastic electron-proton scattering with a mean scattering angle of θ_{lab}=7.9° and a mean energy of 1.149 GeV. The asymmetry result is B_{n}=-5.194±0.067(stat)±0.082 (syst) ppm. This is the most precise measurement of this quantity available to date and therefore provides a stringent test of two-photon exchange models at far-forward scattering angles (θ_{lab}→0) where they should be most reliable.

First Observation of P-odd γ Asymmetry in Polarized Neutron Capture on Hydrogen.

We report the first observation of the parity-violating gamma-ray asymmetry A_{γ}^{np} in neutron-proton capture using polarized cold neutrons incident on a liquid parahydrogen target at the Spallation Neutron Source at Oak Ridge National Laboratory. A_{γ}^{np} isolates the ΔI=1, ^{3}S_{1}→^{3}P_{1} component of the weak nucleon-nucleon interaction, which is dominated by pion exchange and can be directly related to a single coupling constant in either the DDH meson exchange model or pionless effective field theory. We measured A_{γ}^{np}=[-3.0±1.4(stat)±0.2(syst)]×10^{-8}, which implies a DDH weak πNN coupling of h_{π}^{1}=[2.6±1.2(stat)±0.2(syst)]×10^{-7} and a pionless EFT constant of C^{^{3}S_{1}→^{3}P_{1}}/C_{0}=[-7.4±3.5(stat)±0.5(syst)]×10^{-11} MeV^{-1}. We describe the experiment, data analysis, systematic uncertainties, and implications of the result.

First determination of the weak charge of the proton.

The Q(weak) experiment has measured the parity-violating asymmetry in ep elastic scattering at Q(2)=0.025(GeV/c)(2), employing 145 µA of 89% longitudinally polarized electrons on a 34.4 cm long liquid hydrogen target at Jefferson Lab. The results of the experiment's commissioning run, constituting approximately 4% of the data collected in the experiment, are reported here. From these initial results, the measured asymmetry is A(ep)=-279±35 (stat) ± 31 (syst) ppb, which is the smallest and most precise asymmetry ever measured in ep scattering. The small Q(2) of this experiment has made possible the first determination of the weak charge of the proton Q(W)(p) by incorporating earlier parity-violating electron scattering (PVES) data at higher Q(2) to constrain hadronic corrections. The value of Q(W)(p) obtained in this way is Q(W)(p)(PVES)=0.064±0.012, which is in good agreement with the standard model prediction of Q(W)(p)(SM)=0.0710±0.0007. When this result is further combined with the Cs atomic parity violation (APV) measurement, significant constraints on the weak charges of the up and down quarks can also be extracted. That PVES+APV analysis reveals the neutron's weak charge to be Q(W)(n)(PVES+APV)=-0.975±0.010.

Beamline Performance Simulations for the Fundamental Neutron Physics Beamline at the Spallation Neutron Source.

Monte Carlo simulations are being performed to design and characterize the neutron optics components for the two fundamental neutron physics beamlines at the Spallation Neutron Source. Optimization of the cold beamline includes characterization of the guides and benders, the neutron transmission through the 0.89 nm monochromator, and the expected performance of the four time-of-flight choppers. The locations and opening angles of the choppers have been studied using a simple spreadsheet-based analysis that was developed for other SNS chopper instruments. The spreadsheet parameters are then optimized using Monte Carlo techniques to obtain the results presented in this paper. Optimization of the 0.89 nm beamline includes characterizing the double crystal monochromator and the downstream guides. The simulations continue to be refined as components are ordered and their exact size and performance specifications are determined.

New Pulsed Cold Neutron Beam Line for Fundamental Nuclear Physics at LANSCE.

The NPDGamma collaboration has completed the construction of a pulsed cold neutron beam line on flight path12 at the Los Alamos Neutron Science Center (LANSCE). We describe the new beam line and characteristics of the beam. We report results of the moderator brightness and the guide performance measurements. FP12 has the highest pulsed cold neutron intensity for nuclear physics in the world.

Measurement of Parity Violation in np Capture: the NPDGamma Experiment.

The NPDGamma experiment will measure the parity-violating directional gamma ray asymmetry A γ in the reaction [Formula: see text]. Ultimately, this will constitute the first measurement in the neutron-proton system that is sensitive enough to challenge modern theories of nuclear parity violation, providing a theoretically clean determination of the weak pion-nucleon coupling. A new beam-line at the Los Alamos Neutron Science Center (LANSCE) delivers pulsed cold neutrons to the apparatus, where they are polarized by transmission through a large volume polarized (3)He spin filter and captured in a liquid para-hydrogen target. The 2.2 MeV gamma rays from the capture reaction are detected in an array of CsI(Tl) scintillators read out by vacuum photodiodes operated in current mode. We will complete commissioning of the apparatus and carry out a first measurement at LANSCE in 2004-05, which would provide a statistics-limited result for A γ accurate to a standard uncertainty of ±5 × 10(-8) level or better, improving on existing measurements in the neutron-proton system by a factor of 4. Plans to move the experiment to a reactor facility, where the greater flux would enable us to make a measurement with a standard uncertainty of ±1 × 10(-8), are actively being pursued for the longer term.

Commissioning of the NPDGamma Detector Array: Counting Statistics in Current Mode Operation and Parity Violation in the Capture of Cold Neutrons on B 4 C and (27) Al.

The NPDGamma γ-ray detector has been built to measure, with high accuracy, the size of the small parity-violating asymmetry in the angular distribution of gamma rays from the capture of polarized cold neutrons by protons. The high cold neutron flux at the Los Alamos Neutron Scattering Center (LANSCE) spallation neutron source and control of systematic errors require the use of current mode detection with vacuum photodiodes and low-noise solid-state preamplifiers. We show that the detector array operates at counting statistics and that the asymmetries due to B4C and (27)Al are zero to with- in 2 × 10(-6) and 7 × 10(-7), respectively. Boron and aluminum are used throughout the experiment. The results presented here are preliminary.

Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response.

BACKGROUND: Treatment of major depression with antidepressants is generally associated with a delay in onset of clinical response. Functional brain correlates of this phenomenon have not been previously characterized. METHODS: Time course of changes in brain glucose metabolism were measured using positron emission tomography in hospitalized unipolar depressed patients treated with fluoxetine. Time-specific and response-specific effects were examined at 1 and 6 weeks of treatment. RESULTS: Changes were seen over time, and characterized by three distinct patterns: 1) common changes at 1 and 6 weeks, 2) reversal of the 1-week pattern at 6 weeks, and 3) unique changes seen only after chronic treatment. Fluoxetine responders and nonresponders, similar at 1 week, were differentiated by their 6-week pattern. Clinical improvement was uniquely associated with limbic and striatal decreases (subgenual cingulate, hippocampus, insula, and pallidum) and brain stem and dorsal cortical increases (prefrontal, parietal, anterior, and posterior cingulate). Failed response was associated with a persistent 1-week pattern and absence of either subgenual cingulate or prefrontal changes. CONCLUSIONS: Chronic treatment and clinical response to fluoxetine was associated with a reciprocal pattern of subcortical and limbic decreases and cortical increases. Reversal in the week-1 pattern at 6 weeks suggests a process of adaptation in specific brain regions over time in response to sustained serotonin reuptake inhibition. The inverse patterns in responders and nonresponders also suggests that failure to induce these adaptive changes may underlie treatment nonresponse.

Age-related reductions in cerebral vasomotor reactivity and the law of initial value: a 4-year prospective longitudinal study.

A group of 51 neurologically normal, middle-aged and elderly volunteers (aged 35-86 years; mean age 63.24 years) with and without risk factors for stroke were given annual tests of cerebral vasomotor reactivity to assess any changes in the cerebral vascular capacitance associated with advancing age that might alter cerebral vasomotor reactivity. Cerebral vasomotor reactivity was estimated as the difference in bihemisphere gray matter CBF measured by the 133Xe inhalation method in the steady state breathing room air, followed by a second measurement during inhalation of 100% oxygen. There were significant and progressive reductions in cerebral vasomotor reactivity during the 4-year longitudinal study. Positive linear correlations were apparent between initial steady-state mean bihemisphere gray matter CBF levels and degrees of vasomotor reactivity, suggesting that the Law of Initial Value plays an important role. This should be borne in mind when analyzing scores of cerebral vasomotor reactivity. In the present communication, analysis of covariance was used to correct for influences of initial CBF levels on vasomotor responses tested while breathing pure oxygen.

Executive impairment among the functionally dependent: comparisons between schizophrenic and elderly subjects.

OBJECTIVE: Executive deficits have traditionally been associated with frontal lobe brain damage. They are relevant to a variety of disabling mental conditions, including schizophrenia and Alzheimer's disease. To measure these deficits, the authors developed the Executive Interview, a 25-item, 15-minute interview. It has been validated among elderly subjects across a wide range of functional impairment. METHODS: Forty young, chronically ill schizophrenic residents of a state mental health facility and 104 elderly residents, representing three levels of care, of a comprehensive retirement community were tested with the Executive Interview and the Mini-Mental State. RESULTS: When age, gender, education, and number of prescribed medications were controlled, cognitive impairment on the Executive Interview and Mini-Mental State rose with level of care. The Executive Interview alone discriminated between subjects at each level of care, and it was more sensitive to cognitive impairment than the Mini-Mental State. Executive Interview scores correlated the strongest with level of care. Mini-Mental State scores, number of prescribed medications, and age also correlated significantly. Schizophrenic patients showed as much executive impairment on the Executive Interview as elderly subjects at the same level of care despite significant differences in age, sex, and neuroleptic use. Executive Interview and Mini-Mental State scores were highly correlated among the elderly but less so among the schizophrenic patients. Cross-group differences were also found in the pattern of failure on selected Executive Interview items despite similar total Executive Interview scores. CONCLUSIONS: Increasing executive dyscontrol is associated with the need for increasing levels of care and supervision. This finding is neither age nor disease specific. Cross-group differences on selected Executive Interview items suggest the existence of disease-specific patterns of failure. Their recognition could prove useful in the identification of anatomically or pathophysiologically distinct subgroups among patients with executive dyscontrol.

Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness.

OBJECTIVE: Theories of human behavior from Plato to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically "old" and "new" brain regions. Expanding on this theory, this study examined functional interactions between specific limbic and neocortical regions accompanying normal and disease-associated shifts in negative mood state. METHOD: Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patients were examined with two positron emission tomography techniques: [15O]water and [18F]fluorodeoxyglucose, respectively. RESULTS: With sadness, increases in limbic-paralimbic blood flow (subgenual cingulate, anterior insula) and decreases in neocortical regions (right dorsolateral prefrontal, inferior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen--limbic metabolic decreases and neocortical increases. A significant inverse correlation between subgenual cingulate and right dorsolateral prefrontal activity was also demonstrated in both conditions. CONCLUSIONS: Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional reciprocity between these regions with shifts in mood in either direction suggests that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both normal and pathological conditions. The bidirectional nature of this limbic-cortical reciprocity provides additional evidence of potential mechanisms mediating cognitive ("top-down"), pharmacological (mixed), and surgical ("bottom-up") treatments of mood disorders such as depression.

Establishing the limits of the Mini-Mental State. Examination of 'subtests'.

It has been suggested that the Mini-Mental State examination can be used to examine a patient's cognitive profile. We therefore examined the validity of Mini-Mental State subtests and individual items. The memory item, attention-concentration items, and constructional item had satisfactory sensitivity-specificity and correlated significantly with scores on neuropsychological tests. In contrast, four of the five Mini-Mental State language items had very low sensitivity, and three of five failed to correlate with neuropsychological test scores. These findings establish limits with regard to the ability of the Mini-Mental State to generate a cognitive profile. Our data also provide information regarding validity, difficulty level, and optimal cutoff scores for widely used mental status tasks.

Decreased cerebral blood flow precedes multi-infarct dementia, but follows senile dementia of Alzheimer type.

A 7-year prospective study among 181 neurologically normal elderly volunteers (mean age, 70.6 years) revealed an incidence of 3.3%, or 0.47% new cases per year, for Alzheimer's disease (SDAT) and 5.5%, or 0.78% new cases per year, for multi-infarct dementia (MID). The unusually high incidence of MID is considered to reflect preselection of a large percentage of volunteers (48.6%) with risk factors for (but without symptoms of) atherothrombotic stroke. Of 88 volunteers at risk of stroke, 11.4% developed MID within 7 years. In MID patients, cerebral blood flow (CBF) values began to decline around 2 years before onset of symptoms, while in SDAT patients, CBF levels remained normal until symptoms of dementia appeared; thereafter, CBF declined rapidly.

The influence of noncognitive factors on the Mini-Mental State Examination in older Mexican-Americans: findings from the Hispanic EPESE. Established Population for the Epidemiologic Study of the Elderly.

Mini-Mental State Examination data from the Hispanic Established Population for the Epidemiologic Study of the Elderly baseline survey, a population-based study of community-dwelling Mexican Americans aged 65 and older, were used to examine the relationship between cognitive impairment, sociodemographics, and health-related characteristics. The rate of cognitive impairment found in this group of older Mexican Americans, using the conventional cut point of 23/24 on the MMSE, was 36.7%. Using a more conservative cut point of 17/18 indicated an overall rate of severe cognitive impairment of 6.7%. Rates of impairment varied significantly with age, education, literacy, marital status, language of interview, and immigrant status and were associated with high and moderate levels of depressive symptoms, and history of stroke. Importantly, although education was strongly related to poor cognitive performance, it was not a significant predictor of severe cognitive impairment. Multivariate analyses further indicated that as a screen for cognitive impairment in older Mexican Americans, the MMSE is strongly influenced by these noncognitive factors. Scores may reflect test bias, secondary to cultural differences or the level of education in this population.

Bedside assessment of executive cognitive impairment: the executive interview.

OBJECTIVE: This study is a pilot validation of the Executive Interview (EXIT), a novel instrument designed to assess executive cognitive function (ECF) at the bedside. DESIGN: Inter-rater reliability testing and validation using inter-group comparisons across levels of care and measures of cognition and behavior. PARTICIPANTS: Forty elderly subjects randomly selected across four levels of care. SETTING: Settings ranged from independent living apartments to designated Alzheimer's Special Care units in a single 537-bed retirement community. MEASUREMENTS: The EXIT: a 10-minute, 25-item interview scored from 0-50 (higher scores = greater executive dyscontrol) was administered by a physician. Subjects were also administered the Mini-Mental State Exam (MMSE) and traditional tests of "frontal" executive function by a neuropsychologist, and the Nursing Home Behavior Problem Scale (NHBPS) by Licensed Vocational Nurses. RESULTS: Interrater reliability was high (r = .90). EXIT scores correlated well with other measures of ECF. The interview discriminated among residents at each level of care. In contrast, the MMSE did not discriminate apartment-dwelling from residential care residents, or residential care from nursing home residents. The EXIT was highly correlated with disruptive behaviors as measured by the NHBPS (r = .79). CONCLUSIONS: These preliminary findings suggest that the EXIT is a valid and reliable instrument for the assessment of executive impairment at the bedside. It correlates well with level of care and problem behavior. It discriminates residents at earlier stages of cognitive impairment than the MMSE.

The functional significance of symptomatology and cognitive function in schizophrenia.

The relationships between positive and negative symptomatology, cognitive function, and the ability to perform basic activities of daily living in patients with schizophrenia were examined in two studies. In study 1, 112 medicated patients were assessed utilizing the Brief Psychiatric Rating Scale (positive symptoms), the Negative Symptom Assessment (negative symptoms and cognitive function), and the Functional Needs Assessment (activities of daily living). Study 2 (n = 41), utilized the same measures of symptomatology and added a comprehensive neuropsychological test battery. Regression analyses in both studies determined that symptomatology predicts a relatively small amount of the variance in the ability to perform basic activities of daily living. Cognitive function, whether assessed with the Cognition subscale of the Negative Symptom Assessment or a comprehensive neuropsychological test battery, predicted over 40% of the variance in scores on the Functional Needs Assessment. A path model in which cognition predicted both concurrent symptomatology and activities of daily living and where symptomatology had little direct impact upon activities of daily living fit the data. The importance of addressing cognitive deficits in psychosocial intervention programs is discussed.

Effects of captopril and propranolol on cognitive function and cerebral blood flow in aged hypertensive rats.

Chronic hypertension has been reported to produce adverse cognitive effects in elderly individuals, perhaps by altering central nervous system hemodynamics. The beneficial or adverse effects of antihypertensive drugs on these processes are not well understood. We examined the effects of captopril (90 mg/kg/day) and propranolol (80 mg/kg/day) on cognitive function and brain blood flow in hypertensive and normotensive rats. Cognitive function was assessed by the Morris water maze, and regional brain blood flow was measured by the [14C]iodoantipyrine method. Nineteen-month-old propranolol-treated hypertensive rats exhibited poorer performance (p < .05) than control rats and had lower brain blood flows, particularly in white matter regions (p < .01). Captopril-treated hypertensive rats did not differ significantly from control rats with regard to either cognitive performance or brain blood flow. In the normotensive rats, there were no effects of either drug on cognitive performance or brain blood flow. Thus, blood pressure reduction by propranolol but not captopril has an adverse effect on cognitive function and brain blood flow in hypertensive rats.

Cingulate function in depression: a potential predictor of treatment response.

The relationship between pretreatment regional cerebral glucose metabolism and eventual antidepressant drug response was measured using positron emission tomography (PET) in hospitalized patients with unipolar depression. Rostral anterior cingulate metabolism uniquely differentiated eventual treatment responders from non-responders. Hypometabolism characterized non-responders when compared with controls, in contrast to responders who were hypermetabolic. Metabolism in no other region discriminated the two groups, nor did associated demographic, clinical or behavioral measures, including motor speed, cognitive performance, depression severity or illness chronicity. Cingulate hypermetabolism may represent an important adaptive response to depression and failure of this response may underlie poor outcome. A critical role for rostral cingulate area 24a/b in the limbic-cortical network involved in abnormal mood states is proposed.

Effect of depression on dementia presentation: qualitative assessment with the Qualitative Evaluation of Dementia (QED).

Two novel, bedside, dementia assessment instruments, the Executive Interview (EXIT) and the Qualitative Evaluation of Dementia (QED) were used to examine the effects of DSM-III-R major depressive episodes on the clinical presentation of patients diagnosed with NINCDS "possible" AD. Intergroup comparisons were made of the various bedside cognitive measures given to 102 of 118 consecutive patients presenting to a university geriatric assessment clinic and consultation service. The assessment instruments used were: (1) the EXIT: a 15-minute, 25-item bedside interview for the assessment of executive control function (ECF); (2) the QED: a brief, clinically based checklist that operationalizes the approach of a geriatric psychiatrist to the qualitative assessment of dementing illnesses (when QED scores are mapped against EXIT scores, a qualitative picture of dementia typology emerges); and (3) the Mini-Mental State Exam (MMSE): a familiar bedside measure of cognitive function. Depressed and nondepressed patients differed significantly on the QED. There was no overlap in the QED scores of patients with probable AD versus those with depression. The QED discriminated between depressed and nondepressed patients with possible AD. Possible AD patients with depression could not be qualitatively distinguished from those with depression alone, although they could be discriminated by the EXIT. Only 44% of possible AD cases fall within the EXIT x QED 90% confidence limits for probable AD. No differences were found on either the QED or the MMSE between depressed non-AD patients and nondepressed patients exhibiting "dementia with no cortical features." The MMSE was insensitive to cognitive impairment in non-AD cases. NINCDS "possible" AD is a qualitatively heterogeneous group.(ABSTRACT TRUNCATED AT 250 WORDS)