Clustered lot quality assurance sampling: a tool to monitor immunization coverage rapidly during a national yellow fever and polio vaccination campaign in Cameroon, May 2009.

We used the clustered lot quality assurance sampling (clustered-LQAS) technique to identify districts with low immunization coverage and guide mop-up actions during the last 4 days of a combined oral polio vaccine (OPV) and yellow fever (YF) vaccination campaign conducted in Cameroon in May 2009. We monitored 17 pre-selected districts at risk for low coverage. We designed LQAS plans to reject districts with YF vaccination coverage <90% and with OPV coverage <95%. In each lot the sample size was 50 (five clusters of 10) with decision values of 3 for assessing OPV and 7 for YF coverage. We 'rejected' 10 districts for low YF coverage and 14 for low OPV coverage. Hence we recommended a 2-day extension of the campaign. Clustered-LQAS proved to be useful in guiding the campaign vaccination strategy before the completion of the operations.

Comparison of diameter and perimeter methods for tumor volume calculation.

PURPOSE: Lesion volume is often used as an end point in clinical trials of oncology therapy. We sought to compare the common method of using orthogonal diameters to estimate lesion volume (the diameter method) with a computer-assisted planimetric technique (the perimeter method). METHODS: Radiologists reviewed 825 magnetic resonance imaging studies from 219 patients with glioblastoma multiforme. Each study had lesion volume independently estimated via the diameter and perimeter methods. Cystic areas were subtracted out or excluded from the outlined lesion. Inter- and intrareader variability was measured by using multiple readings on 48 cases. Where serial studies were available in noncystic cases, a mock response analysis was used. RESULTS: The perimeter method had a reduced interreader and intrareader variability compared with the diameter method (using SD of differences): intrareader, 1.76 mL v 7.38 mL (P < .001); interreader, 2.51 mL v 9.07 mL (P < .001) for perimeter and diameter results, respectively. Of the 121 noncystic cases, 23 had serial data. In six (26.1%) of those 23, a classification difference occurred when the perimeter method was used versus the diameter method. CONCLUSION: Variability of measurements was reduced with the computer-assisted perimeter method compared with the diameter method, which suggests that changes in volume can be detected more accurately with the perimeter method. The differences between these techniques seem large enough to have an impact on grading the response to therapy.

Dynamic susceptibility contrast MRI of regional cerebral blood volume in Alzheimer's disease.

OBJECTIVE: The purpose of this study was to investigate the potential effectiveness of dynamic susceptibility contrast magnetic resonance imaging (MRI) to discriminate elderly patients with Alzheimer's disease from normal matched comparison subjects. METHOD: Images of regional cerebral blood volume (CBV) were generated from echo-planar MRI with the dynamic susceptibility contrast method in 13 Alzheimer's disease patients and 13 comparison subjects group-matched on age and gender. RESULTS: Temporoparietal cerebral blood volume, expressed as a percentage of the cerebellum value, was reduced 17% bilaterally in the patients with Alzheimer's disease. Blood volume in sensorimotor regions was reduced only 8.5% in the patients. Discriminant function analysis based on left and right temporoparietal measures correctly classified 88.5% of the subjects as patients or comparison subjects. Temporoparietal CBV was reduced even in mildly affected Alzheimer's disease patients (Mini-Mental State scores > 24). CONCLUSIONS: Dynamic susceptibility contrast MRI of regional CBV is promising as a nonradioactive, potentially lower-cost alternative to other functional neuroimaging methods for evaluating Alzheimer's disease.

Group C streptococci isolated from throat swabs: a laboratory and clinical study.

AIMS: To determine the prevalence of beta haemolytic, Lancefield group C streptococci in throat swabs taken in routine clinical practice, and correlate the species identified with presenting clinical features. METHODS: One year, laboratory based prospective study, using a questionnaire to elicit clinical information. RESULTS: 4.4% of throat swabs yielded group C streptococci, of which 38% belonged to S equisimilis and 53% to S anginosus-milleri group (SAM). Pyrexia was more common in patients with S equisimilis, but other clinical features did not differ significantly between the two groups. No S zooepidemicus was isolated. CONCLUSIONS: Species identification of group C streptococci from throat swabs does not appear to be clinically useful in this patient population. However, the prevalence and spectrum of organisms is similar to that reported in N America, where studies suggest a possible role in some cases of severe pharyngitis. Observational studies such as this lack power to resolve the issue of pathogenicity, for which a placebo controlled trial of antibiotic treatment is ideally required.

Dynamic susceptibility contrast MR imaging of regional cerebral blood volume in Alzheimer disease: a promising alternative to nuclear medicine.

BACKGROUND AND PURPOSE: The goal of our study was to evaluate the sensitivity and specificity for Alzheimer disease of semiquantitative dynamic susceptibility contrast (DSC) MR imaging as compared with results of qualitative single-photon emission computed tomography (SPECT) in the same patients and with previously published semiquantitative SPECT results. METHODS: Fifty subjects were studied: 19 patients with probable Alzheimer disease with moderate cognitive impairment, eight mildly impaired patients with possible or probable Alzheimer disease, 18 group-matched elderly healthy comparison subjects, and five elderly comparison patients with psychiatric diagnoses. Relative values of temporoparietal regional cerebral blood volume (rCBV) were measured as a percentage of cerebellar rCBV, and group classification was assessed with logistic regression. The DSC MR imaging results were compared with SPECT scans in these same subjects and with previously published semiquantitative SPECT data. RESULTS: Temporoparietal rCBV ratios were reduced 20% bilaterally in the patients with Alzheimer disease. Using left and right temporoparietal rCBV as index measures, sensitivity was 95% in moderately affected patients with Alzheimer disease and 88% in patients with mild cases. Specificity was 96% in healthy comparison subjects and in psychiatric comparison subjects. Sensitivity with DSC MR imaging was considerably better than with visual clinical readings of SPECT scans (74% in moderate and 50% in mild Alzheimer disease cases), and was similar to previous published SPECT temporoparietal measurements (90%). Specificity with SPECT was 100% visually and 87% based on previous temporoparietal measurements. CONCLUSIONS: DSC MR imaging of rCBV is promising as a safe, potentially lower-cost alternative to nuclear medicine imaging for the evaluation of patients with dementia.

Evaluating the effects of drugs on behavior and quality of life: an alternative strategy for clinical trials.

Conventional clinical trials involve tests of hypotheses with statistics computed from values of dependent variables alone. An alternative is to test hypotheses with statistics computed from benefit/harm scores that measure longitudinal associations between dose and values of the dependent variables. The proposed standardized measure of benefit/harm quantifies the strength of evidence that a patient did either better or worse while on treatment. A benefit/harm score, particularly when obtained from a randomized, N-of-1 trial, indicates a beneficial or harmful treatment effect for the individual. Benefit/harm scores from samples of patients are evaluated with standard statistical tests, with or without group comparisons, to make inferences about populations. The proposed alternative strategy can yield within-patient indicators of treatment effect that are more reliable, valid, comprehensive, and detailed. This, in turn, could help make many population-based clinical trials more informative, cost-effective, and clinically useful for participants.

Disconjugate adaptation of saccades: contribution of binocular and monocular mechanisms.

We studied the effects of prism-induced disparity on static and intrasaccadic alignment in six normal human subjects. A ten diopter base-out prism, calling for convergence, was placed in front of the central field of the right eye, so that at the center the eye viewed through the prism; at left and right, outside the prism. During 15 min of training, subjects made repetitive saccades solely in the right field of vision (C-R-C sequence). This paradigm required relative divergence for centrifugal (C-R) saccades and relative convergence for centripetal (R-C) saccades, as well as increase of the amplitude for all saccades made by the right eye. We found that during training, all subjects incorporated the necessary change in alignment into the saccades. After training the resultant intrasaccadic disconjugacy persisted when tested during monocular viewing, indicating that motor learning had occurred. Subjects demonstrated increased divergence for C-R and increased convergence for R-C saccades, in accordance with the change acquired during adaptation to the prism. In addition, five subjects developed increased divergence for C-L saccades, for which they did not train. Smaller and less consistent divergence was also observed for L-C saccades. Changes in intrasaccadic alignment were accompanied by changes in the relative velocities of the two eyes' saccades and slowing of the peak velocities in both eyes during training. Static alignment showed a general tendency toward convergence that did not parallel the changes in the intrasaccadic alignment, suggesting that saccade adaptation is system-specific. The pattern of transfer of the intrasaccadic disconjugacy to saccades in the untrained field and the changes in the relative speeds of the two eyes cannot be explained by monocular adjustment of the saccades. Our results indicate that both a binocular mechanism--saccade-vergence interaction--and monocular adaptation contribute to disconjugate adaptation of saccades.

Regulation of static and dynamic ocular alignment in patients with trochlear nerve pareses.

Ocular alignment and saccades were studied in seven patients with trochlear nerve pareses, before and after strabismus surgery. Prior to surgery, a position-dependent vertical ocular misalignment was present, and downward saccades were hypometric in the paretic eye. Strabismus surgery reduced the magnitude and position-dependence of the static misalignment. Saccade conjugacy improved in the patients with congenital pareses, and in the patient with a gradual-onset acquired paresis, but less improvement occurred in subjects with traumatic pareses. The post-operative change in saccade conjugacy relative to the change in static alignment correlated with pre-operative vertical vergence, suggesting that changes in saccade yoking depend on an interaction between saccades and vertical vergence.

Influence of advanced recipient and donor age on the outcome of corneal transplantation. Australian Corneal Graft Registry.

AIMS: The aims of this study were to examine the influence of advanced recipient and donor age on the long term outcome of corneal transplantation. METHODS: Records of 1036 penetrating corneal grafts in recipients aged > or = 80 years at surgery (defined as the elderly subset) and 8092 donor corneas used for transplantation were obtained from the Australian Corneal Graft Register database, Kaplan-Meier graft survival plots were compared using log rank statistics. RESULTS: Elderly recipients constituted 15% of the recipient pool. The major indication for corneal transplantation in the elderly was bullous keratopathy. Graft survival fell with increasing recipient age (p < 0.00001); the major cause of graft failure was rejection (33%). The desired outcome in 51% of cases was to improve vision and in 42% of cases to relieve pain; 23% of elderly recipients achieved a Snellen acuity of 6/18 or better in the grafted eye and 66% recorded improved acuity after transplantation. Elderly recipients suffered more complications and comorbidities in the grafted eye than did younger recipients. Donor age (stratified in 10 year intervals) did not influence corneal graft survival significantly (p = 0.10). CONCLUSIONS: Elderly graft recipients fared less well after corneal transplantation than did younger recipients, but outcomes in terms of long term graft survival and visual rehabilitation were still good. Donor age did not affect graft survival.

Functional magnetic resonance imaging of alprazolam-induced changes in humans with familial alcoholism.

This study sought to identify whether subjects with a family history (FH + ) of alcoholism had changes in regional cerebral blood volume (rCBV) after an alprazolam challenge which distinguished them from subjects without a family history (FH -) of alcoholism using functional MRI (fMRI). Twelve FH + and eight FH - subjects were challenged with 1 mg of alprazolam or placebo in a double-blind crossover design. FMRI scans were obtained at baseline, 1 and 2 h after the challenge using the dynamic susceptibility contrast method with gadolinium. Mood scales, the Tufts Addiction Research Center Inventory-Morphine Benzedrine Group Scale and the drug liking scale, were administered every 30 min to assess drug effects. Global analysis of CBV showed a treatment by time decrease on alprazolam relative to placebo, but no effect by family history. The FH + group showed rCBV decreases at 1 h in the left caudate and left inferior prefrontal region, while the FH - group showed rCBV decreases at 2 h in the right inferior prefrontal region and anterior cingulate in response to alprazolam relative to placebo. FH + subjects reported more mood enhancement with alprazolam. This fMRI technique detected global and regional CBV changes induced by alprazolam. The location and rate of alprazolam-induced rCBV changes differed between FH + and FH - subjects. These changes may be related to the increased mood enhancement found in subjects genetically predisposed to alcoholism.

Ocular motor dysfunction in Lesch-Nyhan disease.

Eye movements were assessed in 22 patients with varying degrees of hypoxanthine-guanine phosphoribosyltransferase deficiency. Ocular motility was clinically normal in seven patients with moderate enzyme deficiency but grossly abnormal in 15 patients with severe enzyme deficiency. In patients with severe deficiency, fixation was interrupted by frequent unwanted saccades toward minor visual distractions. Voluntary saccades were associated with an initial head movement and/or eyeblink in all of these patients. When head motion was prevented, voluntary saccades were often delayed and sometimes absent. In contrast, saccade speed, reflexive saccades, and other reflexive eye movements appeared clinically normal. Four patients with severe enzyme deficiency also experienced mild blepharospasm, and two had ocular tics. These disturbances of ocular motility are consistent with dysfunction of the basal ganglia or its connections with ocular motor centers in the prefrontal cortex or midbrain.

The Digit Vigilance Test: reliability, validity, and sensitivity to diazepam.

The Digit Vigilance Test (DVT), a measure of sustained attention and psychomotor speed, was evaluated in terms of test-retest and alternate-form reliability as well as sensitivity to a single dose of diazepam (10 mg). A one-page version was compared to the standard two-page format. Forty undergraduates, randomly assigned in a double-blind manner to either drug or placebo condition, were tested three times in two sessions (1 week apart). Both Page 1 and Total Time scores were found to be highly reliable across time and forms. Repeated measures ANOVAs revealed the Total Time score, but not the Page 1 score, to be significant in discriminating diazepam from placebo across time, supporting the use of the complete DVT for measuring drug effects. Findings based on convergent measures also help to validate the DVT as a measure of sustained attention.

Hypoperfusion of inferior frontal brain regions in abstinent alcoholics: a pilot SPECT study.

OBJECTIVE: This pilot study evaluated hypotheses concerning the relationship between cerebral hypoperfusion and residual deficits in the functioning of frontal brain systems in abstinent long-term alcoholics. METHOD: The participants (N = 22) were 10 healthy, abstinent alcoholics (9 men) and 12 age-equivalent nonalcoholic controls (10 men). Cerebral blood flow was observed through the use of regionally specific computer-derived quantitative analysis of single photon emission computed tomography (SPECT) perfusion images. Measures of alcohol use, abstinence and neuropsychological functioning were also obtained to relate to SPECT findings. RESULTS: A positive relationship was observed between perfusion levels in the left inferior frontal brain region and years of sobriety. Alcoholics with less than 4 years of sobriety had significantly reduced left inferior frontal perfusion compared with both nonalcoholic controls and alcoholics having longer periods of sobriety. CONCLUSIONS: The findings support the hypothesis that frontal brain abnormalities in alcoholics may subside with extended abstinence.

Ocular motor disorders associated with cerebellar lesions: pathophysiology and topical localization.

A number of ocular motor abnormalities can be correlated with damage in specific parts of the cerebellum, especially the vestibulo-cerebellum (flocculus, paraflocculus, nodulus, uvula), and the dorsal vermis and the underlying (posterior) fastigial nuclei. These abnormalities of eye movements reflect both immediate, on-line and long-term adaptive functions of the cerebellum. Various types of image-stabilizing reflexes are in the province of the flocculus (and probably paraflocculus) including pursuit, vestibulo-ocular reflex (VOR) cancellation, and holding the eye steady for fixation, both immediately after saccades and in eccentric positions of gaze. The nodulus (and ventral uvula) modulates "low-frequency" aspects of vestibular responses and hence controls the duration (time constant) of the VOR. The dorsal vermis and underlying (posterior) fastigial nuclei participate in the control of the size of the saccadic pulse of innervation and hence saccadic accuracy. Here we review the eye signs that reflect abnormalities of these clearly defined cerebellar functions. We will also discuss less well localized but presumed cerebellar eye signs and consider a potential role for the cerebellum in the control of both dynamic and static ocular alignment.

The Gravitational Plant Physiology Facility--description of equipment developed for biological research in Spacelab.

In January 1992, the NASA Shuttle mission STS 42 carried a facility designed to perform experiments on plant gravi- and photo-tropic responses. This equipment, the Gravitational Plant Physiology Facility (GPPF) was made up of a number of interconnected units mounted within a Spacelab double rack. The details of these units and the plant growth containers designed for use in GPPF are described. The equipment functioned well during the mission and returned a substantial body of time-lapse video data on plant responses to tropistic stimuli under conditions of orbital microgravity. GPPF is maintained by NASA Ames Research Center, and is flight qualifiable for future Spacelab missions.

Adverse events following yellow fever preventive vaccination campaigns in eight African countries from 2007 to 2010.

BACKGROUND: Serious, but rare adverse events following immunization (AEFI) have been reported with yellow fever (YF) 17D vaccine, including severe allergic reactions, YF vaccine-associated neurologic disease (YEL-AND) and YF vaccine-associated viscerotropic disease (YEL-AVD). The frequency with which YEL-AND and YEL-AVD occur in YF endemic countries is mostly unknown. METHODS: From 2007 to 2010, eight African countries - Benin, Cameroon, Guinea, Liberia, Mali, Senegal, Sierra Leone, and Togo- implemented large-scale YF preventive vaccination campaigns. Each country established vaccine pharmacovigilance systems that included standard case definitions, procedures to collect and transport biological specimens, and National Expert Committees to review data and classify cases. Staff in all countries received training and laboratory capacity expanded. RESULTS: In total, just over 38 million people were vaccinated against YF and 3116 AEFIs were reported of which 164 (5%) were classified as serious. Of these, 22 (13%) were classified as YF vaccine reactions, including 11 (50%) hypersensitivity reactions, six (27%) suspected YEL-AND, and five (23%) suspected YEL-AVD. The incidence per 100,000 vaccine doses administered was 8.2 for all reported AEFIs, 0.43 for any serious AEFI, 0.058 for YF vaccine related AEFIs, 0.029 for hypersensitivity reactions, 0.016 for YEL-AND, and 0.013 for YEL-AVD. Our findings were limited by operational challenges, including difficulties in obtaining recommended biological specimens leading to incomplete laboratory evaluation, unknown case ascertainment, and variable levels of staff training and experience. CONCLUSIONS: Despite limitations, active case-finding in the eight different countries did not find an incidence of YF vaccine associated AEFIs that was higher than previous reports. These data reinforce the safety profile of YF vaccine and support the continued use of attenuated YF vaccine during preventive mass vaccination campaigns in YF endemic areas.