Assessing Bias in Cognitive Testing for Older Adults with Sensory Impairment: An Analysis of Differential Item Functioning in the Baltimore Longitudinal Study on Aging (BLSA) and the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

OBJECTIVES: Vision and hearing impairments affect 55% of people aged 60+ years and are associated with lower cognitive test performance; however, tests rely on vision, hearing, or both. We hypothesized that scores on tests that depend on vision or hearing are different among those with vision or hearing impairments, respectively, controlling for underlying cognition. METHODS: Leveraging cross-sectional data from the Baltimore Longitudinal Study of Aging (BLSA) and the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS), we used item response theory to test for differential item functioning (DIF) by vision impairment (better eye presenting visual acuity worse than 20/40) and hearing impairment (better ear .5-4 kHz pure-tone average > 25 decibels). RESULTS: We identified DIF by vision impairment for tests whose administrations do not rely on vision [e.g., Delayed Word Recall both in ARIC-NCS: .50 logit difference between impaired and unimpaired (p = .04) and in BLSA: .62 logits (p = .02)] and DIF by hearing impairment for tests whose administrations do not rely on hearing [Digit Symbol Substitution test in BLSA: 1.25 logits (p = .001) and Incidental Learning test in ARIC-NCS: .35 logits (p = .001)]. However, no individuals had differences between unadjusted and DIF-adjusted measures of greater than the standard error of measurement. CONCLUSIONS: DIF by sensory impairment in cognitive tests was independent of administration characteristics, which could indicate that elevated cognitive load among persons with sensory impairment plays a larger role in test performance than previously acknowledged. While these results were unexpected, neither of these samples are nationally representative and each has unique selection factors; thus, replication is critical.

The effect of missing data and imputation on the detection of bias in cognitive testing using differential item functioning methods.

BACKGROUND: Item response theory (IRT) methods for addressing differential item functioning (DIF) can detect group differences in responses to individual items (e.g., bias). IRT and DIF-detection methods have been used increasingly often to identify bias in cognitive test performance by characteristics (DIF grouping variables) such as hearing impairment, race, and educational attainment. Previous analyses have not considered the effect of missing data on inferences, although levels of missing cognitive data can be substantial in epidemiologic studies. METHODS: We used data from Visit 6 (2016-2017) of the Atherosclerosis Risk in Communities Neurocognitive Study (N = 3,580) to explicate the effect of artificially imposed missing data patterns and imputation on DIF detection. RESULTS: When missing data was imposed among individuals in a specific DIF group but was unrelated to cognitive test performance, there was no systematic error. However, when missing data was related to cognitive test performance and DIF group membership, there was systematic error in DIF detection. Given this missing data pattern, the median DIF detection error associated with 10%, 30%, and 50% missingness was -0.03, -0.08, and -0.14 standard deviation (SD) units without imputation, but this decreased to -0.02, -0.04, and -0.08 SD units with multiple imputation. CONCLUSIONS: Incorrect inferences in DIF testing have downstream consequences for the use of cognitive tests in research. It is therefore crucial to consider the effect and reasons behind missing data when evaluating bias in cognitive testing.

Reducing occupational distress in veterinary medicine personnel with acceptance and commitment training: a pilot study.

AIMS: To determine whether an educational programme targeting the reaction of veterinary personnel to difficult client interactions reduced burden transfer, stress and burnout in veterinary staff. METHODS: Employees of three small-animal veterinary hospitals in the south-western United States of America were recruited and randomised to intervention (educational programme; n = 16) or control (no intervention; n = 18) groups. Participants of this randomised, parallel arms trial completed pre-programme assessment including the Burden Transfer Inventory (BTI), Perceived Stress Scale, and Copenhagen Burnout Inventory. Assessment was followed by two, group-format educational sessions, based on acceptance and commitment training, tailored to reducing reactivity to difficult veterinary client interactions (intervention group only). After training was completed, both groups were assessed using the same measures and the intervention participants provided use and acceptability ratings. RESULTS: Intervention participants rated the programme as useful and appropriate, and reported that programme techniques were used a median of 43 (min 9, max 68) times during the 2 weeks prior to retesting. Relative to pre-programme scores, median post-programme scores for reaction (subscore of BTI) to difficult client interactions decreased in the intervention group (33 vs. 54; p = 0.047), but not in the control group (51 vs. 59; p = 0.210). Changes in median scores for stress and burnout from pre- to post-programme were non-significant for both groups. CONCLUSIONS: This pilot and feasibility trial showed high rates of acceptability and use by participants, as well as promising reductions in burden transfer. A larger scale clinical trial with follow-up at extended time points is needed to more fully examine the efficacy of this novel programme. CLINICAL RELEVANCE: Preliminary findings suggest this programme may be a useful approach to reducing occupational distress for individuals working in veterinary practice.

Dietary DHA reduces downstream endocannabinoid and inflammatory gene expression and epididymal fat mass while improving aspects of glucose use in muscle in C57BL/6J mice.

OBJECTIVES: Endocannabinoid system (ECS) overactivation is associated with increased adiposity and likely contributes to type 2 diabetes risk. Elevated tissue cannabinoid receptor 1 (CB1) and circulating endocannabinoids (ECs) derived from the n-6 polyunsaturated acid (PUFA) arachidonic acid (AA) occur in obese and diabetic patients. Here we investigate whether the n-3 PUFA docosahexaenoic acid (DHA) in the diet can reduce ECS overactivation (that is, action of ligands, receptors and enzymes of EC synthesis and degradation) to influence glycemic control. This study targets the ECS tonal regulation of circulating glucose uptake by skeletal muscle as its primary end point. DESIGN: Male C57BL/6J mice were fed a semipurified diet containing DHA or the control lipid. Serum, skeletal muscle, epididymal fat pads and liver were collected after 62 and 118 days of feeding. Metabolites, genes and gene products associated with the ECS, glucose uptake and metabolism and inflammatory status were measured. RESULTS: Dietary DHA enrichment reduced epididymal fat pad mass and increased ECS-related genes, whereas it reduced downstream ECS activation markers, indicating that ECS activation was diminished. The mRNA of glucose-related genes and proteins elevated in mice fed the DHA diet with increases in DHA-derived and reductions in AA-derived EC and EC-like compounds. In addition, DHA feeding reduced plasma levels of various inflammatory cytokines, 5-lipoxygenase-dependent inflammatory mediators and the vasoconstrictive 20-HETE. CONCLUSIONS: This study provides evidence that DHA feeding altered ECS gene expression to reduce CB1 activation and reduce fat accretion. Furthermore, the DHA diet led to higher expression of genes associated with glucose use by muscle in mice, and reduced those associated with systemic inflammatory status.

Diversity of Xanthomonas campestris Isolates from Symptomatic Crucifers in New York State.

To assess the diversity of Xanthomonas campestris spp. infecting crucifers in New York, 154 isolates were collected over 10 years across the state. The goal was to determine if isolates of the pathogen were overwintering in New York and serving as primary inoculum in subsequent years, or if novel isolates were entering the state each year. Pure cultures of isolates were characterized using multilocus sequence analysis (MLSA), a greenhouse pathogenicity assay, repetitive element-polymerase chain reaction (Rep-PCR) using the BOX-A1R primer, and enzyme-linked immunosorbent assay. The MLSA scheme proved to be more efficient than Rep-PCR for a large sample population and for comparison with global isolates. X. campestris isolated from crucifers in New York comprised of X. campestris pv. campestris and X. campestris pv. raphani, with X. campestris pv. raphani being predominately isolated from transplants. Evidence for unique haplotypes persisting on the same farm for several years due to improper seedbed rotations was documented in addition to novel haplotypes being spread throughout states through infected transplants and seed. Rep-PCR confirmed the high diversity of X. campestris and was used to generate 15 unique fingerprint patterns from isolates collected in the first 5 years. A worldwide comparison of isolates suggests that the X. campestris pv. campestris population appears to be very homogenous with dominant haplotypes persisting for extended periods and being globally disseminated.

Effectiveness of cold water immersion for treating exertional heat stress when immediate response is not possible.

Immediate treatment with cold water immersion (CWI) is the gold standard for exertional heatstroke. In the field, however, treatment is often delayed due to delayed paramedic response and/or inaccurate diagnosis. We examined the effect of treatment (reduction of rectal temperature to 37.5 °C) delays of 5, 20, and 40 min on core cooling rates in eight exertionally heat-stressed (40.0 °C rectal temperature) individuals. We found that rectal temperature was elevated above baseline (P < 0.05) at the end of all delay periods (5 min: 40.08 ± 0.32; 20 min: 39.92 ± 0.40; 40 min: 39.57 ± 0.29 °C). Mean arterial pressure was reduced (P < 0.05) below baseline (92 ± 1.8 mm Hg) after all delay periods (5 min: 75 ± 2.6; 20 min: 74 ± 1.7; 40 min: 70 ± 2.1 mm Hg; P > 0.05). Rectal core cooling rates were similar among conditions (5 min: 0.20 ± 0.01; 20 min: 0.17 ± 0.02; 40 min: 0.17 ± 0.01 °C/min; P > 0.05). The rectal temperature afterdrop following CWI was similar across conditions (5 min: 35.95; 20 min: 35.61; 40 min: 35.87 °C; P > 0.05). We conclude that the effectiveness of 2 °C CWI as a treatment for exertional heat stress remains high even when applied with a delay of 40 min. Therefore, our results support that CWI is the most appropriate treatment for exertional heatstroke as it is capable of quickly reversing hyperthermia even when treatment is commenced with a significant delay.

Nonoperative treatment for lumbosacral radiculopathy: what factors predict treatment failure?

BACKGROUND: Prior studies of nonoperative treatment for lumbosacral radiculopathy have identified potential predictors of treatment failure, defined by persistent pain, persistent disability, lack of recovery, or subsequent surgery. However, few predictors have been replicated, with the exception of higher leg pain intensity, as a predictor of subsequent surgery. QUESTIONS/PURPOSES: We asked two research questions: (1) Does higher baseline leg pain intensity predict subsequent lumbar surgery? (2) Can other previously identified "candidate" predictors of nonoperative treatment failure be replicated? METHODS: Between January 2008 and March 2009, 154 participants with acute lumbosacral radicular pain were enrolled in a prospective database; 128 participants (83%) received nonoperative treatment and 26 (17%) received surgery over 2-year followup. Ninety-four nonoperative participants (73%) responded to followup questionnaires. We examined associations between previously identified "candidate" predictors and treatment failure defined as (1) subsequent surgery; (2) persistent leg pain on a visual analog scale; (3) persistent disability on the Oswestry Disability Index; or (4) participant-reported lack of recovery over 2-year followup. Confounding variables including sociodemographics, clinical factors, and imaging characteristics were evaluated using an exploratory bivariate analysis followed by a multivariate analysis. RESULTS: With the numbers available, higher baseline leg pain intensity was not an independent predictor of subsequent surgery (adjusted odds ratio [aOR], 1.22 per point of baseline leg pain; 95% confidence interval [CI], 0.98-1.53; p = 0.08). Prior low back pain (aOR, 4.79; 95% CI, 1.01-22.7; p = 0.05) and a positive straight leg raise test (aOR, 4.38; 95% CI, 1.60-11.9; p = 0.004) predicted subsequent surgery. Workers compensation claims predicted persistent leg pain (aOR, 9.04; 95% CI, 1.01-81; p = 0.05) and disability (aOR, 5.99; 95% CI, 1.09-32.7; p = 0.04). Female sex predicted persistent disability (aOR, 3.16; 95% CI, 1.03-9.69; p = 0.05) and perceived lack of recovery (aOR, 2.44; 95% CI, 1.02-5.84; p = 0.05). CONCLUSIONS: Higher baseline leg pain intensity was not confirmed as a predictor of subsequent surgery. However, the directionality of the association seen was consistent with prior reports, suggesting Type II error as a possible explanation; larger studies are needed to further examine this relationship. Clinicians should be aware of potential factors that may predict nonoperative treatment failure, including prior low back pain or a positive straight leg raise test as predictors of subsequent surgery, workers compensation claims as predictors of persistent leg pain and disability, and female sex as a predictor of persistent disability and lack of recovery. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

A physical map and candidate genes in the BRCA1 region on chromosome 17q12-21.

We have constructed a physical map of a 4 cM region on chromosome 17q12-21 that contains the hereditary breast and ovarian cancer gene BRCA1. The map comprises a contig of 137 overlapping yeast artificial chromosomes and P1 clones, onto which we have placed 112 PCR markers. We have localized more than 20 genes on this map, ten of which had not been mapped to the region previously, and have isolated 30 cDNA clones representing partial sequences of as yet unidentified genes. Two genes that lie within a narrow region defined by meiotic breakpoints in BRCA1 patients have been sequenced in breast cancer patients without revealing any deleterious mutations. These new reagents should facilitate the identification of BRCA1.

Increased Labyrinthine T1 Postgadolinium Signal Intensity Is Associated with the Degree of Ipsilateral Sensorineural Hearing Loss in Patients with Sporadic Vestibular Schwannoma.

BACKGROUND AND PURPOSE: Vestibular schwannomas are benign, generally slow-growing tumors, commonly presenting with hearing loss. Alterations in the labyrinthine signal are seen in patients with vestibular schwannoma; however, the association between imaging abnormalities and hearing function remains poorly defined. The purpose of this study was to determine whether labyrinthine signal intensity is associated with hearing in patients with sporadic vestibular schwannoma. MATERIALS AND METHODS: This was an institutional review board-approved retrospective review of patients from a prospectively maintained vestibular schwannoma registry imaged in 2003-2017. Signal-intensity ratios of the ipsilateral labyrinth were obtained using T1, T2-FLAIR, and postgadolinium T1 sequences. Signal-intensity ratios were compared with tumor volume and audiometric hearing threshold data including pure tone average, word recognition score, and American Academy of Otolaryngology-Head and Neck Surgery hearing class. RESULTS: One hundred ninety-five patients were analyzed. Ipsilateral labyrinthine signal intensity including postgadolinium T1 images was positively correlated with tumor volume (correlation coefficient = 0.17, P = .02). Among signal-intensity ratios, postgadolinium T1 was significantly positively associated with pure tone average (correlation coefficient = 0.28, P < .001) and negatively associated with the word recognition score (correlation coefficient = -0.21, P = .003). Overall, this result correlated with impaired American Academy of Otolaryngology-Head and Neck Surgery hearing class (P = .04). Multivariable analysis suggested persistent associations independent of tumor volume with pure tone average (correlation coefficient = 0.25, P < .001) and the word recognition score (correlation coefficient = -0.17, P = .02) but not hearing class (P = .14). No consistent significant associations were noted between noncontrast T1 and T2-FLAIR signal intensities and audiometric testing. CONCLUSIONS: Increased ipsilateral labyrinthine postgadolinium signal intensity is associated with hearing loss in patients with vestibular schwannoma.

Validation of the CogDrisk Instrument as Predictive of Dementia in Four General Community-Dwelling Populations.

BACKGROUND: Lack of external validation of dementia risk tools is a major limitation for generalizability and translatability of prediction scores in clinical practice and research. OBJECTIVES: We aimed to validate a new dementia prediction risk tool called CogDrisk and a version, CogDrisk-AD for predicting Alzheimer's disease (AD) using cohort studies. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Four cohort studies were identified that included majority of the dementia risk factors from the CogDrisk tool. Participants who were free of dementia at baseline were included. The predictors were component variables in the CogDrisk tool that include self-reported demographics, medical risk factors and lifestyle habits. Risk scores for Any Dementia and AD were computed and Area Under the Curve (AUC) was assessed. To examine modifiable risk factors for dementia, the CogDrisk tool was tested by excluding age and sex estimates from the model. RESULTS: The performance of the tool varied between studies. The overall AUC and 95% CI for predicting dementia was 0.77 (0.57, 0.97) for the Swedish National study on Aging and Care in Kungsholmen, 0.76 (0.70, 0.83) for the Health and Retirement Study - Aging, Demographics and Memory Study, 0.70 (0.67,0.72) for the Cardiovascular Health Study Cognition Study, and 0.66 (0.62,0.70) for the Rush Memory and Aging Project. CONCLUSIONS: The CogDrisk and CogDrisk-AD performed well in the four studies. Overall, this tool can be used to assess individualized risk factors of dementia and AD in various population settings.

Relationships among owner consideration of euthanasia, caregiver burden, and treatment satisfaction in canine osteoarthritis.

Although diagnosis of osteoarthritis (OA) has been recently linked to euthanasia in dogs, no prior work has examined the roles of caregiver burden or treatment satisfaction in this relationship. We expected that there would be an indirect effect of caregiver burden on the association between consideration of euthanasia and clinical signs of OA, but that this effect would be influenced by owner satisfaction. Cross-sectional online evaluations were completed by 277 owners of dogs with OA recruited through social media. Canine OA-related pain and functional impairment, owner consideration of euthanasia, caregiver burden, and satisfaction were examined. Relationships among OA-related pain and functional impairment, owner consideration of euthanasia, caregiver burden, and satisfaction were statistically significant (P 0.01 for all). Cross-sectional mediation analysis demonstrated a statistically significant indirect effect of caregiver burden on the relationship between consideration of euthanasia and OA-related clinical signs (bias-corrected 95% confidence interval [BC 95% CI], 0.001-0.009), which was significantly moderated by owner satisfaction (BC 95% CI, -0.003 to -0.0002). Findings align with prior work connecting canine OA to euthanasia. The current study extends past research to demonstrate that caregiver burden in the owner may be partially responsible for this relationship. The moderating role of owner satisfaction suggests that optimizing owner impressions of treatment and the veterinary team could attenuate these relationships, potentially decreasing the likelihood of premature euthanasia for dogs with OA.

The SNF/SWI family of global transcriptional activators.

The yeast SNF/SWI proteins have a global role in transcriptional activation. This set of five proteins assists many gene-specific activators, most likely by altering chromatin structure to relieve repression. Recent work shows that the SNF/SWI proteins function together in a multiprotein complex and that SNF2 has DNA-dependent ATPase activity. SNF/SWI homologs have now been identified in Drosophila, mice and humans, suggesting a conserved role in transcriptional activation.

Non-EPI versus Multishot EPI DWI in Cholesteatoma Detection: Correlation with Operative Findings.

BACKGROUND AND PURPOSE: Although multishot EPI (readout-segmented EPI) has been touted as a robust DWI sequence for cholesteatoma evaluation, its efficacy in disease detection compared with a non-EPI (eg, HASTE) technique is unknown. This study sought to compare the accuracy of readout-segmented EPI with that of HASTE DWI in cholesteatoma detection. MATERIALS AND METHODS: A retrospective review was completed of consecutive patients who underwent MR imaging for the evaluation of suspected primary or recurrent/residual cholesteatomas. Included patients had MR imaging examinations that included both HASTE and readout-segmented EPI sequences and confirmed cholesteatomas on a subsequent operation. Two neuroradiologist reviewers assessed all images, with discrepancies resolved by consensus. The ratio of signal intensity between the cerebellum and any observed lesion was noted. RESULTS: Of 23 included patients, 12 (52.2%) were women (average age, 47.8 [SD, 25.2] years). All patients had surgically confirmed cholesteatomas: Six (26.1%) were primary and 17 (73.9%) were recidivistic. HASTE images correctly identified cholesteatomas in 100.0% of patients. On readout-segmented EPI sequences, 16 (69.6%) were positive, 5 (21.7%) were equivocal, and 2 (8.7%) were falsely negative. Excellent interobserver agreement was noted between reviews on both HASTE (κ = 1.0) and readout-segmented EPI (κ = 0.9) sequences. The average signal intensity ratio was significantly higher on HASTE than in readout-segmented EPI, facilitating enhanced detection (mean difference 0.5; 95% CI, 0.3-0.8; P = .003). CONCLUSIONS: HASTE outperforms readout-segmented EPI in the detection of primary cholesteatoma and disease recidivism.

Beyond Tympanomastoidectomy: A Review of Less Common Postoperative Temporal Bone CT Findings.

Postoperative temporal bone imaging after surgical procedures such as ossiculoplasty, tympanomastoidectomy, cochlear implantation, and vestibular schwannoma resection is often encountered in clinical neuroradiology practice. Less common otologic procedures can present diagnostic dilemmas, particularly if access to prior operative reports is not possible. Lack of familiarity with the less common surgical procedures and expected postoperative changes may render radiologic interpretation challenging. This review illustrates key imaging findings after surgery for Ménière disease, superior semicircular canal dehiscence, temporal encephalocele repairs, internal auditory canal decompression, active middle ear implants, jugular bulb and sigmoid sinus dehiscence repair, and petrous apicectomy.

The Many Faces of Persistent Stapedial Artery: CT Findings and Embryologic Explanations.

Persistent stapedial artery is a vascular anomaly with both clinical and surgical implications. Because of its scarcity, however, it remains underrecognized on imaging. Presented here is a series of 10 cases, demonstrating characteristic CT findings associated with this vascular anomaly and its most common pathognomonic imaging signs. The variable morphologic configurations and their corresponding embryologic underpinnings are described. Clinical and surgical implications of this rare anomaly are discussed.

L-selectin is dispensable for T regulatory cell function postallogeneic bone marrow transplantation.

In murine models, the adoptive transfer of CD4(+) /CD25(+) regulatory T cells (T(regs) ) inhibited graft-versus-host disease (GvHD). Previous work has indicated a critical role for the adhesion molecule L-selectin (CD62L) in the function of T(regs) in preventing GvHD. Here we examined the capacity of naive wild-type (WT), CD62L(-/-) and ex vivo expanded CD62L(Lo) T(regs) to inhibit acute GvHD. Surprisingly, we found that CD62L(-/-) T(regs) were potent suppressors of GvHD, whereas CD62L(Lo) T(regs) were unable to inhibit disease despite being functionally competent to suppress allo T cell responses in vitro. Concomitant with improved outcomes, WT and CD62L(-/-) T(regs) significantly reduced liver pathology and systemic pro-inflammatory cytokine production, although CD62L(-/-) T(regs) were less effective in reducing lung pathology. While accumulation of CD62L(-/-) T(regs) in GvHD target organs was equivalent to WT T(regs) , CD62L(-/-) T(regs) did not migrate as well as WT T(regs) to peripheral lymph nodes (PLNs) over the first 2 weeks posttransplantation. This work demonstrated that CD62L was dispensable for T(reg) -mediated protection from GvHD.

The Forgotten Second Window: A Pictorial Review of Round Window Pathologies.

The round window serves to decompress acoustic energy that enters the cochlea via stapes movement against the oval window. Any inward motion of the oval window via stapes vibration leads to outward motion of the round window. Occlusion of the round window is a cause of conductive hearing loss because it increases the resistance to sound energy and consequently dampens energy propagation. Because the round window niche is not adequately evaluated by otoscopy and may be incompletely exposed during an operation, otologic surgeons may not always correctly identify associated pathology. Thus, radiologists play an essential role in the identification and classification of diseases affecting the round window. The purpose of this review is to highlight the developmental, acquired, neoplastic, and iatrogenic range of pathologies that can be encountered in round window dysfunction.

Structural insight into the Staphylococcus aureus ATP-driven exporter of virulent peptide toxins.

Staphylococcus aureus is a major human pathogen that has acquired alarming broad-spectrum antibiotic resistance. One group of secreted toxins with key roles during infection is the phenol-soluble modulins (PSMs). PSMs are amphipathic, membrane-destructive cytolytic peptides that are exported to the host-cell environment by a designated adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, the PSM transporter (PmtABCD). Here, we demonstrate that the minimal Pmt unit necessary for PSM export is PmtCD and provide its first atomic characterization by single-particle cryo-EM and x-ray crystallography. We have captured the transporter in the ATP-bound state at near atomic resolution, revealing a type II ABC exporter fold, with an additional cytosolic domain. Comparison to a lower-resolution nucleotide-free map displaying an "open" conformation and putative hydrophobic inner chamber of a size able to accommodate the binding of two PSM peptides provides mechanistic insight and sets the foundation for therapeutic design.

Functional and cognitive criteria produce different rates of mild cognitive impairment and conversion to dementia.

OBJECTIVE: To compare rates of mild cognitive impairment (MCI) and rates of progression to dementia using different MCI diagnostic systems. METHODS: MCI was investigated at baseline in 3063 community dwelling non-demented elderly in the Ginkgo Evaluation of Memory (GEM) study who were evaluated every 6 months to identify the presence of dementia. Overall MCI frequency was determined using (1) a Clinical Dementia Rating (CDR) score of 0.5 and (2) neuropsychological (NP) criteria, defined by impairment on standard cognitive tests. RESULTS: 40.2% of participants met CDR MCI criteria and 28.2% met NP MCI criteria (amnestic MCI = 16.6%). 15.7% were classified as MCI by both criteria and 47.4% as normal by both. Discordant diagnoses were observed in 24.5% who met NP normal/CDR MCI and in 12.4% who met NP MCI/CDR normal. Factors associated with CDR MCI among NP normal included lower education, lower NP scores, more instrumental activities of daily living impairment, greater symptoms of depression and subjective health problems. Individuals meeting NP MCI/CDR normal were significantly more likely to develop dementia over the median follow-up of 6.1 years than those meeting NP normal/CDR MCI. CONCLUSIONS: Different criteria produce different MCI rates and different conversion rates to dementia. Although a higher percentage of MCI was identified by CDR than NP, a higher percentage of NP MCI progressed to dementia. These findings suggest that the CDR is sensitive to subtle changes in cognition not identified by the NP algorithm but is also sensitive to demographic and clinical factors probably leading to a greater number of false positives. These results suggest that identifying all individuals with CDR scores of 0.5 as Alzheimer's disease is not advisable.

A yeast gene that is essential for release from glucose repression encodes a protein kinase.

The SNF1 gene plays a central role in carbon catabolite repression in the yeast Saccharomyces cerevisiae, namely that SNF1 function is required for expression of glucose-repressible genes. The nucleotide sequence of the cloned SNF1 gene was determined, and the predicted amino acid sequence shows that SNF1 encodes a 72,040-dalton polypeptide that has significant homology to the conserved catalytic domain of mammalian protein kinases. Specific antisera were prepared and used to identify the SNF1 protein. The protein was shown to transfer phosphate from adenosine triphosphate to serine and threonine residues in an in vitro autophosphorylation reaction. These findings indicate that SNF1 encodes a protein kinase and suggest that protein phosphorylation plays a critical role in regulation by carbon catabolite repression in eukaryotic cells.