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Purpose: In HER2-positive breast cancer (HER2+BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC. Methods:Patients with clinical stage II-III HER2+BC received weekly paclitaxel 80 mg/m2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion. Results:In 30 evaluable patients, the pCR rate was 77% (95% CI 58-90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade >3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade >2 diarrhea (40%) than the standard loading dose (60%). Conclusions:pCR rates with our regimen were as high as reported with TCHP with fewer grade >3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+BC.ClinicalTrials.gov identifier: NCT02789657

We report an experimental study of the static magnetization $M(H,T)$ and high-field electron spin resonance (ESR) of polycrystalline ${\text{Mg}}_{2}{\text{Gd}}_{3}{\text{Sb}}_{3}{\text{O}}_{14}$, a representative member of the newly discovered class of the so-called tripod kagome antiferromagnets where the isotropic ${\mathrm{Gd}}^{3+}$ spins $(S=7/2)$ form a two-dimensional kagome spin-frustrated lattice. It follows from the analysis of the low-$T\phantom{\rule{4pt}{0ex}}M(H)$ curves that the ${\mathrm{Gd}}^{3+}$ spins are coupled by a small isotropic antiferromagnetic (AFM) exchange interaction, $|J|\ensuremath{\approx}0.3$ K. The $M(H,T)$ dependences measured down to 0.5 K evidence a long-range AFM order at ${T}_{N}=1.7\phantom{\rule{0.28em}{0ex}}\mathrm{K}$ and its rapid suppression at higher fields, $\ensuremath{\ge}4$ T. ESR spectra measured in fields up to 15 T are analyzed considering possible effects of demagnetizing fields, single-ion anisotropy, and spin-spin correlations. While the demagnetization effects due to a large sample magnetization in high fields and its shape anisotropy become relevant at low temperatures, the broadening of the ESR line commencing already at $T\ensuremath{\lesssim}30\phantom{\rule{0.28em}{0ex}}\mathrm{K}$ may indicate the onset of the spin-spin correlations far above the ordering temperature due to the geometrical spin frustration in this compound.

BACKGROUND We examined the impact of cavity shave margins (CSMs) on margin status in patients with pure ductal carcinoma in situ (DCIS) undergoing partial mastectomy (PM). METHODS One hundred and nine patients from 2 multicenter, randomized controlled trials were identified with pure DCIS (no invasive cancer). Surgeons performed their best PM, with specimen radiography and resection of selective margins per surgeon discretion. Patients were then randomized to have CSM resected or not. A positive margin was defined as

High-resolution thermal expansion and magnetostriction measurements were performed on single crystals of $\ensuremath{\alpha}\ensuremath{-}{\mathrm{RuCl}}_{3}$ in magnetic fields applied parallel to the Ru-Ru bonds. The length changes were measured in the direction perpendicular to the honeycomb planes. Our data show clear thermodynamic characteristics for the field-induced phase transition at the critical field ${\ensuremath{\mu}}_{0}{H}_{\mathrm{c}1}=7.8(2)\phantom{\rule{0.16em}{0ex}}\mathrm{T}$ where the antiferromagnetic zigzag order is suppressed. At higher fields, a kink in the magnetostriction coefficient signals an additional transition or crossover around ${\ensuremath{\mu}}_{0}{H}_{\mathrm{c}2}\ensuremath{\approx}11\phantom{\rule{0.16em}{0ex}}\mathrm{T}$. The extracted Gr\"uneisen ratio shows typical hallmarks for quantum criticality near ${H}_{\mathrm{c}1}$ but also displays anomalous behavior above ${H}_{\mathrm{c}1}$. We compare our experimental data with spin-wave calculations employing a minimal Kitaev-Heisenberg model in the semiclassical limit. Most of the salient features are in agreement with each other, however, the peculiar features in the region above ${H}_{\mathrm{c}1}$ cannot be accounted for in our semiclassical modeling and hence suggest a genuine quantum nature. We construct a phase diagram for $\ensuremath{\alpha}\ensuremath{-}{\mathrm{RuCl}}_{3}$ in a magnetic field along the Ru-Ru bonds, displaying a zigzag ordered state below ${H}_{\mathrm{c}1}$, a quantum paramagnetic regime between ${H}_{\mathrm{c}1}$ and ${H}_{\mathrm{c}2}$, and a semiclassical partially polarized state above ${H}_{\mathrm{c}2}$.

We report an optimized chemical vapor transport method that enables the growth of FeP single crystals up to 500 mg in mass and $80\phantom{\rule{0.16em}{0ex}}{\mathrm{mm}}^{3}$ in volume. The high quality of the crystals obtained by this method was confirmed by means of energy-dispersive x-ray spectroscopy, high-resolution transmission electron microscopy, low-temperature single-crystal x-ray diffraction, and neutron diffraction experiments. We investigated the transport and magnetic properties of the single crystals, and we calculated the electronic structure of FeP. We show both theoretically and experimentally that the ground state of FeP is metallic. The examination of the magnetic data reveals antiferromagnetic order below ${T}_{\mathrm{N}}=119\phantom{\rule{0.16em}{0ex}}\mathrm{K}$ while transport remains metallic in both the paramagnetic and the antiferromagnetic phase. The analysis of the neutron diffraction data shows an incommensurate magnetic structure with the propagation vector $\mathbf{Q}=(0,0,\ifmmode\pm\else\textpm\fi{}\ensuremath{\delta})$, where \ensuremath{\delta} is close to 0.2. For a full understanding of the magnetic state, further experiments are needed. The successful growth of large high-quality single crystals paves the way for further investigations of itinerant magnets with incommensurate spin structures using a wide range of experimental tools.

Objective Evaluate the psychometric characteristics of the Cognitive Difficulties Scale (CDS; McNair & Kahn, 1983), a 39-item Likert-type self-report instrument that requires a fifth-grade reading level. The CDS is a popular instrument that has been shown to predict cognitive decline. Evaluation included an exploratory factor analysis, measures of internal consistency, relation to demographics, criterion validity, and normative table for raw to T score/percentile transformation. Method Participants were 643 consecutive referrals (71% women, mean age 60.6 and education 14.6 years) for a neuropsychological examination in a memory disorders clinic as part of a broader neurodiagnostic workup for cognitive decline. A principal components analysis was conducted followed by varimax rotation (Kaiser). Factor scores were investigated in relation to multiple internal and external criteria. Results Six dimensions of cognitive complaint emerged accounting for 64% of the variance: Attention/Concentration, Fine Motor Skill, Prospective Memory, Speech Problems, Memory for Names, and Temporal Orientation. Factors showed good internal consistencies (alphas > .850). Correlations with Logical Memory, Visual Reproduction, and Digit Span were all nonsignificant. CDS factor scores were highly predictive of MMPI-2 measures of anxiety, depression, and somatic preoccupation. Percentiles and T-scores were derived for the CDS total score and its six component scales. Conclusion The CDS is a multidimensional measure of subjective cognitive complaints that provides clinicians with a psychometrically sound basis for deriving a profile with six subscale scores. The test has substantial clinical utility, and is a potentially useful tool in exploring subjective cognitive decline as a prodrome to dementia.

Objective We introduce a supplemental measure based on the Logical Memory (LM) subtest of the Wechsler Memory Scale – IV (Wechsler, 2008) to assist in distinguishing deficient memory storage from compromised retrieval operations. A 20-item five-option multiple choice delayed recognition test for the LM stories is described, followed by descriptive data based on a normative sample of 168 female and 105 male neurologically normal outpatient referrals to a neuropsychology clinic. Method Ten 5-option items were developed for each of the three LM stories (A, B, and C) reflecting the stories’ narrative content, yielding 20 items for administration to examinees under 70 (Stories B and C) and older than 69 (Stories A and B). Four distractor options for each item were designed to be “plausible” alternatives for the examinee who had little or no recollection of the narrative material. Examinees (N=360), screened for performance validity (effort), completed the LM Recognition test immediately after delayed LM free recall. Results Internal consistency (Cronbach alpha) was acceptable for both 20-item LM Recognition tests. Individuals’ scaled scores on LM-Recognition were compared with LM-II (free recall). Recognition was superior (> one SD) to free recall performance in 43% (age 18 to 69) and 48.2% (age 70+). Conclusion Delayed free recall scores often underestimate a person’s ability to encode and store new information. For clinical application, separate LM Recognition norms were derived for older (Stories A and B) and younger examinees (stories B and C). This 20-item measure assists clinicians in differentiating between storage and retrieval deficits on the Logical Memory subtest.

Chemistry of materials 31(8), 2795 - 2806 (2019). doi:10.1021/acs.chemmater.8b05017, High-quality single crystals of MnBi2Te4 are grown for the first time by slow cooling within a narrow range between the melting points of Bi$_2$Te$_3$ (586 °C) and MnBi$_2$Te$_4$ (600 °C). Single-crystal X-ray diffraction and electron microscopy reveal ubiquitous antisite defects in both cation sites and, possibly, Mn vacancies (Mn$_{0.85(3)}$Bi$_{2.10(3)}$Te$_4$). Thermochemical studies complemented with high-temperature X-ray diffraction establish a limited high-temperature range of phase stability and metastability at room temperature. Nevertheless, the synthesis of MnBi$_2$Te$_4$ can be scaled-up as powders can be obtained at subsolidus temperatures and quenched at room temperature. Bulk samples exhibit long-range antiferromagnetic ordering below 24 K. The Mn(II) out-of-plane magnetic state is confirmed by the magnetization, X-ray photoemission, X-ray absorption, and linear dichroism measurements. The compound shows a metallic type of resistivity in the range 4.5–300 K and is an n-type conductor that reaches a thermoelectric figure of merit up to ZT = 0.17. Angle-resolved photoemission experiments show a surface state forming a gapped Dirac cone, thus strengthening MnBi$_2$Te$_4$ as a promising candidate for the intrinsic magnetic topological insulator, in accordance with theoretical predictions. The developed synthetic protocols enable further experimental studies of a crossover between magnetic ordering and nontrivial topology in bulk MnBi$_2$Te$_4$., Published by American Chemical Society, Washington, DC

Magnetic topological insulators are narrow-gap semiconductor materials that combine non-trivial band topology and magnetic order. Unlike their nonmagnetic counterparts, magnetic topological insulators may have some of the surfaces gapped, which enables a number of exotic phenomena that have potential applications in spintronics, such as the quantum anomalous Hall effect and chiral Majorana fermions. So far, magnetic topological insulators have only been created by means of doping nonmagnetic topological insulators with 3d transition-metal elements; however, such an approach leads to strongly inhomogeneous magnetic and electronic properties of these materials, restricting the observation of important effects to very low temperatures. An intrinsic magnetic topological insulator—a stoichiometric well ordered magnetic compound—could be an ideal solution to these problems, but no such material has been observed so far. Here we predict by ab initio calculations and further confirm using various experimental techniques the realization of an antiferromagnetic topological insulator in the layered van der Waals compound MnBiTe. The antiferromagnetic ordering that MnBiTe shows makes it invariant with respect to the combination of the time-reversal and primitive-lattice translation symmetries, giving rise to a ℤ topological classification; ℤ = 1 for MnBiTe, confirming its topologically nontrivial nature. Our experiments indicate that the symmetry-breaking (0001) surface of MnBiTe exhibits a large bandgap in the topological surface state. We expect this property to eventually enable the observation of a number of fundamental phenomena, among them quantized magnetoelectric coupling and axion electrodynamics. Other exotic phenomena could become accessible at much higher temperatures than those reached so far, such as the quantum anomalous Hall effect and chiral Majorana fermions., We acknowledge support by the Basque Departamento de Educacion, UPV/EHU (grant number IT-756-13), the Spanish Ministerio de Economia y Competitividad (MINECO grant number FIS2016-75862-P), and the Academic D.I. Mendeleev Fund Program of Tomsk State University (project number 8.1.01.2018). Support from the Saint Petersburg State University grant for scientific investigations (grant ID 40990069), the Russian Science Foundation (grants number 18-12-00062 for part of the photoemission measurements and 18-12-00169 for part of the calculations of topological invariants and tight-binding bandstructure calculations), the Russian Foundation for Basic Research (grant number 18-52-06009), and the Science Development Foundation under the President of the Republic of Azerbaijan (grant number EİF-BGM-4-RFTF-1/2017-21/04/1-M-02) is also acknowledged. M.M.O. acknowledges support by the Diputación Foral de Gipuzkoa (project number 2018-CIEN-000025-01). I.I.K. and A.M.S. acknowledge partial support from the CERIC-ERIC consortium for the stay at the Elettra synchrotron. The ARPES measurements at HiSOR were performed with the approval of the Proposal Assessing Committee (proposal numbers 18AG020, 18BU005). The support of the German Research Foundation (DFG) is acknowledged by A.U.B.W., A.I. and B.B. within Collaborative Research Center 1143 (SFB 1143, project ID 247310070); by A.Z., A.E. and A.I. within Special Priority Program 1666 Topological Insulators; by H.B. and F.R. within Collaborative Research Center 1170; and by A.Z. and A.I. within the ERANET-Chemistry Program (RU 776/15-1). H.B., A.U.B.W., A.A., V.K., B.B., F.R. and A.I. acknowledge financial support from the DFG through the Würzburg-Dresden Cluster of Excellence on Complexity and Topology in Quantum Matter – ct.qmat (EXC 2147, project ID 39085490). A.E. acknowledges support by the OeAD grant numbers HR 07/2018 and PL 03/2018. This work was also supported by the Fundamental Research Program of the State Academies of Sciences, line of research III.23. A.K. was financially supported by KAKENHI number 17H06138 and 18H03683. I.P.R. acknowledges support by the Ministry of Education and Science of the Russian Federation within the framework of the governmental program Megagrants (state task number 3.8895.2017/P220). E.V.C. acknowledges financial support by the Gobierno Vasco-UPV/EHU project (IT1246-19). S.K. acknowledges financial support from an Overseas Postdoctoral Fellowship, SERB-India (OPDF award number SB/OS/PDF-060/2015-16). J.S.-B.acknowledges financial support from the Impuls-und Vernetzungsfonds der Helmholtz-Gemeinschaft under grant number HRSF-0067 (Helmholtz-Russia Joint Research Group). The calculations were performed in Donostia International Physics Center, in the research park of Saint Petersburg State University Computing Center (http://cc.spbu.ru), and at Tomsk State University

Background— The aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin. Methods and Results— We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P P =0.001), and improved net clinical benefit (adjusted P P =0.082 for ischemic stroke and adjusted P =0.109 for major hemorrhage). Conclusions— In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00041938.

We report $^{75}\mathrm{As}$ nuclear magnetic resonance measurements on single crystals of ${\mathrm{RbFe}}_{2}{\mathrm{As}}_{2}$ and ${\mathrm{CsFe}}_{2}{\mathrm{As}}_{2}$. Taking previously reported results for ${\mathrm{KFe}}_{2}{\mathrm{As}}_{2}$ into account, we find that the anisotropic electronic correlations evolve towards a magnetic instability in the $A{\mathrm{Fe}}_{2}{\mathrm{As}}_{2}$ series (with $A=\mathrm{K}$, Rb, Cs). Upon isovalent substitution with larger alkali-metal ions, a drastic enhancement of the anisotropic nuclear spin-lattice relaxation rate and decreasing Knight shift reveal the formation of pronounced spin fluctuations with stripe-type modulation. Furthermore, a decreasing power-law exponent of the nuclear spin-lattice relaxation rate ${(1/{T}_{1})}_{H\ensuremath{\parallel}ab}$, probing the in-plane spin fluctuations, evidences an emergent deviation from Fermi-liquid behavior. All these findings clearly indicate that the expansion of the lattice in the $A{\mathrm{Fe}}_{2}{\mathrm{As}}_{2}$ series tunes the electronic correlations towards a quantum critical point at the transition to a yet unobserved ordered phase.

Recently, the iridate double perovskite ${\mathrm{Sr}}_{2}{\mathrm{YIrO}}_{6}$ has attracted considerable attention due to the report of unexpected magnetism in this ${\mathrm{Ir}}^{5+}$ $(5{d}^{4})$ material, in which according to the ${J}_{\mathrm{eff}}$ model, a nonmagnetic ground state is expected. However, in recent works on polycrystalline samples of the series ${\mathrm{Ba}}_{2\ensuremath{-}x}{\mathrm{Sr}}_{x}{\mathrm{YIrO}}_{6}$ no indication of magnetic transitions have been found. We present a structural, magnetic, and thermodynamic characterization of ${\mathrm{Sr}}_{2}{\mathrm{YIrO}}_{6}$ single crystals, with emphasis on the temperature and magnetic field dependence of the specific heat. As determined by x-ray diffraction, the ${\mathrm{Sr}}_{2}{\mathrm{YIrO}}_{6}$ single crystals have a cubic structure, with space group $Fm\overline{3}m$. In agreement with the expected nonmagnetic ground state of ${\mathrm{Ir}}^{5+}$ $({5d}^{4})$ in ${\mathrm{Sr}}_{2}{\mathrm{YIrO}}_{6}$, no magnetic transition is observed down to 430 mK. Moreover, our results suggest that the low-temperature anomaly observed in the specific heat is not related to the onset of long-range magnetic order. Instead, it is identified as a Schottky anomaly caused by paramagnetic impurities present in the sample, of the order of $n\ensuremath{\sim}0.5(2)%$. These impurities lead to non-negligible spin correlations, which nonetheless, are not associated with long-range magnetic ordering.

The cubic double perovskite Ba$_2$YIrO$_6$ has been investigated by the local probe techniques nuclear magnetic resonance ($^{89}$Y NMR) and muon spin rotation (muSR). Both methods confirm the absence of magnetic long-range order in this compound but find evidence for diluted localized paramagnetic moments. NMR spin-lattice relaxation rate 1/T1 measurements suggest a slowing down of localized spin moments at low temperatures. An increase of the muSR spin-lattice relaxation rate lambda confirms the presence of weak magnetism in Ba$_2$YIrO$_6$ . However, these findings cannot be explained by the recently suggested excitonic type of magnetism. Instead, they point towards tiny amounts of localized paramagnetic spin centers leading to this magnetic response on the background of a simple nonmagnetic ground state of the 5d$^4$ ($J=0)$ electronic configuration of Ir$^{5+}$., Comment: 8 pages, 7 figures

Materials with a $5{d}^{4}$ electronic configuration are generally considered to have a nonmagnetic ground state ($J=0$). Interestingly, ${\mathrm{Sr}}_{2}{\mathrm{YIrO}}_{6}$ (${\mathrm{Ir}}^{5+}$ having $5{d}^{4}$ electronic configuration) was recently reported to exhibit long-range magnetic order at low temperature and the distorted ${\mathrm{IrO}}_{6}$ octahedra were discussed to cause the magnetism in this material. Hence, a comparison of structurally distorted ${\mathrm{Sr}}_{2}{\mathrm{YIrO}}_{6}$ with cubic ${\mathrm{Ba}}_{2}{\mathrm{YIrO}}_{6}$ may shed light on the source of magnetism in such ${\mathrm{Ir}}^{5+}$ materials with $5{d}^{4}$ configuration. Besides, ${\mathrm{Ir}}^{5+}$ materials having $5{d}^{4}$ are also interesting in the context of recently predicted excitonic types of magnetism. Here we report a single-crystal-based analysis of the structural, magnetic, and thermodynamic properties of ${\mathrm{Ba}}_{2}{\mathrm{YIrO}}_{6}$. We observe that in ${\mathrm{Ba}}_{2}{\mathrm{YIrO}}_{6}$ for temperatures down to 0.4 K, long-range magnetic order is absent but at the same time correlated magnetic moments are present. We show that these moments are absent in fully relativistic ab initio band-structure calculations; hence, their origin is presently unclear.

The spectrum of neuropsychological features of familial Creutzfeldt-Jakob disease (CJD) have seldom been reported, possibly because of (a) the rarity of this hereditary form of prion disease; (b) frequent delays in diagnosis, and; (c) the typically rapid demise of the patient, which affords little opportunity for comprehensive testing or serial analysis. Here we describe the neurobehavioral characteristics of a 48-year-old right-handed male (JD) who presented with complaints of poor depth perception, unsteady gait, and unusual sensory experiences in his face and neck. JD was followed serially over the final 4 months of his 5-month illness. Immediately following hospital admission, he underwent a neuropsychological evaluation that revealed moderate to severe impairment of delayed (30-minute) verbal memory, tactual performance in his right hand, and word-finding ability. In contrast, other abilities that are commonly classified within the verbal, visuospatial, and memory domains showed minimal or no compromise. Parallel studies of electroencephalographic activity revealed diffuse slowing and, later, 1-Hz rhythmical discharges over the left hemisphere, and mild prominence of the lateral ventricles and cerebral sulci on magnetic resonance imaging. Autopsy revealed spongiform changes and reactive astrocytosis, and genetic testing demonstrated a codon 200 mutation in the prion protein gene. These findings indicate that CJD can result in clinical manifestations compatible with multifocal asymmetric cerebral involvement before more diffuse neurodegeneration ensues, providing a strong impetus for the study of additional cases. This long-term understanding can help to determine whether the multiple loci of clinical involvement are specified by genetic or epigenetic factors, or both.

A substantial body of research suggests that the MMPI-2 contains a number of items that are sensitive to closed-head trauma (CHT) and other neurologic conditions. A correction procedure was recommended by Gass (1991) using an index consisting of 14 neurologically sensitive items that were extracted from a predominantly male veteran sample of CHT patients. The generalizability of these correction items was assessed in the present study by investigating the MMPI-2 scoring characteristics of an outpatient referral sample of 54 CHT patients (28 male, 26 female) who had sustained recent and mild head trauma. Their frequency of endorsement of MMPI-2 was contrasted with that of the MMPI-2 normative sample (N = 2,600). Chi-square analyses identified the 15 MMPI-2 items that best differentiated this CHT sample from normal subjects. The results indicate that: (a) unlike those in an inpatient psychiatric sample (n = 524), the MMPI-2 items that best distinguished the CHT Ss from normals consisted of neurologic symptom content; (b) of these 15 items, 10 were included in the 14-item correction (Gass, 1991); and (c) 13 of the 14 correction items effectively discriminated the cross-validation sample of CHT Ss from normals. These findings offer empirical support for the application of the MMPI-2 correction with patients who have mild and recent head trauma.

A methodology to assist in distinguishing deficient memory storage from compromised retrieval operations is presented for use with the Logical Memory (LM) and Visual Reproduction (VR) subtests of the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987). A 21-item five-option multiple choice recognition test for LM and a cuing technique for VR are presented, followed by descriptive data based on a sample of 94 psychiatric inpatients (mixed diagnoses) and a sample of 99 brain-injured (BI) patients. The BI sample performed worse than the psychiatric sample on all of the LM and VR measures, with VR-CUED showing the highest degree of discrimination. In both groups, many subjects initially acquired much more information than they reported during the standard free recall format. The supplemental scoring format and reference data reported herein provide clinically useful information regarding a person's ability to store and access new information.

The potential impact of test anxiety on cognitive testing was examined in a sample of 300 predominantly male veteran referrals who were administered a comprehensive neuropsychological test battery. Exclusionary criteria included failure on effort testing (n ¼ 14). Level of test anxiety was significantly related to performance on the WAIS-III Working Memory Index (r ¼ 2.343, p , .001) but not to scores on the Processing Speed, Perceptual Organization, or Verbal Comprehension indexes. Test anxiety was not related to a global index of neuropsychological performance on the HRNES-R (Average Impairment Scale). Level of education had a collinear relationship with test anxiety in predicting cognitive test performance. Regression analyses revealed a more prominent role for education, indicating the possibility that test anxiety may be a reaction to, more than a cause of, deficient working memory performance. These results suggest that clinicians who use these particular tests should be reluctant to attribute poor test performance to anxiety that occurs during the testing process.

A number of studies have investigated the relationship between psychological disturbance and neuropsychological (NP) test performance. The current study is a replication and extension of who found that MMPI-2 indices of psychological disturbance are related to performance on NP tests of attention and memory in psychiatric and head-injured patients. In a large sample (N=381) referred for evaluation after sustaining presumed head injury, we examined the relationship between MMPI-2 indices of psychological disturbance and measures of attention and memory from the Wechsler Memory Scale-Revised (WMS-R), Wechsler Adult Intelligence Scale-Revised (WAIS-R), California Verbal Learning Test (CVLT), and the Memory Assessment Scales (MAS). Although related to other domains, MMPI-2 variables were most consistently related to measures of attention and List Learning. Even when demographic variables, injury severity, and litigation status were controlled, MMPI-2 indices significantly predicted performance on six out of eight tests. However, the correspondence between similar indices on the WMS-R and MAS were relatively low, especially for Verbal Memory and Visual Reproduction. Further, litigation was significant in predicting only 2 of 8 attention and memory indices.

The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) is widely used in neuropsychology, though its length (567 items) is sometimes prohibitive. This study investigated some psychometric characteristics of the 180-item version of the MMPI-2 () in order to delineate its strengths, limitations, and appropriate scope of clinical application. Limited reliability and poor predictive accuracy were recently reported for many of the MMPI-2 short-form scales in a study that used 205 brain-injured patients. In the present investigation, we used a psychiatric sample (N=186) with normal neurological findings to examine short-form accuracy in predicting basic scale scores, profile code types, identifying high-point scales, and classifying scores as pathological (T>/=65) or normal-range. The results suggest that, even as applied to neurologically normal individuals, the proposed short form of the MMPI-2 is unreliable for predicting clinical code types, identifying the high-point scale, or predicting the scores on most of the basic scales. In contrast, this short form can be used to predict whether the full-scale scores fall within the pathological range (T>/=65). These findings suggest that clinicians might be able to salvage a small amount of information from the shortened (180-item) version of the MMPI-2 when MMPI-2 protocols are incomplete. However, clinicians should not use a standard interpretive approach with this test, and routine clinical application is unwarranted. Future evaluations of short-form validity should provide a more detailed examination of individual protocols, including an analysis of the frequency of accurate prediction of full-form scores.

The spectrum of neuropsychological features of familial Creutzfeldt-Jakob disease (CJD) have seldom been reported, possibly because of (a) the rarity of this hereditary form of prion disease; (b) frequent delays in diagnosis, and; (c) the typically rapid demise of the patient, which affords little opportunity for comprehensive testing or serial analysis. Here we describe the neurobehavioral characteristics of a 48-year-old right-handed male (JD) who presented with complaints of poor depth perception, unsteady gait, and unusual sensory experiences in his face and neck. JD was followed serially over the final 4 months of his 5-month illness. Immediately following hospital admission, he underwent a neuropsychological evaluation that revealed moderate to severe impairment of delayed (30-minute) verbal memory, tactual performance in his right hand, and word-finding ability. In contrast, other abilities that are commonly classified within the verbal, visuospatial, and memory domains showed minimal or no compromise. Parallel studies of electroencephalographic activity revealed diffuse slowing and, later, 1-Hz rhythmical discharges over the left hemisphere, and mild prominence of the lateral ventricles and cerebral sulci on magnetic resonance imaging. Autopsy revealed spongiform changes and reactive astrocytosis, and genetic testing demonstrated a codon 200 mutation in the prion protein gene. These findings indicate that CJD can result in clinical manifestations compatible with multifocal asymmetric cerebral involvement before more diffuse neurodegeneration ensues, providing a strong impetus for the study of additional cases. This long-term understanding can help to determine whether the multiple loci of clinical involvement are specified by genetic or epigenetic factors, or both.

Anti-endomysial antibodies are sensitive and specific markers for celiac disease. This antibody has recently been identified as an antibody to tissue transglutaminase, an enzyme that cross-links and stabilizes extracellular matrix proteins.To evaluate the clinical usefulness of an enzyme-linked immunoassay for anti-transglutaminase antibodies, and to compare the results with those of AEA, the current gold standard serological test for celiac disease.Serum samples were collected from 33 patients with biopsy-proven celiac disease and AEA tests were performed. Control samples for anti-transglutaminase were obtained from 155 patients. An ELISA test for immunoglobulin A anti-transglutaminase utilizing guinea pig liver transglutaminase was developed and performed on all sera. Cutoff values for the test were performed using logistic regression and receiver operating curves analysis.An optical density cutoff value of 0.34 was established for the assay. The mean value was 0.18 +/- 0.19 optical density for controls, and 1.65 +/- 1.14 for patients with celiac disease (P0.001). Sensitivity and specificity of the assay were both 90%, while AEA had a sensitivity and specificity of 100% and 94%, respectively.A tissue transglutaminase-based ELISA test is both sensitive and specific for detection of celiac disease.

A substantial body of research suggests that the MMPI-2 contains a number of items that are sensitive to closed-head trauma (CHT) and other neurologic conditions. A correction procedure was recommended by Gass (1991) using an index consisting of 14 neurologically sensitive items that were extracted from a predominantly male veteran sample of CHT patients. The generalizability of these correction items was assessed in the present study by investigating the MMPI-2 scoring characteristics of an outpatient referral sample of 54 CHT patients (28 male, 26 female) who had sustained recent and mild head trauma. Their frequency of endorsement of MMPI-2 was contrasted with that of the MMPI-2 normative sample (N = 2,600). Chi-square analyses identified the 15 MMPI-2 items that best differentiated this CHT sample from normal subjects. The results indicate that: (a) unlike those in an inpatient psychiatric sample (n = 524), the MMPI-2 items that best distinguished the CHT Ss from normals consisted of neurologic symptom content; (b) of these 15 items, 10 were included in the 14-item correction (Gass, 1991); and (c) 13 of the 14 correction items effectively discriminated the cross-validation sample of CHT Ss from normals. These findings offer empirical support for the application of the MMPI-2 correction with patients who have mild and recent head trauma.

A methodology to assist in distinguishing deficient memory storage from compromised retrieval operations is presented for use with the Logical Memory (LM) and Visual Reproduction (VR) subtests of the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987). A 21-item five-option multiple choice recognition test for LM and a cuing technique for VR are presented, followed by descriptive data based on a sample of 94 psychiatric inpatients (mixed diagnoses) and a sample of 99 brain-injured (BI) patients. The BI sample performed worse than the psychiatric sample on all of the LM and VR measures, with VR-CUED showing the highest degree of discrimination. In both groups, many subjects initially acquired much more information than they reported during the standard free recall format. The supplemental scoring format and reference data reported herein provide clinically useful information regarding a person's ability to store and access new information.

ContextObservational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women.ObjectiveTo determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal women.Design, Setting, and ParticipantsA randomized, double-blind, placebo-controlled clinical trial, WHIMS is an ancillary study of geographically diverse, community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995. Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline, 4532 (92.6%) were enrolled in the estrogen plus progestin component of WHIMS. A total of 4381 participants (96.7%) provided at least 1 valid cognitive function score between June 1995 and July 8, 2002.InterventionsParticipants received either 1 daily tablet containing 0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone acetate (n = 2145) or matching placebo (n = 2236).Main Outcome MeasureGlobal cognitive function measured annually with the Modified Mini-Mental State Examination.ResultsThe Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time (mean follow-up of 4.2 years). Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo (P = .03), but these differences were not clinically important. Removing women by censoring them after adjudicated dementia, mild cognitive impairment, or stroke, and nonadherence to study protocol, did not alter the findings. Prior hormone therapy use and duration of prior use did not affect the interpretation of the results, nor did timing of prior hormone therapy initiation with respect to the final menstrual period. More women in the estrogen plus progestin group had a substantial and clinically important decline (≥2 SDs) in Modified Mini-Mental State Examination total score (6.7%) compared with the placebo group (4.8%) (P = .008).ConclusionsAmong postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo. While most women receiving estrogen plus progestin did not experience clinically relevant adverse effects on cognition compared with placebo, a small increased risk of clinically meaningful cognitive decline occurred in the estrogen plus progestin group.

The coronavirus, mouse hepatitis virus strain A59 (MHV-A59), causes mild encephalitis and chronic demyelination. Immunohistochemical techniques showed that MHV-A59-infected C57BL/6 mice contained dense deposits of viral antigen in the subthalamic nucleus and substantia nigra, with fewer signs of infection in other regions of the brain. The animals showed extra- and intracellular vacuolation, neuronal loss, and gliosis in the subthalamic-nigral region. Such localization is unprecedented among known viral encephalitides of humans and other species. This infection by a member of a viral class capable of causing both encephalitis and persistent infection in several species may be related to postencephalitic parkinsonism.