Neurocognitive function in HIV infected patients on antiretroviral therapy

OBJECTIVE To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY ClinicalTrials.gov, NCT01230580

Yours ever (well, maybe): Studies and signposts in letter writing

Electronic mail and other digital communications technologies seemingly threaten to end the era of handwritten and typed letters, now affectionately seen as part of snail mail. In this essay, I analyze a group of popular and scholarly studies about letter writing-including examples of pundits critiquing the use of e-mail, etiquette manuals advising why the handwritten letter still possesses value, historians and literary scholars studying the role of letters in the past and what it tells us about our present attitudes about digital communications technologies, and futurists predicting how we will function as personal archivists maintaining every document including e-mail. These are useful guideposts for archivists, providing both a sense of the present and the past in the role, value and nature of letters and their successors. They also provide insights into how such documents should be studied, expanding our gaze beyond the particular letters, to the tools used to create them and the traditions dictating their form and function. We also can discern a role for archivists, both for contributing to the literature about documents and in using these studies and commentaries, suggesting not a new disciplinary realm but opportunities for new interdisciplinary work. Examining a documentary form makes us more sensitive to both the innovations and traditions as it shifts from the analog to the digital; we can learn not to be caught up in hysteria or nostalgia about one form over another and archivists can learn about what they might expect in their labors to document society and its institutions. At one time, paper was part of an innovative technology, with roles very similar to the Internet and e-mail today. It may be that the shifts are far less revolutionary than is often assumed. Reading such works also suggests, finally, that archivists ought to rethink how they view their own knowledge and how it is constructed and used. © 2010 Springer Science+Business Media B.V

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Low validity of self-report in identifying recent mental health diagnosis among U.S. service members completing Pre-Deployment Health Assessment (PreDHA) and deployed to Afghanistan, 2007: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Since 1998, the U.S. Armed Forces has used the mandatory Pre-Deployment Health Assessment (PreDHA) screening questionnaire as a means of assessing the health and suitability of U.S. service members for deployment. Limited data exists to quantify the validity of the self-reported PreDHA. This study was conducted to assess the validity of self-reporting in PreDHA to identify deployed service members who have had a recent mental health disorder diagnosis.</p> <p>Methods</p> <p>A retrospective cohort study was conducted on 15,195 U.S. service members deployed in support of combat and reconstruction operations in Afghanistan. The Defense Medical Surveillance System (DMSS), the DoD's longitudinal medical surveillance database, was queried to identify cases among the cohort with a recent diagnosis of a pertinent mental health disorder and to obtain those subjects' responses to the PreDHA.</p> <p>Results</p> <p>Of the study cohort, 11,179 (73.6%) subjects had a PreDHA available within the DMSS at the time of analysis. A total of 615 subjects (4.0%) had one or more mental health disorder diagnoses during the pre-deployment period. Out the 615 subjects with diagnosed mental health disorders, 465 had a PreDHA. Among these, only 224, not quite half, answered in the affirmative to the PreDHA question: <it>"During the past year, have you sought counseling or care for your mental health?"</it></p> <p>Conclusion</p> <p>This study demonstrates that the self-reported PreDHA has low validity for identifying service members with diagnosed mental health disorders. The development of electronic decision-support systems which automatically screen electronic health records to identify high-risk service members may prove a valuable component of improved pre-deployment screening processes.</p

The orthodontic-oral surgery interface. Part one: A service evaluation and overview of the diagnosis and management of common anomalies

Introduction: Complex dental anomalies often require multidisciplinary management in secondary care. These anomalies may present to general dental practitioners in the first instance, therefore it is important that all clinicians are aware of such anomalies and their management. / Aims: This service evaluation aimed to profile the dental anomalies presenting to the multidisciplinary joint dento-alveolar clinic at a district general hospital and to outline the management of the common anomalies. / Method: This two-part series details a service evaluation and profiles the dental anomalies presenting to the joint dento-alveolar clinic at a district general hospital. In addition, the features and management of the common dental anomalies are outlined. / Results: Fifty-four percent of patients were female, with a mean age of 17 years. The most common anomalies were impacted canines (49%), followed by supernumerary teeth (16%) and impacted premolars (10%). Other anomalies accounted for only a small percentage of referrals. / Conclusion: A wide range of anomalies presented to the joint dento-alveolar clinic. It is important for all clinicians to be aware of such anomalies, their diagnosis and management. Part one and two of this article therefore provide an overview of the common anomalies and highlight their management

The Saccadic and Neurological Deficits in Type 3 Gaucher Disease

Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic) in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8–28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials

Pretest probability assessment derived from attribute matching

BACKGROUND: Pretest probability (PTP) assessment plays a central role in diagnosis. This report compares a novel attribute-matching method to generate a PTP for acute coronary syndrome (ACS). We compare the new method with a validated logistic regression equation (LRE). METHODS: Eight clinical variables (attributes) were chosen by classification and regression tree analysis of a prospectively collected reference database of 14,796 emergency department (ED) patients evaluated for possible ACS. For attribute matching, a computer program identifies patients within the database who have the exact profile defined by clinician input of the eight attributes. The novel method was compared with the LRE for ability to produce PTP estimation <2% in a validation set of 8,120 patients evaluated for possible ACS and did not have ST segment elevation on ECG. 1,061 patients were excluded prior to validation analysis because of ST-segment elevation (713), missing data (77) or being lost to follow-up (271). RESULTS: In the validation set, attribute matching produced 267 unique PTP estimates [median PTP value 6%, 1(st)–3(rd )quartile 1–10%] compared with the LRE, which produced 96 unique PTP estimates [median 24%, 1(st)–3(rd )quartile 10–30%]. The areas under the receiver operating characteristic curves were 0.74 (95% CI 0.65 to 0.82) for the attribute matching curve and 0.68 (95% CI 0.62 to 0.77) for LRE. The attribute matching system categorized 1,670 (24%, 95% CI = 23–25%) patients as having a PTP < 2.0%; 28 developed ACS (1.7% 95% CI = 1.1–2.4%). The LRE categorized 244 (4%, 95% CI = 3–4%) with PTP < 2.0%; four developed ACS (1.6%, 95% CI = 0.4–4.1%). CONCLUSION: Attribute matching estimated a very low PTP for ACS in a significantly larger proportion of ED patients compared with a validated LRE

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Multicenter European Prevalence Study of Neurocognitive Impairment and Associated Factors in HIV Positive Patients

We conducted a cross-sectional study in 448 HIV positive patients attending five European outpatient clinics to determine prevalence of and factors associated with neurocognitive impairment (NCI) using computerized and pen-and-paper neuropsychological tests. NCI was defined as a normalized Z score ≤-1 in at least 2 out of 5 cognitive domains. Participants' mean age was 45.8 years; 84% male; 87% white; 56% university educated; median CD4 count 550 cells/mm(3); 89% on antiretroviral therapy. 156 (35%) participants had NCI, among whom 26 (17%; 5.8% overall) reported a decline in activities of daily living. Prevalence of NCI was lower in those always able to afford basic needs (adjusted prevalence ratio [aPR] 0.71, 95% confidence interval [CI] 0.54-0.94) or with a university education (aPR 0.72, 95% CI 0.54-0.97) and higher in those with severe depressive symptoms (aPR 1.53, 95% CI 1.09-2.14) or a significant comorbid condition (aPR 1.40, 95% CI 1.03-1.90)