Improving Depression Among HIV-Infected Adults: Transporting the Effect of a Depression Treatment Intervention to Routine Care

Depression affects 20-30% of people with HIV. Randomized controlled trials (RCTs) have demonstrated the effectiveness of interventions to improve depression among HIV-infected adults, but typically have highly selected populations which may limit generalizability. Inverse probability of sampling weights (IPSW) are a recently proposed method to transport (or standardize) findings from RCTs to a specific external target population

Improvements in depression and changes in quality of life among HIV-infected adults

Improving QOL for HIV-infected individuals is an important objective of HIV care, given the considerable physical and emotional burden associated with living with HIV. Although worse QOL has been associated with depression, no research has quantified the potential of improvement in depression to prospectively improve QOL among HIV-infected adults. We analyzed data from 115 HIV-infected adults with depression enrolled in a randomized controlled trial to evaluate the effectiveness of improved depression care on antiretroviral drug adherence. Improvement in depression, the exposure of interest, was defined as the relative change in depression at 6 months compared to baseline and categorized as full response (≥50% improvement), partial response (25%–49% improvement) and no response (<25% improvement). Multivariable linear regression was used to investigate the relationship between improvement in depression and four continuous measures of QOL at 6 months: physical QOL, mental QOL, HIV symptoms, and fatigue intensity. In multivariable analyses, physical QOL was higher among partial responders (MD=2.51, 95% CI −1.51, 6.54) and full responders (MD=3.68, 95% CI −0.36, 7.72) compared to individuals who did not respond. Mental QOL was an average of 4.01 points higher (95% CI −1.01, 9.03) among partial responders and 14.34 points higher (95% CI 9.42, 19.25) among full responders. HIV symptoms were lower for partial responders (MD=−0.69; 95% CI −1.69, 0.30) and full responders (MD=−1.51; 95% CI −2.50, −0.53). Fatigue intensity was also lower for partial responders (MD=−0.94; 95% CI −1.94, 0.07) and full responders (MD=−3.00; 95% CI −3.98, −2.02). Among HIV-infected adults with depression, improving access to high-quality depression treatment may also improve important QOL outcomes

Improvements in Depression and Changes in Fatigue: Results from the SLAM DUNC Depression Treatment Trial

Fatigue and depression are common co-morbid conditions among people with HIV infection. We analyzed a population of HIV-infected adults with depression, who were enrolled in a depression treatment trial, to examine the extent to which improvements in depression over time were associated with improvements in HIV-related fatigue. Data for this analysis come from a randomized controlled trial to evaluate the effectiveness of improved depression treatment on antiretroviral adherence. Fatigue was measured using the HIV-Related Fatigue Scale, and depressive symptoms were measured with the Hamilton Depression Rating Scale. Participants (n = 234) were on average nearly 44 years of age and predominantly male, black or African American, and unemployed. Individuals who experienced stronger depression response (i.e., greater improvement in depression score) had larger decreases in fatigue. However, even among those who demonstrated a full depression response, nearly three-quarters continued to have either moderate or severe fatigue at 6 and 12 months

Regulation of Clock-Controlled Genes in Mammals

The complexity of tissue- and day time-specific regulation of thousands of clock-controlled genes (CCGs) suggests that many regulatory mechanisms contribute to the transcriptional output of the circadian clock. We aim to predict these mechanisms using a large scale promoter analysis of CCGs

Omega 6 fatty acids for the primary prevention of cardiovascular disease

Background Omega 6 plays a vital role in many physiological functions but there is controversy concerning its effect on cardiovascular disease (CVD) risk. There is conflicting evidence whether increasing or decreasing omega 6 intake results in beneficial effects. Objectives The two primary objectives of this Cochrane review were to determine the effectiveness of: 1. Increasing omega 6 (Linoleic acid (LA), Gamma-linolenic acid (GLA), Dihomo-gamma-linolenic acid (DGLA), Arachidonic acid (AA), or any combination) intake in place of saturated or monounsaturated fats or carbohydrates for the primary prevention of CVD. 2. Decreasing omega 6 (LA, GLA, DGLA, AA, or any combination) intake in place of carbohydrates or protein (or both) for the primary prevention of CVD. Search methods We searched the following electronic databases up to 23 September 2014: the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library (Issue 8 of 12, 2014); MEDLINE (Ovid) (1946 to September week 2, 2014); EMBASE Classic and EMBASE (Ovid) (1947 to September 2014); Web of Science Core Collection (Thomson Reuters) (1990 to September 2014); Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment Database, and Health Economics Evaluations Database on the Cochrane Library (Issue 3 of 4, 2014). We searched trial registers and reference lists of reviews for further studies. We applied no language restrictions. Selection criteria Randomised controlled trials (RCTs) of interventions stating an intention to increase or decrease omega 6 fatty acids, lasting at least six months, and including healthy adults or adults at high risk of CVD. The comparison group was given no advice, no supplementation, a placebo, a control diet, or continued with their usual diet. The outcomes of interest were CVD clinical events (all-cause mortality, cardiovascular mortality, non-fatal end points) and CVD risk factors (changes in blood pressure, changes in blood lipids, occurrence of type 2 diabetes). We excluded trials involving exercise or multifactorial interventions to avoid confounding. Data collection and analysis Two review authors independently selected trials for inclusion, extracted the data, and assessed the risk of bias in the included trials. Main results We included four RCTs (five papers) that randomised 660 participants. No ongoing trials were identified. All included trials had at least one domain with an unclear risk of bias. There were no RCTs of omega 6 intake reporting CVD clinical events. Three trials investigated the effect of increased omega 6 intake on lipid levels (total cholesterol, low density lipoprotein (LDL-cholesterol), and high density lipoprotein (HDL-cholesterol)), two trials reported triglycerides, and two trials reported blood pressure (diastolic and systolic blood pressure). Two trials, one with two relevant intervention arms, investigated the effect of decreased omega 6 intake on blood pressure parameters and lipid levels (total cholesterol, LDL-cholesterol, and HDL-cholesterol) and one trial reported triglycerides. Our analyses found no statistically significant effects of either increased or decreased omega 6 intake on CVD risk factors. Two studies were supported by funding from the UK Food Standards Agency and Medical Research Council. One study was supported by Lipid Nutrition, a commercial company in the Netherlands and the Dutch Ministry of Economic Affairs. The final study was supported by grants from the Finnish Food Research Foundation, Finnish Heart Research Foundation, Aarne and Aili Turnen Foundation, and the Research Council for Health, Academy of Finland. Authors’ conclusions We found no studies examining the effects of either increased or decreased omega 6 on our primary outcome CVD clinical endpoints and insufficient evidence to show an effect of increased or decreased omega 6 intake on CVD risk factors such as blood lipids and blood pressure. Very few trials were identified with a relatively small number of participants randomised. There is a need for larger well conducted RCTs assessing cardiovascular events as well as cardiovascular risk factors

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Neurokognitive Untersuchungen typischer und atypischer Entwicklung numerischer Fertigkeiten

Zusammenfassung 15 Summary 17 Introduction 19 0.1 The Development of Numerical Processing 20 0.1.1 A Model of Numerical Development 20 0.1.2 Theoretical Approaches to Cognitive Development 23 0.2 Philosophical Background 24 0.2.1 Platonism in the Philosophy of Mathematics 25 0.2.2 Outline of Contemporary Approaches to Realism in the Philosophy of Mathematics 27 1\. Rechenstörung 41 1.1 Symptomatik 41 1.2 Epidemiologie 45 1.2.1 Prävalenz 45 1.2.2 Geschlechterverteilung 47 1.2.3 Heredität 48 1.2.4 Verlauf und Prognose 49 1.3 Ätiologie 49 1.3.1 Domänenspezifische Defizite als Ursache der Rechenstörung 50 1.3.2 Domänenübergreifende Defizite als Ursache der Rechenstörung 54 1.4 Beeinträchtigungen numerischer Verarbeitung infolge genetischer Störungen 58 1.4.1 Turner-Syndrom 58 1.4.2 Fragiles-X-Syndrom 59 1.4.3 Shprintzen-Syndrom 60 1.5 Komorbidität von Lese-Rechtschreibstörung und Rechenstörung 60 2\. Electrophysiological Correlates of Non-symbolic Numerical Magnitude Processing in Children: Joining the Dots 63 2.1 Methods 65 2.1.1 Participants 65 2.1.2 Materials and Procedures 66 2.1.3 Acquisition and Preprocessing of the Data 68 2.1.4 Data Analysis 69 2.2 Results 70 2.2.1 Behavioral Data 70 2.2.2 Electrophysiological Data 71 2.3 Discussion 74 2.4 Conclusion 79 3\. An Electrophysiological Investigation of Non-Symbolic Magnitude Processing: Numerical Distance Effects in Children with and without Mathematical Learning Disablities 81 3.1. Methods 85 3.1.1 Participants 85 3.1.2 Materials and Procedures 86 3.1.3 Acquisition and Preprocessing of the Data 88 3.1.4 Data Analysis 88 3.2 Results 90 3.2.1 Behavioral Data 90 3.2.2 Electrophysiological Data 91 3.3 Discussion 95 3.4 Conclusion 98 4\. the Eyes Already ‘Know’: Using Eye Movement Measurement to Tap into Children's Implicit Numerical Magnitude Representations 101 4.1 Methods 103 4.1.1 Participants 103 4.1.2 Materials and Procedures 104 4.1.3 Acquisition and Preprocessing of the Data 105 4.1.4 Data analysis 105 4.2 Results 107 4.2.1 Behavioral Data 107 4.2.2 Eye Movement Data 108 4.3 Discussion 110 4.4 Conclusion 112 5\. The Numerical Stroop Effect in Primary School Children: A Comparison of Low, Normal and High Maths Achievers 113 5.1 Methods 117 5.1.2 Participants 117 5.1.3 Materials and Procedures 118 5.1.3 Data Analysis 119 5.2 Results 120 5.2.1 Diagnostic Data 120 5.2.2 Analyses of Overall Task Performance 122 5.2.3 Performance Data Separated by Task 123 5.2.4 Effects of the Interaction of Congruity and Numerical Distance 123 5.3 Discussion 126 5.4 Conclusion 129 6\. General Discussion and Outlook 131 6.1 Numerical Development 132 6.2 Mathematical Knowledge 133 6.2.1 Dehaene's Approach to the What and How of Mathematical Knowledge 133 6.2.2 The Constructivism of Lakoff and Nunez 135 6.2.3 Fitting Experimental Approaches into the Bigger Picture 137 References 141 List of Figures 165 List of Tables 167 Lebenslauf 16This thesis consists of four experimental studies that aim to gain further insight into the development of normal and impaired numerical processing. Behavioral, eye-movement and electrophysiological measures were used to tap into children's representation and processing of numerical magnitude information. In order to shed light on the question whether and in what way enumeration of small and large sets of objects is functionally different, the first study focused on basic numerical magnitude processing in normally developing children. EEG data were collected from sixty primary schoolers performing a non-symbolic numerical comparison task. The second study investigated electro-physiological correlates of basic numerical processing in children with mathematical learning disabilities compared to a matched group of normally developing children. Again, children were tested with a standard non-symbolic numerical comparison paradigm that allowed for a manipulation of numerical distances between stimulus arrays for different quantity ranges. Study three used eye movement measurement to investigate the development of basic knowledge about numerical magnitude in primary school children. Sixty- six children from grades one to three (i.e. 6 to 9 years) were presented with parallel versions of a classic number line estimation task. The fourth study adopted a numerical Stroop paradigm, where children were asked to make numerical and physical size comparisons on digit pairs. The effects of congruity and numerical distance were determined for primary school children, of which a subgroup scored low in a standardized math achievement test, while others were normal or high achievers. The results suggest that (a) numerical magnitude representations undergo relevant qualitative changes during the first years of formal mathematical training (study 3), that (b) for explicit numerical decisions the involvement of domain-specific processing resources in parietal regions does not depend on quantity features of the input, i.e. numerical range (study 1), that (c) impaired numerical processing may not be caused by a lack of automaticity in accessing numerical magnitude representations (study 4), but rather (d) by differential recruitment of domain-specific processing resources in predominantly right parietal regions by low math achievers compared to their normally developing peers (study 2). However, even though these studies allow for certain insights into the behavioral and neurophysiological characteristics of normal and impaired numerical processing in school-aged children, future studies should implement truly developmental approaches so as to provide more fine-grained information about typical and atypical developmental trajectories of basic and higher- level number-related skills.Die vorliegende Dissertation setzt sich aus vier Studien zusammen, die Erkenntnisse über die Entwicklung normaler und gestörter numerischer Verarbeitung generieren. Behaviorale, Blickbewegungs- und elektrophysiologische Parameter wurden eingesetzt, um Repräsentation numerischer Größe sowie entsprechende Verarbeitungsprozesse bei Kindern zu untersuchen. Die erste Studie untersucht, ob bzw. inwiefern sich die Verarbeitung numerischer Größeninformation bei Kindern in Abhängigkeit von der Menge zu erfassender Objekte unterscheidet. Dazu wurden EEG-Daten erhoben während die Kinder Aufgaben lösten, die einen numerischen Größenvergleich nonsymbolischer Stimuli erforderten. Die zweite Studie untersuchte elektrophysiologische Korrelate basaler numerischer Verarbeitung bei Kindern mit Rechenstörung im Vergleich zu Kontrollen. Auch hier wurde ein numerischer Größenvergleich nonsymbolischer Stimuli eingesetzt, um eine Manipulation der numerischen Distanz zu ermöglichen. Die dritte Studie nutzte Blickbewegungsmessung, um die Entwicklung basaler Repräsentation numerischer Größe im Grundschulalter zu untersuchen. Dazu wurden die Kinder mit zwei parallelen Implementierungen einer Zahlenstrahl-Schätzaufgabe konfrontiert, bei der sich eine auf Erhebung behavioraler Daten beschränkte, während die zweite Erhebung von Blickbewegungsdaten beinhaltete. Für die vierte Studie wurde ein numerischer Stroop-Test eingesetzt, bei dem Kinder einerseits einen numerischen Größenvergleich und andererseits einen Vergleich der Schriftgröße von Ziffernpaaren durchführten. Effekte der Manipulation von Kongruenz sowie Distanzeffekte wurden für eine Gruppe von Grundschülern ermittelt, von denen ein Teil unterdurchschnittliche Leistung in einem Mathematikleistungstest zeigte. Die Ergebnisse der Studien deuten darauf hin, dass (a) Repräsentation numerischer Größe qualitative Veränderungen während der ersten Schuljahre durchläuft (Studie 3), dass (b) bei expliziten numerischen Entscheidungsprozessen die Rekrutierung domänenspezifischer Ressourcen, die in parietalen Hirnarealen lokalisiert werden, nicht abhängig von der Anzahl der zu verarbeitenden Objekte ist (Studie 1), dass (c) gestörte numerische Verarbeitung nicht auf ein Automatisierungsdefizit im Bereich der Zugriffs auf numerische Information zurückzuführen ist (Studie 4), sondern (d) eher auf Unterschiede in der Funktionalität domänenspezifischer Verarbeitungssysteme, die in rechtshemisphärischen inferioren parietalen Kortexarealen verankert sind (Studie 2). Es ist festzustellen, dass diese Studien zwar einerseits Rückschlüsse über behaviorale und neurophysiologische Charakteristiken normaler und gestörter Verarbeitung numerischer Information zulassen, dass andererseits aber experimentelle Zugänge gefunden werden sollten, die eine Entwicklungsperspektive implizieren. Nur so werden tiefere Einblicke in typische und abweichende Entwicklungsverläufe basaler und höherer numerischer Fertigkeiten ermöglicht

Gramaticalização e relações semânticas dos itens De e Des / Desde nos séculos XIV, XVI e XVII

Estudo das preposições de e des/ desde, na função de adjunto adverbial, em textos representativos dos séculos XIV, XVI e XVII, tomando-se por base os estudos da gramaticalização e as teorias localista e dos protótipos. Do ponto de vista do localismo, no que se refere a essas preposições, verifica-se que as acepções mais abstratas derivam das menos abstratas e que os sentidos espaciais são mais básicos do que os sentidos temporais. Quanto à aplicação da teoria dos protótipos, no que concerne à semântica atual, constata-se que há um sentido prototípico em cada uma dessas preposições com traços de semelhança de família que, muitas vezes, se mantêm. Também estudaram-se os campos semânticos, em que essas preposições aparecem, fazendo uma análise comparativa do latim do século VI com o português dos séculos citados anteriormente e verificando-se, com base nos corpora selecionados, principalmente, como a preposição de abarcou as acepções de outras preposições e, dessa forma, ampliou sua significação consideravelmente.This work is intended to study the prepositions de and des/ desde which functioned as adverbials in texts of the 14th, 16th and 17th centuries, based on grammaticalization studies and the localist and prototypical theories. From the viewpoint of the localism, in what regards such prepositions, it is observed that the more abstract meanings derive from the less abstract and that spatial meanings are more basic than the temporal ones. As for the application of the theory of the prototypes, as far as the current semantics is concerned, it is seen that there is a prototypical meaning in each of the above mentioned prepositions with similar family features which are usually kept. The semantic fields in which these prepositions appeared were also studied by means of a comparative analysis between the Latin of the 6th century and the Portuguese of the 14th, 16th and 17th centuries. Based on the selected corpora, it was verified that the preposition de encompassed the meanings of other prepositions, thus considerably enlarging its significance