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Yes / Social care is vital to quality of life for people with young onset dementia and their families. Yet care is hugely variable, frequently lacking and poorly coordinated. We aim to establish current practice in English social care for people with young onset dementia and co-produce evidence-based recommendations and resources for improvement. In Work-Package 1, we will gather qualitative data from 25 people with young onset dementia and/or main supporters residing in England. We will ask them about their experiences of social care (broadly defined, including independent and voluntary sector provision) and suggestions for improvement. In Work-Package 2, we will conduct a short on-line survey with a wide range of staff with a role in adult social care in England. We will find out about current awareness, knowledge and practice and suggestions for improvements. Quantitative and qualitative analysis will provide a picture of current practice. In Work-Package 3, we will use convergence analysis to synthesise the findings from Work-Packages 1 and 2 and present the findings to a stakeholder workshop, to identify feasible priorities for improvement. We will establish what is already known about good practice relating to these key priorities using a scoping review and interviews with professionals. This knowledge will then feed into the co-production of resources and recommendations with key stakeholders to improve social care for people with young onset dementia and their families. This study seeks to address a gap in our understanding of social care provision for people with young onset dementia and develop recommendations and practical resources for improvements. The findings will help people with young onset dementia and supporters to receive higher quality social care. Study registration number: ISRCTN10653250. / This study is funded by the National Institute for Health and Care Research (NIHR) Research for Social Care (RfSC) Programme through grant NIHR204266. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

<div>Voice Onset Time (VOT) and onset f0 are known correlates of voicing distinctions in stops and both contribute to the production and perception of voicing (House & Fairbanks, 1953; Abramson & Lisker, 1965; Ohde, 1984). As the values of VOT and onset f0, which correspond to voicing categories, vary cross-linguistically, a second language (L2) learner has to acquire a novel use of these acoustic cues to produce and perceive voicing in their L2. Although the acquisition of the primary voicing cue, VOT, has been studied extensively in L2 research (Flege & Eefting, 1988; Flege 1991; Birdsong et al. 2007), little is known about the acquisition of onset f0. The present study compares the use of VOT and onset f0 in French and English speech produced by American learners of French (23). The study also examines evidence for phonetic drift in L2 learners by comparing their English productions to a monolingual control group (33). Results indicate that although learners’ VOT values in French were heavily influenced by English, their onset f0 production in both English and French were on target, showing that learners are able to manipulate the two cues independently of one another. Little evidence of the effect of learners’ second language on the first language was found.</div><div>This study also examines the role of individual learning history on the realization of VOT and onset f0, determining that average number of hours speaking French and age of L2 acquisition (AOA) reported by learners shows the strongest correlation with the learner’s acoustic productions.</div>

Speech production requires cooperation between cognitive, linguistic and motor processes. It also requires spatial and temporal control of muscles, as well as simultaneous and coordinated activity of respiration, phonation and articulation (Cheng, Murdoch, Goozée &amp; Scott, 2007; Yorkston, Beukelman, Strand &amp; Bell, 1999; Raphael, Borden &amp; Harris, 2011). Voice Onset Time (VOT) reflects the timing between phonation and articulation (Hoit-Dalgaard, Murry &amp; Kopp, 1983). VOT is the most reliable acoustic cue for distinguishing between voiceless or voiced plosives (Auzou et al. 2000). Studies of English-speaking children with phonological impairment have shown atypical VOT-patterns (Bond &amp; Wilson, 1980). The aim of the present study was to investigate Voice Onset Time (VOT) among Swedish children with phonological impairment and to examine if their VOT-values differ from typically developed Swedish children. Participants were 38 children aged 4;2−11;6 distributed over eight age- groups and five developmental stages of phonology. Audio recordings of minimal pairs were made at preschools, schools or at speech pathology clinics. The results indicated that children with phonological impairment produced VOT with deviant values and with a great variability. A marked acoustic difference between voiceless and voiced stop consonants was present, but not in all cases. Since the VOT-values were distributed over the group of children with phonological impairment, no developmental trend toward adult-like values that could be related to increasing age was found for either the acquisition of producing VOT or the acquisition of producing voicing lead. No differences in VOT were seen between the children in different phonological developmental stages or ages. No correlation between the degree of deviance of VOT and the proportion of Procent Phonemes Correct (PPC), age or phonological processes were found. From the results the conclusion can be drawn that children with phonological impairment have deviant VOT-values that could be caused by lack of phonological knowledge, but in particular since the variability did not decrease with increased age, have difficulties with motor execution. / Tal kräver ett samarbete mellan kognitiva, språkliga och motoriska processer. Det kräver även spatial och temporal kontroll av muskler samt samtidig och koordinerad aktivitet av andning, fonation och artikulation (Cheng, Murdoch, Goozée &amp; Scott, 2007; Yorkston, Beukelman, Strand &amp; Bell, 1999; Raphael, Borden &amp; Harris, 2011). Voice Onset Time (VOT) ger en bild av koordinationen mellan fonation och artikulation (Hoit-Dalgaard, Murry &amp; Kopp, 1983). VOT är den mest pålitliga akustiska referensen för att kunna skilja mellan tonande och tonlösa klusiler (Auzou et al., 2000). Engelsktalande barn med fonologisk språkstörning har visat atypiska VOT-mönster (Bond &amp; Wilson, 1980). Syftet med föreliggande studie är att undersöka Voice Onset Time (VOT) hos svensktalande barn med fonologisk språkstörning och utröna huruvida deras VOT-värden skiljer sig från VOT-värden hos barn med typisk språkutveckling. I studien deltog 38 barn i åldrarna 4;2−11;6 fördelade på åtta åldersgrupper och fem fonologiska utvecklingsstadier. Inspelningar av bildbenämning av minimala par skedde på barnens förskola, skola eller logopedmottagning. Resultatet visade att barn med fonologisk språkstörning hade avvikande VOT-värden med stor variation. Det förekom både att grupper kunde och inte kunde producera akustiska skillnader mellan tonlösa och tonande klusiler. Resultaten var så spridda i barngruppen att ingen direkt utveckling mot vuxenlika värden kunde relateras till ökad ålder för varken utveckling av VOT produktion eller vuxenlik förekomst av förton. Ingen skillnad vad gäller VOT sågs mellan barn i olika fonologiska utvecklingsstadier eller åldrar. Hur mycket ett VOT-värde avvek kunde inte förklaras av ålder, språkliga processer eller hur många korrekta fonem (PPC) som producerades. Av resultaten dras slutsatsen att barn med språkstörning har avvikande VOT-värden som delvis kan hänföras till bristande fonologisk kunskap men framförallt, eftersom variabiliteten i barnens värden inte minskade med ökad ålder kan hänföras till svårigheter med det motoriska genomförandet.

Psoriasis is a chronic, clinically heterogeneous, skin condition that affects approximately 2% of the general population. In 1985, Henseler and Christophers, classified psoriasis into early onset (EOP; age at onset ≤40 years-y) and late onset disease (LOP; age at onset >40 y). Previous research suggests that there are genetic and immunological differences between EOP and LOP. In particular, the major genetic determinant for psoriasis, the human leukocyte antigen (HLA)-Cw6 allele, occurs more frequently in EOP (55-80%) compared to LOP (15-20%) patients. Epidermal Langerhans’ cells (LC) migration is also different in these 2 subtypes of psoriasis. The primary aim of this thesis was to further explore the clinical, histological and immunohistochemical (IHC) differences between EOP and LOP. We compared clinical characteristics in a total of 497 subjects, including 340 psoriasis patients (108 recruited prospectively; 76 EOP and 32 LOP, mean age of onset 20.3±9.9 and 55.6±7y respectively, and 232 retrospectively; 202 EOP and 30 LOP, mean age of onset 20.7±9.9 and 55.2±7.2y respectively) and 157 controls (mean age 66±11.2y). Information on demographics, family history of psoriasis, clinical features, treatment and co-morbidities were recorded. Patients were also assessed for health-related quality of life and psychological distress. A total of 31 psoriasis patients, ≥ 50y of age, participated in the histological and IHC evaluation; 17 EOP and 14 LOP, mean age of onset 21.1±8.5 and 55.4±7.7y respectively. Skin biopsies were taken from involved (PP) and uninvolved (PN) skin and stained with haematoxylin and eosin (H&E) and IHC antibodies against various T-cell (CD3, CD4, and CD8) and LC (CD1α) markers. The H&E parameters (morphological and inflammatory) were graded with the use of a study specific histological score, whilst IHC positive epidermal cells were counted per microscopic field at 200X magnification. The dermal IHC infiltrate was assessed with a semi-quantitative (0-3) scale. Gender, body mass index, disease duration and severity, diagnosed hypertension and dyslipidemia were treated as covariates. The clinical data showed that LOP patients had a lower likelihood of having a positive family history of psoriasis (62% of EOP versus 35.6% of LOP patients; chi square-x2, P=0.001). In addition, patients with EOP parent(s) were 91% less likely to develop LOP than EOP (odds ratio-OR=0.093, P=0.025, 95% confidence interval-CI 0.012-0.74). Moreover, compared to LOP, EOP patients had a more severe disease (x2, P=0.021), usually requiring 3rd line treatments (x2; P=0.010). They also experienced frequent flares, following upper respiratory tract infections (x2, P=0.049). When data were segregated by age (≥50years) and after accounting for covariates, we observed that, compared to the non-psoriasis population, LOP patients were approximately 3 times more likely to develop type 2 Diabetes Mellitus (OR=2.56, P=0.05, 95% CI 1.01-6.54), whilst, EOP subjects were 98% less likely to develop autoimmune thyroiditis (OR=0.025, P=0.02, 95% CI 0.001-0.55). Psychologically, LOP patients were found to be a clinically more anxious group compared to EOP (t-test, P=0.006). Microscopically, the results from the H&E study showed an increased total inflammatory infiltrate in LOP, PP sections compared to EOP, PP ones (t-test, P=0.028). With IHC stains, we observed that in the epidermis of LOP PP, there was a significantly higher count of CD4+ cells; mean CD4+ in LOP of 15.1 ± 6.2 versus 6.7±4.6 in EOP (Analysis of variance-ANOVA, P<0.001). This subsequently led to a higher epidermal CD4+/CD8+ ratio of 1.3 in the LOP versus 0.5 for the EOP sections (ANOVA, P=0.002). In the PP dermis, CD4+ were also more abundant in the LOP tissue (x2, P=0.049). To assess whether these CD4+ cells were either T-lymphocytes or LC, we examined for differences in the CD3+ and CD1α+ cells. The mean epidermal CD3+ tended to be higher in LOP PP sections; mean epidermal CD3+ in the LOP 42.8 ± 13.3 versus 31.7 ± 17.5 in the EOP group (ANOVA, P= 0.061), while the dermal infiltrate showed a similar pattern (x2,P=0.067). Finally, there was no difference in epidermal and dermal CD1α+ and CD8+ cells in PP between EOP and LOP sections. These data indicate differences in clinical phenotype, heritability, comorbidities and immunopathomechanism between EOP and LOP. Taken together they provide further evidence that EOP and LOP may be different diseases.

Eine depressive Erkrankung kann sich mit unterschiedlicher Geschwindigkeit innerhalb weniger Stunden oder über Monate hinweg ausbilden. Zur Erfassung dieses bisher wenig untersuchten klinischen Merkmals wurde das Onset of Depression Inventory (ODI), ein standardisiertes klinisches Interview, entwickelt. Die vorliegende Studie prüfte die Test-Retest-Reliabilität des Onset of Depression Inventory und betrachtete die Frage nach dem optimalen Zeitpunkt der Durchführung des Interviews im Krankheitsverlauf. Es konnte gezeigt werden, dass die Patientenangaben zur Geschwindigkeit des Depressionsbeginns über den Beobachtungszeitraum zwischen zwei Untersuchungszeitpunkten stabil sind und auf hohem Niveau signifikant korrelieren. Im Weiteren zeigte sich keine Beeinflussung der Angaben zur Geschwindigkeit des Depressionsbeginns durch die Schwere der depressiven Symptomatik. Die hohe Übereinstimmung der Patientenangaben resultiert in einer hohen Test-Retest-Reliabilität und spricht für die Verlässlichkeit der mit dem ODI erhobenen Daten. Damit ist mit dem ODI ein geeignetes Instrument für die reliable Erfassung der Geschwindigkeit des Depressionsbeginns gegeben, was gleichermaßen für die klinische Arbeit als auch für wissenschaftliche Zwecke anwendbar ist und vor allem im klinischen Kontext eine frühe Differenzierung zwischen Unipolarer Depression und Bipolarer Affektiver Störung ermöglicht.:INHALTSVERZEICHNIS 2 BIBLIOGRAPHISCHE ZUSAMMENFASSUNG 5 ABKÜRZUNGSVERZEICHNIS 6 ABBILDUNGSVERZEICHNIS 8 TABELLENVERZEICHNIS 9 1 EINFÜHRUNG 10 - 28 1.1 Einführung zum Thema affektive Störungen 10 1.1.1 Klassifizierung affektiver Störungen 10 1.1.2 Unipolare Depression 11 1.1.3 Bipolare Affektive Störung 12 1.1.4 Pathogenese, Pathophysiologie 13 1.1.5 Risikofaktoren 14 1.2 Unipolare Depression 15 1.2.1 Epidemiologie 15 1.2.2 Diagnostik 16 1.2.3 Therapie 17 1.2.4 Prognose 18 1.3 Bipolare Affektive Störung 19 1.3.1 Epidemiologie 19 1.3.2 Diagnostik 19 1.3.3 Therapie 20 1.3.4 Prognose 20 1.4 Differenzierung zwischen uni- und bipolarer Depression 21 1.5 Vorgeschichte des Onset of Depression Inventory 22 1.5.1 Betrachtungen der Geschwindigkeit des Depressionsbeginns 23 1.6 Validierung von Testinstrumenten 26 1.6.1 Testtheoretische Vorüberlegungen 27 2 FRAGESTELLUNG 29 2.1 Hypothese 29 2.2 Fragestellungen 29 3 METHODIK 30 - 36 3.1 Allgemeine Überlegungen und Studiensetting 30 3.2 Testpsychologische Instrumente 31 3.2.1 Onset of Depression Inventory 31 3.2.2 Weitere Testinstrumente 33 3.3 Statistische Auswertung 34 3.3.1 SPSS-Datenbank 34 3.3.2 Studienkollektiv und Ausschlusskriterien 35 3.3.3 Kategoriale Einteilung der Geschwindigkeit des Depressionsbeginns 36 4 ERGEBNISSE 37 - 50 4.1 Deskriptive Beschreibung der Stichprobe 37 4.2 Ergebnisse der Erstinterviews („Test“) 38 4.3 Ergebnisse der Zweitinterviews („Retest“) 39 4.4 Vergleich der Angaben zur Geschwindigkeit des Depressionsbeginns 42 4.5 HAM-D-17- und IDS-30-Score-Reduktion 43 4.6 Statistische Testung 44 4.6.1 Wilcoxon-Test 45 4.6.2 Korrelationskoeffizienten nach Spearman-Brown 45 4.6.3 Unabhängigkeit der Angaben zur Geschwindigkeit des Depressionsbeginns von der Schwere der Symptomatik 46 4.6.4 Korrelation der Geschwindigkeit des Beginns von aktueller und vorhergehender depressiver Episode 47 4.7 Abklingen der Beschwerden 47 4.8 Zusammenfassung 48 5 DISKUSSION 51 - 61 5.1 Stabilität der Patientenangaben 51 5.2 Unabhängigkeit der Angaben von der Schwere der depressiven Symptomatik 52 5.3 Zeitwahrnehmung und -angabe durch depressive Patienten 52 5.4 Bezug auf Hypothesen, Haupt- und Nebenfragestellungen 53 5.5 Bedeutung der Retest-Untersuchung für das ODI und seine Anwendung 55 5.6 Wissenschaftliche Relevanz 55 5.7 Klinische Relevanz 56 5.8 Fehlerbetrachtung und Limitationen 57 5.9 Ausblick 61 6 ZUSAMMENFASSUNG 62 - 63 7 LITERATURVERZEICHNIS 64 - 69 8 ANLAGEN 70 Muster des Onset of Depression Inventory (ODI), 3 Seiten 70 Muster der ODI-Kurzversion, 1 Seite 73 SELBSTÄNDIGKEITSERKLÄRUNG 74 PUBLIKATIONEN 75 DANKSAGUNG 76

Quand un stimulus visuel de haut contraste précède et puis succède à la présentation d'une cible de faible contraste à la même position, la cible peut devenir non-reconnaissable ou même non-détectable. Cet effet de masquage a été étudié en profondeur et beaucoup de ses paramètres sont bien définis. Mais en utilisant une nouvelle méthode avec une séquence de masques et de cibles en mouvement, il est maintenant possible de séparer de manière perceptuelle et attentionnelle la cible des masques tout en conservant l'ordre d'apparition des masques et de la cible à chaque endroit. Cette thèse utilise cette technique de stimuli en mouvement pour répondre à trois questions qui ne pourraient pas être résolu en utilisant une méthode de masquage conventionnelle. Dans la première série d'expériences on a testé si l'attention portée au masque influence l'impact de celle-ci sur la cible. Nous avons utilisé un écran où une séquence masque-cible-masque apparaît à une position puis à chaque 'frame' suivant elle apparaît à la position adjacente. Cette méthode permet à l'observateur de suivre attentionellement la cible sur son trajet, tout en évitant les masques distracteurs qui paraissent être à côté de la cible spatialement et non temporellement. Quand les masques sont efficaces, la position de la cible paraît être vide. Nous comparons l'efficacité du masquage quand l'attention n'est pas dirigée vers les masques, à l'efficacité du masquage quand l'attention ne peut pas éviter les masques, comme dans le masquage conventionnel. Nous n'avons trouvé aucune différence significative entre les deux conditions attentionnelles, ce qui indique que l'attention portée sur les masques ne module pas leur efficacité. Ensuite nous avons testé l'importance de l'espacement dans la séquence masque-cible-masque. Il n'y avait pas plus de masquage quand les espacements étaient réduits, ce qui suggère que le masquage n'est pas le résultat de masquage latéral ou de 'crowding' (encombrement spatial) aux distances testées. Enfin nous avons comparé la contribution de chaque masque: celui qui précède la cible (le pré-masque) et celui qui suit la cible (post-masque). Nous avons trouvé que le pré-masque génère la majorité de l'effet de masquage tandis que le post-masque a peu d'influence. Dans la seconde série d'expériences nous avons étudié ce qu'il advient du stimulus masqué. En baissant le contraste de la cible juste en dessous de son seuil de détection et en lui donnant une couleur saillante, nous avons découvert un stade intermédiaire où les caractéristiques ('features') de la cible sont reportées à la position d'un des masques. Avec une série d'expérience nous avons montré que la cible est intégrée avec le masque qui la suit directement et temporellement à la même position. Finalement nous avons étudié si un stimulus qui est masqué à un niveau invisible peut quand même exercer une influence sur une cible proche dans un arrangement de crowding. Nous avons comparé la détection d'une cible avec deux flankers (distracteurs adjacent) dans la zone de crowding, à la détection d'une cible quand les deux flankers sont masqué et que leur position paraît être vide. Pour conclure, la méthode de séquence en mouvement a révélé de nouvelles caractéristiques du masquage qui ne pouvaient pas être examinées en utilisant des techniques de masquage conventionnelles. Premièrement nous avons découvert que l'efficacité du masque est comparable que l'attention soit dirigée sur le masque ou non. Deuxièmement nous avons montré que les caractéristiques d'une cible qui est supprimée à sa position physique peuvent apparaître à la position du masque qui la suit temporellement. Et finalement, nous avons examiné l'effet de flankers masqués sur une cible dans un arrangement de crowding. / When high contrast visual stimuli precede and follow a low contrast target at the same location, the target may become unrecognizable and even undetectable. This masking effect has been extensively studied and many of its parameters are well characterized. However, using a new technique with a moving sequence of masks and targets it is now possible to perceptually and attentionally separate the target from the masks while retaining the same temporal order of masks and target at each location. This thesis exploits this moving stimulus technique to ask three questions that could not be addressed in standard masking paradigms. In the first series of experiments we looked at whether attention to the mask affected its impact on the target. We used a display where the mask-target-mask sequence appears at one location and on each subsequent frame it appears in the adjacent location. This allows observers to attentively track the target across locations without attending to the masks which appear perceptually adjacent in space rather than in time. When the masks are effective, the observer sees a blank space at the target location. We compare the effectiveness of this masking when the masks are unattended to the effectiveness when the masks are attended as in standard masking. We found no significant difference between the two attentional conditions suggesting that attention to the masks does not modulate their effectiveness. We next examined the importance of the spacing within the mask-target-mask sequences. There was no increase in the masking effect as spacing was reduced, suggesting that the masking was not a consequence of lateral masking or crowding at the spacings we tested. Finally, we compared the contributions of each mask individually: the one that preceded the target (pre-mask) and the one that followed (post-mask). We found that the pre-mask generated the majority of the masking effect while the post-mask was of little influence. In the second series of studies we investigated the fate of a masked stimulus. By lowering the target contrast just below its detection threshold and giving it a salient color, we found an intermediate, "lurking" stage where the target's features migrate to one of the mask locations. Through a succession of experiments we found that the target is integrated with the mask directly following it in time at the same location. Finally we looked at whether a stimulus that is masked to invisibility can still exert influence over nearby targets in a crowding array. We compared the detection of a crowded target with two flankers, compared to the detection of a target when the two adjacent flankers are masked so that their locations appear empty. In conclusion, the moving sequence technique revealed new characteristics of masking that could not be examined in standard masking paradigms. First, we found that the effectiveness of a mask was the same whether it is attended or not. Second, we showed that once a masked target has been suppressed from its physical location, its features can be found "lurking" at the location of the mask that follows the target in time. Finally, we examined the effect of masked flankers on a target in a crowding paradigm.

Background: Neonatal sepsis is one of the most important causes for elevated morbidity and mor-tality rates in neonatal intensive care units worldwide. While the clinical manifestations of a neo-natal sepsis tend to be nonspecific, its rapid development and life-threatening potential calls for reliable markers for early detection. Methods: We conducted a retrospective single center study including all neonates suspected of having developed a neonatal sepsis within 2013 - 2016. Perinatal and clinical characteristics, as well as microbiological and laboratory findings were evaluated. Neonatal sepsis was either defined as culture proven sepsis (positive blood culture) or clinical sepsis (at least one symptom and elevated C-reative protein (CRP) concentrations within 72h with nega-tive blood culture). We further differentiated between early-onset (EOS) and late-onset (LOS) sepsis. Results: Microbiological colonisation screening frequently did not detect the organism which sub-sequently caused the sepsis. Depending on the age of the newborn with sepsis (EOS or LOS), as-sociations between different anamnestic and clinical factors (prenatal or postnatal ones) were found. Especially the central-peripheral temperature difference showed a strong association to LOS. Laboratory results useful for the early detection of a neonatal sepsis included interleukin-6 (IL-6) and CRP concentrations. Conclusion: Elevated IL-6 >100 ng/l was a strong marker for neonatal sepsis. When choosing the antibiotics for treatment, data from microbiological colonisation screening should be considered, but not solely relied on. Some indicators for infection depended also on postnatal age.:Einführung 1 Definition 1 Sepsis 1 Pathophysiologie der Sepsis 2 Early-onset Sepsis vs. Late-onset Sepsis 4 Klinik und Diagnostik 6 AWMF-Leitlinie „Bakterielle Infektionen bei Neugeborenen“ 10 Mikrobiologisches Kolonisationsscreening 14 Aufgabenstellung und Zielsetzung 16 Patient:innen und Methoden 18 Datenerhebung 18 Gruppenbildung 20 Statistische Analyse 22 Ergebnisse 23 Early-onset Sepsis mit mikrobiologischem Nachweis 23 Early-onset Sepsis mit nur paraklinischem Nachweis 30 Late-onset Sepsis mit mikrobiologischem Nachweis 36 Late-onset Sepsis mit nur paraklinischem Nachweis 44 Diskussion 50 Art der Erreger in Leipzig 50 Mikrobiologisches Kolonisationsscreening 51 Anamnestische und klinische Risikofaktoren 55 Laborchemische Faktoren 60 Aussagekraft der Blutkultur 69 Grenzen der Studie 71 Weiterer Ausblick 72 Zusammenfassung 75 Literaturverzeichnis 78 Abkürzungsverzeichnis 83 Tabellenverzeichnis 85 Abbildungsverzeichnis 86 Erklärung über die eigenständige Abfassung der Arbeit 88 Curriculum vitae 89 Danksagung 91

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