Graded, multidimensional intra- and intergroup variations in primary progressive aphasia and post-stroke aphasia.

Language impairments caused by stroke (post-stroke aphasia, PSA) and neurodegeneration (primary progressive aphasia, PPA) have overlapping symptomatology, nomenclature and are classically divided into categorical subtypes. Surprisingly, PPA and PSA have rarely been directly compared in detail. Rather, previous studies have compared certain subtypes (e.g. semantic variants) or have focused on a specific cognitive/linguistic task (e.g. reading). This study assessed a large range of linguistic and cognitive tasks across the full spectra of PSA and PPA. We applied varimax-rotated principal component analysis to explore the underlying structure of the variance in the assessment scores. Similar phonological, semantic and fluency-related components were found for PSA and PPA. A combined principal component analysis across the two aetiologies revealed graded intra- and intergroup variations on all four extracted components. Classification analysis was used to test, formally, whether there were any categorical boundaries for any subtypes of PPA or PSA. Semantic dementia formed a true diagnostic category (i.e. within group homogeneity and distinct between-group differences), whereas there was considerable overlap and graded variations within and between other subtypes of PPA and PSA. These results suggest that (i) a multidimensional rather than categorical classification system may be a better conceptualization of aphasia from both causes; and (ii) despite the very different types of pathology, these broad classes of aphasia have considerable features in common.

The cost of being valuable: predictors of extinction risk in marine invertebrates exploited as luxury seafood.

Extinction risk has been linked to biological and anthropogenic variables. Prediction of extinction risk in valuable fauna may not follow mainstream drivers when species are exploited for international markets. We use results from an International Union for Conservation of Nature Red List assessment of extinction risk in all 377 known species of sea cucumber within the order Aspidochirotida, many of which are exploited worldwide as luxury seafood for Asian markets. Extinction risk was primarily driven by high market value, compounded by accessibility and familiarity (well known) in the marketplace. Extinction risk in marine animals often relates closely to body size and small geographical range but our study shows a clear exception. Conservation must not lose sight of common species, especially those of high value. Greater human population density and poorer economies in the geographical ranges of endangered species illustrate that anthropogenic variables can also predict extinction risks in marine animals. Local-level regulatory measures must prevent opportunistic exploitation of high-value species. Trade agreements, for example CITES, may aid conservation but will depend on international technical support to low-income tropical countries. The high proportion of data deficient species also stresses a need for research on the ecology and population demographics of unglamorous invertebrates.

Dust-climate couplings over the past 800,000 years from the EPICA Dome C ice core.

Dust can affect the radiative balance of the atmosphere by absorbing or reflecting incoming solar radiation; it can also be a source of micronutrients, such as iron, to the ocean. It has been suggested that production, transport and deposition of dust is influenced by climatic changes on glacial-interglacial timescales. Here we present a high-resolution record of aeolian dust from the EPICA Dome C ice core in East Antarctica, which provides an undisturbed climate sequence over the past eight climatic cycles. We find that there is a significant correlation between dust flux and temperature records during glacial periods that is absent during interglacial periods. Our data suggest that dust flux is increasingly correlated with Antarctic temperature as the climate becomes colder. We interpret this as progressive coupling of the climates of Antarctic and lower latitudes. Limited changes in glacial-interglacial atmospheric transport time suggest that the sources and lifetime of dust are the main factors controlling the high glacial dust input. We propose that the observed approximately 25-fold increase in glacial dust flux over all eight glacial periods can be attributed to a strengthening of South American dust sources, together with a longer lifetime for atmospheric dust particles in the upper troposphere resulting from a reduced hydrological cycle during the ice ages.

The neural substrates of transdiagnostic cognitive-linguistic heterogeneity in primary progressive aphasia.

BACKGROUND: Clinical variants of primary progressive aphasia (PPA) are diagnosed based on characteristic patterns of language deficits, supported by corresponding neural changes on brain imaging. However, there is (i) considerable phenotypic variability within and between each diagnostic category with partially overlapping profiles of language performance between variants and (ii) accompanying non-linguistic cognitive impairments that may be independent of aphasia magnitude and disease severity. The neurobiological basis of this cognitive-linguistic heterogeneity remains unclear. Understanding the relationship between these variables would improve PPA clinical/research characterisation and strengthen clinical trial and symptomatic treatment design. We address these knowledge gaps using a data-driven transdiagnostic approach to chart cognitive-linguistic differences and their associations with grey/white matter degeneration across multiple PPA variants. METHODS: Forty-seven patients (13 semantic, 15 non-fluent, and 19 logopenic variant PPA) underwent assessment of general cognition, errors on language performance, and structural and diffusion magnetic resonance imaging to index whole-brain grey and white matter changes. Behavioural data were entered into varimax-rotated principal component analyses to derive orthogonal dimensions explaining the majority of cognitive variance. To uncover neural correlates of cognitive heterogeneity, derived components were used as covariates in neuroimaging analyses of grey matter (voxel-based morphometry) and white matter (network-based statistics of structural connectomes). RESULTS: Four behavioural components emerged: general cognition, semantic memory, working memory, and motor speech/phonology. Performance patterns on the latter three principal components were in keeping with each variant's characteristic profile, but with a spectrum rather than categorical distribution across the cohort. General cognitive changes were most marked in logopenic variant PPA. Regardless of clinical diagnosis, general cognitive impairment was associated with inferior/posterior parietal grey/white matter involvement, semantic memory deficits with bilateral anterior temporal grey/white matter changes, working memory impairment with temporoparietal and frontostriatal grey/white matter involvement, and motor speech/phonology deficits with inferior/middle frontal grey matter alterations. CONCLUSIONS: Cognitive-linguistic heterogeneity in PPA closely relates to individual-level variations on multiple behavioural dimensions and grey/white matter degeneration of regions within and beyond the language network. We further show that employment of transdiagnostic approaches may help to understand clinical symptom boundaries and reveal clinical and neural profiles that are shared across categorically defined variants of PPA.

Southern Ocean sea-ice extent, productivity and iron flux over the past eight glacial cycles.

Sea ice and dust flux increased greatly in the Southern Ocean during the last glacial period. Palaeorecords provide contradictory evidence about marine productivity in this region, but beyond one glacial cycle, data were sparse. Here we present continuous chemical proxy data spanning the last eight glacial cycles (740,000 years) from the Dome C Antarctic ice core. These data constrain winter sea-ice extent in the Indian Ocean, Southern Ocean biogenic productivity and Patagonian climatic conditions. We found that maximum sea-ice extent is closely tied to Antarctic temperature on multi-millennial timescales, but less so on shorter timescales. Biological dimethylsulphide emissions south of the polar front seem to have changed little with climate, suggesting that sulphur compounds were not active in climate regulation. We observe large glacial-interglacial contrasts in iron deposition, which we infer reflects strongly changing Patagonian conditions. During glacial terminations, changes in Patagonia apparently preceded sea-ice reduction, indicating that multiple mechanisms may be responsible for different phases of CO2 increase during glacial terminations. We observe no changes in internal climatic feedbacks that could have caused the change in amplitude of Antarctic temperature variations observed 440,000 years ago.

A 'Mini Linguistic State Examination' to classify primary progressive aphasia.

There are few available methods for qualitatively evaluating patients with primary progressive aphasia. Commonly adopted approaches are time-consuming, of limited accuracy or designed to assess different patient populations. This paper introduces a new clinical test-the Mini Linguistic State Examination-which was designed uniquely to enable a clinician to assess and subclassify both classical and mixed presentations of primary progressive aphasia. The adoption of a novel assessment method (error classification) greatly amplifies the clinical information that can be derived from a set of standard linguistic tasks and allows a five-dimensional profile to be defined. Fifty-four patients and 30 matched controls were recruited. Five domains of language competence (motor speech, phonology, semantics, syntax and working memory) were assessed using a sequence of 11 distinct linguistic assays. A random forest classification was used to assess the diagnostic accuracy for predicting primary progressive aphasia subtypes and create a decision tree as a guide to clinical classification. The random forest prediction model was 96% accurate overall (92% for the logopenic variant, 93% for the semantic variant and 98% for the non-fluent variant). The derived decision tree produced a correct classification of 91% of participants whose data were not included in the training set. The Mini Linguistic State Examination is a new cognitive test incorporating a novel and powerful, yet straightforward, approach to scoring. Rigorous assessment of its diagnostic accuracy confirmed excellent matching of primary progressive aphasia syndromes to clinical gold standard diagnoses. Adoption of the Mini Linguistic State Examination by clinicians will have a decisive impact on the consistency and uniformity with which patients can be described clinically. It will also facilitate screening for cohort-based research, including future therapeutic trials, and is suitable for describing, quantifying and monitoring language deficits in other brain disorders.

Pregnancy in an adolescent with maple syrup urine disease: Case report.

Maple syrup urine disease (MSUD, MIM #248600) is an autosomal recessive metabolic disorder that results in elevation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine. Elevation of BCAA and certain alpha keto-acids is associated with a catabolic state and may result in neurological and developmental delays, feeding problems, and a urine and cerumen odor of maple syrup. Pregnancy is a period of multiple adaptations necessary to support fetal growth and development. Both the third trimester of pregnancy and the postpartum period present the possibility for catabolic states. We describe our treatment of an adolescent patient with intermittent MSUD and her resulting positive pregnancy outcome.

High-resolution record of Northern Hemisphere climate extending into the last interglacial period.

Two deep ice cores from central Greenland, drilled in the 1990s, have played a key role in climate reconstructions of the Northern Hemisphere, but the oldest sections of the cores were disturbed in chronology owing to ice folding near the bedrock. Here we present an undisturbed climate record from a North Greenland ice core, which extends back to 123,000 years before the present, within the last interglacial period. The oxygen isotopes in the ice imply that climate was stable during the last interglacial period, with temperatures 5 degrees C warmer than today. We find unexpectedly large temperature differences between our new record from northern Greenland and the undisturbed sections of the cores from central Greenland, suggesting that the extent of ice in the Northern Hemisphere modulated the latitudinal temperature gradients in Greenland. This record shows a slow decline in temperatures that marked the initiation of the last glacial period. Our record reveals a hitherto unrecognized warm period initiated by an abrupt climate warming about 115,000 years ago, before glacial conditions were fully developed. This event does not appear to have an immediate Antarctic counterpart, suggesting that the climate see-saw between the hemispheres (which dominated the last glacial period) was not operating at this time.

Development of a modified in vitro skin absorption method to study the epidermal/dermal disposition of a contact allergen in human skin.

In vitro skin absorption methods exist in Organisation for Economic Co-operation and Development (OECD) guideline form (No. 428) and are used to estimate the degree of systemic penetration of chemicals through skin. More detailed kinetics of permeation through skin compartments are not described well by existing methods. This study was designed to assess the practical feasibility of generating compartmental (stratum corneum/epidermal/dermal) disposition and kinetic data of topically applied chemicals. For chemically induced effects initiated in the skin (e.g., skin allergy), the delivery of tissue concentrations of chemical will impact the incidence and severity of biological effect. Explicit data on the kinetics of chemical disposition in skin have not traditionally been needed for skin allergy risk assessment: current in vivo assays embody delivery implicitly. Under the 7th Amendment to the European Cosmetics Directive, in vivo assays (such as the local lymph node assay for skin sensitization) will not be permitted to assess cosmetic ingredients. New in vitro and in silico alternative approaches and ways of predicting risk of adverse effects in humans need to be developed, and new methods such as that described here provide a way of estimating delivered concentrations and the effect of formulation changes on that delivery. As we continue to deconstruct the contributing factors of skin allergy in humans, it will be useful to have methods available that can measure skin tissue compartment exposure levels delivered from different exposure use scenarios. Here we provide such a method. The method could also be used to generate useful data for developing in silico kinetic models of compartmental skin delivery and for refining data for skin delivery in relation to the evaluation of systemic toxicity.

Xenobiotic metabolism in human skin and 3D human skin reconstructs: a review.

In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental chemical exposure, it is also a potential target organ for adverse health effects. Occupational, accidental or intended-use exposure to toxic chemicals could result in acute or delayed injury to the skin (e.g. inflammation, allergy, cancer). Skin metabolism may play a role in the manifestation or amelioration of adverse effects via the topical route. Today, we have robust testing strategies to assess the potential for local skin toxicity of chemical exposure. Such methods (e.g. the local lymph node assay for assessing skin sensitisation; skin painting carcinogenicity studies) incorporate skin metabolism implicitly in the in vivo model system used. In light of recent European legislation (i.e. 7(th) Amendment to the Cosmetics Directive and Registration Evaluation and Authorisation of existing Chemicals (REACH)), non-animal approaches will be required to reduce and replace animal experiments for chemical risk assessment. It is expected that new models and approaches will need to account for skin metabolism explicitly, as the mechanisms of adverse effects in the skin are deconvoluted. 3D skin models have been proposed as a tool to use in new in vitro alternative approaches. In order to be able to use 3D skin models in this context, we need to understand their metabolic competency in relation to xenobiotic biotransformation and whether functional activity is representative of that seen in human skin.

Control beliefs and health locus of control in Ugandan, German and migrated sub-Saharan African HIV infected individuals.

OBJECTIVES: Little is known about the influence of control beliefs on antiretroviral drug adherence in patients who migrated from sub-Saharan Africa to Europe. The aim of this study was to explore the differences in health locus of control and control beliefs between HIV infected patients from sub-Saharan Africa with and without a lifetime experience of migration. METHODS: A sample of 62 HIV infected consecutive patients referred to the HIV clinics at the University Hospital of Münster (Germany) and at the Rubaga Hospital Kampala (Uganda) were enrolled into this study. We compared three groups of patients: sub-Saharan African migrants, German patients, and local Ugandan patients. We used the German health and illness related control beliefs questionnaire (KKG), the Competence and control beliefs questionnaire (FKK), and the Powe Fatalism Inventory-HIV/AIDS-Version (PFI-HIV/AIDS-Version) and translated these scales into English and Luganda. In addition, the patients' sociodemographic, acculturation, clinical, and immunological data were registered. RESULTS: Significant results were shown in HIV related external locus of control between migrated sub-Saharan African and local Ugandan patients compared to German patients. General control beliefs showed no significant differences. In the PFI-HIV-Version, there was a significant difference between migrated sub-Saharan African and Ugandan patients compared to German patients. CONCLUSIONS: Our data suggest that the experience of migration does not influence the locus of control. Compared to German HIV patients, African patients in general showed a significantly higher external health locus of control which might have implications for drug adherence.

[Tourette's syndrome and antidepressant therapy: exacerbation of nervous tics with paroxetine]. / Tourette-Syndrom und Antidepressiva-Therapie: Exazerbation einer Ticstörung unter Paroxetin.

One possible side effect of selective serotonin re-uptake inhibitors (SSRI) is the exacerbation of nervous tics in a 12-year-old boy treated with tiapride following prescription of paroxetine for a depressive syndrome. Potential causal factors include residual cholinergic activity of paroxetine, the observably increased drive under paroxetine, metabolic properties, and protein binding. The problem of side effects under selective serotonin re-uptake inhibitors, as well as the issues of co-morbidity and co-medication in the treatment of nervous tics and Tourette's Syndrome are discussed.

[Aqueductal stenosis and hydrocephalus in a psychotic adolescent]. / Aquäduktstenose und Hydrocephalus bei einem psychotischen Jugendlichen.

Examination of a 14-year-old male who was admitted to an inpatient unit with an acute paranoid syndrome yielded serious organic findings: macroencephaly, head tilted to one side, strabismus, neurological deficits, hydroencephaly and an expressive speech disorder. The personal and family history revealed a disturbance of motor development since infancy and psychiatric illness in the immediate family. The medication and the surgical procedure selected--endoscopic third ventriculostomy--are described and the difficult differential diagnosis is discussed.

[Child custody restrictions according to sections 1666, 1666a BGB from the child and adolescent psychiatry viewpoint--legal and practical principles]. / Die Sorgerechtseinschränkung nach Sektion 1666, 1666a BGB aus kinder- und jugendpsychiatrischer Sicht--juristische und praktische Grundlagen.

Within the clinical practice of child and adolescent psychiatry, the needs of the child are recurrently endangered by parents' expectations and/or behaviour. The task of the doctors, therapists and local authority social workers is to work together with the child's parents or guardians in order to assess their parental competence and if need be to contravene the latter with a care order. According to German law there are different possibilities of restricting the patients' rights or making a care order for children and adolescents up to the age of 18 years. The local authority social services department may make a care order especially according to the wishes of the child or the adolescent or when other circumstances necessitate it, and obtain parental consent afterwards (section 42 KJHG). The rights of the parents may be restricted in either single areas eg the place of the child's residence (section 1666 BGB) or completely (section 1666a BGB) in cooperation with the guardianship judge. The task of the judge is to decide within the legal context whether such a restriction of parental responsibility is necessary to protect the child.

[Problems in expert assessment in child custody cases according to sections 1666, 1666a BGB in the controversy between control and assistance]. / Gutachterliche Probleme beim Sorgerechtsentzugsverfahren nach sections 1666, 1666a BGB im Spannungsfeld zwischen Kontrolle und helfender Funktion.

The restriction of parental rights includes not only legal but also therapeutic aspects. The therapeutic aspects refer first to the child's disorder and then to its resulting needs. Furthermore a restriction of parental rights could be necessary for therapeutic reasons when the parents' reaction to reality is insufficient, usually caused by parental psychiatric disorders. The expert's counsel should facilitate the communication with disturbed parents thus engendering an improved reality-insight by the parents. Successful helping strategies can thus be made workable. The expert, the judge and the local authority social services should mutually respect specifically defined role-functions. The communication barriers between parents and helpers can only this way be partially resolved. The expert's evidence requires a high professional competence and responsibility and goes over and above the professional contribution from family therapy.

Determining epidermal disposition kinetics for use in an integrated nonanimal approach to skin sensitization risk assessment.

Development of risk assessment methods for skin sensitization in the absence of toxicological data generated in animals represents a major scientific and technical challenge. The first step in human skin sensitization induction is the transport of sensitizer from the applied dose on the skin surface to the epidermis, where innate immune activation occurs. Building on the previous development of a time course in vitro human skin permeation assay, new kinetic data for 10 sensitizers and 2 nonsensitizers are reported. Multicompartmental modeling has been applied to analyze the data and determine candidate dose parameters for use in integrated risk assessment methods: the area under the curve (AUC) and maximum concentration (C(max)) in the epidermis. A model with two skin compartments, representing the stratum corneum and viable skin (epidermis and dermis), was chosen following a formal model selection process. Estimates of the uncertainty, as well as average values of the epidermal disposition kinetics parameters, were made by fitting to the time course skin permeation data from individual skin donors. A potential reduced time course method is proposed based on two time points at 4 and 24 h, which gives results close to those from the full time course for the current data sets. The time course data presented in this work have been provided as a resource for development of predictive in silico skin permeation models.

Rare earth elements determined in Antarctic ice by inductively coupled plasma--time of flight, quadrupole and sector field-mass spectrometry: An inter-comparison study.

Inductively coupled plasma mass spectrometry (ICP-MS) is a suitable tool for multi-element analysis at low concentration levels. Rare earth element (REE) determinations in standard reference materials and small volumes of molten ice core samples from Antarctica have been performed with an ICP-time of flight-MS (ICP-TOF-MS) system. Recovery rates for REE in e.g. SPS-SW1 amounted to approximately 103%, and the relative standard deviations were 3.4% for replicate analysis at REE concentrations in the lower ngL(-1) range. Analyses of REE concentrations in Antarctic ice core samples showed that the ICP-TOF-MS technique meets the demands of restricted sample mass. The data obtained are in good agreement with ICP-Quadrupole-MS (ICP-Q-MS) and ICP-Sector Field-MS (ICP-SF-MS) results. The ICP-TOF-MS system determines accurately and precisely REE concentrations exceeding 5ngL(-1) while between 0.5 and 5ngL(-1) accuracy and precision are element dependent.

[Relation of maturity for responsibility according to section 3 JGG to the legal liability question according to sections 20, 21 StGB]. / Das Verhältnis der Verantwortungsreife gem. section 3 JGG zur Schuldfähigkeitsfrage nach sections 20, 21 StGB.

Psychiatric Assessment of juvenile offenders deals with criteria of maturity on the one hand as well as psychiatric disorders as factors of lessened responsibility on the other. Rivalry of both in German criminal legislation for youths between 14 and 18 is discussed, especially as regards aspects of practical proceedings.

[The forensic-psychiatric evaluation of young persons in accordance with 105 JGG between punishment and therapeutic help]. / Die forensisch-psychiatrische Begutachtung Heranwachsender nach section 105JGG zwischen Strafe und therapeutischer Hilfe.

105 of the the German Jugendgerichtsgesetz (JGG, law on criminal cases involving offenders between 14 and 17 years of age) allows the use of this special law also for offenders between 18 and 21 years of age if they can be considered juveniles with regard to their personal development or the type of crime they have committed. Assessment of the "maturity" of young people in this age group has been the subject of great controversy in forensic psychiatry since the first JGG went into effect in 1953. In spite of numerous attempts to operationalize the term "Jugendlicher", for example in the Marburg guidelines, it has not yet been possible to establish clear-cut criteria defining the characteristics of those who are juveniles in the sense of the JGG. Neither child and adolescent psychiatry nor criminal law nor criminology has provided an adequate basis for such a definition. The wide range of discretionary decisions in forensic psychiatry and the associated lack of legal uniformity may, however, be a necessary prerequisite for an adequate assessment of an individual case. Although the chances of a change in criminal law governing those between 18 and 21 are small, creation of a law specifically for this age group, with a separation of the educational-therapeutic aspects from the punishment aspects, could be a great help to those preparing expert opinions in forensic psychiatry and to the juvenile courts because it would necessitate greater clarity in decisions relating to this group of offenders. Elimination of Section 105 JGG and the subsequent use of either general criminal law or that governing those under age 18 only, which has been proposed repeatedly, is not recommended.

[Aspects of the legal concession and its procedures concerning the commitment of juveniles to safe custody institutions in youth welfare care according to German (section sign) 1631 b BGB -- an Inquiry into 101 cases of adolescent psychiatric expertise]. / Rechtliche Aspekte im Verfahren der geschlossenen Unterbringung Minderjähriger in der Jugendhilfe gemäss section sign 1631 b BGB -- Untersuchung anhand 101 jugendpsychiatrischer Gutachten.

OBJECTIVES: Legal procedures concerning the legal concession of juveniles to safe custody care in youth welfare according to German section sign 1631 b BGB were to be examined. METHOD: 101 cases of adolescent psychiatric expertise were retrospectively examined. RESULTS: Legal procedures were unsatisfactory. A guardian ("Verfahrenspfleger" according to German law) was usually not named (79.2 %), especially not in cases of juveniles under 14 years of age (94 %) who cannot take part in the procedure on their own right, and not in cases of foreigners (89 %). In a number of cases the adolescence psychiatrist did not agree with statement of the youth welfare office regarding the juvenile confinement. In cases where the expert's counsel was a "process diagnosis" evaluating the juvenile's concrete ability to cooperate and to accept alternative forms of placement, closed commitment could be reduced significantly. Experts did not precisely term of commitment in a number of cases (15.9 %). CONCLUSIONS: Legal procedures concerning the legal commitment of juveniles to safe custody care in youth welfare institutions are partly unsatisfactory, especially according to the juvenile's rights regarding the legal procedure and the ways, how these rights are safeguarded.