Variation at GRN 3′-UTR rs5848 Is Not Associated with a Risk of Frontotemporal Lobar Degeneration in Dutch Population

Background: A single nucleotide polymorphism (rs5848) located in the 3′- untranslated region of GRN has recently been associated with a risk of frontotemporal lobar degeneration (FTLD) in North American population particularly in pathologically confirmed cases with neural inclusions immunoreactive for ubiquitin and TAR DNA-binding protein 43 (TDP-43), but negative for tau and alpha-synuclein (FTLD-TDP). Methodology/Principal Findings: In an effort to replicate these results in a different population, rs5848 was genotyped in 256 FTLD cases and 1695 controls from the Netherlands. Single SNP gender-adjusted logistic regression analysis revealed no significant association between variation at rs5848 and FTLD. Fisher's exact test, failed to find any significant association between rs5848 and a subset of 23 pathology confirmed FTLD-TDP cases. Conclusions/Significance: The evidence presented here suggests that variation at rs5848 does not contribute to the etiology of FTLD in the Dutch population

Social participation for older people with aphasia: The impact of communication disability on friendships

Purpose: The language changes experienced by a person with aphasia following a stroke often have sudden and long-lasting negative impact on friendships. Friendship relationships are core to social engagement, quality of life, and emotional well-being. The aims of this study were to describe everyday communication with friends for older people with and without aphasia and to examine the nature of actual friendship conversations involving a person with aphasia. Method: This naturalistic inquiry drew data from two phases of research: a participant observation study of 30 older Australians, 15 of whom had aphasia following a stroke, and a collective case study using stimulated recall to examine friendship conversations involving an older person with aphasia. Results: People with aphasia communicated with fewer friends and had smaller social networks. "Friendship" was a core domain of communication for older people and participation in leisure and educational activities was focal in everyday communication with friends. Case study data of conversations between three older people with aphasia and their friends illuminated features of "time," the role of humour, and friends having shared interests. Conclusion: Aphasia has been found to impact on friendships. A need exists for research and intervention programs to address communication with friends for older people with aphasia

PAUSED for thought? Using verbal protocol analysis to understand the situational and temporal cues in the decision-making of residential burglars

Using verbal protocol analysis (VPA) alongside semi-structured interviews, this research aimed to explicate the situational dynamics that inform the decision-making and target selection of residential burglars. Focusing on the VPA method, novel to criminological research, the paper considers the contribution of this empirical approach for studying the decision-making of offenders in situ. The findings reveal a series of cues, encapsulated in the ‘PAUSED’ model, that are drawn upon by residential burglars to assess the suitability of a target; determining whether it is profitable, accessible, uninterruptible, surveillable, escapable and/or dishonourable. The PAUSED model is unpacked to articulate a collection of visual stimuli that serve to disrupt and suspend the otherwise rapid flow of target appraisal. Discussion of the strengths and limitations of the VPA method, and how it can compliment other approaches to understanding the decision-making of residential burglars, is provided

Assessing Susceptibility from Early-Life Exposure to Carcinogens

Cancer risk assessment methods currently assume that children and adults are equally susceptible to exposure to chemicals. We reviewed available scientific literature to determine whether this was scientifically supported. We identified more than 50 chemicals causing cancer after perinatal exposure. Human data are extremely limited, with radiation exposures showing increased early susceptibility at some tumor sites. Twenty-seven rodent studies for 18 chemicals had sufficient data after postnatal and adult exposures to quantitatively estimate potential increased susceptibility from early-life exposure, calculated as the ratio of juvenile to adult cancer potencies for three study types: acute dosing, repeated dosing, and lifetime dosing. Twelve of the chemicals act through a mutagenic mode of action. For these, the geometric mean ratio was 11 for lifetime exposures and 8.7 for repeat exposures, with a ratio of 10 for these studies combined. The geometric mean ratio for acute studies is 1.5, which was influenced by tissue-specific results [geometric mean ratios for kidney, leukemia, liver, lymph, mammary, nerve, reticular tissue, thymic lymphoma, and uterus/vagina > 1 (range, 1.6–8.1); forestomach, harderian gland, ovaries, and thyroid < 1 (range, 0.033–0.45)]. Chemicals causing cancer through other modes of action indicate some increased susceptibility from postnatal exposure (geometric mean ratio is 3.4 for lifetime exposure, 2.2 for repeat exposure). Early exposures to compounds with endocrine activity sometimes produce different tumors after exposures at different ages. These analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals acting through a mutagenic mode of action

FTLD-TDP with motor neuron disease, visuospatial impairment and a progressive supranuclear palsy-like syndrome: broadening the clinical phenotype of TDP-43 proteinopathies. A report of three cases

<p>Abstract</p> <p>Background</p> <p>Frontotemporal lobar degeneration with ubiquitin and TDP-43 positive neuronal inclusions represents a novel entity (FTLD-TDP) that may be associated with motor neuron disease (FTLD-MND); involvement of extrapyramidal and other systems has also been reported.</p> <p>Case presentation</p> <p>We present three cases with similar clinical symptoms, including Parkinsonism, supranuclear gaze palsy, visuospatial impairment and a behavioral variant of frontotemporal dementia, associated with either clinically possible or definite MND. Neuropathological examination revealed hallmarks of FTLD-TDP with major involvement of subcortical and, in particular, mesencephalic structures. These cases differed in onset and progression of clinical manifestations as well as distribution of histopathological changes in the brain and spinal cord. Two cases were sporadic, whereas the third case had a pathological variation in the progranulin gene 102 delC.</p> <p>Conclusions</p> <p>Association of a "progressive supranuclear palsy-like" syndrome with marked visuospatial impairment, motor neuron disease and early behavioral disturbances may represent a clinically distinct phenotype of FTLD-TDP. Our observations further support the concept that TDP-43 proteinopathies represent a spectrum of disorders, where preferential localization of pathogenetic inclusions and neuronal cell loss defines clinical phenotypes ranging from frontotemporal dementia with or without motor neuron disease, to corticobasal syndrome and to a progressive supranuclear palsy-like syndrome.</p

A case report of isolated distal upper extremity weakness due to cerebral metastasis involving the hand knob area

Unilateral weakness of an upper extremity is most frequently caused by traumatic nerve injury or compression neuropathy. In rare cases, lesion of the central nervous system may result in syndromes suggesting peripheral nerve damage by the initial examination. Pseudoperipheral hand palsy is the best known of these, most frequently caused by a small lesion in the contralateral motor cortex of the brain. The 'hand knob' area refers to a circumscribed region in the precentral gyrus of the posterior frontal lobe, the lesion of which leads to isolated weakness of the upper extremity mimicking peripheral nerve damage. The etiology of this rare syndrome is almost exclusively related to an embolic infarction.We present the case of a 70-year-old male patient with isolated left sided upper extremity weakness and clumsiness without sensory disturbance suggesting a lesion of the radial nerve. Nerve conduction studies had normal results excluding peripheral nerve damage. Neuroimaging (cranial CT and MRI) detected 3 space occupying lesions, one of them in the right precentral gyrus. An irregularly shaped tumor was found by CT in the left lung with multiple associated lymph node conglomerates. The metastasis from this mucinous tubular adenocarcinoma with solid anaplastic parts to the 'hand knob' area was responsible for the first clinical sign related to the pulmonary malignancy.Pseudoperipheral palsy of the upper extremity is not necessarily the consequence of an embolic stroke. If nerve conduction studies have normal results, neuroimaging - preferably MRI - should be performed, as lesion in the hand-knob area of the precentral gyrus can also be caused by a malignancy

The impact of language barriers on trust formation in multinational teams

This study systematically investigates how language barriers influence trust formation in multinational teams (MNTs). Based on 90 interviews with team members, team leaders, and senior managers in 15 MNTs in three German automotive corporations, we show how MNT members’ cognitive and emotional reactions to language barriers influence their perceived trustworthiness and intention to trust, which in turn affect trust formation. We contribute to diversity research by distinguishing the exclusively negative language effects from the more ambivalent effects of other diversity dimensions. Our findings also illustrate how surface-level language diversity may create perceptions of deep-level diversity. Furthermore, our study advances MNT research by revealing the specific influences of language barriers on team trust, an important mediator between team inputs and performance outcomes. It thereby encourages the examination of other team processes through a language lens. Finally, our study suggests that multilingual settings necessitate a reexamination and modification of the seminal trust theories by Mayer, Davis and Schoorman (1995) and McAllister (1995). In terms of practical implications, we outline how MNT leaders can manage their subordinates’ problematic reactions to language barriers and how MNT members can enhance their perceived trustworthiness in multilingual settings

Neural correlates of audiovisual motion capture

Visual motion can affect the perceived direction of auditory motion (i.e., audiovisual motion capture). It is debated, though, whether this effect occurs at perceptual or decisional stages. Here, we examined the neural consequences of audiovisual motion capture using the mismatch negativity (MMN), an event-related brain potential reflecting pre-attentive auditory deviance detection. In an auditory-only condition occasional changes in the direction of a moving sound (deviant) elicited an MMN starting around 150 ms. In an audiovisual condition, auditory standards and deviants were synchronized with a visual stimulus that moved in the same direction as the auditory standards. These audiovisual deviants did not evoke an MMN, indicating that visual motion reduced the perceptual difference between sound motion of standards and deviants. The inhibition of the MMN by visual motion provides evidence that auditory and visual motion signals are integrated at early sensory processing stages