Two-microphone spatial filtering provides speech reception benefits for cochlear implant users in difficult acoustic environments

This article introduces and provides an assessment of a spatial-filtering algorithm based on two closely-spaced (∼1 cm) microphones in a behind-the-ear shell. The evaluated spatial-filtering algorithm used fast (∼10 ms) temporal-spectral analysis to determine the location of incoming sounds and to enhance sounds arriving from straight ahead of the listener. Speech reception thresholds (SRTs) were measured for eight cochlear implant (CI) users using consonant and vowel materials under three processing conditions: An omni-directional response, a dipole-directional response, and the spatial-filtering algorithm. The background noise condition used three simultaneous time-reversed speech signals as interferers located at 90°, 180°, and 270°. Results indicated that the spatial-filtering algorithm can provide speech reception benefits of 5.8 to 10.7 dB SRT compared to an omni-directional response in a reverberant room with multiple noise sources. Given the observed SRT benefits, coupled with an efficient design, the proposed algorithm is promising as a CI noise-reduction solution.National Institutes of Health (U.S.) (Grant R01 DC 000117)National Institutes of Health (U.S.) (Grant R01 DC DC7152)National Institutes of Health (U.S.) (Grant 2R44DC010524-02

Border skirmishes and the question of belonging: An authoethnographic account of everyday exclusion in multicultural society

Transnational migration has transformed most European countries, making the problem of how to 'integrate' an increasingly popular topic in public debates and social policy. It is assumed that as long as the newcomer learns the language, adapts to the local customs and finds work, s/he will be integrated and welcomed with open arms as a full-fledged member of society. Based on an autoethnography of our experiences as US-born, long-term and fully 'integrated' residents of the Netherlands, one of Europe's most multicultural societies, we have explored some of the subtle, well-intentioned practices of distancing and exclusion that are part of the fabric of everyday life. We will show how, contrary to the official discourse of integration, 'Dutch-ness' as a white/ethnic national identity is continuously constructed as a 'we', which excludes all 'others'. And, indeed, we have discovered that, paradoxically, the closer the 'other' comes to being completely assimilated into Dutch society, the more the symbolic borders of national belonging may need to be policed and tightened. © The Author(s) 2011

Attributional style, self-esteem, and celebrity worship

Two studies were carried out to investigate the relationship between attributional style (Study 1), self-esteem (Study 2), and different forms of celebrity worship. Entertainment social celebrity worship (the most normal form considered) was unrelated to attributional style or self-esteem; intense personal celebrity worship was related positively to self-esteem but also to a propensity toward stable and globalattributions; and borderline pathological celebrity worship (the most negative form considered) was related to external, stable, and global attributions. These results were independent of whether participants were located in Europe or North America, and are discussed in terms of whether celebrity worship should be regarded as positive or negative and as a unitary concept

Risk of Parkinson disease in carriers of parkin mutations : estimation using the kin-cohort method

Objective: To estimate the risk of Parkinson disease (PD) in individuals with mutations in the Parkin gene. Design: We assessed point mutations and exon deletions and duplications in the Parkin gene in 247 probands with PD (age at onset 50 years) and 104 control probands enrolled in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. For each first-degree relative, a consensus diagnosis of PD was established. The probability that each relative carried a mutation was estimated from the proband's Parkin carrier status using Mendelian principles and from the relationship of the relative to the proband. Setting: Tertiary care movement disorders center. Patients: Cases, controls, and their first-degree relatives were enrolled in the GEPD study. Main Outcome Measures: Estimated age-specific penetrance in first-degree relatives. Results: Parkin mutations were identified in 25 probands with PD (10.1%), 18 (72.0%) of whom were heterozygotes. One Parkin homozygote was reported in 2 siblings with PD. The cumulative incidence of PD to age 65 years in carrier relatives (age-specific penetrance) was estimated to be 7.0% (95% confidence interval, 0.4%-71.9%), compared with 1.7% (95% confidence interval, 0.8%-3.4%) in noncarrier relatives of the cases (P = .59) and 1.1% (95% confidence interval, 0.3%-3.4%) in relatives of the controls (compared with noncarrier relatives, P = .52). Conclusions: The cumulative risk of PD to age 65 years in a noncarrier relative of a case with an age at onset of 50 years or younger is not significantly greater than the general population risk among controls. Age-specific penetrance among Parkin carriers, in particular heterozygotes, deserves further study. Mutations in the Parkin gene (PARK2; GenBank AB009973) are associated primarily with early-onset Parkinson disease (PD), defined as age at onset (AAO) ranging from 45 years or younger to 55 years or younger, but have also been described in PD cases with an AAO older than 70 years. In PD cases with an AAO of 45 years or younger with a mode of inheritance consistent with autosomal recessive transmission, the frequency of Parkin mutations may be as high as 49%, whereas in cases without a family history of PD the range is 15% to 18%. Age at onset is inversely correlated with the frequency of Parkin mutations in both familial and sporadic cases. Several studies have compared the AAO of PD in heterozygous, compound heterozygous, and homozygous Parkin mutation carriers and found that heterozygous cases, both familial and sporadic, have an older AAO. Heterozygous Parkin mutation carriers are more frequently reported among sporadic than familial cases. Information on the risk of PD in individuals who carry Parkin mutations in either the homozygous, compound heterozygous, or heterozygous state (or penetrance) is essential for genetic counseling. The penetrance of Parkin mutations has only been reported for isolated families. Most of the previous study designs sampled PD cases based on family history of PD, which would bias penetrance estimates upwards. To obtain an unbiased estimate of risk, a population-based random sample would be desirable, but Parkin mutations are so rare in the population that such a sample would have to be extremely large to obtain sufficient precision in penetrance estimates. To obtain unbiased estimates of the risk of PD in Parkin carriers despite the low population frequency of Parkin mutations, we used a kin-cohort study design applied to participants in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. The kin-cohort design is highly efficient for estimating penetrance because the relatives' mutation status is not required for the analyses, thus reducing costs for genetic analysis

Does it bite? The role of stimuli characteristics on preschoolers’ interactions with robots, insects and a dog

While there is increasing interest in the impact of animal interactions upon children’s wellbeing and attitudes, there has been less attention paid to the specific characteristics of the animals which attract and engage children. We used a within-subjects design to explore how differences in animal features (such as their animacy, size, and texture) impacted upon pre-school children’s social and emotional responses. This study examined pre-schoolers’ interactions with two animal-like robots (Teksta and Scoozie), two insect types (stick insects and hissing cockroaches) and a dog (Teasel, a West Highland Terrier). Nineteen preschool participants aged 35-57 months were videoed while interacting with the experimenter, a peer and each stimulus (presented individually). We used both verbal and nonverbal behaviours to evaluate interactions and emotional responses to the stimuli and found that these two measures could be incongruent, highlighting the need for systematic approaches to evaluating children’s interactions with animals. We categorised the content of children’s dialogues in relation to psychological and biological attributes of each stimulus and their distinctions between living and non-living stimuli; the majority of comments were biological, with psychological terms largely reserved for the dog and mammal-like robot only. Comments relating to living qualities revealed ambiguity towards attributes that denote differences between living and non-living creatures. We used a range of nonverbal measures, including willingness to approach and touch stimuli, rates of self-touching, facial expressions of emotion, and touch to others. Insects (hissing cockroaches and stick insects) received the most negative verbal and nonverbal responses. The mammal-like robot (rounded, fluffy body shape, large eyes, and sympathetic sounds) was viewed much more positively than its metallic counterpart, as was the real dog. We propose that these interactions provide information on how children perceive animals and a platform for the examination of human socio-emotional and cognitive development more generally. The children engaged in social referencing to the adult experimenter rather than familiar peers when uncertain about the stimuli presented, suggesting that caregivers have a primary role in shaping children’s responses to animals

Sustaining entrepreneurial business: a complexity perspective on processes that produce emergent practice

This article examines the management practices in an entrepreneurial small firm which sustain the business. Using a longitudinal qualitative case study, four general processes are identified (experimentation, reflexivity, organising and sensing), that together provide a mechanism to sustain the enterprise. The analysis draws on concepts from entrepreneurship and complexity science. We suggest that an entrepreneur’s awareness of the role of these parallel processes will facilitate their approaches to sustaining and developing enterprises. We also suggest that these processes operate in parallel at multiple levels, including the self, the business and inter-firm networks. This finding contributes to a general theory of entrepreneurship. A number of areas for further research are discussed arising from this result

Case-control study of the parkin gene in early-onset Parkinson disease

Background: Mutations in parkin are estimated to account for as much as 50% of familial Parkinson disease (PD) and 18% of sporadic PD. Single heterozygous mutations in parkin in both familial and sporadic cases may also increase susceptibility to PD. To our knowledge, all previous studies have been restricted to PD cases; this is the first study to systematically screen the parkin coding regions and exon deletions and duplications in controls. Objective: To determine the frequency and spectrum of parkin variants in early-onset PD cases (aged 50 years) and controls participating in a familial aggregation study. Patients and Methods: We sequenced the parkin gene in 101 cases and 105 controls. All cases and controls were also screened for exon deletions and duplications by semiquantitative multiplex polymerase chain reaction. Results: Thirteen (12.9% [95% confidence interval, 7%-21%]) of the 101 cases had a previously described parkin mutation: 1 was homozygous, 11 were heterozygous, and 1 was a compound heterozygote. The mutations Arg42Pro (exon 2) and Arg275Trp (exon 7) were recurrent. The previously reported synonymous substitution Leu261Leu (c.884A>G) was identified in 4 (3.9%) of 101 cases and 2 (2%) of 105 controls (P = .44). Excluding the synonymous substitution Leu261Leu (heterozygotes), 10 (9.9% [95% confidence interval, 4.6%-17.5%]) carried mutations. Conclusions: The frequency of mutations among cases that were not selected based on family history of PD is similar to what has previously been reported in sporadic PD. The similar frequency of Leu261Leu in cases and controls suggests it is a normal variant rather than a disease-associated mutation. We confirmed that heterozygous parkin mutations may increase susceptibility for early-onset PD

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib

Background: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. Patients and methods: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. Results: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). Conclusions: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. ClincalTrials.gov number: NCT02184195

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change &#8805;2) and significantly altered in GBM (p &#8804; 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

Sphenopalatine ganglion stimulation upregulates transport of temozolomide across the blood-brain barrier

Sphenopalatine ganglion (SPG) stimulation has been shown to reversibly alter blood-brainbarrier (BBB) permeability. It is widely used for the treatment of cluster headaches in Europe and iswell tolerated in humans. The therapeutic potential for SPG stimulation in other central nervoussystem (CNS) diseases has yet to be explored. Glioblastoma Multiforme (GBM) remains one of themost difficult primary CNS neoplasms to treat, with an average survival of approximately 18 months atthe time of diagnosis. Since 2004, the gold standard of treatment for GBM in the United States includessurgery followed by treatment with temozolomide (TMZ) and radiation. We sought to determine ifSPG stimulation could increase chemotherapy concentrations in rodent brains with an intact BBB.Here, we show a statistically significant (p=0.0006), five-fold upregulation of TMZ crossing the BBBand reaching brain parenchyma in rats receiving low-frequency (LF, 10 Hz) SPG stimulation. All themeasurements were performed using a highly sensitive liquid chromatography mass spectrometry(LCMS) method that was developed for quantitation of TMZ in plasma and brain tissue. Our treatmentparadigm shows novel delivery route by which we could more effectively and safely deliver TMZ ina targeted manner, to minimize systemic toxicity and maximize action at the target tissue