Processing of acoustic cues for voicing in English: a MMN study

Speech perception normally utilizes multiple acoustic cues in perception of specific speech sound contrast. This study investigates which acoustic cues are responsible for syllable final stop consonant voicing in English using speech and non-speech stimuli. Specifically we study vocalic duration and F1 offset frequency cues using three experimental paradigms. Two paradigms used behavioural methods and explored identification (Exp1) and discrimination (Exp2) and one an electrophysiological method to investigate the neural correlates of processing in a mismatch negativity (MMN) experiment (Exp3). In Exp1 we presented the [bot]-[bod] continuum varying either in duration or F1 cues. Exps 2 and 3 employed a 2 (Frequency: high low) x 2 (Duration (long, short) design resulting in four different versions of English non-words [bot] and [bod] and their corresponding non-speech analogues. Nine subjects participated in Exp 1 and eight in Exps 2 & 3. The findings from Exp 1 revealed that the duration cue plays an important role in British English syllable final stop voicing. Further support for this finding was revealed in Exp 3 with larger MMN amplitude for the duration cue compared with the frequency cue

Study of Fundamental Rights Limitations for Online Enforcement through Self-Regulation

The use of self-regulatory or privatized enforcement measures in the online environment can give rise to various legal issues that affect the fundamental rights of internet users. First, privatized enforcement by internet services, without state involvement, can interfere with the effective exercise of fundamental rights by internet users. Such interference may, on occasion, be disproportionate, but there are legal complexities involved in determining the precise circumstances in which this is the case. This is because, for instance, the private entities can themselves claim protection under the fundamental rights framework (e.g. the protection of property and the freedom to conduct business). Second, the role of public authorities in the development of self-regulation in view of certain public policy objectives can become problematic, but has to be carefully assessed. The fundamental rights framework puts limitations on government regulation that interferes with fundamental rights. Essentially, such limitations involve the (negative) obligation for States not to interfere with fundamental rights. Interferences have to be prescribed by law, pursue a legitimate aim and be necessary in a democratic society. At the same time, however, States are also under the (positive) obligation to take active measures in order to ensure the effective exercise of fundamental rights. In other words, States must do more than simply refrain from interference. These positive obligations are of specific interest in the context of private ordering impact on fundamental rights, but tend to be abstract and hard to operationalize in specific legal constellations. This study’s central research question is: What legal limitations follow from the fundamental rights framework for self-regulation and privatized enforcement online? It examines the circumstances in which State responsibility can be engaged as a result of selfregulation or privatized enforcement online. Part I of the study provides an overview and analysis of the relevant elements in the European and international fundamental rights framework that place limitations on privatized enforcement. Part II gives an assessment of specific instances of self-regulation or other instances of privatized enforcement in light of these elements

Identification of signaling pathways in early mammary gland development by mouse genetics

The mammary gland develops as an appendage of the ectoderm. The prenatal stage of mammary development is hormone independent and is regulated by sequential and reciprocal signaling between the epithelium and the mesenchyme. A number of recent studies using human and mouse genetics, in particular targeted gene deletion and transgenic expression, have identified some of the signals that control specific steps in development. This process involves cell specification and proliferation, reciprocal tissue interactions and cell migration. Since some of these events are recapitulated during tumorigenesis, an understanding of these signaling pathways may contribute to the development of targeted therapies and novel drugs

Dermoscopy for melanoma detection and triage in primary care: a systematic review.

OBJECTIVE: Most skin lesions first present in primary care, where distinguishing rare melanomas from benign lesions can be challenging. Dermoscopy improves diagnostic accuracy among specialists and is promoted for use by primary care physicians (PCPs). However, when used by untrained clinicians, accuracy may be no better than visual inspection. This study aimed to undertake a systematic review of literature reporting use of dermoscopy to triage suspicious skin lesions in primary care settings, and challenges for implementation. DESIGN: A systematic literature review and narrative synthesis. DATA SOURCES: We searched MEDLINE, Cochrane Central, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and SCOPUS bibliographic databases from 1 January 1990 to 31 December 2017, without language restrictions. INCLUSION CRITERIA: Studies including assessment of dermoscopy accuracy, acceptability to patients and PCPs, training requirements, and cost-effectiveness of dermoscopy modes in primary care, including trials, diagnostic accuracy and acceptability studies. RESULTS: 23 studies met the review criteria, representing 49 769 lesions and 3708 PCPs, all from high-income countries. There was a paucity of studies set truly in primary care and the outcomes measured were diverse. The heterogeneity therefore made meta-analysis unfeasible; the data were synthesised through narrative review. Dermoscopy, with appropriate training, was associated with improved diagnostic accuracy for melanoma and benign lesions, and reduced unnecessary excisions and referrals. Teledermoscopy-based referral systems improved triage accuracy. Only three studies examined cost-effectiveness; hence, there was insufficient evidence to draw conclusions. Costs, training and time requirements were considered important implementation barriers. Patient satisfaction was seldom assessed. Computer-aided dermoscopy and other technological advances have not yet been tested in primary care. CONCLUSIONS: Dermoscopy could help PCPs triage suspicious lesions for biopsy, urgent referral or reassurance. However, it will be important to establish further evidence on minimum training requirements to reach competence, as well as the cost-effectiveness and patient acceptability of implementing dermoscopy in primary care. TRIAL REGISTRATION NUMBER: CRD42018091395.CRU

The price of anarchy in series-parallel graphs

Abstract Congestion games model self-interested agents competing for resources in communication networks. The price of anarchy quantifies the deterioration in performance in such games compared to the optimal solution. Recent research has shown that, when the social cost is defined as the maximum cost of all players, specific graph topologies impose a bound on the price of anarchy. We extend this research by providing bounds on the price of anarchy for congestion games on series-parallel networks. First we show that parallel composition does not increase the price of anarchy. This result is then used to show that the price of anarchy is bounded above by both the diameter of the graph and the number of players in the game, and that these bounds are tight. Finally we identify an important aspect of proofs for bounds on the price of anarchy: when a bound is achieved by restricting multiple parameters of the game, one should also prove that this bound cannot be realized using only a subset of these restrictions

Retrospective study of long-term outcomes of enzyme replacement therapy in Fabry disease: Analysis of prognostic factors

Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR 90. In addition, men with classical disease and a baseline eGFR 60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension

Artificial intelligence and machine learning algorithms for early detection of skin cancer in community and primary care settings: a systematic review.

Skin cancers occur commonly worldwide. The prognosis and disease burden are highly dependent on the cancer type and disease stage at diagnosis. We systematically reviewed studies on artificial intelligence and machine learning (AI/ML) algorithms that aim to facilitate the early diagnosis of skin cancers, focusing on their application in primary and community care settings. We searched MEDLINE, Embase, Scopus, and Web of Science (from Jan 1, 2000, to Aug 9, 2021) for all studies providing evidence on applying AI/ML algorithms to the early diagnosis of skin cancer, including all study designs and languages. The primary outcome was diagnostic accuracy of the algorithms for skin cancers. The secondary outcomes included an overview of AI/ML methods, evaluation approaches, cost-effectiveness, and acceptability to patients and clinicians. We identified 14 224 studies. Only two studies used data from clinical settings with a low prevalence of skin cancers. We reported data from all 272 studies that could be relevant in primary care. The primary outcomes showed reasonable mean diagnostic accuracy for melanoma (89·5% [range 59·7-100%]), squamous cell carcinoma (85·3% [71·0-97·8%]), and basal cell carcinoma (87·6% [70·0-99·7%]). The secondary outcomes showed a heterogeneity of AI/ML methods and study designs, with high amounts of incomplete reporting (eg, patient demographics and methods of data collection). Few studies used data on populations with a low prevalence of skin cancers to train and test their algorithms; therefore, the widespread adoption into community and primary care practice cannot currently be recommended until efficacy in these populations is shown. We did not identify any health economic, patient, or clinician acceptability data for any of the included studies. We propose a methodological checklist for use in the development of new AI/ML algorithms to detect skin cancer, to facilitate their design, evaluation, and implementation