Experiences of people with dual sensory loss in various areas of life: A qualitative study.

Individuals with dual sensory loss (DSL) appear to have limited ability to compensate for their visual impairment with residual hearing, or for their hearing impairment with residual vision, resulting in challenges in various areas of life. The aim of this qualitative study was to explore the diverse experiences facing individuals with DSL as well as to determine how they experience sensory compensation. Semi-structured interviews were carried out in twenty adults with DSL (13 females and 7 males, mean age 47 years). The causes of DSL severity varied amongst participants. Sensory compensation and experiences in regards to access to information, mobility, communication and fatigue were discussed. Interviews were audio recorded and transcribed verbatim. Framework analysis was used to summarize and interpret the data. In relation to access to information, our results show that, despite various challenges, the use of assistive technology such as voice command functions, enabled participants to operate effectively. Regarding mobility, most participants were capable of finding their way in familiar environments. However, if the setting was unfamiliar, assistance from others or reliance on navigation applications was necessary. Participants experienced little issues with having conversations in quiet settings, however, crowded settings were considered very difficult. The final results showed that most participants suffered from fatigue. Carefully considering which daily activities were feasible and having a daily routine helped to cope with fatigue. This study revealed the experiences of individuals with DSL in important areas of life. The results suggest that, even though many challenges are experienced, individuals with DSL are resourceful in finding compensation strategies. However, capturing participants' sensory compensation experiences was challenging.

Cellular therapy and tissue engineering for cartilage repair.

Articular cartilage (AC) has limited capacity for repair. The first attempt to repair cartilage using tissue engineering was reported in 1977. Since then, cell-based interventions have entered clinical practice in orthopaedics, and several tissue engineering approaches to repair cartilage are in the translational pipeline towards clinical application. Classically, these involve a scaffold, substrate or matrix to provide structure, and cells such as chondrocytes or mesenchymal stromal cells to generate the tissue. We discuss the advantages and drawbacks of the use of various cell types, natural and synthetic scaffolds, multiphasic or gradient-based scaffolds, and self-organizing or self-assembling scaffold-free systems, for the engineering of cartilage constructs. Several challenges persist including achieving zonal tissue organization and integration with the surrounding tissue upon implantation. Approaches to improve cartilage thickness, organization and mechanical properties include mechanical stimulation, culture under hypoxic conditions, and stimulation with growth factors or other macromolecules. In addition, advanced technologies such as bioreactors, biosensors and 3D bioprinting are actively being explored. Understanding the underlying mechanisms of action of cell therapy and tissue engineering approaches will help improve and refine therapy development. Finally, we discuss recent studies of the intrinsic cellular and molecular mechanisms of cartilage repair that have identified novel signals and targets and are inspiring the development of molecular therapies to enhance the recruitment and cartilage reparative activity of joint-resident stem and progenitor cells. A one-fits-all solution is unrealistic, and identifying patients who will respond to a specific targeted treatment will be critical.

PHASE: An Open-Source Program for the Analysis of DrosophilaPhase, Activity, and Sleep Under Entrainment.

The problem of entrainment is central to circadian biology. In this regard, Drosophila has been an important model system. Owing to the simplicity of its nervous system and the availability of powerful genetic tools, the system has shed significant light on the molecular and neural underpinnings of entrainment. However, much remains to be learned regarding the molecular and physiological mechanisms underlying this important phenomenon. Under cyclic light/dark conditions, Drosophila melanogaster displays crepuscular patterns of locomotor activity with one peak anticipating dawn and the other anticipating dusk. These peaks are characterized through an estimation of their phase relative to the environmental light cycle and the extent of their anticipation of light transitions. In Drosophila chronobiology, estimations of phases are often subjective, and anticipation indices vary significantly between studies. Though there is increasing interest in building flexible analysis tools in the field, none incorporates objective measures of Drosophila activity peaks in combination with the analysis of fly activity/sleep in the same program. To this end, we have developed PHASE, a MATLAB-based program that is simple and easy to use and (i) supports the visualization and analysis of activity and sleep under entrainment, (ii) allows analysis of both activity and sleep parameters within user-defined windows within a diurnal cycle, (iii) uses a smoothing filter for the objective identification of peaks of activity (and therefore can be used to quantitatively characterize them), and (iv) offers a series of analyses for the assessment of behavioral anticipation of environmental transitions.

Anemia in young children living in the Surinamese interior: the influence of age, nutritional status and ethnicity.

PURPOSE: This study investigates the prevalence of anemia in young children living in the interior of Suriname and the influence of the associated factors age, nutritional status and ethnicity. RESULTS: In this cross-sectional observational study, 606 children aged 1-5 years from three different regions of Suriname's interior were included, and hemoglobin levels and anthropometric measurements were collected. Logistic regression models were computed to examine independent associations between anemic and nonanemic groups and to measure the influence of age, nutritional status and ethnicity. RESULTS: A total of 606 children were included, of whom 330 (55%) were aged 1-3 years and 276 were aged 4-5 years. The overall prevalence of anemia was 63%. Younger age was associated with anemia (odds ratio [OR]=1.78; 95% confidence interval [CI]: 1.27-2.51). Anemia was less prevalent in Amerindian than in Maroon children (OR=0.51; 95% CI: 0.34-0.76). Hemoglobin level was not influenced by nutritional status nor by sex. CONCLUSION: The prevalence of anemia in children aged 1-5 years living in Suriname's interior is high (63%) compared to that in similar aged children in Latin America and the Caribbean (4-45%). Children aged 1-3 years were more affected than those aged 4-5 years as were Maroon children compared to Amerindian children. Nutritional status and sex were not of influence.

Anaemia in young children living in the Surinamese interior: the influence of age, nutritional status and ethnicity

OBJECTIVE: Anaemia may lead to poor motor development and impaired neurocognitive function and affects 43% of children 1–5 years worldwide. Currently, there is little information on the prevalence of anaemia in young children living in the interior of Suriname. This study investigates the prevalence of anaemia in these children and the influence of the associated factors of age, nutritional status and ethnicity. SUBJECTS AND METHODS: Haemoglobin levels and anthropometric measurements of children aged 1–5 years were collected, after informed consent was provided, in three different interior regions of Suriname in the period September–October 2015. World Health Organization(WHO) standards for anaemia and underweight assessment were applied. Logistic regression models were computed to examine independent associations between the anaemic and non-anaemic groups and were expressed as odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Six hundred and six children were included: 330(55%) very young (1–3 years) and 276 older (4–5 years). Younger age was associated with anaemia (OR = 2.45;95% CI 1.75, 3.45). Anaemia was less prevalent in Amerindian than in Maroon children (OR = 0.51; 95% CI0.34, 0.76). Haemoglobin level was not influenced by nutritional status. CONCLUSIONS: The prevalence of anaemia in children 1–5years old living in Suriname’s interior is high (55%) compared to similar aged children in Latin America and the Caribbean (4–45%). Children 1–3 years of age were more affected than 4–5-year old children, as were Maroon children compared to Amerindian children. Nutritional status was not of influence. These findings call for further studies and may support adaptation of anaemia prevention and control programmes in young children in Suriname.

In vivo phenotypic characterisation of nucleoside label-retaining cells in mouse periosteum.

Periosteum is known to contain cells that, after isolation and culture-expansion, display properties of mesenchymal stromal/stem cells (MSCs). However, the equivalent cells have not been identified in situ mainly due to the lack of specific markers. Postnatally, stem cells are slow-cycling, long-term nucleoside-label-retaining cells. This study aimed to identify and characterise label-retaining cells in mouse periosteum in vivo. Mice received iodo-deoxy-uridine (IdU) via the drinking water for 30 days, followed by a 40-day washout period. IdU+ cells were identified by immunostaining in conjunction with MSC and lineage markers. IdU-labelled cells were detected throughout the periosteum with no apparent focal concentration, and were negative for the endothelial marker von Willebrand factor and the pan-haematopoietic marker CD45. Subsets of IdU+ cells were positive for the mesenchymal/stromal markers vimentin and cadherin-11. IdU+ cells expressed stem cell antigen-1, CD44, CD73, CD105, platelet-derived growth factor receptor-α and p75, thereby displaying an MSC-like phonotype. Co-localisation was not detectable between IdU and the pericyte markers CD146, alpha smooth muscle actin or NG2, nor did IdU co-localise with ß-galactosidase in a transgenic mouse expressing this reporter gene in pericytes and smooth muscle cells. Subsets of IdU+ cells expressed the osteoblast-lineage markers Runx2 and osteocalcin. The IdU+ cells expressing osteocalcin were lining the bone and were negative for the MSC marker p75. In conclusion, mouse periosteum contains nucleoside-label-retaining cells with a phenotype compatible with MSCs that are distinct from pericytes and osteoblasts. Future studies characterising the MSC niche in vivo could reveal novel therapeutic targets for promoting bone regeneration/repair.

Cell-based approaches to joint surface repair: a research perspective.

Repair of lesions of the articular cartilage lining the joints remains a major clinical challenge. Surgical interventions include osteochondral autograft transfer and microfracture. They can provide some relief of symptoms to patients, but generally fail to durably repair the cartilage. Autologous chondrocyte implantation has thus far shown the most promise for the durable repair of cartilage, with long-term follow-up studies indicating improved structural and functional outcomes. However, disadvantages of this technique include the need for additional surgery, availability of sufficient chondrocytes for implantation, and maintenance of their phenotype during culture-expansion. Mesenchymal stem cells offer an attractive alternative cell-source for cartilage repair, due to their ease of isolation and amenability to ex vivo expansion while retaining stem cell properties. Preclinical and clinical studies have demonstrated the potential of mesenchymal stem cells to promote articular cartilage repair, but have also highlighted several key challenges. Most notably, the quality and durability of the repair tissue, its resistance to endochondral ossification, and its effective integration with the surrounding host tissue. In addition, challenges exist related to the heterogeneity of mesenchymal stem cell preparations and their quality-control, as well as optimising the delivery method. Finally, as our knowledge of the cellular and molecular mechanisms underlying articular cartilage repair increases, promising studies are emerging employing bioactive scaffolds or therapeutics that elicit an effective tissue repair response through activation and mobilisation of endogenous stem and progenitor cells.

Bisphosphonates: molecular mechanisms of action and effects on bone cells, monocytes and macrophages.

Bisphosphonates are widely used in the treatment of diseases involving excessive bone resorption, such as osteoporosis, cancer-associated bone disease, and Paget's disease of bone. They target to the skeleton due to their calcium-chelating properties, where they primarily act by inhibiting osteoclast-mediated bone resorption. The simple bisphosphonates, clodronate, etidronate and tiludronate, are intracellularly metabolised to cytotoxic ATP analogues, while the more potent, nitrogen-containing bisphosphonates act by inhibiting the enzyme FPP synthase, thereby preventing the prenylation of small GTPases that are necessary for the normal function and survival of osteoclasts. In recent years, these concepts have been refined, with an increased understanding of the exact mode of inhibition of FPP synthase and the consequences of inhibiting this enzyme. Recent studies further suggest that the R2 side chain, as well as determining the potency for inhibiting the target enzyme FPP synthase, also influences bone mineral binding, which may influence distribution within bone and duration of action. While bisphosphonates primarily affect the function of resorbing osteoclasts, it is becoming increasingly clear that bisphosphonates may also target the osteocyte network and prevent osteocyte apoptosis, which could contribute to their anti-fracture effects. Furthermore, increasing evidence implicates monocytes and macrophages as direct targets of bisphosphonate action, which may explain the acute phase response and the anti-tumour activity in certain animal models. Bone mineral affinity is likely to influence the extent of any such effects of these agents on non-osteoclast cells. While alternative anti-resorptive therapeutics are becoming available for clinical use, bisphosphonates currently remain the principle drugs used to treat excessive bone resorption.

Differential effects of stress on adult hippocampal cell proliferation in low and high aggressive mice.

Male wild house mice selected for a long (LAL) or a short (SAL) latency to attack a male intruder generally show opposing behavioural coping responses to environmental challenges. LAL mice, unlike SAL mice, adapt to novel challenges with a highly reactive hypothalamic-pituitary-adrenal axis and show an enhanced expression of markers for hippocampal plasticity. The present study aimed to test the hypothesis that these features of the more reactive LAL mice are reflected in parameters of hippocampal cell proliferation. The data show that basal cell proliferation in the subgranular zone (SGZ) of the dentate gyrus, assessed by the endogenous proliferation marker Ki-67, is lower in LAL than in SAL mice. Furthermore, application of bromodeoxyuridine (BrdU) over 3 days showed an almost two-fold lower cell proliferation rate in the SGZ in LAL versus SAL mice. Exposure to forced swimming resulted, 24 h later, in a significant reduction in BrdU + cell numbers in LAL mice, whereas cell proliferation was unaffected by this stressor in SAL mice. Plasma corticosterone and dentate gyrus glucocorticoid receptor levels were higher in LAL than in SAL mice. However, no differences between the SAL and LAL lines were found for hippocampal NMDA receptor binding. In conclusion, the data suggest a relationship between coping responses and hippocampal cell proliferation, in which corticosterone may be one of the determinants of line differences in cell proliferation responses to environmental challenges.

Set size and repetition matter: comment on Caramazza and Costa (2000).

Caramazza and Costa, 2000 (Cognition 75, B51--B64) report three picture-word interference experiments testing the response set mechanism of the WEAVER+ + model of spoken word production. They argue that their findings are problematic for WEAVER+ + and that the model's architecture needs to be changed. I show that there is no need to fundamentally modify the model. Instead, the findings of Caramazza and Costa, and all previous findings, are explained by assuming that only a limited number of responses can be kept in short-term memory and that memory improves with response repetition.

A theory of lexical access in speech production.

Preparing words in speech production is normally a fast and accurate process. We generate them two or three per second in fluent conversation; and overtly naming a clear picture of an object can easily be initiated within 600 msec after picture onset. The underlying process, however, is exceedingly complex. The theory reviewed in this target article analyzes this process as staged and feed-forward. After a first stage of conceptual preparation, word generation proceeds through lexical selection, morphological and phonological encoding, phonetic encoding, and articulation itself. In addition, the speaker exerts some degree of output control, by monitoring of self-produced internal and overt speech. The core of the theory, ranging from lexical selection to the initiation of phonetic encoding, is captured in a computational model, called WEAVER++. Both the theory and the computational model have been developed in interaction with reaction time experiments, particularly in picture naming or related word production paradigms, with the aim of accounting for the real-time processing in normal word production. A comprehensive review of theory, model, and experiments is presented. The model can handle some of the main observations in the domain of speech errors (the major empirical domain for most other theories of lexical access), and the theory opens new ways of approaching the cerebral organization of speech production by way of high-temporal-resolution imaging.

A case for the lemma/lexeme distinction in models of speaking: comment on Caramazza and Miozzo (1997)

In a recent series of papers, Caramazza and Miozzo [Caramazza, A., 1997. How many levels of processing are there in lexical access? Cognitive Neuropsychology 14, 177-208; Caramazza, A., Miozzo, M., 1997. The relation between syntactic and phonological knowledge in lexical access: evidence from the 'tip-of-the-tongue' phenomenon. Cognition 64, 309-343; Miozzo, M., Caramazza, A., 1997. On knowing the auxiliary of a verb that cannot be named: evidence for the independence of grammatical and phonological aspects of lexical knowledge. Journal of Cognitive Neuropsychology 9, 160-166] argued against the lemma/lexeme distinction made in many models of lexical access in speaking, including our network model [Roelofs, A., 1992. A spreading-activation theory of lemma retrieval in speaking. Cognition 42, 107-142; Levelt, W.J.M., Roelofs, A., Meyer, A.S., 1998. A theory of lexical access in speech production. Behavioral and Brain Sciences, (in press)]. Their case was based on the observations that grammatical class deficits of brain-damaged patients and semantic errors may be restricted to either spoken or written forms and that the grammatical gender of a word and information about its form can be independently available in tip-of-the-tongue states (TOTs). In this paper, we argue that though our model is about speaking, not taking position on writing, extensions to writing are possible that are compatible with the evidence from aphasia and speech errors. Furthermore, our model does not predict a dependency between gender and form retrieval in TOTs. Finally, we argue that Caramazza and Miozzo have not accounted for important parts of the evidence motivating the lemma/lexeme distinction, such as word frequency effects in homophone production, the strict ordering of gender and phoneme access in LRP data, and the chronometric and speech error evidence for the production of complex morphology.

The WEAVER model of word-form encoding in speech production.

Lexical access in speaking consists of two major steps: lemma retrieval and word-form encoding. In Roelofs (Roelofs, A. 1992a. Cognition 42. 107-142; Roelofs. A. 1993. Cognition 47, 59-87.), I described a model of lemma retrieval. The present paper extends this work by presenting a comprehensive model of the second access step, word-form encoding. The model is called WEAVER (Word-form Encoding by Activation and VERification). Unlike other models of word-form generation, WEAVER is able to provide accounts of response time data, particularly from the picture-word interference paradigm and the implicit priming paradigm. Its key features are (1) retrieval by spreading activation, (2) verification of activated information by a production rule, (3) a rightward incremental construction of phonological representations using a principle of active syllabification, syllables are constructed on the fly rather than stored with lexical items, (4) active competitive selection of syllabic motor programs using a mathematical formalism that generates response times and (5) the association of phonological speech errors with the selection of syllabic motor programs due to the failure of verification.

Orthographic effects on phoneme monitoring.

A widely used task in the research on spoken word recognition is phoneme monitoring, in which subjects have to detect phonemes in spoken words. It is generally assumed that this task is performed using phonetic or phonological representations of words only. To test whether an orthographic representation of the words is employed as well, an experiment was conducted in which Dutch subjects monitored for phonemes with either a primary or secondary spelling in phonologically matched spoken words and nonwords. Phoneme monitoring times were slower when the phoneme had a secondary spelling than when it had a primary spelling. The effect was greater after than before the uniqueness point of the word, and monitoring times were faster for words than for nonwords. These findings indicate that an orthographic representation of words is engaged in phoneme monitoring.

Testing a non-decompositional theory of lemma retrieval in speaking: retrieval of verbs.

Theories of lexical access in speaking differ in whether they assume that words are accessed in a conceptually decomposed or non-decomposed way. In this paper, two experiments are reported that test the non-decompositional theory and computer model proposed by Roelofs (1992a). Subjects had to name pictured actions using verbs and ignore distractor verbs superimposed on the pictures. According to the theory, semantic inhibition should be obtained from distractor cohyponym verbs that are the names of other pictures in the experiment. By contrast, semantic facilitation should be obtained from hyponyms of the target verbs. Both predictions were empirically confirmed, both qualitatively and quantitatively. These findings support the proposed non-decompositional theory and computer model. Furthermore, they refute a recent attempt to deal with a class of retrieval problems within the decompositional framework. Bierwisch and Schreuder (1992) propose to solve the hyperonym problem (Levelt, 1989) by an inhibitory channel in the mental lexicon between a word and its hyperonyms. This predicts semantic inhibition by hyponyms, instead of the observed facilitation.

A spreading-activation theory of lemma retrieval in speaking.

This paper presents a spreading-activation theory of conceptually driven lemma retrieval--the first stage of lexical access in speaking, where lexical items specified with respect to meaning and syntactic properties are activated and selected. The mental lexicon is conceived of as a network consisting of concept, lemma, and word-form nodes and labelled links, with each lexical concept represented as an independent node. A lemma is retrieved by enhancing the activation level of the node representing the to-be-verbalized concept. This activation then spreads towards the lemma level, and the highest activated lemma node is selected. The theory resolves questions such as the hypernym problem (Levelt, 1989). Furthermore, a computer model that implements the theory is shown to be able to account for many basic findings on the time course of object naming, object categorization, and word categorization in the picture-word interference paradigm. In addition, non-trivial predictions regarding the time course of semantic facilitation for hypernyms, hyponyms, and cohyponyms are experimentally tested, and shown to be valid.