Ultra-simple wearable local sweat volume monitoring patch based on swellable hydrogels.

Quantifiably monitoring sweat rate and volume is important to assess the stress level of individuals and/or prevent dehydration, but despite intense research, a convenient, continuous, and low-cost method to monitor sweat rate and total sweat volume loss remains an un-met need. We present here an ultra-simple wearable sensor capable of measuring sweat rate and volume accurately. The device continuously monitors sweat rate by wicking the produced sweat into hydrogels that measurably swell in their physical geometry. The device has been designed as a simple to fabricate, low-cost, disposable patch. This patch exhibits stable and predictable operation over the maximum variable chemistry expected for sweat (pH 4-9 and salinity 0-100 mM NaCl). Preliminary in vivo testing of the patch has been achieved during aerobic exercise, and the sweat rates measured via the patch accurately follow actual sweat rates.

[Side Effects of Occupational Group Therapy]. / Nebenwirkungen von Ergotherapiegruppen.

Background: Occupational therapy is an important co-therapy in psychiatric therapy. It is a common belief that no risks are associated with occupational therapy. Negative effects caused by group therapy, especially occupational therapy, have not been in the focus of research yet. In this study we want to illustrate possible types and intensities of group side effects through occupational therapy. Patients and Methods: Patients of an inpatient rehabilitation facility filled out the Adverse Treatment Reaction Group Checklist. The checklist contains 47 items divided in six dimensions: group size, content, group participants, group outcome and global. The self-rating used a 5-point likert scale (0 = not at all; 4 = very much, extremely stressful) and gives information about types and intensities of the side effects. Results: 88.9 % of 45 patients reported negative effects of occupational group therapy. 28.9 % of the patients rated the side effect as at least severe. Discussion: Occupational therapy is associated with side effects as every other group therapy. Possible side effects caused by group therapy should be considered while planning and implementing occupational therapy.

A Modular Repository-based Infrastructure for Simulation Model Storage and Execution Support in the Context of In Silico Oncology and In Silico Medicine.

The plethora of available disease prediction models and the ongoing process of their application into clinical practice - following their clinical validation - have created new needs regarding their efficient handling and exploitation. Consolidation of software implementations, descriptive information, and supportive tools in a single place, offering persistent storage as well as proper management of execution results, is a priority, especially with respect to the needs of large healthcare providers. At the same time, modelers should be able to access these storage facilities under special rights, in order to upgrade and maintain their work. In addition, the end users should be provided with all the necessary interfaces for model execution and effortless result retrieval. We therefore propose a software infrastructure, based on a tool, model and data repository that handles the storage of models and pertinent execution-related data, along with functionalities for execution management, communication with third-party applications, user-friendly interfaces to access and use the infrastructure with minimal effort and basic security features.

Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data.

BACKGROUND: Antiangiogenic agents have been recently added to the oncological armamentarium with bevacizumab probably being the most popular representative in current clinical practice. The elucidation of the mode of action of these agents is a prerequisite for personalized prediction of antiangiogenic treatment response and selection of patients who may benefit from this kind of therapy. To this end, having used as a basis a preexisting continuous vascular tumour growth model which addresses the targeted nature of antiangiogenic treatment, we present a paper characterized by the following three features. First, the integration of a two-compartmental bevacizumab specific pharmacokinetic module into the core of the aforementioned preexisting model. Second, its mathematical modification in order to reproduce the asymptotic behaviour of tumour volume in the theoretical case of a total destruction of tumour neovasculature. Third, the exploitation of a range of published animal datasets pertaining to antitumour efficacy of bevacizumab on various tumour types (breast, lung, head and neck, colon). RESULTS: Results for both the unperturbed growth and the treatment module reveal qualitative similarities with experimental observations establishing the biologically acceptable behaviour of the model. The dynamics of the untreated tumour has been studied via a parameter analysis, revealing the role of each relevant input parameter to tumour evolution. The combined effect of endogenous proangiogenic and antiangiogenic factors on the angiogenic potential of a tumour is also studied, in order to capture the dynamics of molecular competition between the two key-players of tumoural angiogenesis. The adopted methodology also allows accounting for the newly recognized direct antitumour effect of the specific agent. CONCLUSIONS: Interesting observations have been made, suggesting a potential size-dependent tumour response to different treatment modalities and determining the relative timing of cytotoxic versus antiangiogenic agents administration. Insight into the comparative effectiveness of different antiangiogenic treatment strategies is revealed. The results of a series of in vivo experiments in mice bearing diverse types of tumours (breast, lung, head and neck, colon) and treated with bevacizumab are successfully reproduced, supporting thus the validity of the underlying model.

Self-reported workplace perception as indicators of work anxieties.

BACKGROUND: Work anxiety is a potentially disabling mental health problem, which can cause (long-term) sickness absence. In many cases patients do not openly report their anxieties and tend to give externalizing explanations of inner problems. Therefore people with work anxiety may perceive their workplace more negatively than those without such anxiety. AIMS: To investigate the relation between subjective work description and work anxiety. METHODS: Work anxiety was investigated with a standardized interview in a sample of employed psychosomatic rehabilitation inpatients suffering from common mental disorders. We assessed their subjective perception and evaluation of workplace conditions with the 'Short Questionnaire for Job Analysis' (KFZA) and compared their results with those from a sample of employees in the general population. RESULTS: There were 148 inpatient participants and 8015 general population controls. Patients with work anxiety described their workplace significantly more negatively than patients without work anxiety and employees in the general population, with no differences in workplace descriptions between psychosomatic patients without work anxiety and the general population sample. The type of complaint about work conditions was related to the specific type of work anxiety. CONCLUSIONS: Reports about workplace burdens can be indicative of work anxiety and should prompt further in-depth assessments. The content of complaints about work conditions may point to the type of underlying work anxiety.

The effect of temperature elevation on cryopreserved mesenchymal stem cells.

BACKGROUND: Cryopreservation is of particular importance in stem cell research and regenerative medicine as it permits long term stabilisation of biological cells. Cells retain their regenerative capacity after years of storage at cryogenic temperatures. However, elevation of temperature may occur due to variety of reasons, for example in the event of equipment malfunction or during delays in transportation. To date, a limited amount research has been carried out to examine the effects of temperature elevation on stem cell survival during cryopreservation. METHODS: Mesenchymal Stem Cells (MSCs) obtained from 8-12 week Sprague Dawley male rats were cryopreserved according to the standard procedures. Under experimental conditions, cryopreserved specimens were exposed to elevated temperatures ranging from -20 C to 37 C and cellular membrane integrity assessed via trypan-blue exclusion at various time points. RESULTS: An approximating model of multiple regression was fitted to the experimental data and optimisation of model parameters was carried out. This model provides an approximation of cell viability in response to elevated temperature conditions. DISCUSSION: The results demonstrate that elevation of temperature has a dramatic effect, even over short periods of time, on the viability of cryopreserved specimens. The model presented here could be used to predict the damage suffered by a specimen due to exposure to elevated temperature over a defined period of time.

The significance of job-anxiety in a working population.

BACKGROUND: Job-anxiety, as distinguished from trait-anxiety, is associated with long-term sickness absence. The prevalence of job-anxiety within a working population is not known. Identifying individuals who would benefit from intervention might be useful. AIMS: To investigate job-anxiety in employees not undergoing treatment for mental health illness, firstly by assessing the level of job-anxiety and work-related avoidance tendencies in a working sample, and secondly by testing whether job-anxiety is distinguishable from trait-anxiety. METHODS: Cross-sectional survey of a convenience sample obtained through personal contact distribution. Employees from different professional settings completed an anonymous questionnaire and provided information on their employment status. The State-Trait-Anxiety Inventory (STAI-T) was used to measure trait-anxiety and the Job-Anxiety-Scale (JAS) was used to assess job (state) anxiety. RESULTS: There was a 69% response rate (240 responses); 188 responses were available for analysis of whom 62% were women. There were no employees with high trait-anxiety. Ten employees (5%) reported increased job-anxiety and of these nine employees reported high 'tendencies of avoidance and workplace absence'. Avoidance was most often accompanied by the comorbid job-anxieties 'job-related social anxiety', 'fear of changes at work' and 'fears of existence', 'anticipatory' and 'conditioned' job-anxiety and 'panic symptoms'. CONCLUSIONS: In this sample, self-reported job-anxiety appeared as a specific type of anxiety as opposed to trait-anxiety. In the workplace job-anxiety can present as job-avoidance and sickness absence and should be distinguished from trait-anxiety. In practice, employers and occupational health practitioners should be aware of those employees prone to sickness absence.

Naming and categorization in young children: v. manual sign training.

Following pre-training with everyday objects, 8 children aged from 2 to 4 years learned to produce one manual sign (fists placed one above the other, in front of body) to one stimulus and an alternative manual sign (shoulders touched with ipsilateral hands) to the other stimulus, with each of three pairs of different arbitrary wooden shapes (Set 1). The six stimuli then were presented in category match-to-sample tests, which all subjects passed. Three of the children were next trained to produce the manual signs (denoted as fist/shoulder) for an additional six arbitrary stimuli, Set 2. All 3 children went on to pass category match-to-sample tests for Set 2, and for Set 1 and Set 2 combined. In the final experimental phase, 2 of the children were trained, for one of the six stimulus pairs, to produce the vocal tact "zag" to one stimulus and "vek" to the other. Both children showed category transfer of these vocalizations in test trials with each of the remaining five stimulus pairs, and all the stimuli combined in a 12-stimulus array. In line with Horne and Lowe's (1996) naming account, manual sign naming was found to be as effective as vocal naming in establishing arbitrary stimulus categorization, measured in terms of category sorting and transfer of function. The findings also have implications for the training of verbal repertoires in people with learning disabilities.

Specific heat and thermal conductivity in the mixed state of MgB2.

The specific heat C and the electronic and phononic thermal conductivities kappa(e) and kappa(ph) are calculated in the mixed state for magnetic fields H near H(c2), including the effects of supercurrent flow and Andreev scattering. The resulting function C(H) is nearly linear while kappa(e)(H) exhibits an upward curvature near H(c2). The slopes decrease with impurity scattering which improves the agreement with the data on MgB2. The ratio of phonon relaxation times tau(n)/tau(s)=g(omega(0),H) for phonon energy omega(0) is smeared out around omega(0)=2Delta and tends to one for increasing H. This leads to a rapid reduction of kappa(ph)(H) in MgB2 for relatively small fields due to the rapid suppression of the smaller energy gap.

Effect of spin-orbit scattering on the magnetic and superconducting properties of nearly ferromagnetic metals: application to granular Pt.

We calculate the effect of scattering on the static, exchange enhanced, spin susceptibility and show that, in particular, spin-orbit scattering leads to a reduction of the giant moments and spin glass freezing temperature due to dilute magnetic impurities. The harmful spin fluctuation contribution to the intragrain pairing interaction is strongly reduced opening the way for BCS superconductivity. We are thus able to explain the superconducting and magnetic properties recently observed in granular Pt as being due to scattering effects in single small grains.

Naming and categorization in young children: vocal tact training.

In three experiments, 2- to 4-year-old children, following pretraining with everyday objects, were presented with arbitrary stimuli of differing shapes. In Experiment 1A, 9 subjects were trained one common tact response, "zag," to three of these and a second tact, "vek," to another three. In category match-to-sample Test 1, 4 subjects sorted accurately when required only to look at the sample before selecting from five comparisons. The remaining 5 subjects succeeded in Test 2, in which they were required to tact the sample before selecting comparisons. Experiment 1B showed, for 2 of these subjects, that tact training with 12 arbitrary stimuli established two six-member classes that were still intact 6 weeks later. In Experiment 2, 3 new subjects participated in a common tact training procedure that ensured that none of the exemplars from the same class were presented together prior to the test for three-member classes. Two subjects passed category Test 1 and the third passed Test 2. Tests showed subjects' listener behavior in response to hearing /zog/ and /vek/ to be in place. These experiments indicate that common naming is effective in establishing arbitrary stimulus classes and that category match-to-sample testing provides a robust measure of categorization.

Mutations in cye-1, a Caenorhabditis elegans cyclin E homolog, reveal coordination between cell-cycle control and vulval development.

We have identified strong loss-of-function mutations in the C. elegans cyclin E gene, cye-1. Mutations in cye-1 lead to the underproliferation of many postembryonic blast lineages as well as defects in fertility and gut-cell endoreduplication. In addition, cye-1 is required maternally, but not zygotically for embryonic development. Our analysis of vulval development in cye-1 mutants suggests that a timing mechanism may control the onset of vulval cell terminal differentiation: once induced, these cells appear to differentiate after a set amount of time, rather than a specific number of division cycles. cye-1 mutants also show an increase in the percentage of vulval precursor cells (VPCs) that adopt vulval cell fates, indicating that cell-cycle length can play a role in the proper patterning of vulval cells. By analyzing cul-1 mutants, we further demonstrate that vulval cell terminal differentiation can be uncoupled from associated changes in vulval cell division planes.

The synthetic multivulval genes of C. elegans: functional redundancy, Ras-antagonism, and cell fate determination.

Development of the C. elegans vulva requires coordination between a strikingly complex set of molecular regulators and pathways. In particular, the correct specification of vulval cell-fates requires both the activation of RTK/Ras/Map kinase members as well as negative regulation by a set of genes known as the SynMuvs. SynMuvs comprise two functionally redundant sets of genes that appear to antagonize Ras pathway signaling. In this way, SynMuv genes act to limit the number of cells adopting vulval fates. Recently, a number of SynMuv genes have been shown to encode worm homologs of the Rb transcriptional-regulatory complex. These and other results are discussed and we present several models for understanding the role of SynMuv genes in vulval development.

A Caenorhabditis elegans homologue of hunchback is required for late stages of development but not early embryonic patterning.

We have cloned a Caenorhabditis elegans homologue of the Drosophila gap gene hunchback (hb) and have designated it hbl-1 (hunchback-like). hbl-1 encodes a predicted 982-amino-acid protein, containing two putative zinc-finger domains similar to those of Drosophila Hunchback. The gene is transcribed embryonically, but unlike the maternally expressed Drosophila hb, its mRNA is not detected in C. elegans oocytes. A hbl-1::gfp reporter is expressed primarily in ectodermal cells during embryonic and larval development. Double-stranded RNA-interference (RNAi) was used to indicate hbl-1 loss-of-function phenotypes. Progeny of hbl-1(RNAi) hermaphrodites exhibit a range of defects; the most severely affected progeny arrest as partially elongated embryos or as hatching, misshapen L1 larvae. Animals that survive to adulthood exhibit variably dumpy (Dpy), uncoordinated (Unc), and egg-laying defective (Egl) phenotypes, as well as defects in vulval morphology (Pvl). Abnormal organization of hypodermal cells and expression of a hypodermal marker in hbl-1(RNAi) animals suggests that most of the phenotypes observed could be due to improper specification of hypodermal cells. The pattern of hbl-1 expression is similar to that reported for the leech hunchback homologue Lzf-2, suggesting that these proteins may have similar biological functions in diverse species with cellular embryos.

In vivo aggregation of beta-amyloid peptide variants.

Transgenic Caenorhabditis elegans animals have been engineered to express wild-type and single-amino acid variants of a long form of human beta-amyloid peptide (A beta 1-42). These animals express high levels (approximately 300 ng of A beta/mg of total protein) of apparently full-length peptide, as determined by quantitative immunoblot. Expression of wild-type A beta in these animals leads to rapid production of amyloid deposits reactive with Congo red and thioflavin S. This model system has been used to examine the effect of Leu17Pro, Leu17Val, Ala30Pro, Met35Cys, and Met35Leu substitutions on the in vivo production of amyloid deposits. We find that the Leu17Pro and Met35Cys substitutions completely block the formation of thioflavin S-reactive deposits, implicating these as key residues for in vivo amyloid formation. We have also constructed transgenic strains expressing a novel A beta variant, the single-chain dimer. Animals expressing high levels of this variant also fail to produce thioflavin S-reactive deposits.

Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint.

The Rad53 protein kinase of Saccharomyces cerevisiae is required for checkpoints that prevent cell division in cells with damaged or incompletely replicated DNA. The Rad9 protein was phosphorylated in response to DNA damage, and phosphorylated Rad9 interacted with the COOH-terminal forkhead homology-associated (FHA) domain of Rad53. Inactivation of this domain abolished DNA damage-dependent Rad53 phosphorylation, G2/M cell cycle phase arrest, and increase of RNR3 transcription but did not affect replication inhibition-dependent Rad53 phosphorylation. Thus, Rad53 integrates DNA damage signals by coupling with phosphorylated Rad9. The hitherto uncharacterized FHA domain appears to be a modular protein-binding domain.

Mutations in SPK1/RAD53 that specifically abolish checkpoint but not growth-related functions.

SPK1/RAD53/SAD1/MEC2 encodes an essential protein kinase of Saccharomyces cerevisiae and is required for the execution of checkpoint arrest at multiple stages of the cell cycle. We have isolated two mutant alleles of SPK1 (spk1K227A and spk1-1A208P) that are defective for checkpoint-arrest functions but retain wild-type levels of SPK1-associated growth activity. Both mutations occur within conserved regions of the kinase domain of SPK1 resulting in a substantial reduction in the catalytic activity of Spk1. Thus, while minimal levels of Spk1 kinase activity are capable of supporting normal rates of growth, higher levels are required for checkpoint functions. In addition, using deletional analysis we have identified a region within the N-terminus of Spk1 outside of the conserved kinase domain that is required for checkpoint functions. Interestingly, this region may be important in the regulation of Spk1 kinase activity.