Physiological and behavioral contagion/buffering effects of chronic unpredictable stress in a socially enriched environment: A preliminary study.

Rodents are sensitive to the emotional state of conspecifics. While the presence of affiliative social partners mitigates the physiological response to stressors (buffering), the partners of stressed individuals show behavioral and endocrine changes indicating that stress parameters can be transmitted across the group members (contagion). In this study, we investigated the social contagion/buffering phenomena in behavior and neuroendocrine mechanisms after exposure to chronic stress, in groups of rats living in the PhenoWorld (PhW). Three groups were tested (8 stressed rats, 8 unstressed rats, and a mixed group with 4 and 4) and these were analyzed under 4 conditions: stressed (pure stress group, n = 8), unstressed (naive control group, n = 8), stressed from mixed group (stressed companion group, n = 8), unstressed from mixed group (unstressed companion group, n = 8. While naive control animals remained undisturbed, pure stress group animals were all exposed to stress. Half of the animals under the mixed-treatment condition were exposed to stress (stressed companion group) and cohabitated with their unstressed partners (unstressed companion group). We confirmed the well-established chronic unpredictable stress (CUS) effects in physiological, behavioral, and neuroendocrine endpoints; body weight gain, open arm entries and time in EPM, and oxytocin receptor expression levels in the amygdala decreased by stress exposure, whereas adrenal weight was increased by stress. Furthermore, we found that playing, rearing and solitary resting behaviors decreased, whereas huddling behavior increased by CUS. In addition, we detected significant increases (stress-buffering) in body weight gain and huddling behaviors between pure stress and stress companion animals, and significant stress contagion effects in emotional behavior and oxytocin receptor expression levels between naive control and control companion groups. Hence, we demonstrate buffering and contagion effects were evident in physiological parameters, emotional behaviors, and social home-cage behaviors of rats and we suggest a possible mediation of these effects by oxytocin neurotransmission. In conclusion, the results herein suggest that the stress status of animals living in the same housing environment influences the behavior of the group.

Shaping social behavior in an enriched environment.

Access to vital needs shapes social orders. In rats, social systems tend to maintain a certain stability, but alterations in the physical environment can change inter-individual relations, which consequently can alter social orders. Principles governing social systems are, however, difficult to study and most analyses have been restricted to dyads of animals over short periods of time, hardly capturing the complexity and temporal dynamics of social interactions. Herein, we studied social interactions in a colony of six rats living in a customized enriched environment (PhenoWorld, PhW), under variable conditions of access/availability to limited resources. Reductions in food accessibility and availability resulted in a marked heterogeneity in sniffing, chasing and fighting/struggling behaviors, and, in the latter condition, an overall increase of these displays. The introduction of the possibility of interaction with a female rat also increased the amount of sniffing and fighting/struggling in a homogeneous manner. Results also showed that individual food retrieval success had no association with fighting/struggling when food pellets are delivered to the animals. However, there was a statistically significant correlation between fighting/struggling and impulsivity as measured by the amount of premature responses in the Variable-to-Signal-Test outside of the PhW providing external validation to our measures. To sum up, through continuous monitoring of a group of rats in the PhW, we demonstrated how variations in access to reinforcers modulate social behavior.

New Horizons for Phenotyping Behavior in Rodents: The Example of Depressive-Like Behavior.

The evolution of the field of behavioral neuroscience is significantly dependent on innovative disruption triggered by our ability to model and phenotype animal models of neuropsychiatric disorders. The ability to adequately elicit and measure behavioral parameters are the fundaments on which the behavioral neuroscience community establishes the pathophysiological mechanisms of neuropsychiatric disorders as well as contributes to the development of treatment strategies for those conditions. Herein, we review how mood disorders, in particular depression, are currently modeled in rodents, focusing on the limitations of these models and particularly on the analyses of the data obtained with different behavioral tests. Finally, we propose the use of new paradigms to study behavior using multidimensional strategies that better encompasses the complexity of psychiatric conditions, namely depression; these paradigms provide holistic phenotyping that is applicable to other conditions, thus promoting the emergence of novel findings that will leverage this field.

Reliability of a Novel Hematological Malignancy Specific Patient-Reported Outcome Measure: HM-PRO.

BACKGROUND: Patients' experience of symptoms often goes undetected during consultation in an outpatient clinic, and the use of a patient-reported outcome measure (PRO) in such a setting could be useful to aid treatment decision-making. A new PRO measure, the HM-PRO (Hematological Malignancy Specific Patient-Reported Outcome Measure) has been recently developed to evaluate hematological malignancy (HM) patients' health-related quality of life (HRQoL) and their symptom experience in daily clinical practice as well as in research. The objectives of the study were to assess: the internal consistency of the scores for Part A (impact) and its four domains (physical behavior; social well-being; emotional behavior; and eating and drinking habits) and Part B (signs and symptoms); and the test-retest reliability of the individual items of the newly developed hematological malignancy specific composite measure, the HM-PRO. METHODS: This was a prospective longitudinal observational study where 150 patients with different HMs and different stage of disease (male n = 98 (65.3%); mean age 64.9 ± 14.4 years, range 17.9-89.2 years; mean time since diagnosis 3.7 ± 4.9 years, range 0.04-25.8 years) completed the HM-PRO at baseline (assessment 1 at t1) and after 7 days (assessment 2 at t2). Data analysis was performed using IBMSPSS 23 statistical software. RESULTS: The Cronbach's alpha estimates of the HM-PRO for both assessment points (t1 and t2) were above 0.9 for Part A, and above 0.8 for Part B, showing strong stability of the measurement. The level of agreement for the reproducibility between the two assessments, using intra-class correlation coefficients (ICC), was very strong with Part A: ICC = 0.93 (95% CI = 0.90-0.95), and Part B: ICC = 0.91 (0.88-0.93). The ICC for the four domains of Part A ranged from 0.85-0.91. The ICC was greater than 0.8 for overall score of Part A and Part B for all the 10 diagnoses, confirming strong reliability. CONCLUSION: This study clearly indicates that the HM-PRO possesses strong test-retest reliability for both Part A and Part B. The Cronbach's alpha confirmed acceptable internal consistency. The extensive reliability testing described in this study supports the generic nature of the HM-PRO for use in hematological malignancies in both routine clinical practice, to aid treatment decisions, as well as in research.

Hematological Malignancy Specific Patient-Reported Outcome Measure (HM-PRO): Construct Validity Study.

BACKGROUND: Validity is the ability of an instrument to measure what it claims to measure. It means the degree to which the empirical evidence supports the trustworthiness of interpretations based on the calculated scores. The hematological malignancy (HM) specific patient reported outcome measure (HM-PRO), is a newly developed instrument for use in daily clinical practice as well as in research. This study, provides the evidence for construct validity of the HM-PRO, specifically focusing on the convergent and divergent validity compared to the other established instruments used in hematology. METHODS: This validation study adopted a prospective cross-sectional design where a heterogeneous group of patients diagnosed with different HMs and different disease state were recruited. A total of 905 patients were recruited from seven secondary care hospitals in the UK and online through five patient organizations. Patients were asked to complete the HM-PRO and other cancer specific PRO's, FACT-G and EORTC QLQ C-30. Data analysis was performed using IBM SPSS 23 statistical software. RESULTS: A total of 486 males (53.7%) and 419 females (46.3%), with a mean age of 64.3 (± 12.4) years and mean time since diagnosis of 4.6 ( ± 5.2) were recruited. The total score of Part A of the HM-PRO highly correlated with the five functional scales of the EORTC QLQ-C30 (Physical = -0.71, Role = -0.72, Emotional = -0.64, Cognitive = -0.58, Social = -0.74-p < 0.001). With respect to correlation with FACT-G, the total score of Part A of the HM-PRO highly correlated with Physical (-0.74), Emotional (-0.57), Functional (-0.66) domains and overall score of FACT-G (-0.74). Similarly, the total score of Part B of the HM-PRO highly correlated with three symptoms scales of EORTC QLQ-C30 (Fatigue scale = -0.74, Nausea and Vomiting = -0.52, Pain = -0.59-p < 0.001) and individual symptom items (Dyspnea = 0.51, Insomnia= 0.43, Appetite loss = 0.54-p < 0.001). CONCLUSION: The construct validity evidence presented in this research is a testimony to the HM-PRO's ability to measure HRQoL issues which it intends to measure. This is of utmost importance when a PRO is used in routine clinical practice so that the interpretation of the scores or response to an individual item is understood by the clinicians/nurses as intended by the patients.

COVID-19 en Latinoamérica: una revisión sistemática de la literatura y análisis bibliométrico / COVID-19 in Latin America: a systematic review and bibliometric analysis

RESUMEN Objetivo Describir y analizar la actividad científica sobre la COVID-19 en Latinoamérica. Materiales y Métodos Mediante una revisión sistemática de la literatura en PubMed, LILACS y los repositorios preimpresos BioRxiv y medRxiv, se recuperaron todos los documentos disponibles sobre la COVID-19 en Latinoamérica desde el primero de enero hasta el 24 de abril de 2020, para su análisis bibliométrico. Resultados Un total de 29 publicaciones fueron incluidas en el análisis. El país con más producción científica fue Brasil (10/29; 34,4%), seguido de Colombia (6/29; 20,6%) y México (6/29; 20,6%). La universidad con más artículos fue la Universidad Tecnológica de Pereira, Colombia (5/29; 17,24%). El 41,3% de las publicaciones fueron documentos preimpresos. La mayoría de los estudios excluidos fueron comentarios editoriales u opiniones de expertos. Tres de cada cuatro investigaciones tenían un enfoque epidemiológico (21/29; 72,4%); limitados estudios sobre el diagnóstico (5/29; 17,2%), la fisiopatogenia (2/29; 2,8%) y los aspectos terapéuticos (1/29; 3,4%) fueron encontrados. Conclusión Pese al crecimiento exponencial de publicaciones en el mundo, existe una limitada cantidad de información sobre el comportamiento de esta infección en Latinoamérica. Se requiere la publicación de estudios con alta calidad metodológica, que aporten conocimiento sobre el impacto de la pandemia en la región.(AU)

ABSTRACT Objective Describe and analyze scientific activity on COVID-19 in Latin America. Materials and Methods Through a systematic review of the literature in PubMed, LILACS, and the preprinted repositories BioRxiv and medRxiv, all available documents on COVID-19 in Latin America from January 1 to April 24, 2020, were retrieved for review and bibliometric analysis. Results A total of 29 publications were included in the analysis. The country with the most scientific production was Brazil (10/29; 34,4%) followed by Colombia (6/29; 20,6%) and Mexico (6/29; 20,6%). The university with the most articles was the Technological University of Pereira, Colombia (5/29; 17,2%). 41,3% of the publications were preprinted documents. Most of the excluded studies were editorial comments or expert opinions. Three out of four investigations had an epidemiological focus (21/29; 72,4%); Limited studies on diagnosis (5/29; 17,24%), pathophysiology (2/29, 2,8%) and therapeutic Conclusion Despite the exponential growth of publications in the world, there is a limited amount of information on the behavior of this infection in Latin America. The publication of studies with high methodological quality is required, which provide knowledge of the impact of the pandemic in the region.(AU)

[COVID-19 in Latin America: a systematic review and bibliometric analysis]. / COVID-19 en Latinoamérica: una revisión sistemática de la literatura y análisis bibliométrico.

OBJECTIVE: Describe and analyze scientific activity on COVID-19 in Latin America. MATERIALS AND METHODS: Through a systematic review of the literature in PubMed, LILACS, and the preprinted repositories BioRxiv and medRxiv, all available documents on COVID-19 in Latin America from January 1 to April 24, 2020, were retrieved for review and bibliometric analysis. RESULTS: A total of 29 publications were included in the analysis. The country with the most scientific production was Brazil (10/29; 34,4%) followed by Colombia (6/29; 20,6%) and Mexico (6/29; 20,6%). The university with the most articles was the Technological University of Pereira, Colombia (5/29; 17,2%). 41,3% of the publications were preprinted documents. Most of the excluded studies were editorial comments or expert opinions. Three out of four investigations had an epidemiological focus (21/29; 72,4%); Limited studies on diagnosis (5/29; 17,24%), pathophysiology (2/29, 2,8%) and therapeutic. CONCLUSION: Despite the exponential growth of publications in the world, there is a limited amount of information on the behavior of this infection in Latin America. The publication of studies with high methodological quality is required, which provide knowledge of the impact of the pandemic in the region.

Preclinical toxicology and safety pharmacology of the first-in-class GADD45ß/MKK7 inhibitor and clinical candidate, DTP3.

Aberrant NF-κB activity drives oncogenesis and cell survival in multiple myeloma (MM) and many other cancers. However, despite an aggressive effort by the pharmaceutical industry over the past 30 years, no specific IκBα kinase (IKK)ß/NF-κB inhibitor has been clinically approved, due to the multiple dose-limiting toxicities of conventional NF-κB-targeting drugs. To overcome this barrier to therapeutic NF-κB inhibition, we developed the first-in-class growth arrest and DNA-damage-inducible (GADD45)ß/mitogen-activated protein kinase kinase (MKK)7 inhibitor, DTP3, which targets an essential, cancer-selective cell-survival module downstream of the NF-κB pathway. As a result, DTP3 specifically kills MM cells, ex vivo and in vivo, ablating MM xenografts in mice, with no apparent adverse effects, nor evident toxicity to healthy cells. Here, we report the results from the preclinical regulatory pharmacodynamic (PD), safety pharmacology, pharmacokinetic (PK), and toxicology programmes of DTP3, leading to the approval for clinical trials in oncology. These results demonstrate that DTP3 combines on-target-selective pharmacology, therapeutic anticancer efficacy, favourable drug-like properties, long plasma half-life and good bioavailability, with no target-organs of toxicity and no adverse effects preclusive of its clinical development in oncology, upon daily repeat-dose administration in both rodent and non-rodent species. Our study underscores the clinical potential of DTP3 as a conceptually novel candidate therapeutic selectively blocking NF-κB survival signalling in MM and potentially other NF-κB-driven cancers.

"The challenge of managing insecurities": Parents' experiences with the care for their child with congenital diaphragmatic hernia.

PURPOSE: Last decennia remarkable advances have been made in decreasing the mortality rate of children with congenital diaphragmatic hernia (CDH), resulting in a relatively growing patient group with long-term complications and complex care needs. These consequences have a huge impact on the quality of life of both children and their families. To provide practical recommendations for improving the quality of care for this patient group, the present study sought to obtain insights into the experiences and needs of parents with a child with CDH. DESIGN AND METHODS: A qualitative study was conducted on the experiences and needs of parents with a child with CDH living in the Netherlands. Data was obtained by means of a discourse analyses of 17 weblogs written by parents and three online focus groups with 8-12 parents per group (n = 29). The data was analysed thematically and structured by using the model of Lawoko (2007) on parental satisfaction with care. RESULTS: Although parents were generally satisfied with the delivered care, they frequently encountered challenges in managing insecurities throughout the care process. Besides the unpredictable disease progress, insecurities were exacerbated by: (a) limited specialized knowledge of long-term consequences, (b) logistical problems, and (c) nontransparent communication. Providing security through, for instance, a clear care plan and by engaging parents in the decision-making process helped them feel more in control. PRACTICE IMPLICATIONS: This study showed that parents' main challenge was to manage insecurities. Creating securities by providing a care plan and involving parents in the decision-making process helped parents to feel more in control. To improve quality of care for children with CDH, future measures should, therefore, focus on reducing insecurities by managing expectations, improving transparency and stimulating engagement.

PD-L1 expression in medulloblastoma: an evaluation by subgroup.

BACKGROUND: This study evaluated the expression of PD-L1 and markers of immune mediated resistance in human medulloblastoma (MB), the most common malignant pediatric brain tumor. RESULTS: Overall levels of PD-L1 in human MB were low; however, some cases demonstrated robust focal expression associated with increased immune infiltrates. The case with highest PD-L1 expression was a sonic hedgehog (SHH) MB. In cell lines, SHH MB, which are low-MYC expressing, demonstrated both constitutive and inducible expression of PD-L1 while those in Group 3/4 that expressed high levels of MYC had only inducible expression. In vitro, IFN-γ robustly stimulated the expression of PD-L1 in all cell lines while radiation induced variable expression. Forced high MYC expression did not significantly alter PD-L1. METHODS: Human MB tumor samples were evaluated for expression of PD-L1 and immune cell markers in relation to molecular subgroup assignment. PD-L1 expression was functionally analyzed under conditions of interferon gamma (IFN-γ), radiation, and MYC overexpression. CONCLUSIONS: MB expresses low levels of PD-L1 facilitating immune escape. Importantly, TH1 cytokine stimulation appears to be the most potent inducer of PD-L1 expression in vitro suggesting that an inflamed tumor microenvironment is necessary for PD-1 pathway activation in this tumor.

PhenoWorld: addressing animal welfare in a new paradigm to house and assess rat behaviour.

The use of animals is essential in biomedical research. The laboratory environment where the animals are housed has a major impact on them throughout their lives and influences the outcome of animal experiments. Therefore, there has been an increased effort in the refinement of laboratory housing conditions which is explicitly reflected in international regulations and recommendations. Since housing conditions affect behaviour and brain function as well as well-being, the validation of an animal model or paradigm to study the brain and central nervous system disorders is not complete without an evaluation of its implication on animal welfare. Here we discuss several aspects of animal welfare, comparing groups of six rats living in the PhenoWorld (PhW), a recently developed and validated paradigm for studying rodent behaviour, with standard-housed animals (in cages of six rats or pair-housed). In this study we present new data on home-cage behaviour showing that PhW animals have a clearer circadian pattern of sleep and social interaction. We conclude that, by promoting good basic health and functioning, together with the performance of natural behaviours, and maintaining animals' control over some of their environment but still keeping some physical and social challenges, the PhW stimulates positive affective states and higher motivation in rats, which might contribute to an increased welfare for animals living in the PhW.

Bridging the Gap between Evidence and Practice for Adults with Medically Refractory Temporal Lobe Epilepsy: Is a Change in Funding Policy Needed to Stimulate a Shift in Practice?

Objective. Surgery for medically refractory epilepsy (MRE) in adults has been shown to be effective but underutilized. Comprehensive health economic evaluations of surgery compared with continued medical management are limited. Policy changes may be necessary to influence practice shift. Methods. A critical review of the literature on health economic analyses for adults with MRE was conducted. The MEDLINE, EMBASE, CENTRAL, CRD, and EconLit databases were searched using relevant subject headings and keywords pertaining to adults, epilepsy, and health economic evaluations. The screening was conducted independently and in duplicate. Results. Four studies were identified (1 Canadian, 2 American, and 1 French). Two were cost-utility analyses and 2 were cost-effectiveness evaluations. Only one was conducted after the effectiveness of surgery was established through a randomized trial. All suggested surgery to be favorable in the medium to long term (7-8 years and beyond). The reduction of medication use was the major cost-saving parameter in favor of surgery. Conclusions. Although updated evaluations that are more generalizable across settings are necessary, surgery appears to be a favorable option from a health economic perspective. Given the limited success of knowledge translation endeavours, funder-level policy changes such as quality-based purchasing may be necessary to induce a shift in practice.

Online formative tests linked to microlectures improving academic achievement.

BACKGROUND: Online formative tests (OFTs) are powerful tools to direct student learning behavior, especially when enriched with specific feedback. AIM: In the present study, we have investigated the effect of OFTs enriched with hyperlinks to microlectures on examination scores. METHODS: OFTs, available one week preceding each midterm and the final exams, could be used voluntarily. The use of OFTs was related to scores on midterm and final exams using ANOVA, with prior academic achievement as a covariate. RESULTS: On average, 74% of all students used the online formative tests (OFT+) while preparing for the summative midterm exam. OFT+ students obtained significantly higher grades compared to OFT-students, both without and with correction for previous academic achievement. Two out of three final exam scores did not significantly improve. CONCLUSION: Students using online formative tests linked to microlectures receive higher grades especially in highly aligned summative tests.

Thermodynamic Analysis of the Selectivity Enhancement Obtained by Using Smart Hydrogels That Are Zwitterionic When Detecting Glucose With Boronic Acid Moieties.

Because the boronic acid moiety reversibly binds to sugar molecules and has low cytotoxicity, boronic acid-containing hydrogels are being used in a variety of implantable glucose sensors under development, including sensors based on optical, fluorescence, and swelling pressure measurements. However, some method of glucose selectivity enhancement is often necessary, because isolated boronic acid molecules have a binding constant with glucose that is some forty times smaller than their binding constant with fructose, the second most abundant sugar in the human body. In many cases, glucose selectivity enhancement is obtained by incorporating pendant tertiary amines into the hydrogel network, thereby giving rise to a hydrogel that is zwitterionic at physiological pH. However, the mechanism by which incorporation of tertiary amines confers selectivity enhancement is poorly understood. In order to clarify this mechanism, we use the osmotic deswelling technique to compare the thermodynamic interactions of glucose and fructose with a zwitterionic smart hydrogel containing boronic acid moieties. We also investigate the change in the structure of the hydrogel that occurs when it binds to glucose or to fructose using the technique of small angle neutron scattering.

Development, Fabrication, and Characterization of Hydrogel Based Piezoresistive Pressure Sensors with Perforated Diaphragms.

Hydrogels have been demonstrated to swell in response to a number of external stimuli including pH, CO(2), glucose, and ionic strength making them useful for detection of metabolic analytes. To measure hydrogel swelling pressure, we have fabricated and tested novel perforated diaphragm piezoresistive pressure sensor arrays that couple the pressure sensing diaphragm with a perforated semi-permeable membrane. The 2×2 arrays measure approximately 3 × 5 mm(2) and consist of four square sensing diaphragms with widths of 1.0, 1.25, and 1.5 mm used to measure full scale pressures of 50, 25, and 5 kPa, respectively. An optimized geometry of micro pores was etched in silicon diaphragm to allow analyte diffusion into the sensor cavity where the hydrogel material is located. The 14-step front side wafer process was carried out by a commercial foundry service (MSF, Frankfurt (Oder), Germany) and diaphragm pores were created using combination of potassium hydroxide (KOH) etching and deep reactive ion etching (DRIE).Sensor characterization was performed (without the use of hydrogels) using a custom bulge testing apparatus that simultaneously measured deflection, pressure, and electrical output. Test results are used to quantify the sensor sensitivity and demonstrate proof-of-concept. Simulations showed that the sensitivity was slightly improved for the perforated diaphragm designs while empirical electrical characterization showed that the perforated diaphragm sensors were slightly less sensitive than solid diaphragm sensors. This discrepancy is believed to be due to the influence of compressive stress found within passivation layers and poor etching uniformity. The new perforated diaphragm sensors were fully functional with sensitivities ranging from 23 to 252 µV/V-kPa (FSO= 5 to 80mV), and show a higher nonlinearity at elevated pressures than identical sensors with solid diaphragms. Sensors (1.5×1.5 mm(2)) with perforated diaphragms (pores=40 µm) have a nonlinearity of approximately 10% while for the identical solid diaphragm sensor it was roughly 3 % over the entire 200 kPa range. This is the first time piezoresistive pressure sensors with integrated diffusion pores for detection of hydrogel swelling pressure have been fabricated and tested.

Osmotic Swelling Pressure Response of Smart Hydrogels Suitable for Chronically-Implantable Glucose Sensors.

In the last few years, a new type of glucose-sensitive hydrogel (GSH) has been developed that shrinks with increasing glucose concentration due to the formation of reversible crosslinks The first osmotic swelling pressure results measured for any member of this new class of GSH are reported, so that their suitability for use in sensors combining pressure transducers and smart gels can be evaluated. Comparison is also made with results obtained for an older type of GSH that expands with increasing glucose concentration due to an increase in the concentration of counterions within the gel. The newer type of GSH exhibits both faster kinetics and weaker fructose interference, and therefore is more suitable for in vivo glucose sensing.

A systematic, holistic and integrative process of self-control for voicing with optimal coping effects in teachers. 1. A process of awareness--an expert's opinion.

A learning strategy is presented for eustress-euvoicing, which prevails over distress-disvoicing. It is based on the understanding of the mechanisms of stress-voicing, conceived as a dynamic circular process of interacting entities, i.e. stressors/signals-arousal/activation-emotion-coping-effects (SAECE), which is the rationale for a multidisciplinary approach in coaching professional voice users. A systematic, holistic and integrative process of self-control (SHIPS) is directed by functional analysis and consists of awareness and change. Emotion, a mixture of appraisal, affect and movement, is the pivot in SHIPS. SHIPS with (student) teachers aims at the competence of voicing (V) in an optimal (O) way of coping (C), which means vocal communication that is effective (E) to meet a balance in physical, interpersonal and existential wellness when responding to demands and challenges in the individual teacher's (T) field of communication (VOCE-T). The process of awareness intends to understand the course of multiple interactions in SAECE that condition eustressors and distressors related to (non)-integrated coping. The (student) teacher and coach are conscious and active participants in the process of awareness that is dynamic and evolving and aims at the preparedness to change non-desirable habits and skill modes into VOCE-T.

A systematic, holistic and integrative process of self-control for voicing with optimal coping effects in teachers. 2. A process of change--an expert's opinion.

A learning strategy is presented for eustress-euvoicing, which prevails over distress-disvoicing. It is based on the understanding of the mechanisms of stress-voicing, conceived as a dynamic circular process of interacting entities, i.e. stressors/signals-arousal/activation-emotion-coping-effects (SAECE), which is the rationale for a multidisciplinary approach in coaching professional voice users. A systematic, holistic and integrative process of self-control (SHIPS) is directed by functional analysis and consists of awareness and change. Emotion, a mixture of appraisal, affect and movement, is the pivot in SHIPS. SHIPS with (student) teachers aims at the competence of voicing (V) in an optimal (O) way of coping (C), which means vocal communication that is effective (E) to meet a balance in physical, interpersonal and existential wellness when responding to demands and challenges in the individual teacher's (T) field of communication (VOCE-T). The process of change intends to influence the course of multiple interactions in SAECE. SHIPS (de)conditions distressors and eutressors related to (non)-integrated coping. The (student) teacher and coach are conscious and active participants in the process of change that aims at (un)learning of attitudes and skills for coping by VOCE-T.

Hydrogel based sensor arrays (2 × 2) with perforated piezoresistive diaphragms for metabolic monitoring (in vitro).

This report details the first experimental results from novel hydrogel sensor array (2 × 2) which incorporates analyte diffusion pores into a piezoresistive diaphragm for the detection of hydrogel swelling pressures and hence chemical concentrations. The sensor assembly was comprised of three components, the active four sensors, HPMA/DMA/TEGDMA (hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMA) and crosslinker tetra-ethyleneglycol dimethacrylate (TEGDMA)) hydrogel, and backing plate. Each of the individual sensors of the array can be used with various hydrogels used to measure the presence of a number of stimuli including pH, ionic strength, and glucose concentrations. Ideally, in the future, these sensors will be used for continuous metabolic monitoring applications and implanted subcutaneously. In this paper and to properly characterize the sensor assembly, hydrogels sensitive to changes ionic strength were synthesized using hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMA) and crosslinker tetra-ethyleneglycol dimethacrylate (TEGDMA) and inserted into the sensor assembly. This hydrogel quickly and reversibly swells when placed environments of physiological buffer solutions (PBS) with ionic strengths ranging from 0.025 to 0.15 M, making it ideal for proof-of-concept testing and initial characterization. The assembly was wire bonded to a printed circuit board and coated with 3 ± 0.5 µm of Parylene-C using chemical vapor deposition (CVD) to protect the sensor and electrical connections during ionic strength wet testing. Two versions of sensors were fabricated for comparison, the first incorporated diffusion pores into the diaphragm, and the second used a solid diaphragm with perforated backing plate. This new design (perforated diaphragm) was shown to have slightly higher sensitivity than solid diaphragm sensors with separate diffuse backing plates when coupled with the hydrogel. The sensitivities for the 1 mm × 1 mm, 1.25 mm × 1.25 mm, 1.5 mm × 1.5 mm perforated diaphragm sensors were 53.3 ± 6.5, 171.7 ± 8.8, and 271.47 ± 27.53 mV/V-M, respectively. These results show that perforations in the diaphragm can be used not only to allow the diffusion of analyte into the cavity but to increase mechanical stress in the piezoresistive diaphragm, thereby increasing sensor output signal. The time constants for swelling (τswelling) and contracting (τcontracting) were calculated by fitting the sensor output half cycles to an exponential growth function. We found that the sensors' response was initially retarded during the preliminary hydrogel conditioning period then improved after 3-5 cycles with values of approximately 9 and 7 min for τswelling and τcontracting. For all sensors tested τswelling > τcontracting. This may be due to the increased loading on the hydrogel from the diaphragm during the swelling process. During contraction the diaphragm aids the hydrogel by reversibly applying mechanical pressure and therefore reducing τcontracting. Long term stability testing showed the sensors remained functional for upwards of 2 weeks in the test phosphate buffer solution (PBS).