Perspectives on speech and language pathology practices and service provision in adult critical care settings in Ireland and international settings: A cross-sectional survey.

PURPOSE: Patients admitted to critical care (CC) are at risk of impaired swallowing and communication function. Speech-language pathologists (SLPs) play an important role in this context. In Ireland and internationally speech-language pathology CC guidelines are lacking, with possible variations in practice. To compare clinical practices in dysphagia, communication and tracheostomy management among SLPs working in adult CC units in Ireland and internationally, and explore their perspectives on training, skills and resources. METHOD: Participants were SLPs working in CC. An international online survey sought information on (i) SLP workforce demographics and staffing levels, (ii) current dysphagia and communication assessment and management practices, (iii) practices and perspectives on training, skills and resources. RESULT: 366 responses were received across 29 countries. 18.03% (66/366) of these respondents worked in Ireland. Findings showed similarities and differences in practices. Total CC SLP whole-time equivalent (WTE) at each staff grade was lower (mean difference: -0.21 to -0.65 WTE p <.001) than desired for optimal service delivery. Negative effects of under-staffing were reported. Recommendations that all tracheostomised patients receive SLP input was unmet in 66% (220/334) of services. CONCLUSION: SLP input in CC is limited in terms of dedicated posts, multidisciplinary team (MDT) involvement, consistent management approaches and training opportunities internationally. Implications of findings are discussed.

Heinz-resistant tomato cultivars exhibit a lignin-based resistance to field dodder (Cuscuta campestris) parasitism.

Cuscuta species (dodders) are agriculturally destructive, parasitic angiosperms. These parasitic plants use haustoria as physiological bridges to extract nutrients and water from hosts. Cuscuta campestris has a broad host range and wide geographical distribution. While some wild tomato relatives are resistant, cultivated tomatoes are generally susceptible to C. campestris infestations. However, some specific Heinz tomato (Solanum lycopersicum) hybrid cultivars exhibit resistance to dodders in the field, but their defense mechanism was previously unknown. Here, we discovered that the stem cortex in these resistant lines responds with local lignification upon C. campestris attachment, preventing parasite entry into the host. Lignin Induction Factor 1 (LIF1, an AP2-like transcription factor), SlMYB55, and Cuscuta R-gene for Lignin-based Resistance 1, a CC-NBS-LRR (CuRLR1) are identified as factors that confer host resistance by regulating lignification. SlWRKY16 is upregulated upon C. campestris infestation and potentially negatively regulates LIF1 function. Intriguingly, CuRLR1 may play a role in signaling or function as an intracellular receptor for receiving Cuscuta signals or effectors, thereby regulating lignification-based resistance. In summary, these four regulators control the lignin-based resistance response in specific Heinz tomato cultivars, preventing C. campestris from parasitizing resistant tomatoes. This discovery provides a foundation for investigating multilayer resistance against Cuscuta species and has potential for application in other essential crops attacked by parasitic plants.

A strategy for formulating regulation on CSTDs.

This article identifies what steps need to be taken to ensure the mandatory use of closed system transfer devices by all health professionals involved in the hazardous drug journey.

An ecological process model of female sex offending: the role of victimization, psychological distress, and life stressors.

Female sex offenders may be implicated in up to one fifth of all sex crimes committed in the United States. Despite previous research findings that suggest unique patterns of offending among female sex offenders, limited empirical research has investigated the motivations and processes involved. The present study qualitatively examined female sex offenders' offense-related experiences and characterized the internal and external factors that contributed to offending. Semi-structured interviews with 24 female sex offenders were analyzed by a team of coders with limited exposure to the existing literature using grounded theory analysis. A conceptual framework emerged representing distinctive processes for solo- and co-offending, contextualized within ecological layers of social and environmental influence. This model extends previous work by offering an example of nested vulnerabilities proximal to female sexual offending. Implications for future research, prevention, and treatment are discussed.

Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model.

Plasmacytoid dendritic cells (pDCs) have long been implicated in the pathogenesis of lupus. However, this conclusion has been largely based on a correlative link between the copious production of IFN-α/ß by pDCs and the IFN-α/ß "signature" often seen in human lupus patients. The specific contribution of pDCs to disease in vivo has not been investigated in detail. For this reason, we generated a strain of BXSB lupus-prone mice in which pDCs can be selectively depleted in vivo. Early, transient ablation of pDCs before disease initiation resulted in reduced splenomegaly and lymphadenopathy, impaired expansion and activation of T and B cells, reduced antibodies against nuclear autoantigens and improved kidney pathology. Amelioration of pathology coincided with decreased transcription of IFN-α/ß-induced genes in tissues. PDC depletion had an immediate impact on the activation of immune cells, and importantly, the beneficial effects on pathology were sustained even though pDCs later recovered, indicating an early pDC contribution to disease. Together, our findings demonstrate a critical function for pDCs during the IFN-α/ß-dependent initiation of autoimmune lupus and point to pDCs as an attractive therapeutic target for the treatment of SLE.

Activation of Ras overcomes B-cell tolerance to promote differentiation of autoreactive B cells and production of autoantibodies.

Newly generated immature B cells are selected to enter the peripheral mature B-cell pool only if they do not bind (or bind limited amount of) self-antigen. We previously suggested that this selection relies on basal extracellular signal-regulated kinase (Erk) activation mediated by tonic B-cell antigen receptor (BCR) signaling and that this signal can be replaced by an active rat sarcoma (Ras), which are small GTPase proteins. In this study we compared the activity of Ras and Erk in nonautoreactive and autoreactive immature B cells and investigated whether activation of Ras can break tolerance. Our results demonstrate lower levels of active Erk and Ras in autoreactive immature B cells, although this is evident only when these cells display medium/high avidity for self-antigen. Basal activation of Erk in immature B cells is proportional to surface IgM and dependent on sarcoma family kinases, whereas it is independent of B-cell activating factor, IFN, and Toll-like receptor signaling. Ectopic expression of the constitutively active mutant Ras form N-RasD12 in autoreactive cells raises active Erk, halts receptor editing via PI3 kinase, and promotes differentiation via Erk, breaking central tolerance. Moreover, when B cells coexpress autoreactive and nonautoreactive BCRs, N-RasD12 leads also to a break in peripheral tolerance with the production of autoantibodies. Our findings indicate that in immature B cells, basal activation of Ras and Erk are controlled by tonic BCR signaling, and that positive changes in Ras activity can lead to a break in both central and peripheral B-cell tolerance.

Self-determination and substance use: is effortful control a mediator?

BACKGROUND: Alcohol and other drug use among college students are highly common in the United States. This study examined the relationships between 2 motivational orientations (i.e., autonomy and controlled orientations) and substance use and related problems among college students. It also examined whether effortful control mediated the relationship between these motivational orientations and substance use. METHODS: Study participants were 644 undergraduate students (67.2% female; 87.2% Caucasian) who completed a series of online questionnaires as a part of a larger longitudinal study on sleep and substance use. The mean age of participants was 23.58 (SD = 6.861). RESULTS: Students with a higher autonomy orientation were more likely than their counterparts to report that they did not drink in the last 6 months. In contrast, students with a higher controlled orientation were less likely to report that they did not drink. Among those who drank in the last 6 months, effortful control significantly mediated the effects of autonomy orientation and controlled orientation on frequency of alcohol use within that time frame. Autonomy orientation positively predicted effortful control, which was associated with a decrease in the expected frequency of drinking. In contrast, controlled orientation negatively predicted effortful control, which was associated with an increase in the expected frequency of drinking. Controlled orientation also significantly predicted the presence of alcohol-related problems and illicit drug use. CONCLUSIONS: Intervention and prevention programs on college drinking could incorporate education about strategies for self-control, including strategies for withstanding peer pressure and diverting one's attention to activities unrelated to substance use. Focusing on strategies of self-control may be a useful starting point for a more in-depth discussion about the motivations, values, and psychological needs satisfaction that are associated with drinking and other drug use.

Antigen and cytokine receptor signals guide the development of the naïve mature B cell repertoire.

Immature B cells are generated daily in the bone marrow tissue. More than half of the newly generated immature B cells are autoreactive and bind a self-antigen, while the others are nonautoreactive. A selection process has evolved on the one hand to thwart development of autoreactive immature B cells and, on the other hand, to promote further differentiation of nonautoreactive immature B cells into transitional and mature B cells. These negative and positive selection events are carefully regulated by signals that emanate from the antigen receptor, whether antigen-mediated or tonic, and are influenced by signals that are generated by receptors that bind cytokines, chemokines, and other factors produced in the bone marrow tissue. These signals, therefore, are the predominant driving forces for the generation of a B cell population that is capable of protecting the body from infections while maintaining self-tolerance. Here, we review recent findings from our group and others that describe how tonic antigen receptor signaling and bone marrow cytokines regulate the selection of immature B cells.

BAFF receptor signaling aids the differentiation of immature B cells into transitional B cells following tonic BCR signaling.

BAFF is an important prosurvival cytokine for mature B cells. However, previous studies have shown that BAFFR is already expressed at the immature B cell stage, and that the prosurvival protein Bcl-2 does not completely complement the B cell defects resulting from the absence of BAFFR or BAFF. Thus, we hypothesized that BAFF also functions to aid the differentiation of nonautoreactive immature B cells into transitional B cells and to promote their positive selection. We found that BAFFR is expressed at higher levels on nonautoreactive than on autoreactive immature B cells and that its expression correlates with that of surface IgM and with tonic BCR signaling. Our data indicate that BAFFR signaling enhances the generation of transitional CD23(-) B cells in vitro by increasing cell survival. In vivo, however, BAFFR signaling is dispensable for the generation of CD23(-) transitional B cells in the bone marrow, but it is important for the development of transitional CD23(-) T1 B cells in the spleen. Additionally, we show that BAFF is essential for the differentiation of CD23(-) into CD23(+) transitional B cells both in vitro and in vivo through a mechanism distinct from that mediating cell survival, but requiring tonic BCR signaling. In summary, our data indicate that BAFFR and tonic BCR signals cooperate to enable nonautoreactive immature B cells to differentiate into transitional B cells and to be positively selected into the naive B cell repertoire.

Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation.

B cell receptors (BCRs) generate tonic signals critical for B cell survival and early B cell development. To determine whether these signals also mediate the development of transitional and mature B cells, we examined B cell development using a mouse strain in which nonautoreactive immunoglobulin heavy and light chain-targeted B cells express low surface BCR levels. We found that reduced BCR expression translated into diminished tonic BCR signals that strongly impaired the development of transitional and mature B cells. Constitutive expression of Bcl-2 did not rescue the differentiation of BCR-low B cells, suggesting that this defect was not related to decreased cell survival. In contrast, activation of the Ras pathway rescued the differentiation of BCR-low immature B cells both in vitro and in vivo, whereas extracellular signal-regulated kinase (Erk) inhibition impaired the differentiation of normal immature B cells. These results strongly suggest that tonic BCR signaling mediates the differentiation of immature into transitional and mature B cells via activation of Erk, likely through a pathway requiring Ras.

Updraft gasification of salmon processing waste.

The purpose of this study was to judge the feasibility of gasification for the disposal of waste streams generated through salmon harvesting. Gasification is the process of converting carbonaceous materials into combustible "syngas" in a high temperature (above 700 degrees C), oxygen deficient environment. Syngas can be combusted to generate power, which recycles energy from waste products. At 66% to 79% moisture, raw salmon waste streams are too wet to undergo pyrolysis and combustion. Ground raw or de-oiled salmon whole fish, heads, viscera, or frames were therefore "dried" by mixing with wood pellets to a final moisture content of 20%. Ground whole salmon with moisture reduced to 12% moisture was gasified without a drying agent. Gasification tests were performed in a small-scale, fixed-bed, updraft gasifer. After an initial start-up period, the gasifier was loaded with 1.5 kg of biomass. Temperature was recorded at 6 points in the gasifier. Syngas was collected during the short steady-state period during each gasifier run and analyzed. Percentages of each type of gas in the syngas were used to calculate syngas heating value. High heating value (HHV) ranged from 1.45 to 1.98 MJ/kg. Bomb calorimetry determined maximum heating value for the salmon by-products. Comparing heating values shows the efficiency of gasification. Cold gas efficiencies of 13.6% to 26% were obtained from the various samples gasified. Though research of gasification as a means of salmon waste disposal and energy production is ongoing, it can be concluded that pre-dried salmon or relatively low moisture content mixtures of waste with wood are gasifiable.

Cross language phonetic influences on the speech of French-English bilinguals.

We examined the voice onset times (VOTs) of monolingual and bilingual speakers of English and French to address the question whether cross language phonetic influences occur particularly in simultaneous bilinguals (that is, speakers who learned both languages from birth). Speakers produced sentences in which there were target words with initial /p/, /t/ or /k/. In French, natively bilingual speakers produced VOTs that were significantly longer than those of monolingual French speakers. French VOTs were even longer in bilingual speakers who learned English before learning French. The outcome was analogous in English speech. Natively bilingual speakers produced shorter English VOTs than monolingual speakers. English VOTs were even shorter in the speech of bilinguals who learned French before English. Bilingual speakers had significantly longer VOTs in their English speech than in their French. Accordingly, the cross language effects do not occur because natively bilingual speakers adopt voiceless stop categories intermediate between those of native English and French speakers that serve both languages. Monolingual speakers of French or English in Montreal had VOTs nearly identical respectively to those of monolingual Parisian French speakers and those of monolingual Connecticut English speakers. These results suggest that mere exposure to a second language does not underlie the cross language phonetic effect; however, these findings must be resolved with others that appear to show an effect of overhearing.

A novel mechanism for TNFR-associated factor 6-dependent CD40 signaling.

Members of the TNFR family play critical roles in the regulation of the immune system. One member of the family critical for efficient activation of T-dependent humoral immune responses is CD40, a cell surface protein expressed by B cells and other APC. The cytoplasmic domain of CD40 interacts with several members of the TNFR-associated factor (TRAF) family, which link CD40 to intracellular signaling pathways. TRAF2 and 6 appear to play particularly important roles in CD40 signaling. Previous studies suggest that the two molecules have certain overlapping roles in signaling, but that unique roles for each molecule also exist. To better define the roles of TRAF2 and TRAF6 in CD40 signaling, we used somatic cell gene targeting to generate TRAF-deficient mouse B cell lines. A20.2J cells deficient in TRAF6 exhibit marked defects in CD40-mediated JNK activation and the up-regulation of CD80. Our previous experiments with TRAF2-deficient B cell lines suggest that TRAF6 and TRAF2 may have redundant roles in CD40-mediated NF-kappaB activation. Consistent with this hypothesis, we found CD40-mediated activation of NF-kappaB intact in TRAF6-deficient cells and defective in cells lacking both TRAF2 and TRAF6. Interestingly, we found that TRAF6 mutants defective in CD40 binding were able to restore CD40-mediated JNK activation and CD80 up-regulation in TRAF6-deficient cells, indicating that TRAF6 may be able to contribute to certain CD40 signals without directly binding CD40.

Receptor editing can lead to allelic inclusion and development of B cells that retain antibodies reacting with high avidity autoantigens.

Receptor editing is a major B cell tolerance mechanism that operates by secondary Ig gene rearrangements to change the specificity of autoreactive developing B cells. In the 3-83Igi mouse model, receptor editing operates in every autoreactive anti-H-2K(b) B cell, providing a novel receptor without additional cell loss. Despite the efficiency of receptor editing in generating nonautoreactive Ag receptors, we show in this study that this process does not inactivate the autoantibody-encoding gene(s) in every autoreactive B cell. In fact, receptor editing can generate allelically and isotypically included B cells that simultaneously express the original autoreactive and a novel nonautoreactive Ag receptors. Such dual Ab-expressing B cells differentiate into transitional and mature B cells retaining the expression of the autoantibody despite the high avidity interaction between the autoantibody and the self-Ag in this system. Moreover, we find that these high avidity autoreactive B cells retain the autoreactive Ag receptor within the cell as a consequence of autoantigen engagement and through a Src family kinase-dependent process. Finally, anti-H-2K(b) IgM autoantibodies are found in the sera of older 3-83Igi mice, indicating that dual Ab-expressing autoreactive B cells are potentially functional and capable of differentiating into IgM autoantibody-secreting plasma cells under certain circumstances. These results demonstrate that autoreactive B cells reacting with ubiquitous membrane bound autoantigens can bypass mechanisms of central tolerance by coexpressing nonautoreactive Abs. These dual Ab-expressing autoreactive B cells conceal their autoantibodies within the cell manifesting a superficially tolerant phenotype that can be partially overcome to secrete IgM autoantibodies.

Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling.

CD40 function is initiated by tumor necrosis factor (TNF) receptor-associated factor (TRAF) adapter proteins, which play important roles in signaling by numerous receptors. Characterizing roles of individual TRAFs has been hampered by limitations of available experimental models and the poor viability of most TRAF-deficient mice. Here, B cell lines made deficient in TRAF2 using a novel homologous recombination system reveal new roles for TRAF2. We demonstrate that TRAF2 participates in synergy between CD40 and B cell antigen receptor signals, and in CD40-mediated, TNF-dependent IgM production. We also find that TRAF2 participates in the degradation of TRAF3 associated with CD40 signaling, a role that may limit inhibitory actions of TRAF3. Finally, we show that TRAF2 and TRAF6 have overlapping functions in CD40-mediated NF-kappaB activation and CD80 up-regulation. These findings demonstrate previously unappreciated roles for TRAF2 in signaling by TNF receptor family members, using an approach that facilitates the analysis of genes critical to the viability of whole organisms.