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Purpose: There are increasing demands for aphasia assessment and intervention services to be delivered remotely. The purpose of this scoping review was to address what is known about the delivery of assessments and interventions using telehealth for people with poststroke aphasia. Specifically, the review sought to (a) identify which telehealth assessment protocols have been used, (b) identify which telehealth intervention protocols have been used, and (c) describe evidence on the effectiveness and feasibility of telehealth for people with poststroke aphasia. Method: A scoping review of the literature published in English since 2013 was conducted by searching MEDLINE, Embase, PsycINFO, CINAHL, and Scopus databases to identify relevant studies. A total of 869 articles were identified. Two reviewers screened records independently, finding 25 articles eligible for inclusion. Data extraction was conducted once and validated by the second reviewer. Results: Two of the included studies examined telehealth assessment protocols, whereas the remaining studies focused on the delivery of telehealth interventions. The results of the included studies illustrated both effectiveness and feasibility regarding telehealth for people with poststroke aphasia. However, a lack of procedural variation among the studies was found. Conclusions: Overall, this scoping review yielded continued support for the use of telehealth practices as an alternate mode of delivering both assessment and intervention services to people with poststroke aphasia. However, further research is needed to investigate the range of aphasia assessment and intervention protocols that can be offered via telehealth, such as assessments or interventions that use patient-reported measures or address extralinguistic cognitive abilities.

Ensuring timely patient discharges is central to managing a hospital’s patient flow; however, discharges are dependent on the coordination of multiple care teams and thus are highly decentralized in nature. Many large hospitals have established capacity management centers to centrally direct and inform flow and support clinical teams across the hospital system, but they often lack transparency into what are the actionable, high-yield barriers to discharge that they need to focus on to be most effective. Moreover, these barriers are patient-specific and context-dependent, i.e., a patient’s clinical-operational context determines what issues must be resolved and with which urgency. In this study, we leverage a machine learning model that predicts which patients are likely to be discharged in the next 24 hours together with a mixed-integer prescriptive optimization model to identify a subset of issues calledminimal barriersthat stand in the way of discharging a patient. Such barriers balance two aims: a high likelihood that the patient will be discharged from the hospital in the next 24 hours if these barriers are resolved; and a high likelihood that these barriers will indeed be resolved. We empirically demonstrate the efficacy of the proposed formulation and solution methodology in identifying a small number of minimal barriers using real data from a large academic medical center.

The original version of this Data Descriptor omitted the following information from the Acknowledgements.

Immunoglobulin replacement therapy is a mainstay therapy for patients with primary immunodeficiency (PID). The content of these preparations was studied extensively. Nevertheless, data regarding the effective specific antibodies content (especially in the nadir period), and, in different groups of PID patients is limited. We studied trough IgG concentrations as well as anti-Pneumococcus, anti-Haemophilus influenzae b, anti-Tetanus, and anti-Measles antibody concentrations in 17 PID patients receiving intravenous immunoglobulin (IVIg) compared with healthy controls matched for age and ethnicity. We also analyzed these results according to the specific PID diagnosis: X-linked agammaglobulinemia (XLA), combined immunodeficiency (CID), and ataxia telangiectasia (AT). We recorded a higher concentration of anti-pneumococcal polysaccharide antibodies in healthy controls compared to the entire group of PID patients. We also found significantly higher anti-tetanus toxoid antibody concentrations in the XLA patients, compared to CID patients. Anti-Haemophilus Influenzae b antibody titers were overall similar between all the groups. Interestingly, there were overall low titers of anti-Measles antibodies below protective cutoff antibody concentrations in most patients as well as in healthy controls. We conclude that relying on total IgG trough levels is not necessarily a reflection of effective specific antibodies in the patient’s serum. This is especially relevant to CID patients who may have production of nonspecific antibodies. In such patients, a higher target trough IgG concentration should be considered. Another aspect worth considering is that the use of plasma from adult donors with a waning immunity for certain pathogens probably affects the concentrations of specific antibodies in IVIg preparations.

SLP76 is a key molecule involved in the T cell signaling pathway; therefore, SLP76 deficiency can lead to a severe type of immunodeficiency. By reporting on a patient with germline mutation in SLP76, deficiency in this gene is linked, for the first time, to a human disease., The T cell receptor (TCR) signaling pathway is an ensemble of numerous proteins that are crucial for an adequate immune response. Disruption of any protein involved in this pathway leads to severe immunodeficiency and unfavorable clinical outcomes. Here, we describe an infant with severe immunodeficiency who was found to have novel biallelic mutations in SLP76. SLP76 is a key protein involved in TCR signaling and in other hematopoietic pathways. Previous studies of this protein were performed using Jurkat-derived human leukemic T cell lines and SLP76-deficient mice. Our current study links this gene, for the first time, to a human immunodeficiency characterized by early-onset life-threatening infections, combined T and B cell immunodeficiency, severe neutrophil defects, and impaired platelet aggregation. Hereby, we characterized aspects of the patient's immune phenotype, modeled them with an SLP76-deficient Jurkat-derived T cell line, and rescued some consequences using ectopic expression of wild-type SLP76. Understanding human diseases due to SLP76 deficiency is helpful in explaining the mixed T cell and neutrophil defects, providing a guide for exploring human SLP76 biology.

The opportunistic pathogen Pseudomonas aeruginosa employs a hierarchical quorum-sensing network to regulate virulence factor production that cooperatively benefit the population at a cost to the individual. It has been argued that the evolution of a cooperative mutant in a quorum sensing-suppressed population would be hampered through its exploitation by neighboring non-mutant cells. It remains unclear whether mechanisms which overcome this exploitation exist. Here we investigate the regain of quorum-sensing cooperation by evolving a mutant of the lasR master quorum-sensing regulator. The mutant regained partial cooperative growth through null mutations in mexT, which codes for an activator of the MexEF-OprN multidrug-resistant pump. We find that these mutations enhance cooperative growth in both the lasR mutant and wild-type backgrounds through the activation of the RhlIR system. We show that the regain of cooperation in mexT mutants is mediated by the reduction in MexEF-OprN activity, whereas an additional source of private benefit is mostly mexEF-oprN-independent. Finally, we show that addition of antibiotics for which resistance is mediated by MexEF-OprN prevents the selection of increased cooperation at sub-MIC concentrations. MexT, therefore, not only links private and public goods, but also exposes conflicts between selection for antibiotic resistance and enhanced cooperation.

In this study, we challenged science teachers’ views of inquiry-based learning as being merely experimental, causal, and controlled. We studied science teachers enrolled in professional development programs that consisted of three different inquiry-based learning experiences in the outdoors: ecology, sociology, and archeology. These three cycles of investigation included online collaborative planning, fieldwork and collaborative online data analysis, and online communication. Data collection included pre- and post-PD, open-ended questionnaires, interviews and written reflections. Qualitative content analysis was informed by the literature referring to procedural and epistemic aspects of inquiry-based learning. Other themes that emerged from the data included the place of collaborative learning, the use of technology, and the contribution of the outdoor environment. We found a clear shift in teachers’ views about inquiry which ranged from vague explanations and descriptions of inquiry as merely student-centered learning, to more sophisticated views. The teachers valued the outdoor environment highly for learning and provided interesting insights into how to integrate in-school and out-of-school learning. Collaborative learning supported by technology was perceived as an effective vehicle for meaningful learning. An incomplete shift into the highest epistemic explanations is explained by insufficient opportunities for face-to-face explicit discussions about scientific inquiry and inquiry-based learning.

Background Idiopathic pulmonary fibrosis is a devastating fibrotic diffuse parenchymal lung disorder that remains refractory to pharmacological therapies. Therefore, novel treatments are urgently required. CCAAT/enhancer binding protein delta (C/EBPδ) is a transcription factor that mediates critical cellular functions in pathophysiology and which was recently suggested to be a key regulatory component in IPF. The purpose of this study was to prove or refute the importance of C/EBPδ in pulmonary fibrosis. Methods Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and C/EBPδ deficient mice. At different time intervals after bleomycin instillation, fibrosis was assessed by hydroxyproline analysis, histochemistry and q-PCR for fibrotic marker expression. Results C/EBPδ deficient mice developed pulmonary fibrosis to a similar degree as wildtype mice as evident from similar Ashcroft scores, hydroxyproline levels and expression levels of collagen, fibronectin and α-smooth muscle actin at both 14 and 21 days after bleomycin instillation. The resolution of fibrosis, assessed at 48 days after bleomycin instillation, was also similar in wildtype and C/EBPδ deficient mice. In line with the lack of effect of C/EBPδ on fibrosis progression/resolution, macrophage recruitment and/or differentiation were also not different in wildtype or C/EBPδ deficient mice. Conclusions Overall, C/EBPδ does not seem to affect bleomycin-induced experimental pulmonary fibrosis and we challenge the importance of C/EBPδ in pulmonary fibrosis. Relevance for patients This study shows that the transcription factor C/EBPδ does not play a major role in the development of pulmonary fibrosis. Pharmacological targeting of C/EBPδ is therefore not likely to have a beneficial effect for patients suffering from pulmonary fibrosis.

Background Idiopathic pulmonary fibrosis is a devastating fibrotic diffuse parenchymal lung disorder that remains refractory to pharmacological therapies. Therefore, novel treatments are urgently required. CCAAT/enhancer binding protein delta (C/EBPδ) is a transcription factor that mediates critical cellular functions in pathophysiology and which was recently suggested to be a key regulatory component in IPF. The purpose of this study was to prove or refute the importance of C/EBPδ in pulmonary fibrosis. Methods Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and C/EBPδ deficient mice. At different time intervals after bleomycin instillation, fibrosis was assessed by hydroxyproline analysis, histochemistry and q-PCR for fibrotic marker expression. Results C/EBPδ deficient mice developed pulmonary fibrosis to a similar degree as wildtype mice as evident from similar Ashcroft scores, hydroxyproline levels and expression levels of collagen, fibronectin and α-smooth muscle actin at both 14 and 21 days after bleomycin instillation. The resolution of fibrosis, assessed at 48 days after bleomycin instillation, was also similar in wildtype and C/EBPδ deficient mice. In line with the lack of effect of C/EBPδ on fibrosis progression/resolution, macrophage recruitment and/or differentiation were also not different in wildtype or C/EBPδ deficient mice. Conclusions Overall, C/EBPδ does not seem to affect bleomycin-induced experimental pulmonary fibrosis and we challenge the importance of C/EBPδ in pulmonary fibrosis. Relevance for patients This study shows that the transcription factor C/EBPδ does not play a major role in the development of pulmonary fibrosis. Pharmacological targeting of C/EBPδ is therefore not likely to have a beneficial effect for patients suffering from pulmonary fibrosis.

Implementing inquiry in the outdoors introduces many challenges for teachers, some of which can be dealt with using mobile technologies. For productive use of these technologies, teachers should be provided with the opportunity to develop relevant knowledge and practices. In a professional development (PD) program in this design-based research, 24 teachers were involved in adaptation of a learning environment supporting inquiry in the outdoors that included the use of mobile technologies. They first experienced the learning environment as learners, then adapted it for their own use, and finally, enacted the adapted environment with peers. We examined the scope and character of teacher involvement in adaptation, and the consequent professional growth, by analyzing observations, questionnaires, interviews and the adapted learning-environments. Findings indicate that all teachers demonstrated change processes, including changes in knowledge and practice, but the coherence of the learning environments decreased when substantial adaptations were made. Some teachers demonstrated professional growth, as reflected by their implementation of ideas learned in the PD program in their daily practice, long after the PD program had ended. This study demonstrates how the Teachers as Designers approach can support teacher learning and illustrates productive use of scaffolds for teacher growth and professional development.

Proteases were traditionally viewed as mere protein-degrading enzymes with a very restricted spectrum of substrates. A major expansion in protease research has uncovered a variety of novel substrates, and it is now evident that proteases are critical pleiotropic actors orchestrating pathophysiological processes. Recent findings evidenced that the net proteolytic activity also relies upon interconnections between different protease and protease inhibitor families in the protease web.In this review, we provide an overview of these novel concepts with a particular focus on pulmonary pathophysiology. We describe the emerging roles of several protease families including cysteine and serine proteases.The complexity of the protease web is exemplified in the light of multidimensional regulation of serine protease activity by matrix metalloproteases through cognate serine protease inhibitor processing. Finally, we will highlight how deregulated protease activity during pulmonary pathogenesis may be exploited for diagnosis/prognosis purposes, and utilised as a therapeutic tool using nanotechnologies.Considering proteases as part of an integrative biology perspective may pave the way for the development of new therapeutic targets to treat pulmonary diseases related to intrinsic protease deregulation.

We propose a new problem we refer to as goal recognitiondesign (grd), in which we take a domain theory and a set ofgoals and ask the following questions: to what extent do theactions performed by an agent within the model reveal its objective, and what is the best way to modify a model so thatany agent acting in the model reveals its objective as early aspossible. Our contribution is the introduction of a new measure we call worst case distinctiveness (wcd) with which weassess a grd model. The wcd represents the maximal lengthof a prefix of an optimal path an agent may take within a system before it becomes clear at which goal it is aiming. Tomodel and solve the grd problem we choose to use the models and tools from the closely related field of automated planning. We present two methods for calculating the wcd of agrd model, one of which is based on a novel compilation to aclassical planning problem. We then propose a way to reducethe wcd of a model by limiting the set of available actions anagent can perform and provide a method for calculating theoptimal set of actions to be removed from the model. Our empirical evaluation shows the proposed solution to be effectivein computing and minimizing wcd.

Cathepsin S (CatS) is upregulated in the lungs of patients with cystic fibrosis (CF). However, its role in CF lung disease pathogenesis remains unclear.In this study, β-epithelial Na+channel-overexpressing transgenic (βENaC-Tg) mice, a model of CF-like lung disease, were crossed with CatS null (CatS−/−) mice or treated with the CatS inhibitor VBY-999.Levels of active CatS were elevated in the lungs of βENaC-Tg mice compared with wild-type (WT) littermates. CatS−/−βENaC-Tg mice exhibited decreased pulmonary inflammation, mucus obstruction and structural lung damage compared with βENaC-Tg mice. Pharmacological inhibition of CatS resulted in a significant decrease in pulmonary inflammation, lung damage and mucus plugging in the lungs of βENaC-Tg mice. In addition, instillation of CatS into the lungs of WT mice resulted in inflammation, lung remodelling and upregulation of mucin expression. Inhibition of the CatS target, protease-activated receptor 2 (PAR2), in βENaC-Tg mice resulted in a reduction in airway inflammation and mucin expression, indicating a role for this receptor in CatS-induced lung pathology.Our data indicate an important role for CatS in the pathogenesis of CF-like lung disease mediated in part by PAR2 and highlight CatS as a therapeutic target.

This study expands our understanding of treatment attrition by investigating factors predicting treatment dropout in a large national data set of clinic-referred children and parents seeking trauma...

Goal recognition design involves the offline analysis of goal recognition models by formulating measures that assess the ability to perform goal recognition within a model and finding efficient ways to compute and optimize them. In this work we relax the full observability assumption of earlier work by offering a new generalized model for goal recognition design with non-observable actions. A model with partial observability is relevant to goal recognition applications such as assisted cognition and security, which suffer from reduced observability due to sensor malfunction or lack of sufficient budget. In particular we define a worst case distinctiveness (wcd) measure that represents the maximal number of steps an agent can take in a system before the observed portion of his trajectory reveals his objective. We present a method for calculating wcd based on a novel compilation to classical planning and propose a method to improve the design using sensor placement. Our empirical evaluation shows that the proposed solutions effectively compute and improve wcd.

The inverse relationship between economic status and mental illness is well established. Less is known, however, about the nature of this relationship. A comparison of poor suburban and rural youth receiving services for their emotional and behavioral problems revealed more similarities than differences. Family income increased during the first year of service for a small percentage of families. A small but significant relationship was found between increased income and caregiver strain as well as child outcomes. For families who are poor and have a child with a disability, highly individualized services and support that reduce caregiver strain are necessary to improve child outcomes.