Emotional support has traditionally been conceived as something a breast cancer patient receives. However, this framework may obscure a more complex process, facilitated by the emerging social media environment, which includes the effects of composing and sending messages to others. Accordingly, this study explores the effects of expression and reception of emotional support messages in online groups and the importance of bonding as a mediator influencing the coping strategies of breast cancer patients.
Data were collected as part of two National Cancer Institute–funded randomized clinical trials. Eligible subjects were within 2 months of diagnosis of primary breast cancer or recurrence. Expression and reception of emotionally supportive messages were tracked and coded for 237 breast cancer patients. Analysis resulted from merging 1) computer-aided content analysis of discussion posts, 2) action log analysis of system use, and 3) longitudinal survey data.
As expected, perceived bonding was positively related to all four coping strategies (active coping: β = 0.251, P = .000; positive reframing: β = 0.288, P = .000; planning: β = 0.213, P = .006; humor: β = 0.159, P = .009). More importantly, expression (γ = 0.138, P = .027), but not reception (γ = −0.018, P = .741), of emotional support increases perceived bonding, which in turn mediates the effects on patients’ positive coping strategies.
There is increasing importance for scholars to distinguish the effects of expression from reception to understand the processes involved in producing psychosocial benefits. This study shows that emotional support is more than something cancer patients receive; it is part of an active, complex process that can be facilitated by social media.
Angiogenesis inhibitors have become standard of care for advanced and/or metastatic renal cell carcinoma (RCC), but data on the impact of adverse events (AEs) and treatment modifications associated with these agents are limited. Medical records were abstracted at 10 tertiary oncology centers in Europe for 291 patients ≥18 years old treated with sunitinib as first-line treatment for advanced RCC (no prior systemic treatment for advanced disease). Logistic regression models were estimated to compare dose intensity among patients who did and did not experience AEs during the landmark periods (18, 24, and 30 weeks). Cox proportional hazard models were used to explore the possible relationship of low-dose intensity (defined using thresholds of 0.7, 0.8, and 0.9) and treatment modifications during the landmark periods to survival. 64.4% to 67.9% of patients treated with sunitinib reported at least one AE of any grade, and approximately 10% of patients experienced at least one severe (grade 3 or 4) AE. Patients reporting severe AEs were statistically significantly more likely to have dose intensities below either 0.8 or 0.9. Dose intensity below 0.7 and dose discontinuation during all landmark periods were statistically significantly associated with shorter survival time. This study of advanced RCC patients treated with sunitinib in Europe found a significant relationship between AEs and dose intensity. It also found correlations between dose intensity and shorter survival, and between dose discontinuation and shorter survival. These results confirm the importance of tolerable treatment and maintaining dose intensity.
Angiogenesis; clinical observations; statistical methods; urological oncology
Despite the importance of family environment and computer-mediated social support (CMSS) for women with breast cancer, little is known about the interplay of these sources of care and assistance on patients' coping strategies. To understand this relation, the authors examined the effect of family environment as a predictor of the use of CMSS groups as well as a moderator of the relation between group participation and forms of coping. Data were collected from 111 patients in CMSS groups in the Comprehensive Health Enhancement Support System “Living with Breast Cancer” intervention. Results indicate that family environment plays a crucial role in (a) predicting breast cancer patient's participation in CMSS groups and (b) moderating the effects of use of CMSS groups on breast cancer patients' coping strategies such as problem-focused coping and emotion-focused coping.
The genetic modification of peripheral blood lymphocytes using retroviral vectors to redirect T cells against tumor cells has been recently used as a means to generate large numbers of antigen-specific T cells for adoptive cell therapy protocols. However, commonly used retroviral vector-based genetic modification requires T cells to be driven into cell division; this potent mitogenic stimulus is associated with the development of an effector phenotype that may adversely impact upon the long-term engraftment potential and subsequent antitumor effects of T cells. To investigate whether the cytokines used during culture impact upon the engraftment potential of gene-modified T cells, a humanized model employing T cells engrafted with a MART-1-specific T cell receptor adoptively transferred into NOD/Shi-scid IL-2rγ−/− (NSG) immune-deficient mice bearing established melanoma tumors was used to compare the effects of the common γ chain cytokines IL-2, IL-7, and IL-15 upon gene-modified T cell activity. MART-1-specific T cells cultured in IL-7 and IL-15 demonstrated greater relative in vitro proliferation and viability of T cells compared with the extensively used IL-2. Moreover, the IL-15 culture prolonged the survival of animals bearing melanoma tumors after adoptive transfer. However, the combination of IL-7 and IL-15 produced T cells with improved engraftment potential compared with IL-15 alone; however, a high rate of xenogeneic graft-versus-host disease prevented the identification of a clear improvement in antitumor effect of these T cells. These results clearly demonstrate modulation of gene-modified T cell engraftment in the NSG mouse, which supports the future testing of the combination of IL-7 and IL-15 in adoptive cell therapy protocols; however, this improved engraftment is also associated with the long-term maintenance of xenoreactive T cells, which limits the ultimate usefulness of the NSG mouse model in this situation.
In this study, Alcantar-Orozco and colleagues investigate whether the cytokines used during culture impact the engraftment potential of gene-modified T cells in a humanized animal model (the NSG immune-deficient mouse). Using this approach, they find that T cells cultured in IL-7 and IL-15 demonstrate greater relative in vitro proliferation and viability as compared to T cells cultured in IL-2. Moreover, they find that IL-7 and IL-15 cultured cells have higher engraftment potential compared to cells cultured in IL-15 alone.
eHealth resources for people facing health crises must balance the expert knowledge and perspective of developers and clinicians against the very different needs and perspectives of prospective users. This formative study explores the information and support needs of posttreatment prostate cancer patients and their partners as a way to improve an existing eHealth information and support system called CHESS (Comprehensive Health Enhancement Support System).
Focus groups with patient survivors and their partners were used to identify information gaps and information-seeking milestones.
Both patients and partners expressed a need for assistance in decision making, connecting with experienced patients, and making sexual adjustments. Female partners of patients are more active in searching for cancer information. All partners have information and support needs distinct from those of the patient.
Findings were used to develop a series of interactive tools and navigational features for the CHESS prostate cancer computer-mediated system.
The Weber derotation osteotomy is an uncommon procedure that typically is reserved for patients with engaging Hill-Sachs defects who have had other surgical treatments for shoulder instability fail. It is unknown whether the desired humeral derotation actually is achieved with the Weber osteotomy.
The purposes of this study were to answer the following questions: (1) What are the complication (including redislocation) and reoperation rates of the Weber osteotomy? (2) What are the American Shoulder and Elbow Surgeons (ASES) and functional (ROM in internal rotation, self care) results? (3) What fraction of the patients had humeral derotation within 10° of the desired rotation?
A chart review of 19 Weber osteotomies and clinical assessment of 10 Weber osteotomies were performed by independent clinicians. The chart review, at a mean followup of 51 months (range, 13–148 months), focused on the complication rate and the frequency of redislocation. The clinical and CT assessments, at a mean followup of 54 months (range, 26–151 months), focused on ASES scores, ability of patients to perform self care with the affected arm, and CT scans to measure change in humeral retroversion.
There were 25 complications and nine reoperations in 17 patients (19 shoulders), including pain (six patients, of whom one had complex regional pain syndrome), hematoma, infection, nonunion, delayed union, reoperations related to hardware and other noninstability-related causes (five patients), and internal rotation deficit. Redislocation occurred in one patient, who underwent repeat surgery, and subjective instability developed in two others. The mean ASES score was 78 points (of 100 points); six of the 10 patients (11 procedures) evaluated in person found it difficult or were unable to wash their backs with the affected arm. Humeral derotation varied from 7° to 77°; only three of the nine patients for whom CT scans were available had derotation within 10° of the desired rotation.
Complication rates with the Weber osteotomy were much higher than previously reported. Because seven of 17 patients were lost to followup, the redislocation rate may be higher than we observed here. Given the unpredictable variability in humeral derotation achieved with a Weber osteotomy, an improved surgical technique is critical to avoid osteoarthritis and loss of internal rotation associated with overrotation.
Level of Evidence
Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.
Using available communication technologies, clinicians may offer timely support to family caregivers in managing symptoms in patients with advanced cancer at home.
To assess the effects of an online symptom reporting system on caregiver preparedness, physical burden, and negative mood.
A pooled analysis of two randomized trials (NCT00214162 and NCT00365963) was conducted to compare caregiver outcomes at 6 and 12 months after intervention between two randomized, unblinded groups using General Linear Mixed Modeling. Caregivers in one group (Comprehensive Health Enhancement Support System-Only) were given access to an interactive cancer communication system, the Comprehensive Health Enhancement Support System. Those in the other group (Comprehensive Health Enhancement Support System + Clinician Report) received access to Comprehensive Health Enhancement Support System plus an online symptom reporting system called the Clinician Report. Clinicians of patients in the Comprehensive Health Enhancement Support System + Clinician Report group received e-mail alerts notifying them when a symptom distress was reported over a predetermined threshold.
Dyads (n=235) of advanced-stage lung, breast, and prostate cancer patients and their adult caregivers were recruited at five outpatient oncology clinics in the United States.
Caregivers in the Comprehensive Health Enhancement Support System + Clinician Report group reported less negative mood than those in the Comprehensive Health Enhancement Support System-Only group at both 6 months (p=0.009) and 12 months (p=0.004). Groups were not significantly different on caregiver preparedness or physical burden at either time point.
This study provides new evidence that by using an online symptom reporting system, caregivers may experience less emotional distress due to the Clinician Report’s timely communication of caregiving needs in symptom management to clinicians.
Caregivers; palliative care; communication barriers; signs and symptoms; eHealth; cancer
Nitric oxide (NO) is thought to be involved in several forms of learning in vivo and synaptic plasticity in vitro, but very little is known about the role of NO during physiological forms of plasticity that occur during learning. We addressed that question in a simplified preparation of the Aplysia siphon-withdrawal reflex. We first used in situ hybridization to show that the identified L29 facilitator neurons express NO synthase. Furthermore, exogenous NO produced facilitation of sensory–motor neuron EPSPs, and an inhibitor of NO synthase or an NO scavenger blocked behavioral conditioning. Application of the scavenger to the ganglion or injection into a sensory neuron blocked facilitation of the EPSP and changes in the sensory–neuron membrane properties during conditioning. Injection of the scavenger into the motor neuron reduced facilitation without affecting sensory neuron membrane properties, and injection of an inhibitor of NO synthase had no effect. Postsynaptic injection of an inhibitor of exocytosis had effects similar to injection of the scavenger. However, changes in the shape of the EPSP during conditioning were not consistent with postsynaptic AMPA-like receptor insertion but were mimicked by presynaptic spike broadening. These results suggest that NO makes an important contribution during conditioning and acts directly in both the sensory and motor neurons to affect different processes of facilitation at the synapses between them. In addition, they suggest that NO does not come from either the sensory or motor neurons but rather comes from another source, perhaps the L29 interneurons.
nitric oxide; classical conditioning; Aplysia; facilitation; sensory neuron; motor neuron
This study examined the effectiveness of an online support system (CHESS) versus the Internet in relieving physical symptom distress in patients with nonsmall cell lung cancer (NSCLC).
285 informal caregiver-patient dyads were randomly assigned to standard care plus the Internet or CHESS for up to 25 months. Caregivers agreed to use CHESS or the Internet and complete bimonthly surveys; for patients, these tasks were optional. The primary endpoint, patient symptom distress, was measured by caregiver reports using a modified Edmonton Symptom Assessment Scale (ESAS).
Caregivers in the CHESS arm consistently reported lower patient physical symptom distress than caregivers in the Internet arm, with significant differences at 4 months (P = .031, Cohen’s d = .42) and 6 months (P = .004, d = .61). Similar but marginally significant effects were observed at 2 months (P = .051, d = .39) and 8 months (P = .061, d = .43). Exploratory analyses showed that survival curves did not differ significantly between the arms (log rank, P = .172), although a survival difference in an exploratory subgroup analysis suggests an avenue for further study.
An online support system may reduce patient symptom distress. The effect on survival bears further investigation.
lung cancer; symptom distress; palliative care; quality of life; survival; eHealth; communication and information technology
AIM: To assess NY-ESO-1 expression in a cohort of esophageal adenocarcinomas.
METHODS: A retrospective search of our tissue archive for esophageal resection specimens containing esophageal adenocarcinoma was performed, for cases which had previously been reported for diagnostic purposes, using the systematised nomenclature of human and veterinary medicine coding system. Original haematoxylin and eosin stained sections were reviewed, using light microscopy, to confirm classification and tumour differentiation. A total of 27 adenocarcinoma resection specimens were then assessed using immunohistochemistry for NY-ESO-1 expression: 4 well differentiated, 14 moderately differentiated, 4 moderate-poorly differentiated, and 5 poorly differentiated.
RESULTS: Four out of a total of 27 cases of esophageal adenocarcinoma examined (15%) displayed diffuse cytoplasmic and nuclear expression for NY-ESO-1. They displayed a heterogeneous and mosaic-type pattern of diffuse staining. Diffuse cytoplasmic staining was not identified in any of these structures: stroma, normal squamous epithelium, normal submucosal gland and duct, Barrett’s esophagus (goblet cell), Barrett’s esophagus (non-goblet cell) and high grade glandular dysplasia. All adenocarcinomas showed an unexpected dot-type pattern of staining at nuclear, paranuclear and cytoplasmic locations. Similar dot-type staining, with varying frequency and size of dots, was observed on examination of Barrett’s metaplasia, esophageal submucosal gland acini and the large bowel negative control, predominantly at the crypt base. Furthermore, a prominent pattern of apical (luminal) cytoplasmic dot-type staining was observed in some cases of Barrett’s metaplasia and also adenocarcinoma. A further morphological finding of interest was noted on examination of haematoxylin and eosin stained sections, as aggregates of lymphocytes were consistently noted to surround submucosal glands.
CONCLUSION: We have demonstrated for the first time NY-ESO-1 expression by esophageal adenocarcinomas, Barrett’s metaplasia and normal tissues other than germ cells.
Esophageal adenocarcinoma; Immunohistochemistry; NY-ESO-1; Stem cells; Vesicle trafficking
Improvement of cancer therapy by introducing new concepts is still urgent even though there have been major advancements lately. Immunotherapy is well on the way to becoming an established tool in the cancer treatment armory. It seems that a combination of (1) activation of immune effector cells and selective targeting of them to tumors and (2) the inhibition of immune suppression often induced by the tumor itself are necessary to achieve the therapeutic goal. The immunotoxin naptumomab estafenatox was developed in an effort to activate and target the patient’s own T cells to their tumor, by fusing a superantigen (SAg) variant that activates T lymphocytes to the Fab moiety of a tumor-reactive monoclonal antibody. Naptumomab estafenatox targets the 5T4 tumor antigen, a 72-kDa oncofetal trophoblast protein expressed on many carcinomas, including renal cell carcinoma. The therapeutic effect is associated with activation of SAg-binding T cells. The SAg-binding T lymphocytes expand, differentiate to effector cells, and infiltrate the tumor. The therapeutic efficacy is most likely related to the dual mechanism of tumor cell killing: (1) direct lysis by cytotoxic T lymphocytes of tumor cells expressing the antigen recognized by the antibody moiety of the fusion protein and (2) secretion of cytokines eliminating antigen-negative tumor cell variants. Naptumomab estafenatox has been clinically tested in a range of solid tumors with focus on renal cell carcinoma. This review looks at the clinical experience with the new immunotoxin and its potential.
Immunotherapy; Immunotoxin; Tumor-targeted superantigen; 5T4 tumor antigen; Carcinoma; Kidney cancer; Renal cell carcinoma; Evolving therapies; Naptumomab estafenatox
Despite the proliferation of health information technology (IT) interventions, descriptions of the unique considerations for conducting randomized trials of health IT interventions intended for patient use are lacking.
Our purpose is to evaluate Pocket PATH® (Personal Assistant for Tracking Health), a novel health IT intervention, as an exemplar of how to address issues that may be unique to a randomized controlled trial to evaluate health IT intended for patient use.
An overview of the study protocol is presented. Unique considerations for health IT intervention trials and strategies to maintain equipoise, monitor data safety and intervention fidelity, and keep pace with changing technology during such trials are described.
The sovereignty granted to technology, the rapid pace of changes in technology, ubiquitous use in health care and obligation to maintain the safety of research participants challenge researchers to address these issues in ways that maintain the integrity of intervention trials designed to evaluate the impact of health IT interventions intended for patient use.
Our experience evaluating the efficacy of Pocket PATH may provide practical guidance to investigators about how to comply with established procedures for conducting randomized controlled trials and include strategies to address the unique issues associated with the evaluation of health IT for patient use.
Pocket PATH® (Personal Assistant for Tracking Health); health information technology (health IT); randomized; controlled trials (RCT); consumer health technology; trial of intervention efficacy
The aim of this study was to assess the treatment patterns and safety of sunitinib, sorafenib and bevacizumab in real-world clinical settings in US, Europe and Asia. Medical records were abstracted at 18 community oncology clinics in the US and at 21 tertiary oncology centers in US, Europe and Asia for 883 patients ≥18 years who had histologically/cytologically confirmed diagnosis of advanced RCC and received sunitinib (n=631), sorafenib (n=207) or bevacizumab (n=45) as first-line treatment. No prior treatment was permitted. Data were collected on all adverse events (AEs) and treatment modifications, including discontinuation, interruption and dose reduction. Treatment duration was estimated using Kaplan-Meier analysis. Demographics were similar across treatment groups and regions. Median treatment duration ranged from 6.1 to 10.7 months, 5.1 to 8.5 months and 7.5 to 9.8 months for sunitinib, sorafenib and bevacizumab patients, respectively. Grade 3/4 AEs were experienced by 26.0, 28.0 and 15.6% of sunitinib, sorafenib and bevacizumab patients, respectively. Treatment discontinuations occurred in 62.4 (Asia) to 63.1% (US) sunitinib, 68.8 (Asia) to 90.0% (Europe) sorafenib, and 66.7 (Asia) to 81.8% (US) bevacizumab patients. Globally, treatment modifications due to AEs occurred in 55.1, 54.2 and 50.0% sunitinib, sorafenib and bevacizumab patients, respectively. This study in a large, global cohort of advanced RCC patients found that angiogenesis inhibitors are associated with high rates of AEs and treatment modifications. Findings suggest an unmet need for more tolerable agents for RCC treatment.
renal cell carcinoma; angiogenesis inhibitors; safety; treatment patterns; interruption; dose reduction
Understanding the ecological principles underlying the structure and function of microbial communities remains an important goal for microbial ecology. We examined two biogeochemically important taxa, the sulfate-reducing bacterial genus, Desulfobulbus, and the methanogenic archaeal genus, Methanosaeta, to compare and contrast niche partitioning by these two taxa that are ecologically linked as anaerobic terminal oxidizers of organic material. An observational approach utilizing functional gene pyrosequencing was combined with a community-based reciprocal incubation experiment and characterization of a novel Desulfobulbus isolate. To analyze the pyrosequencing data, we constructed a data analysis pipeline, which we validated with several control data sets. For both taxa, particular genotypes were clearly associated with certain portions of an estuarine gradient, consistent with habitat or niche partitioning. Methanosaeta genotypes were generally divided between those found almost exclusively in the marine habitat (∼30% of operational taxonomic units (OTUs)), and those which were ubiquitously distributed across all or most of the estuary (∼70% of OTUs). In contrast to this relatively monotonic distribution, for Desulfobulbus, there were many more genotypes, and their distributions represented a wide range of inferred niche widths from specialist genotypes found only at a single site, to ubiquitous or generalist genotypes found in all 10 sites examined along the full estuarine gradient. Incubation experiments clearly showed that, for both taxa, communities from opposite ends of the estuary did not come to resemble one another, regardless of the chemical environment. Growth of a Desulfobulbus isolated into pure culture indicated that the potential niche of this organism is significantly larger than the realized niche. We concluded that niche partitioning can be an important force structuring microbial populations, with biotic and abiotic components having very different effects depending on the physiology and ecology of each taxon.
methanogenesis; niche partitioning; pyrosequencing; sulfate reduction
Research suggests communicating too much about one’s self within an online support group may amplify breast cancer patients’ focus on their own problems and exacerbate negative emotions while focusing on others may have the opposite effects. This study explored how pronoun usage within an online support group was associated with subsequent mental health outcomes. There were 286 patients recruited into the study who filled out the pre-test and 231 completed post-tests 4 months later with survey measures including breast cancer-related concerns and negative emotions. Messages were analyzed using a program counting first-person and relational pronouns. A positive relationship was found between use of first person pronouns and negative emotions.
Breast cancer; online support groups; pronouns; self focus; social support
Based upon Fredrickson’s Broaden-and-Build Theory of Positive Emotions, this study examined the role of expressing positive emotions in online support groups for women with breast cancer. Underserved women with breast cancer in rural Wisconsin and Detroit, Michigan were recruited from 2001 to 2003, and they were given access to online support groups. Both pretest and a 4-month posttest surveys were conducted with a sample of 231 women. Messages from 96 active participants were analyzed using a computerized text analysis program. Psychological benefits that occurred following the expression of positive emotions were greater among those who expressed more negative emotions.
Positive emotions; Emotional expression; Online support groups; Breast cancer
Test whether three mediating processes of Self-Determination Theory are involved in intervention effects on quality of life for breast cancer patients.
A randomized clinical trial recruited newly diagnosed breast cancer patients for 6 months of (1) Internet training and access, (2) access to an integrated eHealth system for breast cancer (CHESS), (3) a series of phone conversations with a Human Cancer Information Mentor, or (4) both (2) and (3).
This paper reports results after the initial 6 weeks of intervention, at which point patients in the combined condition had higher quality of life scores than those in the other three conditions. All three Self-Determination Theory constructs (autonomy, competence, and relatedness) mediated that effect as hypothesized. In addition, the single-intervention groups were superior to the Internet-only group on relatedness, though perhaps this was too soon for that to carry through to quality of life as well.
The SDT constructs do mediate these interventions’ effects.
Intervention design can profitably focus on enhancing autonomy, competence and relatedness.
e-Health; Internet; Patient mentoring; Self-Determination Theory; Interactive cancer communication systems; Quality of life; Breast cancer
Numerous studies have investigated the effect of Interactive Cancer Communication Systems (ICCSs) on system users’ improvements in psychosocial status. Research in this area, however, has focused mostly on cancer patients, rather than caregivers, and the direct effects of ICCSs on improved outcomes, rather than the psychological mechanisms of ICCS effects. In an effort to understand the underlying mechanisms, this study examines the mediating role of perceived caregiver bonding in the relationship between one ICCS (the Comprehensive Health Enhancement Support System, CHESS) use and caregivers’ coping strategies. To test the hypotheses, secondary analysis of data was conducted on 246 caregivers of lung cancer patients. They were randomly assigned to either the Internet with links to high-quality lung cancer websites or access to CHESS, which integrated information, communication and interactive coaching tools. Findings suggest that perceived bonding has positive impacts on caregivers’ appraisal and problem-focused coping strategies, and it mediates the effect of ICCS on the coping strategies 6 months after the intervention began.
By developing a number of measures distinguishing amount, type of content, and when and how that content is used, the current study revealed effective patterns of use that are associated with quality of life benefits during an eHealth intervention. Results generally suggest that the benefits depend on how a patient uses the system, far more than on sheer amount of exposure or even what type of content is chosen. The next generation of eHealth system should focus on providing new and varying content over time, but even more on encouraging intensity of use and long-term commitment to the system.
Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the ‘Immunoscore’ into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
Trans-synaptic interactions between neurons are essential during both developmental and learning-related synaptic growth. We have used Aplysia neuronal cultures to examine the contribution of trans-synaptic signals in both types of synapse formation. We find that during de novo synaptogenesis, specific presynaptic innervation is required for the clustering of postsynaptic AMPA-like but not NMDA-like receptors. We further find that the cell adhesion molecule Dscam is involved in these trans-synaptic interactions. Inhibition of Dscam either pre- or postsynaptically abolishes the emergence of synaptic transmission and the clustering of AMPA-like receptors. Remodeling of both AMPA-like and NMDA-like receptors also occurs during learning-related synapse formation and again requires the reactivation of Dscam-mediated trans-synaptic interactions. Taken together, these findings suggest that learning-induced synapse formation recapitulates, at least in part, aspects of the mechanisms that govern de novo synaptogenesis.
Despite the proliferation of health technologies, descriptions of the unique considerations and practical guidance for evaluating intervention fidelity of technology-based behavioral interventions are lacking.
To: (a) discuss how technology-based behavioral interventions challenge conventions about how intervention fidelity is conceptualized and evaluated, (b) propose an intervention fidelity framework that may be more appropriate for technology-based behavioral interventions, and (c) present a plan for operationalizing each concept in the framework using the intervention fidelity monitoring plan for Pocket PATH®, a mobile health technology designed to promote self-care behaviors after lung transplantation, as an exemplar.
The literature related to intervention fidelity and technology acceptance was used to identify the issues that are unique to fidelity of technology-based behavioral interventions and thus important to include in a proposed intervention fidelity framework. An intervention fidelity monitoring plan for technology-based behavioral interventions was developed as an example.
The intervention fidelity monitoring plan was deemed feasible and practical to implement, and showed utility in operationalizing the concepts such as assessing interventionists’ delivery and participants’ acceptance of the technology-based behavioral intervention.
The framework has the potential to guide the development of implementation fidelity monitoring tools for other technology-based behavioral interventions. Further application and testing of this framework will allow for a better understanding of the role that technology acceptance plays in adoption and enactment of the behaviors that technology-based behavioral interventions are intended to promote.
treatment fidelity; technology acceptance; behavioral intervention studies