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BACKGROUND: Patients with borderline personality disorder (BPD) typically present emotion dysregulation (ED) when faced with adversity. However, it is argued that altered stress response may be more influenced by ED than BPD-specific traits. Here, we investigated this issue with functional magnetic resonance imaging using another ED condition as clinical control, i.e., bipolar disorder (BD), and controlling for ED traits.METHODS: We recruited 17 patients with BD, 24 patients with BPD, and 32 healthy control (HC) subjects. We adapted a functional magnetic resonance imaging-compatible psychosocial stressor task (Montreal Imaging Stress Task) in which participants are placed under time pressure when performing mental calculations and then receive immediate performance feedback (positive, negative, and neutral). ED traits were measured via self-report questionnaires targeting cognitive emotion dysregulation, affective lability, and trait anger and anxiety.RESULTS: Relative to patients with BD and HC subjects, patients with BPD exhibited overactive corticolimbic reactivity across all conditions, particularly in self-monitoring and emotion regulation regions such as the orbitofrontal cortex and anterior insula, even when controlling for ED. Conversely, patients with BD exhibited hypoactive corticolimbic reactivity to all feedback conditions compared with patients with BPD and HC subjects, even after controlling for ED. HC subjects exhibited significantly lower amygdala/hippocampus activity compared with both clinical groups, although this did not survive when controlling for ED.CONCLUSIONS: This study provides new insight into BPD-specific neural stress responding, suggesting hyperactive self-and emotion-regulatory neural psychosocial stress responding, independent of ED traits. The findings also highlight the importance of considering BPD as a diagnostic profile distinguishable from other ED disorder clinical groups.

OBJECTIVE: To describe how emergency medicine resident physicians discuss diagnostic uncertainty during a simulated ED discharge discussion. METHODS: A secondary content analysis of simulated clinical encounter audiotapes completed by emergency medicine residents across two sites. RESULTS: When discussing lack of diagnosis, residents explained the evaluation revealed no cause for symptoms, noted concerning diagnoses that were excluded, and acknowledged both symptoms and patients’ feelings. Residents used explicit and implicit language to discuss diagnostic uncertainty with similar frequency. Almost half of the residents discussed the ED role as focused on emergent illness to give patients context for their uncertain diagnoses. However, 28% of residents in this study did not discuss diagnostic uncertainty in any form. All residents provided reassurance. CONCLUSION: Residents use a range of approaches to discuss diagnostic uncertainty with patients at the time of a simulated ED discharge, with some residents omitting discussion of uncertainty entirely. PRACTICE IMPLICATIONS: These findings represent the current state of communication, which needs improvement. These findings do not immediately transfer to clinical practice recommendations, but rather support a need for both further study and development of formal communication training on this topic.

Objective Despite well-established treatment guidelines, diabetes is difficult to manage for many individuals. The importance of using shared decision making to optimize diabetes treatment is recognized, yet what matters most to individuals with diabetes is not well established. Our goal was to identify patients’ goals and priorities for diabetes management. Methods We engaged 141 participants through interviews and group concept mapping to identify patient-important outcomes (PIOs) for diabetes care. We generated a master list of PIOs by aggregating interview data coded to “goals” and ideas brainstormed during concept mapping, and then a patient advisory board sorted the PIOs into higher-level domains. Results We identified 41 PIOs sorted into 7 broad domains: optimize daily self-care, optimize long term health, learn about diabetes, achieve measurable goals, manage medications, manage diet and best utilize medical / professional services. Conclusions Most (4/7) of PIO domains focused on personal and life goals, not medically-oriented goals. Use of these PIOs and domains may facilitate more effective SDM discussions for patients with diabetes. Practice implications Use of PIOs from this work can enable the empowerment of patients to voice their priorities during SDM conversations, thus facilitating development of truly individualized diabetes treatment plans.

Background/Objectives: Home health care (HHC) agencies provide an important role in helping to transition patients from acute care to independent residential living. Telehealth has the potential to transform care delivery in HHC, however the majority of studies in HHC have focused on the use of telemonitoring for patients with specific chronic conditions. The objective of this study was to examine reasons HHC patients use acute care services and assess the acceptability of on-demand telehealth services among HHC patients, caregivers and personnel to help alleviate the need for seeking in-person acute care. Design/Setting/Participants/Measures: This study was a secondary analysis of qualitative data from in-depth interviews of 30 HHC personnel, patients and caregivers from a Medicare-certified HHC agency affiliated with a large healthcare system from January through May 2020. A conventional content analysis approach was used to identify themes. Results: Themes associated with reasons for seeking acute care included: sense of urgency, behavioral and psychosocial factors, and access to care. Participants described their perceptions of the benefits, usability and acceptability and barriers to using telehealth. Patients and HHC personnel agreed that on-demand telehealth should not replace in-person visits but all identified roles that on-demand telehealth services could play in improving communication and access to care. The biggest barriers to use of telehealth identified by HHC personnel were cost, access and ability to use technology by HHC patients. Conclusion: This study identified reasons HHC patients seek unscheduled acute care and the usability and acceptability of on-demand telehealth services to increase access to care among HHC patients. These findings underscore the need to improve communication and coordination between patients, HHC personnel, and primary care providers and the role that on-demand telehealth services can have in transforming HHC.

Social-distancing guidelines from the COVID-19 pandemic have potential to compound morbidity in persons with dementia (PwD) and increase caregiver burden. This qualitative study utilized semi-structured interviews between August-November 2020 to explore the impact of COVID-19 on PwD and caregivers. Conventional qualitative content analysis was used. Inter-coder reliability was confirmed using the kappa coefficient. Twenty-five interviews were completed with four themes emerging: disruption of socialization, fear and risk mitigation, coping strategies, and caregiver burden. Participants described how lack of socialization and confinement led to feelings of loneliness, depression, and worsening memory problems. Caregivers reported increased burden and heightened feelings of responsibility for their loved one. Increased isolation imposed by the pandemic has a detrimental impact on PwD. Further work is needed to develop interventions to support PwD and other cognitive impairments and caregivers during the pandemic and when in-person socialization is not possible.

Background We conducted in-depth interviews to characterize reasons for COVID-19 vaccine hesitancy in emergency department (ED) patients and developed messaging platforms that may address their concerns. In this trial, we seek to determine whether provision of these COVID-19 vaccine messaging platforms in EDs will be associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients. Methods This is a cluster-randomized controlled trial (RCT) evaluating our COVID-19 vaccine messaging platforms in seven hospital EDs (mix of academic, community, and safety-net EDs) in four US cities. Within each study site, we randomized 30 1-week periods to the intervention and 30 1-week periods to the control. Adult patients who have not received a COVID-19 vaccine are eligible with these exclusions: (1) major trauma, intoxication, altered mental status, or critical illness; (2) incarceration; (3) psychiatric chief complaint; and (4) suspicion of acute COVID-19 illness. Participants receive an orally administered Intake survey. During intervention weeks, participants then receive three COVID-19 vaccine messaging platforms (4-min video, one-page informational flyer and a brief, scripted face-to-face message delivered by an ED physician or nurse); patients enrolled during non-intervention weeks do not receive these platforms. Approximately, an hour after intake surveys, participants receive a Vaccine Acceptance survey during which the primary outcome of acceptance of the COVID-19 vaccine in the ED is ascertained. The other primary outcome of receipt of a COVID-19 vaccine within 32 days is ascertained by electronic health record review and phone follow-up. To determine whether provision of vaccine messaging platforms is associated with a 7% increase in vaccine acceptance and uptake, we will need to enroll 1290 patients. Discussion Highlighting the difficulties of trial implementation during the COVID-19 pandemic in acute care settings, our novel trial will lay the groundwork for delivery of public health interventions to vulnerable populations whose only health care access occurs in EDs. Conclusions Toward addressing vaccine hesitancy in vulnerable populations who seek care in EDs, our cluster-RCT will determine whether implementation of vaccine messaging platforms is associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients. Trial status We began enrollment in December 2021 and expect to continue through 2022. Trial registration ClinicalTrials.govNCT05142332. Registered 02 December 2021.

Background: Rare variants in PLCG2 (p.P522R), ABI3 (p.S209F), and TREM2 (p.R47H, p.R62H) have been associated with late onset Alzheimer’s disease (LOAD) risk in Caucasians. After the initial report, several studies have found positive results in cohorts of different ethnic background and with different phenotype. Objective: In this study, we aim to evaluate the association of rare coding variants in PLCG2, ABI3, and TREM2 with LOAD risk and their effect at different time points of the disease. Methods: We used a European American cohort to assess the association of the variants prior onset (using CSF Aβ42, tau, and pTau levels, and amyloid imaging as endophenotypes) and after onset (measured as rate of memory decline). Results: We confirm the association with LOAD risk of TREM2 p.R47H, p.R62H and ABI3 p.S209F variants, and the protective effect of PLCG2 p.P522R. In addition, ABI3 and TREM2 gene-sets showed significant association with LOAD risk. TREM2 p.R47H and PLCG2 p.P522R variants were also statistically associated with increase of amyloid imaging and AD progression, respectively. We did not observe any association of ABI3 p.S209F with any of the other AD endophenotypes. Conclusion: The results of this study highlight the importance of including biomarkers and alternative phenotypes to better understand the role of novel candidate genes with the disease.

PURPOSE: The purpose of this study was to develop the Oncology Opportunity Cost Assessment Tool (OOCAT), a survey instrument to evaluate the opportunity costs patients experience when seeking medical oncology care. METHODS: Development of the OOCAT involved extensive patient engagement through both focus groups and interviews. First, the study team developed a list of opportunity cost concepts, which included patients' logistical and financial considerations related to seeking care. We conducted focus groups with patients to expand upon this list of concepts, and then developed a set of questions that incorporated all the concepts generated during the focus groups. To refine these questions, we next performed cognitive interviews with another set of patients to ensure content validity and clarity of instrument items, refining the OOCAT iteratively on the basis of feedback. RESULTS: We engaged 23 participants (17 patients and six caregivers) across four focus groups and 17 participants in cognitive interviews. Focus group participants generated 112 concepts, which resulted in an initial OOCAT with 16 questions. Cognitive interviews resulted in modification of 12 questions and addition of two questions (related to coordination of transportation and impact on home responsibilities). The final OOCAT consisted of 18 items examining time requirements for appointments, financial implications of traveling to appointments for the patient and the caregiver, and logistical and quality-of-life challenges associated with traveling for appointments. CONCLUSION: We developed the OOCAT, an instrument designed to evaluate patient-level opportunity costs of seeking medical oncology care. Further studies to validate the OOCAT are underway.

PURPOSE: The COVID-19 pandemic necessitated a rapid expansion of telehealth use in oncology, a specialty in which prior utilization was low in part because of barriers perceived by providers. Understanding the changing perceptions of medical oncology providers during the pandemic is critical for continued expansion and improvement of telehealth in cancer care. This study was designed to identify medical oncology providers' perceptions of telehealth video visits as influenced by the COVID-19 pandemic. METHODS: We conducted semi-structured interviews with medical oncology providers from November 20, 2020, to January 27, 2021, at the Sidney Kimmel Cancer Center at Thomas Jefferson University, a National Cancer Institute–designated cancer center in an urban, academic health system in Philadelphia, PA. We assessed provider perceptions of the impact of the COVID-19 pandemic on (1) provider-level comfort and willingness for telehealth, (2) provider-perceived patient comfort and willingness to engage in telehealth, and (3) continued barriers to successful telehealth use. RESULTS: Volunteer and convenience sampling resulted in the participation of 25 medical oncology providers, including 18 physicians and seven advanced practice providers, in semi-structured interviews. Of the 25 participants, 13 (52%) were female and 19 (76%) were White, with an average age of 48.5 years (standard deviation = 12.6). Respondents largely stated an increased comfort level and willingness for use of video visits. In addition, respondents perceived a positive change in patient comfort and willingness, mostly driven by convenience, accessibility, and reduced risk of COVID-19 exposure. However, several reported technologic issues and limited physical examination capability as remaining barriers to telehealth adoption. CONCLUSION: The rapid adoption of telehealth necessitated by the COVID-19 pandemic has increased provider-level and provider-perceived patient comfort and willingness to engage in video visits for cancer care. As both providers and patients increasingly accept telehealth across many use cases, future work should focus on further addressing technology and physical examination barriers and ensuring continued reimbursement for telehealth as a routine part of covered care.

PURPOSE Telehealth in medical oncology has expanded secondary to the COVID-19 pandemic. However, quantitative research on medical oncology telehealth use shows conflicting results on patient satisfaction, whereas qualitative data are sparse. Our qualitative study aimed to identify the factors influencing patient acceptability of video visits for medical oncology care before and at the onset of the expansion of telehealth because of the COVID-19 pandemic. METHODS Semi-structured interviews were conducted between November 2019 and April 2020 with 20 patients who participated in a telehealth visit with a medical oncology provider at Thomas Jefferson University. RESULTS Of the 20 participants, 13 (65%) were female and 15 (75%) were White, with a mean (standard deviation) age of 60.5 years (11.8). Patients identified convenience, anxiety, COVID-19, and provider preference as positively influencing the acceptability of video visits; however, some patients noted limitations in provider connection, physical examinations, and visit length as disadvantages. Regarding receipt of serious or bad news, some preferred video visits for privacy, immediacy of results, news processing, and family comfort. Others preferred in-person encounters for provider support and the ability to receive written information and in-person referrals. CONCLUSION Patient-perceived factors influencing general acceptability, appropriateness of serious and bad news delivery, and future uses of telehealth were unique to each individual, but shared common themes. Understanding each patient's perspective of telehealth acceptability and tailoring use to their preferences is critical for continued utilization. Further research is needed to understand and address reasons for lack of telehealth uptake among certain patients.

The spinal cord emerges from a niche of neuromesodermal progenitors (NMPs) formed and maintained by WNT/fibroblast growth factor (FGF) signals at the posterior end of the embryo. NMPs can be generated from human pluripotent stem cells and hold promise for spinal cord replacement therapies. However, NMPs are transient, which compromises production of the full range of rostrocaudal spinal cord identities in vitro. Here we report the generation of NMP-derived pre-neural progenitors (PNPs) with stem cell-like self-renewal capacity. PNPs maintain pre-spinal cord identity for 7-10 passages, dividing to self-renew and to make neural crest progenitors, while gradually adopting a more posterior identity by activating colinear HOX gene expression. The HOX clock can be halted through GDF11-mediated signal inhibition to produce a PNP and NC population with a thoracic identity that can be maintained for up to 30 passages.

Interoceptive signalling has been shown to contribute to action regulation and action experience. Here, we assess whether motor behaviour can be influenced by anticipated homeostatic feeling states induced through different predictable contexts. Participants performed a reward incentive paradigm in which accurate responses increased (gain) or avoided the depletion (averted loss) of a credit score. Across two types of blocks, we varied the predictability of the outcome state. In predictable blocks, a cue signaled a gain, loss or control trial (motor response did not affect the credit score). This allowed participants to anticipate the interoceptive feeling state associated with the outcome. In unpredictable blocks, the cue had no relation to the type of outcome. Thus, participants were unable to anticipate the feeling state it produced. Via EEG, we measured the Heartbeat Evoked Potential (HEP) and the Contingent Negative Variation (CNV) as indices of interoceptive and motor processing respectively. In addition, we measured feedback P3 amplitude following outcome presentation and accuracy and reaction times of the required motor response. We observed higher HEP and CNV amplitudes as well as faster and more accurate motor responses in predictable compared to unpredictable outcome blocks. Similarly, feedback-related P3 amplitudes were significantly lower for predictable relative to unpredictable outcomes. Crucially, HEP amplitudes measured prior to feedback predicted feedback-related P3 amplitudes for anticipated outcome events. Results suggest that accurate anticipation of homeostatic feeling states associated with gain, loss or control outcomes facilitates motor execution and outcome evaluation. Findings are hereby the first to empirically assess the link between interoceptive and motor domains and provide primary evidence for a joint processing structure.

Key Points Question How do medical oncologists perceive telehealth video visits for cancer care? Findings In this qualitative study, in which 29 medical oncology health professionals were interviewed prior to the coronavirus disease 2019 (COVID-19) pandemic, the barriers to and benefits of telehealth video visits were elucidated. Although oncologists disagreed on the scope of a virtual physical examination and the financial impact of video visits, most recognized the benefit of eliminating travel and the challenge of delivering serious or bad news. Meaning Differing opinions of medical oncology health professionals regarding the barriers to and benefits of telehealth video visits provide insight into the challenges that limit telehealth quality as well as its expansion potential., This qualitative study surveyed physicians and other health professionals working in oncology to determine the perceived advantages and disadvantages of telehealth video visits in cancer care., Importance Telehealth has emerged as a means of improving access and reducing cost for medical oncology care; however, use by specialists prior to the coronavirus disease 2019 (COVID-19) pandemic still remained low. Medical oncology professionals’ perceptions of telehealth for cancer care are largely unknown, but are critical to telehealth utilization and expansion efforts. Objective To identify medical oncology health professionals’ perceptions of the barriers to and benefits of telehealth video visits. Design, Setting, and Participants This qualitative study used interviews conducted from October 30, 2019, to March 5, 2020, of medical oncology health professionals at the Thomas Jefferson University Hospital, an urban academic health system in the US with a cancer center. All medical oncology physicians, physicians assistants, and nurse practitioners at the hospital were eligible to participate. A combination of volunteer and convenience sampling was used, resulting in the participation of 29 medical oncology health professionals, including 20 physicians and 9 advanced practice professionals, in semistructured interviews. Main Outcomes and Measures Medical oncology health professionals’ perceptions of barriers to and benefits of telehealth video visits as experienced by patients receiving cancer treatment. Results Of the 29 participants, 15 (52%) were women and 22 (76%) were White, with a mean (SD) age of 48.5 (12.0) years. Respondents’ perceptions were organized using the 4 domains of the National Quality Forum framework: clinical effectiveness, patient experience, access to care, and financial impact. Respondents disagreed on the clinical effectiveness and potential limitations of the virtual physical examination, as well as on the financial impact on patients. Respondents also largely recognized the convenience and improved access to care enabled by telehealth for patients. However, many reported concern regarding the health professional–patient relationship and their limited ability to comfort patients in a virtual setting. Conclusions and Relevance Medical oncology health professionals shared conflicting opinions regarding the barriers to and benefits of telehealth in regard to clinical effectiveness, patient experience, access to care, and financial impact. Understanding oncologists’ perceptions of telehealth elucidates potential barriers that need to be further investigated or improved for telehealth expansion and continued utilization; further research is ongoing to assess current perceptions of health professionals and patients given the rapid expansion of telehealth during the COVID-19 pandemic.

Neuroscientific studies have mainly focused on the way humans perceive and interact with the external world. Recent work in the interoceptive domain indicates that the brain predictively models information from inside the body such as the heartbeat and that the efficiency with which this is executed can have implications for exteroceptive processing. However, to date direct evidence underpinning these hypotheses is lacking. Here, we show how the brain predictively refines neural resources to process afferent cardiac feedback and uses these interoceptive cues to enable more efficient processing of external sensory information. Participants completed a repetition-suppression paradigm consisting of a neutral repeating face. During the first face presentation, they heard auditory feedback of their heartbeat which either coincided with the systole of the cardiac cycle, the time at which cardiac events are registered by the brain or the diastole during which the brain receives no internal cardiac feedback. We used electroencephalography to measure the heartbeat evoked potential (HEP) as well as auditory (AEP) and visual evoked potentials (VEP). Exteroceptive cardiac feedback which coincided with the systole produced significantly higher HEP amplitudes relative to feedback timed to the diastole. Elevation of the HEP in this condition was followed by significant suppression of the VEP in response to the repeated neutral face and a stepwise decrease of AEP amplitude to repeated heartbeat feedback. Our results hereby show that exteroceptive heartbeat feedback coinciding with interoceptive signals at systole enhanced interoceptive cardiac processing. Furthermore, the same cue facilitating interoceptive integration enabled efficient suppression of a visual stimulus, as well as repetition suppression of the AEP across successive auditory heartbeat feedback. Our findings provide evidence that the alignment of external to internal signals can enhance the efficiency of interoceptive processing and that cues facilitating this process in either domain have beneficial effects for internal as well as external sensory processing.

Background A family history of diabetes and family members’ experiences with diabetes may influence individuals’ beliefs and expectations about their own diabetes. No qualitative studies have explored the relationship between family history and experiences and individuals’ diabetes illness representations. Methods Secondary data analysis of 89 exploratory, semi-structured interviews with adults with type 1 or type 2 diabetes seeking care in an urban health system. Participants had a recent diabetes-related ED visit/hospitalization or hemoglobin A1c > 7.5%. Interviews were conducted until thematic saturation was achieved. Demographic data were collected via self-report and electronic medical record review. Interviews were audio-recorded, transcribed, and coded using a conventional content analysis approach. References to family history and family members’ experiences with diabetes were analyzed using selected domains of Leventhal’s Common Sense Model of Self-Regulation. Results Participants cited both genetic and behavioral family history as a major cause of their diabetes. Stories of relatives’ diabetes complications and death figured prominently in their discussion of consequences; however, participants felt controllability over diabetes through diet, physical activity, and other self-care behaviors. Conclusions Findings supported an important role of family diabetes history and experience in development of diabetes illness representations. Further research is needed to expand our understanding of the relationships between these perceptions, self-management behaviors, and outcomes. Family practice providers, diabetes educators and other team members should consider expanding assessment of current family structure and support to also include an exploration of family history with diabetes, including which family members had diabetes, their self-care behaviors, and their outcomes, and how this history fits into the patient’s illness representations.

Background Missing action completion signals are assumed to trigger repetitive behavior and feelings of the action “not being right”. This proposal is based mostly on individual’s self-reports. Here, we investigated the influence of experimentally manipulated action completion experience and the obsessive-compulsive (OC) trait of incompleteness on behavioral and neurophysiological measures of action inhibition. Methods Action completion was manipulated in an adapted Go/NoGo task, and OC trait incompleteness was assessed in healthy participants. More commission errors and faster responses were expected after missing action completion, especially for individuals with high OC trait incompleteness. The inhibition-related event-related potentials (ERPs) N200 and P300 were also measured. Results High OC trait incompleteness led to more errors following omitted- and faster responses during commission errors following incongruent outcomes. Furthermore, lower N200 was associated with worse response inhibition, and high OC trait incompleteness was associated with reduced N200, but not reduced P300 amplitude. These findings provide evidence that trait-like feelings of incompleteness may underlie maladaptive action repetition and impaired inhibitory control as observed in OCD.

Verifying that conceptualisations of emotions are consistent across languages and cultures is a critical precondition for meaningful cross-cultural research on emotional experience. For achievement-related emotions tied to successes or failures, such evidence is virtually non-existent. To address this gap, we compared Canadian, German, Colombian, and Chinese university students’ (NTotal = 126) perceptions of affective, cognitive, motivational, physiological, and expressive characteristics of 16 achievement-related emotions using a psycholinguistic tool for profiling emotion concepts (Achievement Emotions CoreGRID). Cross-cultural similarity of emotion concepts quantified through double-entry intraclass correlations was generally high, and highest for their affective, cognitive, and motivational components. However, results also point to cultural variation, particularly for physiological and expressive components. Variation in perceived physiological characteristics was most pronounced for boredom, and for comparisons of Canada, Germany, and Colombia with China. Implications for theoretical propositions of universality of emotion concepts and future research on achievement-related emotions are discussed.

Objective The objective was to examine the relationship between patient uncertainty at the time of emergency department (ED) discharge as measured by the "Uncertainty Scale" (U-Scale) and 30-day return ED visits. We hypothesized that a higher score on the U-Scale predicts a higher likelihood of a 30-day return ED visit. Methods This was a cross-sectional single-site pilot study performed with adult patients discharged from an urban academic ED to assess the relationship of U-Scale total and subscale scores with 30-day return ED visits. We collected demographic and U-Scale scores at the time of ED discharge and subsequent 30-day ED utilization data by follow-up telephone call. Results No association was found between the total U-Scale score and subsequent ED utilization. Patients with higher uncertainty on the Treatment Quality subscale of the U-Scale had higher odds of a 30-day return ED visit (adjusted odds ratio [AOR] = 1.16), while patients with lower uncertainty on the Decision to Seek Care subscale had higher odds of a 30-day return ED visit (AOR = 0.68). Conclusion Patient uncertainty as measured by the U-Scale total score was not predictive of subsequent ED utilization. However, uncertainty related to treatment quality and the decision to seek care as measured by the U-Scale subscales may be important in predicting repeat ED utilization. Unlike individual patient factors such as age and race that have been associated with frequent ED visits in prior studies, these domains of uncertainty are potentially modifiable. Providers and health systems may successfully prevent recurrent acute care encounters through implementation of interventions designed to address patient uncertainty. Further work is needed to refine the U-Scale and test its predictive utility among a larger patient cohort.

Interoception refers to the processing of homeostatic bodily signals. Research demonstrates that interoceptive markers can be modulated via exteroceptive stimuli and suggests that the emotional content of this information may produce distinct interoceptive outcomes. Here, we explored the impact of differently valenced exteroceptive information on the processing of interoceptive signals. Participants completed a repetition-suppression paradigm viewing repeating or alternating faces. In experiment 1, faces wore either angry or pained expressions to explore the interoceptive response to different types of negative stimuli in the observer. In experiment 2, expressions were happy or sad to compare interoceptive processing of positive and negative information. We measured the heartbeat evoked potential (HEP) and visual evoked potentials (VEPs) as a respective marker of intero- and exteroceptive processing. We observed increased HEP amplitude to repeated sad and pained faces coupled with reduced HEP and VEP amplitude to repeated angry faces. No effects were observed for positive faces. However, we found a significant correlation between suppression of the HEP and VEP to repeating angry faces. Results highlight an effect of emotional expression on interoception and suggest an attentional trade-off between internal and external processing domains as a potential account of this phenomenon.

Humans are sensitive to gaze direction from early life, and gaze has social and affective values. Borderline personality disorder (BPD) is a clinical condition characterized by emotional dysregulation and enhanced sensitivity to affective and social cues. In this study we wanted to investigate the temporal-spatial dynamics of spontaneous gaze processing in BPD. We used a 2-back-working-memory task, in which neutral faces with direct and averted gaze were presented. Gaze was used as an emotional modulator of event-related-potentials to faces. High density EEG data were acquired in 19 females with BPD and 19 healthy women, and analyzed with a spatio-temporal microstates analysis approach. Independently of gaze direction, BPD patients showed altered N170 and P200 topographies for neutral faces. Source localization revealed that the anterior cingulate and other prefrontal regions were abnormally activated during the N170 component related to face encoding, while middle temporal deactivations were observed during the P200 component. Post-task affective ratings showed that BPD patients had difficulty to disambiguate neutral gaze. This study provides first evidence for an early neural bias toward neutral faces in BPD independent of gaze direction and also suggests the importance of considering basic aspects of social cognition in identifying biological risk factors of BPD.

Introduction: The Retro-IDEAL (ILUVIEN Implant for chronic DiabEtic MAcuLar edema) study is a retrospective study designed to assess real-world outcomes achieved with the ILUVIEN® (0.19 mg fluocinolone acetonide (FAc)) in patients with chronic diabetic macular edema (DME) in clinical practices in Germany. Methods: This study was conducted across 16 sites in Germany and involved 81 eyes (63 patients) with persistent or recurrent DME and a prior suboptimal response to a first-line intravitreal therapy (primarily anti-VEGF intravitreal therapies). Results: Patients were followed-up for 30.8 ± 11.3 months (mean ± standard deviation) and had a mean age of 68.0 ± 10.4 years. Best-recorded visual acuity (BRVA) improved by +5.5 letters at month 9 (P ⩽ 0.005, n=56; from a baseline of 49 letters) and this was maintained through to month 30 (P ⩽ 0.05, n = 42). There was a concurrent improvement in central macular thickness with a reduction from 502 µm at baseline to 338 µm at year 1 (P ⩽ 0.0001, n = 43). This effect was sustained to year 3 (i.e. 318 µm; P ⩽ 0.0001, n = 29). Mean intraocular pressure (IOP) remained constant between baseline and year 3 with a peak change of 1.9 mm Hg occurring at year 1. Elevated IOP was observed in a similar percentage of patients prior to (22.2% of cases) and following (27.2%) treatment with the FAc implant. In the majority of cases, these elevations were managed effectively with IOP medications. Conclusions: Despite substantial amounts of prior intravitreal treatments – primarily with anti–vascular endothelial growth factor (VEGF) drugs – this real-world study showed that sustained structural and functional improvements can last for up to 3 years with a single FAc implant.

Background Data are limited regarding how to effectively and efficiently identify patient priorities for research or clinical care. Our goal was to compare the comprehensiveness and efficiency of group concept mapping (GCM), a group participatory method, to interviews for identifying patient goals when seeking care. Methods We engaged patients with moderately- to poorly-controlled diabetes mellitus in either GCM or an individual interview. The primary outcome was the comprehensiveness of GCM brainstorming (the first stage of GCM) as compared to interviews for eliciting patient-important outcomes (PIOs) related to seeking care. Secondary outcomes included 1) comprehensiveness of GCM brainstorming and interviews compared to a master list of PIOs and 2) efficiency of GCM brainstorming, the entire GCM process and interviews. Results We engaged 89 interview participants and 52 GCM participants (across 3 iterations of GCM) to identify outcomes most important to patients when making decisions related to diabetes management. We identified 26 PIOs in interviews, 33 PIOs in the first GCM brainstorming session, and 38 PIOs across all three GCM brainstorming sessions. The initial GCM brainstorming session identified 77% (20/26) of interview PIOs, and all 3 GCM brainstorming sessions combined identified 88% (23/26). When comparing GCM brainstorming and interviews to the master list of PIOs, the initial GCM brainstorming sessions identified 80% (33/41), all 3 GCM brainstorming sessions identified 93% (38/41) and interviews identified 63% (26/41) of all PIOs. Compared to interviews, GCM brainstorming required less research team time, more patient time, and had a lowest cost. The entire GCM process still required less research team time than interviews, though required more patient time and had a higher cost than interviews. Conclusions GCM brainstorming is a powerful tool for effectively and efficiently identifying PIOs in certain scenarios, though it does not provide the breadth and depth of individual interviews or the higher level conceptual organization of the complete process of GCM. Selection of the optimal method for patient engagement should include consideration of multiple factors including depth of patient input desired, research team expertise, resources, and the population to be engaged. Trial registration Registered on ClinicalTrials.gov, NCT02792777. Registration information submitted 6/2/2016, with the registration first posted on the ClinicalTrials.gov website 6/8/2016. Data collection began on 4/29/2016. Electronic supplementary material The online version of this article (10.1186/s12874-018-0656-x) contains supplementary material, which is available to authorized users.

We need to be able to learn new behaviour, but also be capable of changing existing routines, when they start conflicting with our long-term goals. Little is known about to what extent blank-slate learning of new and adjustment of existing behavioural routines rely on different neural and bodily mechanisms. In the current study, participants first acquired novel stimulus-response contingencies, which were subsequently randomly changed to create the need for flexible adjustments. We measured midfrontal theta oscillations via EEG as an indicator of neural conflict processing, as well as heart rate as a proxy of autonomic activity. Participants' trial-wise learning progress was estimated via computation modelling. Theta power and heart rate significantly differed between correct and incorrect trials. Differences between correct and incorrect trials in both neural and cardiac feedback processing were more pronounced for adjustments compared to blank-slate learning. This indicates that both midfrontal and cardiac processing are sensitive to changes in stimulus-response contingencies. Increases in individual learning rates predicted lower impact of performance feedback on midfrontal theta power, but higher impact on heart rate. This suggests that cardiac and midfrontal reactivity are partially reflective of different mechanisms related to feedback learning. Our results shed new light on the role of neural and autonomic mechanisms for learning and behavioural adjustments.

BACKGROUND Because >60 rotavirus strains have been reported worldwide, concerns exist about strain replacement after the introduction of rotavirus vaccines, particularly in developing countries with diverse strains and lower efficacy. METHODS We used the case-control design in 4 hospitals in Nicaragua to assess strain-specific vaccine effectiveness (VE) of a pentavalent rotavirus vaccine (RotaTeq) against rotavirus diarrhea. Cases were identified through prospective strain surveillance with reverse transcription-polymerase chain reaction for 3 years among children hospitalized for diarrhea, and controls were children negative for rotavirus. RESULTS We enrolled 1178 case-patients, 1082 (92%) with G and P typing, and 4927 controls. A different strain predominated each year with increasing age of the vaccine-eligible cohort during the study period: G2P[4] in 2008 (97%; mean age, 11.9 months), G1P[8] in 2009 (55%; mean age, 17.0 months), and G3P[8] in 2010 (78%; mean age, 17.3 months). Overall VE was 45% (95% confidence interval, 25%-59%). Regardless of the strain, VE estimates were 12%-79% lower among children aged ≥12 months relative to those 6-11 months of age. The lower VE for G3P[8] was related to the higher mean age of cases (17.3 months) compared with the G2P[4] strains (11.9 months), with a significant trend (R(2)= 0.819;P< .001) of declining effectiveness with increasing mean age of the cases. CONCLUSIONS Introduction of RotaTeq did not result in sustained emergence of any particular strain in Nicaragua. Variation in strain-specific effectiveness was due to an age-related decline in effectiveness rather than differences in protection against the observed strains.

Biodegradable materials play a crucial role in both material and medical sciences and are frequently used as a primary commodity for implants generation. Due to their material inherent properties, they are supposed to be entirely resorbed by the patients' body after fulfilling their task as a scaffold. This makes a second intervention (e.g. for implant removal) redundant and significantly enhances a patient’s post-operative life quality. At the moment, materials for resorbable and biodegradable implants (e.g. polylactic acid or poly-caprolactone polymers) are still intensively studied. They are able to provide mandatory demands such as mechanical strength and attributes needed for high-quality implants. Implants, however, not only need to be made of adequate material, but must also to be personalized in order to meet the customers’ needs. Combining three dimensional-printing and high-resolution imaging technologies a new age of implant production comes into sight. Three dimensional images (e.g. magnetic resonance imaging or computed tomography) of tissue defects can be utilized as digital blueprints for personalized implants. Modern additive manufacturing devices are able to use a variety of materials to fabricate custom parts within short periods of time. The combination of high-quality resorbable materials and personalized three dimensional-printing for the custom application will provide the patients with the best suitable and sustainable implants. In this study, we evaluated and compared four resorbable and three dimensional printable materials for their in vitro biocompatibility, in vitro rate of degradation, cell adherence and behavior on these materials as well as support of osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells. The tests were conducted with model constructs of 1 cm2 surface area fabricated with fused deposition modeling three dimensional-printing technology.

Contains fulltext : 181132.pdf (Publisher’s version ) (Open Access) In the present study, we applied Machine Learning (ML) methods to identify psychobiological markers of cognitive processes involved in the process of emotion elicitation as postulated by the Component Process Model (CPM). In particular, we focused on the automatic detection of five appraisal checks - novelty, intrinsic pleasantness, goal conduciveness, control, and power - in electroencephalography (EEG) and facial electromyography (EMG) signals. We also evaluated the effects on classification accuracy of averaging the raw physiological signals over different numbers of trials, and whether the use of minimal sets of EEG channels localized over specific scalp regions of interest are sufficient to discriminate between appraisal checks. We demonstrated the effectiveness of our approach on two data sets obtained from previous studies. Our results show that novelty and power appraisal checks can be consistently detected in EEG signals above chance level (binary tasks). For novelty, the best classification performance in terms of accuracy was achieved using features extracted from the whole scalp, and by averaging across 20 individual trials in the same experimental condition (UAR = 83.5 ± 4.2; N = 25). For power, the best performance was obtained by using the signals from four pre-selected EEG channels averaged across all trials available for each participant (UAR = 70.6 ± 5.3; N = 24). Together, our results indicate that accurate classification can be achieved with a relatively small number of trials and channels, but that averaging across a larger number of individual trials is beneficial for the classification for both appraisal checks. We were not able to detect any evidence of the appraisal checks under study in the EMG data. The proposed methodology is a promising tool for the study of the psychophysiological mechanisms underlying emotional episodes, and their application to the development of computerized tools (e.g., Brain-Computer Interface) for the study of cognitive processes involved in emotions. 19 p.

Study objective Although diagnosis is a valuable tool for health care providers, and often the reason patients say they are seeking care, it may not serve the same needs for patients as for providers. The objective of this study is to explore what patients specifically want addressed when seeking a diagnosis at their emergency department (ED) visit. We propose that understanding these needs will facilitate a more patient-centered approach to acute care delivery. Methods This qualitative study uses semistructured telephone interviews with participants recently discharged from the ED of a large urban academic teaching hospital to explore their expectations of their ED visit and postdischarge experiences. Results Thirty interviews were analyzed. Many participants reported wanting a diagnosis as a primary reason for seeking emergency care. When further asked to identify the functions of a diagnosis, they described wanting an explanation for their symptoms, treatment and guidance for symptoms, and clear communication about testing, treatment, and diagnosis. For many, a diagnosis was viewed as a necessary step toward achieving these goals. Conclusion Although diagnosis may not be a feasible outcome of every acute care visit, addressing the needs associated with seeking a diagnosis may be achievable. Reframing acute care encounters to focus on addressing specific patient needs, and not just identifying a diagnosis, may lead to more effective transitions home and improved patient outcomes.

Summary Social touch plays a powerful role in human life, with important physical and mental health benefits in development and adulthood. Touch is central in building the foundations of social interaction, attachment, and cognition [1–5], and early, social touch has unique, beneficial neurophysiological and epigenetic effects [6–9]. The recent discovery of a separate neurophysiological system for affectively laden touch in humans has further kindled scientific interest in the area [10, 11]. Remarkably, however, little is known about what motivates and sustains the human tendency to touch others in a pro-social manner. Given the importance of social touch, we hypothesized that active stroking elicits more sensory pleasure when touching others’ skin than when touching one’s own skin. In a set of six experiments (total N = 133) we found that healthy participants, mostly tested in pairs to account for any objective differences in skin softness, consistently judged another’s skin as feeling softer and smoother than their own skin. We further found that this softness illusion appeared selectively when the touch activated a neurophysiological system for affective touch in the receiver. We conclude that this sensory illusion underlies a novel, bodily mechanism of socio-affective bonding and enhances our motivation to touch others., Highlights • The social softness illusion reflects the sensory hedonics of active social touch • Stroking others’ skin feels softer and smoother than stroking our own skin • The illusion appears when the touch activates the receiver’s affective touch system • The illusion reflects a tactile mechanism of emotional sharing between individuals, Gentsch et al. report a novel illusion—the social softness illusion—revealing that we habitually perceive others’ skin as being softer than our own skin. The illusion reflects a tactile mechanism of emotional sharing between individuals and demonstrates the hedonic benefits of social touch in humans.

The transcription factor brachyury (T, BRA) is one of the first markers of gastrulation and lineage specification in vertebrates. Despite its wide use and importance in stem cell and developmental biology, its functional genomic targets in human cells are largely unknown. Here, we use differentiating human embryonic stem cells to study the role of BRA in activin A-induced endoderm and BMP4-induced mesoderm progenitors. We show that BRA has distinct genome-wide binding landscapes in these two cell populations, and that BRA interacts and collaborates with SMAD1 or SMAD2/3 signalling to regulate the expression of its target genes in a cell-specific manner. Importantly, by manipulating the levels of BRA in cells exposed to different signalling environments, we demonstrate that BRA is essential for mesoderm but not for endoderm formation. Together, our data illuminate the function of BRA in the context of human embryonic development and show that the regulatory role of BRA is context dependent. Our study reinforces the importance of analysing the functions of a transcription factor in different cellular and signalling environments., Summary: In differentiating hESCs, BRACHYURY has cell type-specific targets and functions: it acts with SMAD1 to promote mesoderm specification, while in the endoderm it interacts with SMAD2/3.

Comprehensive reviews of pre licensure rotavirus strain prevalence data indicated the global importance of six rotavirus genotypes, G1P[8], G2P[4], G3P[8], G4P[8], G9P[8] and G12P[8]. Since 2006, two vaccines, the monovalent Rotarix (RV1) and the pentavalent RotaTeq (RV5) have been available in over 100 countries worldwide. Of these, 60 countries have already introduced either RV1 or RV5 in their national immunization programs. Post licensure vaccine effectiveness is closely monitored worldwide. This review aimed at describing the global changes in rotavirus strain prevalence over time. The genotype distribution of the nearly 47,000 strains that were characterized during 2007–2012 showed similar picture to that seen in the preceding period. An intriguing finding was the transient predominance of heterotypic strains, mainly in countries using RV1. Unusual and novel antigen combinations continue to emerge, including some causing local outbreaks, even in vaccinated populations. In addition, vaccine strains have been found in both vaccinated infants and their contacts and there is evidence for genetic interaction between vaccine and wild-type strains. In conclusion, the post-vaccine introduction strain prevalence data do not show any consistent pattern indicative of selection pressure resulting from vaccine use, although the increased detection rate of heterotypic G2P[4] strains in some countries following RV1 vaccination is unusual and this issue requires further monitoring.

Interoception refers to the signaling of internal bodily commands. Here, we explore repetition suppression of intero- and exteroceptive neural markers to test whether the perception and predictability of exteroceptive stimulus material affects their expression. Participants completed a repetition suppression paradigm in which angry or neutral facial expressions repeated or alternated. Participants received either an implicit (experiment 1) or explicit (experiment 2) cue enabling the formation of expectations regarding the upcoming facial expression. We measured the heartbeat-evoked potential (HEP) indexing cardiac processing and visual evoked potentials (VEP) in response to viewing the second (repeated or alternated) face. Repeating angry facial expressions produced repetition suppression of both HEP and VEP amplitude while repeating neutral expressions led to repetition enhancement of HEP amplitude. This effect was magnified when participants were explicitly aware of predictive cues. Furthermore, repetition suppression of HEP amplitude correlated with neural attenuation of VEP activity. Results highlight repetition effects for interoceptive as well as exteroceptive neural markers and support top-down, expectation-based accounts of the phenomenon. Furthermore, results demonstrate that the perception of exteroceptive stimulus information has an effect on the processing of interoceptive signals and suggest a direct neural connection between the processing of external and internal sensory information.

Little is known about the impact of context on the meaning of emotion words. In the present study, we used a semantic profiling instrument (GRID) to investigate features representing five emotion components (appraisal, bodily reaction, expression, action tendencies, and feeling) of 11 emotion words in situational contexts involving success or failure. We compared these to the data from an earlier study in which participants evaluated the typicality of features out of context. Profile analyses identified features for which typicality changed as a function of context for all emotion words, except contentment, with appraisal features being most frequently affected. Those context effects occurred for both hypothesised basic and non-basic emotion words. Moreover, both data sets revealed a four-dimensional structure. The four dimensions were largely similar (valence, power, arousal, and novelty). The results suggest that context may not change the underlying dimensionality but affects facets of the meaning of emotion words.

The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction.We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs).Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children.Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea.

Since 2008, the World Health Organization (WHO) has coordinated the Global Rotavirus Surveillance Network, a network of sentinel surveillance hospitals and laboratories that report to ministries of health (MoHs) and WHO clinical features and rotavirus testing data for children aged5 years hospitalized with acute gastroenteritis. In 2013, WHO conducted a strategic review to assess surveillance network performance, provide recommendations for strengthening the network, and assess the network's utility as a platform for other vaccine-preventable disease surveillance. The strategic review team determined that during 2011 and 2012, a total of 79 sites in 37 countries met reporting and testing inclusion criteria for data analysis. Of the 37 countries with sites meeting inclusion criteria, 13 (35%) had introduced rotavirus vaccine nationwide. All 79 sites included in the analysis were meeting 2008 network objectives of documenting presence of disease and describing disease epidemiology, and all countries were using the rotavirus surveillance data for vaccine introduction decisions, disease burden estimates, and advocacy; countries were in the process of assessing the use of this surveillance platform for other vaccine-preventable diseases. However, the review also indicated that the network would benefit from enhanced management, standardized data formats, linkage of clinical data with laboratory data, and additional resources to support network functions. In November 2013, WHO's Strategic Advisory Group of Experts on Immunization (SAGE) endorsed the findings and recommendations made by the review team and noted potential opportunities for using the network as a platform for other vaccine-preventable disease surveillance. WHO will work to implement the recommendations to improve the network's functions and to provide higher quality surveillance data for use in decisions related to vaccine introduction and vaccination program sustainability.

Out-of-hospital cardiac arrest is a frequent cause of death in Europe. Hypoxic ischemic encephalopathy (HIE) often develops in initial survivors, and the question of treatment limitation arises in severely affected patients. To establish a poor prognosis with a high level of certainty, the use of a combination of prognostic parameters such as neurological examination, somatosensory evoked potentials, and neuron-specific enolase is common practice. A few recent studies suggest that gray–white matter ratio (GWR) determined from cranial computed tomography (CT) scans is an additional reliable predictor of poor prognosis. The standard GWR determination method involves measurements of 16 different regions of interest (ROIs). We tested whether a simplified method to obtain GWR has equivalent reliability for poor outcome prediction. We retrospectively analyzed 98 patients after cardiac arrest who had been treated with hypothermia. CT scans were obtained within the first 7 days after cardiac arrest. Neurological outcome was determined at intensive care unit discharge. Four different methods to obtain GWR were compared in a receiver-operating characteristic curve analysis with respect to their prognostic value for poor outcome prediction. The simplest method using only four ROIs (putamen and internal capsule bilaterally) had the same prognostic value compared with the standard method using 16 ROIs. The simplified GWR predicted poor outcome with a sensitivity of 44 % at 100 % specificity. Our results indicate that for poor outcome prediction in survivors of cardiac arrest, a simplified GWR determination is feasible and has the same reliability as the complex standard procedure.

Since 2006, the availability of two new rotavirus vaccines has raised enthusiasm to consider the eventual control and elimination of severe rotavirus diarrhea through the global use of vaccines. Rotavirus remains the most severe cause of acute diarrhea in children worldwide responsible for several hundred thousands of deaths in low income countries and up to half of hospital admissions for diarrhea around the world. The new vaccines have been recommended by WHO for all infants and in more than 47 countries, their introduction into routine childhood immunization programs has led to a remarkable decline in hospital admissions and even deaths within 3 years of introduction. Challenges remain with issues of vaccine finance globally and the problem that these live oral vaccines perform less well in low income settings where they are needed most. Ongoing research that will accompany vaccine introduction might help address these issues of efficacy and new vaccines and novel financing schemes may both help make these vaccines universally available and affordable in the decade.

We compared rotavirus detection rates in children with acute gastroenteritis (AGE) and in healthy controls using enzyme immunoassays (EIAs) and semiquantitative real-time reverse transcription PCR (qRT-PCR). We calculated rotavirus vaccine effectiveness using different laboratory-based case definitions to determine which best identified the proportion of disease that was vaccine preventable. Of 648 AGE patients, 158 (24%) were EIA positive, and 157 were also qRT-PCR positive. An additional 65 (10%) were qRT-PCR positive but EIA negative. Of 500 healthy controls, 1 was EIA positive and 24 (5%) were qRT-PCR positive. Rotavirus vaccine was highly effective (84% [95% CI 71%–91%]) in EIA-positive children but offered no significant protection (14% [95% CI −105% to 64%]) in EIA-negative children for whom virus was detected by qRT-PCR alone. Children with rotavirus detected by qRT-PCR but not by EIA were not protected by vaccination, suggesting that rotavirus detected by qRT-PCR alone might not be causally associated with AGE in all patients.

Group A rotaviruses (RV-A) are the leading cause of viral gastroenteritis in children worldwide and genotype G9P[8] is one of the five most common genotypes detected in humans. In order to gain insight into the degree of genetic variability of G9P[8] strains circulating in Cameroon, stool samples were collected during the 1999–2000 rotavirus season in two different geographic regions in Cameroon (Southwest and Western Regions). By RT-PCR, 15 G9P[8] strains (15/89 = 16.8%) were identified whose genomic configurations was subsequently determined by complete or partial gene sequencing. In general, all Cameroonian G9 strains clustered into current globally-spread sublineages of the VP7 gene and displayed 86.6–100% nucleotide identity amongst themselves and 81.2–99.5% nucleotide identity with global G9 strains. The full genome classification of all Cameroonian strains was G9-P[8]-I1–R1–C1–M1–A1–N1–T1–E1–H1 but phylogenetic analysis of each gene revealed that the strains were spread across 4 or more distinct lineages. An unusual strain, RVA/Human-wt/CMR/6788/1999/G9P[8], which shared the genomic constellation of other Cameroonian G9P[8] strains, contained a novel G9 subtype which diverged significantly (18.8% nucleotide and 19% amino acid distance) from previously described G9 strains. Nucleotide and amino acid alignments revealed that the 3′ end of this gene is highly divergent from other G9 VP7 genes suggesting that it arose through extensive accumulation of point mutations. The results of this study demonstrate that diverse G9 strains circulated in Cameroon during 1999–2000.

India accounts for 22% of the 453,000 global rotavirus deaths among children5 years annually. The Indian Rotavirus Strain Surveillance Network provides clinicians and public health partners with valuable rotavirus disease surveillance data. Our analysis offers policy-makers an update on rotavirus disease burden with emphasis on regional shifts in rotavirus strain epidemiology in India.Children5 years requiring hospitalization for acute gastroenteritis were selected from 10 representative hospitals in 7 cities throughout India between November 2005 through June 2009. We used a modified World Health Organization protocol for rotavirus surveillance; stool specimens were collected and tested for rotavirus using enzyme immunoassay and reverse-transcription polymerase chain reaction.A total of 7285 stool specimens collected were tested for rotavirus, among which 2899 (40%) were positive for rotavirus. Among the 2899 rotavirus detections, a G-type could not be determined for 662 (23%) and more than one G type was detected in 240 (8%). Of 1997 (69%) patients with only one G-type, the common types were G1 (25%), G2 (21%), G9 (13%), and G12 (10%). The proportion of rotavirus infections attributed to G12 infections rose from 8% to 39% in the Northern region and from 8% to 24% in the Western region.This study highlights the large, ongoing burden of rotavirus disease in India, as well as interesting regional shifts in rotavirus strain epidemiology, including an increasing detection of G12 rotavirus strains in some regions. While broad heterotypic protection from rotavirus vaccination is expected based on pre- and post-licensure data from other settings, effectiveness assessments and rotavirus strain monitoring after vaccine introduction will be important.

Background. We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) visits in US children. Methods. We enrolled children

This article presents an innovative method for capturing the content of adolescents' electronic communication on handheld devices: text messaging, e-mail, and instant messaging. In an ongoing longitudinal study, adolescents were provided with BlackBerry devices with service plans paid for by the investigators, and use of text messaging was examined when participants were 15 years old and in the 10th grade (N = 175; 81 girls). BlackBerries were configured so that the content of all text messages, e-mail messages, and instant messages was saved to a secure server and organized in a highly secure, searchable, online archive. This article describes the technology used to devise this method and ethical considerations. Evidence for validity is presented, including both information on use of text messaging to show that participants used these devices heavily and frequencies of profane and sexual language in a 2-day sample of text messaging to demonstrate that they were communicating openly.

This study examines the neurocognitive mechanisms underlying the sense of agency, that is, the experience of causing and controlling events in our environment. Specifically, we tested the hypothesis that the sense of agency depends on an optimal integration of different anticipatory signals, generated by motor and nonmotor systems. An established marker of pre-reflective agency experience is the suppression of cortical responses to actively generated feedback as compared to passively observed feedback, which was measured here by event-related potentials (ERPs). Sensory expectations based on motor-related and unrelated signals were induced by varying the probabilistic contingency between action and feedback, and by priming the feedback prior to the action. Moreover, simultaneous conscious agency judgments were assessed. A reduction of visual N1 response was found to self- as compared to externally generated feedback. In addition, the N1 was modulated by accurate anticipations based on prime stimuli, independent of the precision of motor predictions. Conscious agency judgments, in contrast, were enhanced by prime stimuli only in situations where no precise motor predictions of the action feedback were available. These results indicate that anticipatory signals arising from motor and nonmotor systems are integrated differently depending on the level of agency processing. Our findings suggest that, at a pre-reflective level, the brain's agency system relies on both embodied signals and nonmotor sensory expectations. At higher cognitive levels, motor and nonmotor cues are weighted differently depending on their relative reliability in a given context, thereby providing a basis for robust agentive self-awareness.

In 2009, three children were hospitalized in Rochester, NY, with sequence-confirmed G8P[4] rotavirus gastroenteritis—the first U.S. detection of this uncommon strain more typically found in Africa. Continued monitoring of G8P[4] and other rotavirus genotypes not represented in current vaccines is essential to assess whether vaccination will result in an increase in prevalence of these strains.

After discovery in the early 1980s, Rotavirus A serotype G9 was detected infrequently for almost a decade. Since the mid-1990s, however, serotype G9 has emerged to become a globally common strain linked to the introduction of a single, new genetic variant of G9 VP7 gene. Studies have demonstrated that genetically divergent G9 strains co-circulated at low frequency with the emerging variants. Examples include unique U.S. G9 strains Om46/Hu/USA/1998 and Om67/Hu/USA/1998, isolated in Omaha during the 1997–1998 rotavirus season, that are more closely related phylogenetically to reference strains from the 1980s than to most emerging G9 strains from the U.S. and globally. Here, we sequenced the VP7 full open reading frame for all available G9 strains (n = 12) identified in Omaha during 1996–2000 seasons to investigate their epidemiology and evolution. In addition, the full or partial length open reading frames of the remaining 10 genes for five divergent Om46-like strains and one modern G9 variant were sequenced to evaluate their potential origin. Our findings suggest that Om46-like G9 strains may have been introduced into humans recently, perhaps in 1997–1998 when it was first detected, and the presumed original host of this VP7 gene variant may have been an animal species based on the unexpected detection of porcine rotavirus related NSP2 gene in the genome. The relatively high fitness of Om46-like strains during the 1997–1998 rotavirus season, 1 year after the globally important G9 variant was documented to be already spreading in the study area and other sites of the United States, appears to parallel findings on seasonal replacement of various genetic and antigenic variants of other common human rotavirus antigen specificities.