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This research examines Japanese tours abroad, specifically those to Southeast Asia, focusing on ways that \"first-hand experience\" and \"culture\" are made into products, and how that standardization and replication in turn affect cultural knowledge. The thesis is a full-length ethnography of tourists and tour production. Fieldwork took place at a tour wholesale company in Osaka, with two months in Southeast Asia. Part I describes the front stage tour experience. In this time-and-place apart from daily reality, the tour organizes the basic building blocks of cultural knowledge: the body, social relations, time, and space. I then look at ways tourists take their experience back to Japan through photos, gifts, and telling tales. Part II examines how marketing affects the content and the consumption of tours. I describe the types of tourists who buy these packaged tours, then analyze the ways in which dreams and feelings are linked with foreign geographies. Part III lays out the complex logistics of producing uniform quality. These chapters look at how Japanese corporations and overseas subcontractors design tours, making arrangements for each customer, and stage the tour with cosmopolitan facilities and Japanese-style service. I conclude that packaged overseas tours allow Japanese tourists to gain self-confidence in negotiating a wider territory, and to explore their identities vis-a-vis both Asians and westerners. Packaged tours greatly expand access to these experiences, however the many constraints on tour production limit the kinds of experiences tourists have, and consequently narrow the society's available range of interpretations and information about foreign peoples and places.

Background Enhanced Recovery After Surgery (ERAS ® ) Society guidelines integrate evidence-based practices into multimodal care pathways that have improved outcomes in multiple adult surgical specialties. There are currently no pediatric ERAS ® Society guidelines. We created an ERAS ® guideline designed to enhance quality of care in neonatal intestinal resection surgery. Methods A multidisciplinary guideline generation group defined the scope, population, and guideline topics. Systematic reviews were supplemented by targeted searching and expert identification to identify 3514 publications that were screened to develop and support recommendations. Final recommendations were determined through consensus and were assessed for evidence quality and recommendation strength. Parental input was attained throughout the process. Results Final recommendations ranged from communication strategies to antibiotic use. Topics with poor-quality and conflicting evidence were eliminated. Several recommendations were combined. The quality of supporting evidence was variable. Seventeen final recommendations are included in the proposed guideline. Discussion We have developed a comprehensive, evidence-based ERAS guideline for neonates undergoing intestinal resection surgery. This guideline, and its creation process, provides a foundation for future ERAS guideline development and can ultimately lead to improved perioperative care across a variety of pediatric surgical specialties.

The psychological nature of the association between MPFC modulation and social evaluation remains poorly understood. Despite confounds, small samples, and mixed results in existing research, MPFC activation is often interpreted as a reflection of socioemotional association and/or perceived similarity between the self and an evaluation target. The present research addressed issues from the existing literature by examining whether MPFC is modulated by (a) socioemotional associations unconfounded by previous knowledge (memory effects (Study 1, N = 48), repetition suppression (Study 2, N = 43), multi-voxel pattern analysis (Study 1 & 2)) and (b) perceived similarity to self (Study 2). MPFC was modulated by self-reference and trait-relevance, but there was not significant empirical support for the interpretation that MPFC modulation reflects socioemotional association or perceived similarity. These findings highlight the weak basis for prevailing assumptions about the psychological significance of MPFC in social evaluation and the need for studies which test multiple mechanisms.

Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously 1 – 3 . Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21–68); 8 patients were male. Common symptoms at illness onset were cough ( n  = 8) and fever ( n  = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2–3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness. Detailed clinical and virologic characteristics of the first 12 individuals with COVID-19 in the United States from the US Centers for Disease Control and Prevention.

Socrates said that in order to lead a balanced life one must, “know thyself.” In two fMRI experiments, the present study examined the mechanisms mediating two ways in which the self can be known: through direct appraisals (i.e., an individual's own self-beliefs) and reflected appraisals (i.e., an individual's perception of how others view him or her). Experiment 1 examined the common and distinct neural bases of direct appraisals of the self, close others, and normative judgments of trait desirability. All three judgment types activated medial prefrontal cortex (MPFC) to a similar degree. Experiment 2 examined the common and distinct neural bases of (1) direct appraisals of self, a close other or a non-close other, and (2) reflected appraisals made from the perspective of a close or a non-close other. Consistent with Experiment 1, all judgment types activated MPFC. Direct appraisals of the self as compared to others more strongly recruited MPFC and right rostrolateral PFC. Direct appraisals as compared to reflected appraisals recruited regions associated with a first-person perspective (posterior cingulate), whereas reflected as compared to direct appraisals recruited regions associated with emotion and memory (insula, orbitofrontal, and temporal cortex). These results support models suggesting that MPFC mediates meta-cognitive processes that may be recruited for direct and reflected self appraisals depending upon the demands of a specific task.

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63 , whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies. The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity. Complexity in oesophageal carcinomas The Cancer Genome Atlas Research Network reports integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus. They identify genomic and molecular features that differentiate oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. They find that the genomic profiles of oesophageal adenocarcinomas are more similar to those for gastric adenocarcinoma, suggesting that these might be classified together. Separate consideration of adenocarcinoma and squamous cell carcinoma—and further molecular characterization of these cancers—may be helpful in clinical trials and for developing targeted drug therapies.

Abstract Despite robust associations between the ventral anterior cingulate cortex (vACC) and social evaluation, the role of vACC in social evaluation remains poorly understood. Two hypotheses have emerged from existing research: detection of positive valence and detection of opportunities for subjective reward. It has been difficult to understand whether one or both hypotheses are supported because previous research conflated positive valence with subjective reward. Therefore, the current functional magnetic resonance imaging study drew on a social evaluation paradigm that disentangled positive valence and subjective reward. Participants evaluated in-group and out-group politicians in a social evaluation paradigm that crossed trait valence with opportunity for subjectively rewarding affirmation (i.e. a chance to affirm positive traits about in-group politicians and affirm negative traits about out-group politicians). Participants rated in-group politicians more positively and out-group politicians more negatively. One subregion of vACC was modulated by positive valence and another relatively posterior region of vACC was modulated by opportunity for subjective reward (i.e. a politician × valence interaction). The current findings demonstrate the importance of incorporating vACC function into models of social cognition and provide new avenues for sharpening our understanding of the psychological significance of vACC function in social evaluation and related domains such as reward and affect.

Lacerations are the most common traumatic reason for children to visit an emergency department (ED), accounting for almost half of all procedures performed. Children experience considerable distress during laceration repair, despite routine application of local anesthetic. Pharmacologic anxiolysis may mitigate the negative practice of forcefully restraining a child, however, evidence for the most effective agent is lacking. We aim to determine the most effective anxiolytic agent for laceration repair in children. This is a multicentre, phase III, three-arm, adaptive, randomized, open-label, trial. We will include children 2-12 years with a single laceration requiring suture repair in the ED. Participants will be randomized to receive intranasal dexmedetomidine (IND) 3 mcg/kg, intranasal midazolam (INM) 0.4 mg/kg, or inhaled 50% nitrous oxide (N2O). The primary outcome is the weighted mean anxiolysis score using the Observational Scale of Behavioral Distress - Revised (OSBD-R) from initial positioning to tying of the last suture. Secondary outcomes include need for additional anxiolytic, need for physical restraint, adverse events (AEs), and delayed maladaptive behaviors. The primary analysis will be conducted by intention-to-treat. Results will report posterior means, standard deviations (SDs), and 95% high density posterior credible intervals for Total Distress Score on the OSBD-R. We will rank interventions based on the probability that an intervention is superior (Pbest) and the Surface Area Under the Cumulative Ranking Curve (SUCRA) to indicate relative anxiolytic efficacy. The mean difference in Total Distress Score and secondary outcomes will be estimated using Bayesian models. Ethics approval will be obtained from institutional review boards of the participating sites. Informed consent will be obtained from guardians of all participants in addition to assent from all participants. Study data will be submitted for publication. Clinicaltrials.gov NCT05383495.

Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is supported by a lytic form of cell death, termed pyroptosis. Innate immune cells, such as macrophages or dendritic cells, express and activate inflammasomes. However, it has also been demonstrated that human primary keratinocytes activate different types of inflammasomes in vitro, for example, upon UVB irradiation or viral infection. Keratinocytes are the main cell type of the epidermis, the outermost layer of the body, and form a protective barrier consisting of a stratified multi-layered epithelium. In human, gain-of-function mutations of the NLRP1 gene cause syndromes mediated by inflammasome activation in keratinocytes that are characterised by skin inflammation and skin cancer susceptibility. Here we demonstrate that murine keratinocytes do not activate inflammasomes in response to stimuli, which induce IL-1β and -18 secretion by human keratinocytes. Whereas murine keratinocytes produced caspase-1 and proIL-18, expression of the inflammasome proteins Nlrp1, Nlrp3, Aim2, Asc, and proIL-1β was, compared to human keratinocytes or murine dendritic cells, very low or even undetectable. Priming of murine keratinocytes with cytokines commonly used for induction of proIL-1β and inflammasome protein expression did not rescue inflammasome activation. Nevertheless, UVB-induced inflammation and neutrophil recruitment in murine skin was dependent on IL-1β and caspase-1. However, also under these conditions, we did not detect expression of proIL-1β by keratinocytes in murine skin, but by immune cells. These results demonstrate a higher immunological competence of human compared to murine keratinocytes, which is reflected by stress-induced IL-1β secretion that is mediated by inflammasomes. Therefore, keratinocytes in human skin can exert immune functions, which are carried out by professional immune cells in murine skin.