An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission.

Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE participants, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unclear features of EoE. Active disease displays enrichment of ALOX15+ macrophages, PRDM16+ dendritic cells expressing the EoE risk gene ATP10A, and cycling mast cells, with concomitant reduction of TH17 cells. Ligand-receptor expression uncovers eosinophil recruitment programs, increased fibroblast interactions in disease, and IL-9+IL-4+IL-13+ TH2 and endothelial cells as potential mast cell interactors. Resolution of inflammation-associated signatures includes mast and CD4+ TRM cell contraction and cell type-specific downregulation of eosinophil chemoattractant, growth, and survival factors. These cellular alterations in EoE and remission advance our understanding of eosinophilic inflammation and opportunities for therapeutic intervention.

Independent and synergistic effects of microplastics and endocrine-disrupting chemicals on the reproductive social behavior of fathead minnows (Pimephales promelas).

Microplastics (MPs) have become an environmental concern in recent years, with most research focused on the physiological effects of exposure. Comparatively little consideration has been given to the potential behavioral impacts of exposure, which may also have fitness consequences for individuals. Moreover, MPs can serve as vectors for endocrine-disrupting chemicals and other locally co-occurring contaminants known to impair behavioral responses. This project aimed to determine whether MPs alone or in association with a common environmental EDC (17-alpha ethinyl estradiol; EE2) alter reproductive behavior and decision-making in fish. Male and female fathead minnows (Pimephales promelas) were exposed to MPs associated with either a low (10 ng/L; MPEE2 10) or high (50 ng/L, MPEE2 50) concentration of EE2, or MPs without EE2 (MPvirgin) for 30 days via a dietary feeding protocol. Behavioral trials were conducted on Day 31 to determine the effects of exposure on male-female social interactions. The expression of male sexually selected traits, including courtship, was unaffected by exposure. However, non-exposed females in all treatment groups trended toward discrimination against exposed males, which reached statistical significance for the MPEE2 50 group. Female fish exposed to MPs, alone or in association with EE2, were equally likely to approach and associate with non-exposed and exposed males. The results from this study suggest that MPs may alter social behavior in fishes and that the behavioral impacts of exposure may be more strongly pronounced in females than males. Such individual-level changes in fitness have the potential to impact population size, with downstream effects on the broader aquatic community.

Psychosocial interventions for survivors of rape and sexual assault experienced during adulthood.

BACKGROUND: Exposure to rape, sexual assault and sexual abuse has lifelong impacts for mental health and well-being. Prolonged Exposure (PE), Cognitive Processing Therapy (CPT) and Eye Movement Desensitisation and Reprocessing (EMDR) are among the most common interventions offered to survivors to alleviate post-traumatic stress disorder (PTSD) and other psychological impacts. Beyond such trauma-focused cognitive and behavioural approaches, there is a range of low-intensity interventions along with new and emerging non-exposure based approaches (trauma-sensitive yoga, Reconsolidation of Traumatic Memories and Lifespan Integration). This review presents a timely assessment of international evidence on any type of psychosocial intervention offered to individuals who experienced rape, sexual assault or sexual abuse as adults. OBJECTIVES: To assess the effects of psychosocial interventions on mental health and well-being for survivors of rape, sexual assault or sexual abuse experienced during adulthood. SEARCH METHODS: In January 2022, we searched CENTRAL, MEDLINE, Embase, 12 other databases and three trials registers. We also checked reference lists of included studies, contacted authors and experts, and ran forward citation searches. SELECTION CRITERIA: Any study that allocated individuals or clusters of individuals by a random or quasi-random method to a psychosocial intervention that promoted recovery and healing following exposure to rape, sexual assault or sexual abuse in those aged 18 years and above compared with no or minimal intervention, usual care, wait-list, pharmacological only or active comparison(s). We classified psychosocial interventions according to Cochrane Common Mental Disorders Group's psychological therapies list. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 36 studies (1991 to 2021) with 3992 participants randomly assigned to 60 experimental groups (3014; 76%) and 23 inactive comparator conditions (978, 24%). The experimental groups consisted of: 32 Cognitive Behavioural Therapy (CBT); 10 behavioural interventions; three integrative therapies; three humanist; five other psychologically oriented interventions; and seven other psychosocial interventions. Delivery involved 1 to 20 (median 11) sessions of traditional face-to-face (41) or other individual formats (four); groups (nine); or involved computer-only interaction (six). Most studies were conducted in the USA (n = 26); two were from South Africa; two from the Democratic Republic of the Congo; with single studies from Australia, Canada, the Netherlands, Spain, Sweden and the UK. Five studies did not disclose a funding source, and all disclosed sources were public funding. Participants were invited from a range of settings: from the community, through the media, from universities and in places where people might seek help for their mental health (e.g. war veterans), in the aftermath of sexual trauma (sexual assault centres and emergency departments) or for problems that accompany the experience of sexual violence (e.g. sexual health/primary care clinics). Participants randomised were 99% women (3965 participants) with just 27 men. Half were Black, African or African-American (1889 participants); 40% White/Caucasian (1530 participants); and 10% represented a range of other ethnic backgrounds (396 participants). The weighted mean age was 35.9 years (standard deviation (SD) 9.6). Eighty-two per cent had experienced rape or sexual assault in adulthood (3260/3992). Twenty-two studies (61%) required fulfilling a measured PTSD diagnostic threshold for inclusion; however, 94% of participants (2239/2370) were reported as having clinically relevant PTSD symptoms at entry. The comparison of psychosocial interventions with inactive controls detected that there may be a beneficial effect at post-treatment favouring psychosocial interventions in reducing PTSD (standardised mean difference (SMD) -0.83, 95% confidence interval (CI) -1.22 to -0.44; 16 studies, 1130 participants; low-certainty evidence; large effect size based on Cohen's D); and depression (SMD -0.82, 95% CI -1.17 to -0.48; 12 studies, 901 participants; low-certainty evidence; large effect size). Psychosocial interventions, however, may not increase the risk of dropout from treatment compared to controls, with a risk ratio of 0.85 (95% CI 0.51 to 1.44; 5 studies, 242 participants; low-certainty evidence). Seven of the 23 studies (with 801 participants) comparing a psychosocial intervention to an inactive control reported on adverse events, with 21 events indicated. Psychosocial interventions may not increase the risk of adverse events compared to controls, with a risk ratio of 1.92 (95% CI 0.30 to 12.41; 6 studies; 622 participants; very low-certainty evidence). We conducted an assessment of risk of bias using the RoB 2 tool on a total of 49 reported results. A high risk of bias affected 43% of PTSD results; 59% for depression symptoms; 40% for treatment dropout; and one-third for adverse events. The greatest sources of bias were problems with randomisation and missing outcome data. Heterogeneity was also high, ranging from I2 = 30% (adverse events) to I2 = 87% (PTSD). AUTHORS' CONCLUSIONS: Our review suggests that survivors of rape, sexual violence and sexual abuse during adulthood may experience a large reduction in post-treatment PTSD symptoms and depressive symptoms after experiencing a psychosocial intervention, relative to comparison groups. Psychosocial interventions do not seem to increase dropout from treatment or adverse events/effects compared to controls. However, the number of dropouts and study attrition were generally high, potentially missing harms of exposure to interventions and/or research participation. Also, the differential effects of specific intervention types needs further investigation. We conclude that a range of behavioural and CBT-based interventions may improve the mental health of survivors of rape, sexual assault and sexual abuse in the short term. Therefore, the needs and preferences of individuals must be considered in selecting suitable approaches to therapy and support. The primary outcome in this review focused on the post-treatment period and the question about whether benefits are sustained over time persists. However, attaining such evidence from studies that lack an active comparison may be impractical and even unethical. Thus, we suggest that studies undertake head-to-head comparisons of different intervention types; in particular, of novel, emerging therapies, with one-year plus follow-up periods. Additionally, researchers should focus on the therapeutic benefits and costs for subpopulations such as male survivors and those living with complex PTSD.

Assessing the priority of human rights and mental health: the PHRAME approach.

BACKGROUND: Protecting all human rights of people with mental health conditions is globally important. However, to facilitate practical implementation of rights, it is often necessary to decide which of these rights should be given priority, especially when they conflict with each other. AIMS: The aim of the Priorities of Human Rights and Mental Health (PHRAME) project is to develop a replicable approach to establish a proposed set of high-priority human rights of people with mental health conditions, to facilitate practical decision-making and implementation of such rights. METHOD: A two-stage Delphi-style study with stakeholders was conducted to generate a list of key rights of people with mental health conditions, and rank priorities among these rights in terms of feasibility, urgency and overall importance. RESULTS: The stakeholders in this study consistently ranked three rights as top priorities: (a) the right to freedom from torture, cruel inhuman treatment and punishment; (b) the right to health and access to services/treatment; and (c) the right to protection and safety in emergency situations. CONCLUSIONS: Insights from PHRAME can support decision-making about the priority to be given to human rights, to guide practical action. This approach can also be used to assess how human rights are prioritised in different settings and by different stakeholders. This study identifies the clear need for a central voice for people with lived experience in research and implementation of decisions about the priority of human rights, ensuring that action respects the opinion of people whose rights are directly affected.

The landscape of immune dysregulation in Crohn's disease revealed through single-cell transcriptomic profiling in the ileum and colon.

Crohn's disease (CD) is a chronic gastrointestinal disease that is increasing in prevalence worldwide. CD is multifactorial, involving the complex interplay of genetic, immune, and environmental factors, necessitating a system-level understanding of its etiology. To characterize cell-type-specific transcriptional heterogeneity in active CD, we profiled 720,633 cells from the terminal ileum and colon of 71 donors with varying inflammation status. Our integrated datasets revealed organ- and compartment-specific responses to acute and chronic inflammation; most immune changes were in cell composition, whereas transcriptional changes dominated among epithelial and stromal cells. These changes correlated with endoscopic inflammation, but small and large intestines exhibited distinct responses, which were particularly apparent when focusing on IBD risk genes. Finally, we mapped markers of disease-associated myofibroblast activation and identified CHMP1A, TBX3, and RNF168 as regulators of fibrotic complications. Altogether, our results provide a roadmap for understanding cell-type- and organ-specific differences in CD and potential directions for therapeutic development.

Survivor, family and professional experiences of psychosocial interventions for sexual abuse and violence: a qualitative evidence synthesis.

BACKGROUND: It is well-established that experiencing sexual abuse and violence can have a range of detrimental impacts; a wide variety of interventions exist to support survivors in the aftermath. Understanding the experiences and perspectives of survivors receiving such interventions, along with those of their family members, and the professionals who deliver them is important for informing decision making as to what to offer survivors, for developing new interventions, and enhancing their acceptability. OBJECTIVES: This review sought to: 1. identify, appraise and synthesise qualitative studies exploring the experiences of child and adult survivors of sexual abuse and violence, and their caregivers, regarding psychosocial interventions aimed at supporting survivors and preventing negative health outcomes in terms of benefits, risks/harms and barriers; 2. identify, appraise and synthesise qualitative studies exploring the experiences of professionals who deliver psychosocial interventions for sexual abuse and violence in terms of perceived benefits, risks/harms and barriers for survivors and their families/caregivers; 3. develop a conceptual understanding of how different factors influence uptake, dropout or completion, and outcomes from psychosocial interventions for sexual abuse and violence; 4. develop a conceptual understanding of how features and types of interventions responded to the needs of different user/survivor groups (e.g. age groups; types of abuse exposure; migrant populations) and contexts (healthcare/therapeutic settings; low- and middle-income countries (LMICs)); 5. explore how the findings of this review can enhance our understanding of the findings from the linked and related reviews assessing the effectiveness of interventions aimed at supporting survivors and preventing negative health outcomes. SEARCH METHODS: In August 2021 we searched MEDLINE, Embase, PsycINFO and nine other databases. We also searched for unpublished reports and qualitative reports of quantitative studies in a linked systematic review, together with reference checking, citation searches and contacting authors and other researchers to identify relevant studies. SELECTION CRITERIA: We included qualitative and mixed-methods studies (with an identifiable qualitative component) that were linked to a psychosocial intervention aimed at supporting survivors of sexual abuse and violence. Eligible studies focused on at least one of three participant groups: survivors of any age, gender, sexuality, ethnicity or [dis]ability who had received a psychosocial intervention; their carers, family members or partners; and professionals delivering such interventions. We placed no restrictions in respect of settings, locations, intervention delivery formats or durations. DATA COLLECTION AND ANALYSIS: Six review authors independently assessed the titles, abstracts and full texts identified. We extracted data using a form designed for this synthesis, then used this information and an appraisal of data richness and quality in order to stratify the studies using a maximum variation approach. We assessed the methodological limitations using the Critical Skills Appraisal Programme (CASP) tool. We coded directly onto the sampled papers using NVivo and synthesised data using a thematic synthesis methodology and used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. We used a narrative synthesis and matrix model to integrate our qualitative evidence synthesis (QES) findings with those of intervention review findings. MAIN RESULTS: We identified 97 eligible studies and sampled 37 of them for our analysis. Most sampled studies were from high-income countries, with four from middle-income and two from low-income countries. In 27 sampled studies, the participants were survivors, in three they were intervention facilitators. Two included all three of our stakeholder groups, and five included two of our groups. The studies explored a wide range of psychosocial interventions, with only one type of intervention explored in more than one study. The review indicates that features associated with the context in which interventions were delivered had an impact on how individuals accessed and experienced interventions. This included organisational features, such as staff turnover, that could influence survivors' engagement with interventions; the setting or location in which interventions were delivered; and the characteristics associated with who delivered the interventions. Studies that assess the effectiveness of interventions typically assess their impact on mental health; however, as well as finding benefits to mental health, our QES found that study participants felt interventions also had positive impacts on their physical health, mood, understanding of trauma, interpersonal relationships and enabled them to re-engage with a wide range of areas in their lives. Participants explained that features of interventions and their contexts that best enabled them to benefit from interventions were also often things that could be a barrier to benefiting from interventions. For example, the relationship with the therapist, when open and warm was a benefit, but if such a relationship could not be achieved, it was a barrier. Survivors' levels of readiness and preparedness to both start and end interventions could have positive (if they were ready) or negative (if they were not) impacts. Study participants identified the potential risks and harms associated with completing interventions but felt that it was important to face and process trauma. Some elements of interventions were specific to the intervention type (e.g. faith-based interventions), or related to an experience of an intervention that held particular relevance to subgroups of survivors (e.g. minority groups); these issues could impact how individuals experienced delivering or receiving interventions. AUTHORS' CONCLUSIONS: We had high or moderate confidence in all but one of our review findings. Further research in low- and middle-income settings, with male survivors of sexual abuse and violence and those from minority groups could strengthen the evidence for low and moderate confidence findings. We found that few interventions had published quantitative and qualitative evaluations. Since this QES has highlighted important aspects that could enable interventions to be more suitable for survivors, using a range of methodologies would provide valuable information that could enhance intervention uptake, completion and effectiveness. This study has shown that although survivors often found interventions difficult, they also appreciated that they needed to work through trauma, which they said resulted in a wide range of benefits. Therefore, listening to survivors and providing appropriate interventions, at the right time for them, can make a significant difference to their health and well-being.

A Pex7 Deficient Mouse Series Correlates Biochemical and Neurobehavioral Markers to Genotype Severity-Implications for the Disease Spectrum of Rhizomelic Chondrodysplasia Punctata Type 1.

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisome biogenesis disorder caused by defects in PEX7 leading to impairment in plasmalogen (Pls) biosynthesis and phytanic acid (PA) oxidation. Pls deficiency is the main pathogenic factor that determines the severity of RCDP. Severe (classic) RCDP patients have negligible Pls levels, congenital cataracts, skeletal dysplasia, growth and neurodevelopmental deficits, and cerebral hypomyelination and cerebellar atrophy on brain MRI. Individuals with milder or nonclassic RCDP have higher Pls levels, better growth and cognitive outcomes. To better understand the pathophysiology of RCDP disorders, we generated an allelic series of Pex7 mice either homozygous for the hypomorphic allele, compound heterozygous for the hypomorphic and null alleles or homozygous for the null allele. Pex7 transcript and protein were almost undetectable in the hypomorphic model, and negligible in the compound heterozygous and null mice. Pex7 deficient mice showed a graded reduction in Pls and increases in C26:0-LPC and PA in plasma and brain according to genotype. Neuropathological evaluation showed significant loss of cerebellar Purkinje cells over time and a decrease in brain myelin basic protein (MBP) content in Pex7 deficient models, with more severe effects correlating with Pex7 genotype. All Pex7 deficient mice exhibited a hyperactive behavior in the open field environment. Brain neurotransmitters analysis of Pex7 deficient mice showed a significant reduction in levels of dopamine, norepinephrine, serotonin and GABA. Also, a significant correlation was found between brain neurotransmitter levels, the hyperactivity phenotype, Pls level and the severity of Pex7 genotype. In conclusion, our study showed evidence of a genotype-phenotype correlation between the severity of Pex7 deficiency and several clinical and neurobiochemical phenotypes in RCDP1 mouse models. We propose that PA accumulation may underlie the cerebellar atrophy seen in older RCDP1 patients, as even relatively low tissue levels were strongly associated with Purkinje cells loss over time in the murine models. Also, our data demonstrate the interrelation between Pls, brain neurotransmitter deficiencies and the neurobehavioral phenotype, which could be further used as a valuable clinical endpoint for therapeutic interventions. Finally, these models show that incremental increases in Pex7 levels result in dramatic improvements in phenotype.

Evidence-based practices in developing and maintaining clinical nurse preceptors: An integrative review.

OBJECTIVES: This integrative review of literature explores the best practice for establishing and maintaining a hospital-based nurse preceptor program. The intent is to provide nurse leadership and educators with guidance for optimizing preceptor programs in order to improve patient, staff, and organizational outcomes. DESIGN: The project team conducted an integrative review of literature to inform best practice using the Johns Hopkins Evidence-Based Practice Model and Guidelines. DATA SOURCES: Data sources included the PubMed, CINAHL, and Cochrane databases. REVIEW METHODS: Each applicable article underwent a rigorous review and appraisal by the project team. The team used the Johns Hopkins Evidence-Based Practice Model to guide the appraisal process and to synthesize results to generate a comprehensive list of recommendations. RESULTS: The search yielded 115 unique articles that answered the evidence-based practice question. What are best practices for establishing and maintaining a hospital-based nursing preceptor program? Due to the abundance of data, the practice question was divided into three separate sub questions that explored preceptor development, continuous preceptor support, and essential competencies of preceptors. Relevant evidence included one level I article, seven level II articles, and one level IV article. Most of the evidence was found in articles ranking as level III (n = 54) and level V (n = 52). CONCLUSIONS: Many preceptorship themes and recommendations resonate throughout multiple levels of evidence. Recommendations include implementing an evidence-based, standardized curriculum that features diverse teaching modalities, critical thinking, and clinical reasoning. Common themes in the literature echo that preceptors need ongoing education, training, and support to improve nursing satisfaction, retention, and the quality of nursing care.

Multi-disciplinary Evaluation of Sexual Assault Referral Centres (SARCs) for better Health (MESARCH): protocol for a 1-year cohort study examining health, well-being and cost outcomes in adult survivors of sexual assault attending SARCs in England.

INTRODUCTION: Sexual violence is commonplace and has serious adverse consequences for physical and mental health. Sexual Assault Referral Centres (SARCs) are viewed as a best practice response. Little is known about their effectiveness and cost-effectiveness. Long-term data on the health and well-being of those who have experienced rape and sexual assault are also lacking. METHODS AND ANALYSIS: This is a mixed-methods protocol for a 1-year cohort study aiming to examine the health and well-being in survivors of sexual violence after attending a SARC in England. Quantitative measures are being taken at baseline, 6 and 12 months. Post-traumatic stress (PTS) is the primary outcome (target N=270 at 12-month follow-up). Secondary measures include anxiety, depression, substance use and sexual health and well-being. Using mixed-effects regression, our main analysis will examine whether variation in SARC service delivery and subsequent mental healthcare is associated with improvement in trauma symptoms after 12 months. An economic analysis will compare costs and outcomes associated with different organisational aspects of SARC service delivery and levels of satisfaction with care. A nested qualitative study will employ narrative analysis of transcribed interviews with 30 cohort participants and 20 survivors who have not experienced SARC services. ETHICS AND DISSEMINATION: The research is supported by an independent study steering committee, data monitoring and ethics committee and patient and public involvement (PPI) group. A central guiding principle of the research is that being involved should feel diametrically opposed to being a victim of sexual violence, and be experienced as empowering and supportive. Our PPI representatives are instrumental in this, and our wider stakeholders encourage us to consider the health and well-being of all involved. We will disseminate widely through peer-reviewed articles and non-academic channels to maximise the impact of findings on commissioning of services and support for survivors. TRIAL REGISTRATION NUMBER: ISRCTN30846825.

Feasibility, implementation, and outcomes of in situ simulation-based curriculum to manage common emergencies in the pediatric post-anesthesia care unit.

PURPOSE: Studies have shown that most critical events that occur in the post-anesthesia care unit (PACU), including cardiac arrests, are preventable and respiratory in origin. Admission to the PACU necessitates transfer of care from anesthesiology staff to PACU nurses. The aim of the study is to assess a) feasibility in implementing an in-situ curriculum for PACU nurses to manage common pediatric emergencies, b) the effectiveness of the curriculum in improving self-confidence of the PACU nurses in performing essential skills c) nurses'' perception of such an offering. DESIGN AND METHODS: This was a single center curricular evaluation study. Anonymous surveys were used to assess curriculum effectiveness by comparing self-reported confidence in the execution of key technical skills and application of knowledge in a real clinical environment at three time points: baseline, immediately post-simulation, and 3 months later. RESULTS: Of 50 PACU nurses, 80%, 98% and 58% responded to the targeted needs assessment, post-simulation and follow up (at 3 months) survey respectively. Self-reported confidence levels for most of the essential skills were significantly increased immediately after simulation and at 3 months. Most of the participants responded that the simulation training helped them improve care of hypoxic (83%) and hypotensive (62%) patients in the PACU. CONCLUSION: Implementation of in situ curriculum for PACU nurses was feasible. The self-reported confidence in performing essential skills increased significantly and the nurses could apply these skills in real clinical environment. PRACTICE IMPLICATIONS: Interprofessional simulation should be implemented in all high risk units to optimize safety of children.

Oil induced cardiac effects in embryonic sheepshead minnows, Cyprinodon variegatus.

Following the Deepwater Horizon oil spill in April 2010, much research has been conducted on the cardiotoxic effects of oil on fish. Sensitive life history stages, such as the embryonic period, have been targeted to elucidate the effects of polycyclic aromatic hydrocarbons (PAHs) on the developing cardiovascular systems of fish. However, much of this research has focused on rapidly developing pelagic species, with little emphasis on estuarine species with longer embryological periods. Moreover, previous studies have used heart rate as the primary endpoint to measure cardiac performance in embryos and larvae; an endpoint that on its own may overlook impairment in cardiac performance. This study aims to fill these knowledge gaps and provide a more holistic approach for assessing the effects of PAHs on cardiac function by exposing sheepshead minnow (Cyprinodon variegatus) embryos to two oil doses (150 and 300 µg/L tPAH nominally) throughout embryonic development and measuring cardiac responses through the identification of cardiotoxic phenotypes (pericardial edema) as well as calculation of cardiac output at 4 days post fertilization. Results of this study show significant increases in pericardial edema at both oil doses relative to controls as well as significantly reduced cardiac output - driven by reductions in ventricular stroke volume. This study is one of the first to assess cardiac output in embryonic fish exposed to oil and methods described here allow for more physiologically relevant measures of cardiac performance in early life stages through established and non-invasive measures.

Bar, stripe and spot development in sand-dwelling cichlids from Lake Malawi.

BACKGROUND: Melanic patterns such as horizontal stripes, vertical bars and spots are common among teleost fishes and often serve roles in camouflage or mimicry. Extensive research in the zebrafish model has shown that the development of horizontal stripes depends on complex cellular interactions between melanophores, xanthophores and iridophores. Little is known about the development of horizontal stripes in other teleosts, and even less is known about bar or spot development. Here, we compare chromatophore composition and development of stripes, bars and spots in two cichlid species of sand-dwellers from Lake Malawi-Copadichromis azureus and Dimidiochromis compressiceps. RESULTS: (1) In D. compressiceps, stripes are made of dense melanophores underlaid by xanthophores and overlaid by iridophores. Melanophores and xanthophores are either loose or absent in interstripes, and iridophores are dense. In C. azureus, spots and bars are composed of a chromatophore arrangement similar to that of stripes but are separated by interbars where density of melanophores and xanthophores is only slightly lower than in stripes and iridophore density appears slightly greater. (2) Stripe, bar and spot chromatophores appear in the skin at metamorphosis. Stripe melanophores directly differentiate along horizontal myosepta into the adult pattern. In contrast, bar number and position are dynamic throughout development. As body length increases, new bars appear between old ones or by splitting of old ones through new melanophore appearance, not migration. Xanthophore and iridophore distributions follow melanophore patterns. (3) Metamorphic pigmentation arises in cichlids in a fashion similar to that described in zebrafish: melanophore progenitors derived from the medial route of neural crest migration migrate from the vicinity of the neural tube to the skin during metamorphosis. CONCLUSION: The three pigment cell types forming stripes, bars and spots arise in the skin at metamorphosis. Stripes develop by differentiation of melanophores along horizontal myosepta, while bars do not develop along patent anatomical boundaries and increase in number in relation with body size. We propose that metamorphic melanophore differentiation and migratory arrest upon arrival to the skin lead to stripe formation, while bar formation must be supported by extensive migration of undifferentiated melanophores in the skin.

Information sharing in interteam responses to disaster.

Research demonstrates that information sharing is facilitated by familiarity, and having a common understanding of problems, use of lexicon, and semantic meaning. These factors can be difficult to develop within extreme environments such as disasters as members of the multi-agency system that responds often have limited experience of working together. Public inquiries repeatedly highlight the impact of information sharing difficulties on public safety, but limited academic research has focused on identifying concrete behaviours that facilitate interteam information sharing within such environments. This paper presents a case study of a national disaster response exercise involving 1,000 emergency responders. Data consist of structured observations, recordings of interteam meetings, and interviews with emergency responders. Results of mixed-method analysis indicate that interteam information sharing is delayed by limited situation awareness and poor articulation. Conversely, adopting behaviours that promote common frames for understanding interteam capabilities and information requirements improves information sharing and potentially reduces cognitive effort required to process information. Findings contribute to interteam communication theory by highlighting that in complex, time-constrained environments, having a shared understanding of responsibilities and information requirement is important for minimizing redundant deliberation and improving relevance and speed. PRACTITIONER POINTS: Facilitating the exchange and interpretation of relevant information is important for improving situation assessment, decision-making, and the implementation of appropriate actions for addressing risks.Interteam information sharing can be particularly challenging when teams are comprised of members from across different organizations with different language and cultures that must form ad hoc to rapidly respond to problems in extreme environments.Adopting communication strategies that develop common frames-of-reference can facilitate information sharing and interteam responses to disasters.

Identifying and accommodating statistical outliers when setting prospective payment rates for inpatient rehabilitation facilities.

OBJECTIVE: To demonstrate how a Bayesian outlier accommodation model identifies and accommodates statistical outlier hospitals when developing facility payment adjustments for Medicare's prospective payment system for inpatient rehabilitation care. DATA SOURCES/STUDY SETTING: Administrative data on costs and facility characteristics of inpatient rehabilitation facilities (IRFs) for calendar years 1998 and 1999. STUDY DESIGN: Compare standard linear regression and the Bayesian outlier accommodation model for developing facility payment adjustors for a prospective payment system. DATA COLLECTION: Variables describing facility average cost per case and facility characteristics were derived from several administrative data sources. PRINCIPAL FINDINGS: Evidence was found of non-normality of regression errors in the data used to develop facility payment adjustments for the inpatient rehabilitation facilities prospective payment system (IRF PPS). The Bayesian outlier accommodation model is shown to be appropriate for these data, but the model is largely consistent with the standard linear regression used in the development of the IRF PPS payment adjustors. CONCLUSIONS: The Bayesian outlier accommodation model is more robust to statistical outlier IRFs than standard linear regression for developing facility payment adjustments. It also allows for easy interpretation of model parameters, making it a viable policy alternative to standard regression in setting payment rates.

Measuring function for Medicare inpatient rehabilitation payment.

We studied 186,766 Medicare discharges to the community in 1999 from 694 inpatient rehabilitation facilities (IRF). Statistical models were used to examine the relationship of functional items and scales to accounting cost within impairment categories. For most items, more independence leads to lower costs. However, two items are not associated with cost in the expected way. The probable causes of these anomalies are discussed along with implications for payment policy. We present the rules used to construct administratively simple, homogeneous, resource use groups that provide reasonable incentives for access and quality care and that determine payments under the new IRF prospective payment system (PPS).

Medicare calibration of the clinically detailed risk information system for cost.

The clinically detailed risk information system for cost (CD-RISC) contains definitions for several hundred severity-adjusted conditions that can be used to predict future health care costs. We develop a prospective Medicare CD-RISC model using a 5-percent sample of Medicare beneficiaries and data that contain 1996 diagnostic information and 1997 annualized costs. The CD-RISC model has a hierarchical structure that implies that only the most expensive condition-severity variable within a body system affects payments. This minimizes incentives to game the system by entering multiple related codes for the same condition. The R2 for the CD-RISC model is 11 percent.