Lung transplant recipients' experiences of and attitudes towards self-management: a qualitative systematic review.

OBJECTIVE: The objective of this review was to identify lung transplant recipients' experiences of and attitudes towards self-management. INTRODUCTION: Lung transplantation is an established treatment to improve the survival of patients with end-stage lung diseases and has been performed on over 40,000 patients worldwide. The current focus of care for lung transplant recipients is on their long-term management. Patients need to adapt and adhere to complex self-management tasks to prevent complications and to enable them to keep the transplanted graft as long as possible. However, to date, no qualitative systematic review exists that identifies lung transplant recipients' experiences of and attitudes towards self-management. INCLUSION CRITERIA: This review included adults over 18 years of age who had received a lung transplant and were able to perform their self-management tasks independently. All studies that investigated lung transplant recipients' experiences of and attitudes towards self-management in any setting were included in this review. All types of studies that focused on qualitative data, including, but not limited to, phenomenology, grounded theory, ethnography, action research, and feminist research were considered for inclusion. Mixed methods studies were included only when qualitative data could be extracted separately, and if they reported results relating to the phenomena of interest. Studies published in English or German were considered for inclusion in this review. METHODS: The search strategy aimed to find published studies from 6 databases from the database inception to March 2022. Methodological quality of studies was independently assessed by 2 independent reviewers using the JBI checklist for qualitative research. A standardized data extraction tool from JBI was used by 2 reviewers for data collection. Meta-aggregation was undertaken to synthesize the data, and the final synthesis of the findings was reached through discussion. Results were graded according to ConQual. RESULTS: Ten studies with a sample size from 8 to 73 participants from North America and Central/Northern Europe were included in the review. The critical appraisal scores of the included studies varied from 3 to 9 out of 10. A total of 137 findings were extracted and aggregated to form 19 categories and the following 4 aggregated syntheses: i) Changes in routines, beliefs, and sense of responsibility are essential for better adaptation and self-management after lung transplantation; ii) Life after transplantation is characterized by both positive and negative feelings and experiences; iii) Better adjustment and self-management after a lung transplant require dealing with one's own feelings and beliefs; iv) After transplantation, engaging with relatives, friends, medical team and donors is essential to improve experiences and adapt to being a transplant recipient. Based on the ConQual scores, 2 synthesized findings were graded as moderate and 2 as low. CONCLUSIONS: Nuanced emotional, social, relational, and psychological adjustment is required of lung transplant recipients to be able to successfully self-manage. Loved ones and health professionals contribute significantly to this process, but psychosocial or peer support may further facilitate this transition. SUPPLEMENTAL DIGITAL CONTENT: A German-language version of the abstract of this review is available as Supplemental Digital Content [http://links.lww.com/SRX/A46].

An exploration of managing emotional labour and maintaining professional integrity in children's hospice nursing.

BACKGROUND: Research exploring nurse-parent relationships in children's hospices is rare. AIM: To investigate how children's hospice nurses manage emotional labour and professional integrity in their long-term relationships with parents. METHODS: A purposive sample of six children's nurses, from hospices across England, recorded audio diaries and participated in telephone interviews. Narratives were thematically analysed. FINDINGS: Three overarching, cross-cutting themes were identified-purposeful positioning; balancing personability and professionalism; coping with and counterbalancing emotional labour. All themes were indicative of and/or built upon emotional intelligence constructs, such as self-awareness, self-regulation, appropriate (managed) empathy, social skills and intrinsic motivation. Innate features of children's hospice work were important for perpetuating intrinsic motivation and satisfaction. CONCLUSION: This study provided an insight into the management of emotional labour and professional integrity by experienced children's hospice nurses. The identification of emotional intelligence skills merits further exploration in this environment, as well as other children's palliative care settings.

Gender disparity of invited speakers at the American Association of Orthodontists Annual Session: A cross-sectional analysis 2015-2023.

INTRODUCTION: The American Association of Orthodontists (AAO) Annual Session aims to educate members using expert speakers in the field. Selection to speak is an honor and can help further an orthodontist's career and credibility. A European study found a significant gender discrepancy in selected speakers at their orthodontic meeting. This has not been investigated in the United States. METHODS: Speaker names from the 2015-2023 AAO Annual Sessions were obtained and analyzed for gender and then compared with active membership and orthodontic faculty percentages. In addition, the gender of each General Chair and Doctors' Program Chair was analyzed and then compared with the female speaker and membership percentages. Because AAO research award winners are selected blindly, show expertise in the field, and are provided an opportunity to speak at the Annual Session, their gender was also confirmed and compared with membership percentage and female speaker percentage. Two-way chi-square tests were used, and P values of <0.05 were considered statistically significant. Mann-Kendall trend tests analyzed any potential changes in gender representation among AAO active memberships and AAO Annual Session speakers. RESULTS: Female doctors were underrepresented as speakers (P values ranged from <0.001 to <0.05) in every year studied except 2020 compared with active membership and female faculty percentages. Female doctors were also significantly underrepresented as Annual Session General Chairs and Doctors' Program Chairs (P <0.01). The difference in female doctor representation among research awards winners (63%) compared with the Annual Session speakers (19%) was highly significant. Female representation in AAO active membership shows a significant increase from 2015 to 2023. The ratio of female-to-male speakers appears to be increasing but did not reach statistical significance. CONCLUSIONS: Female doctors are underrepresented as selected speakers at the AAO Annual Session but comprise the majority of research award recipients. Efforts to provide opportunities for women to showcase their knowledge should be implemented.

Real-world adjuvant chemotherapy treatment patterns and outcomes over time for resected stage II and III colorectal cancer.

BACKGROUND: The administration of adjuvant chemotherapy (AC) to colorectal cancer (CRC) patients in Australia and impact of recent trial data has not been well reported. We aim to evaluate temporal trends in AC treatment and outcomes in real-world Australian patients. METHODS: CRC patients were analyzed from 13 hospitals, stratified by stage (II or III) and three 5-year time periods (A: 2005-2009, B: 2010-2014, C: 2015-2019). Stage III was further stratified as pre- and post publication of the International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration (March 2018). AC prescription, time-to-recurrence (TTR), and overall survival (OS) was compared across the time periods. RESULTS: Of 3977 identified patients, 1148 (stage II: 640, stage III: 508), 1525 (856 vs. 669), and 1304 (669 vs. 635) were diagnosed in Period A, B, and C, respectively. Fewer patients in Period C received AC compared to Period B in stage II (10% vs. 15%, p <.01) and III (70% vs. 79%, p <.01). Post-IDEA, the proportion of patients receiving ≤3 months of oxaliplatin-based AC increased (45% vs. 13%, p <.01). The proportion of patients who remained recurrence free at 3 years was similar between time periods in stage II (A: 89% vs. B: 88% vs. C: 90%, p = .53) and stage III (72% vs. 76% vs. 72%, p = .08). OS significantly improved for stage II (80%-85%, p = .04) and stage III (69%-77%, <.01) from period A to B. CONCLUSION: AC use has moderately decreased over time with no impact on recurrence rates. Improved survival in more recent years despite similar recurrence rates may be related to improved baseline staging, better postrecurrence treatment, and reduced noncancer-related mortality.

Early Death After Chemotherapy as a Quality Indicator-Is It Time to Bench the Benchmark?

This Viewpoint examines chemotherapy at the end of life as a quality metric.

Using mobile phones, WhatsApp and phone interviews to explore how children's hospice nurses manage long-term relationships with parents: a feasibility pilot.

BACKGROUND: Mobile phones are familiar to most nurses, but the applications available for voice recording and transfer of audio files in research may not be. AIM: To provide an overview of a pilot study which trialled the use of mobile phones, WhatsApp and phone interviews as a safe and reliable means of collecting data. DISCUSSION: A pilot study was designed to test the use of: mobile phones as a safe and reliable way to record audio diaries as research data; WhatsApp to transmit the audio files; and phone interviews to explore them. Undertaking the pilot demonstrated that the tools proposed for collecting data were useable and acceptable to the target population and that the researcher's guidance for doing so was satisfactory. CONCLUSION: New technologies enable innovation but trialling them for useability is important. Confidentiality and consent need to be carefully managed when using WhatsApp to ensure a study is compliant with data protection regulations. IMPLICATIONS FOR PRACTICE: Collection of research data digitally and remotely has become increasingly mainstream and relied on during the COVID 19 pandemic. The methods discussed in this article provide solutions for timely data collection that are particularly useful when the researcher is geographically distant from participants. The 'in the moment' reflective nature of the audio diaries could also be applicable to non-research settings - for example, as a method of assisting ongoing professional development and/or collection of reflective accounts.

Factors Associated With Disordered Eating Behavior Among Adolescent Girls: Screening and Education.

INTRODUCTION/OBJECTIVES: An unhealthy relationship with food can lead to disordered eating in adolescence, highlighting the importance of screening. This study describes the frequency of disordered eating behavior among female adolescents, as well as associated characteristics and health behaviors. METHODS: Data are from a multidimensional risk factor screening survey administered at a university medical center's adolescent clinic from 2016 to 2018. The instrument was adapted from existing screening tools such as the Rapid Assessment for Adolescent Preventive Services (RAAPS), the American Medical Association's Guidelines for Adolescent Preventive Services (GAPS), and the Youth Risk Behavior Survey (YRBS). Analysis was limited to self-reported responses provided by females aged 10 to 21 years (N = 915). Statistical analyses included chi-square tests and independent sample T-tests. RESULTS: Of the N = 915 females who reported on disordered eating behavior, n = 57 (6.2%) had engaged in some form of disordered eating behavior within the past 12 months. Disordered eating was significantly associated (P < .001) with not consistently wearing a helmet while biking, having tried e-cigarettes, being bullied in the past 30 days, having an adverse childhood experience (ACE), and being African American (P = .005). Subgroup analysis of the relationship between disordered eating and bullying, by race, yielded significant findings: disordered eating was more highly associated with being bullied in the past 30 days among African American females (P = .038). The relationship between disordered eating and ACE was also significant (P < .001) among Caucasian girls when stratified by race. CONCLUSIONS: Adolescent risk behaviors often co-occur, and disordered eating behavior may be differentially observed by race. Findings highlight the importance of education and screening to prevent the development of disordered eating, and identify those who may be struggling. These results can be useful to community health education and in healthcare to develop and implement health promotion and eating disorder prevention strategies. Further studies are needed to assess additional factors that promote or protect against disordered eating to improve prevention.

Uptake of bone-modifying agents in patients with HER2+ metastatic breast cancer with bone metastases - prospective data from a multi-site Australian registry.

BACKGROUND: International practice guidelines recommend administration of bone-modifying agents (BMA) in metastatic breast cancer (MBC) patients with bone metastases to reduce skeletal-related events (SRE). Optimal delivery of BMA in routine clinical practice, including agent selection and prescribing intervals, remains unclear. AIM: To describe real-world practice of Australian breast oncologists. METHODS: Prospective data from February 2015 to July 2020 on BMA delivery to MBC patients with bone metastases was analysed from Treatment of Advanced Breast Cancer in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Australian Patient (TABITHA), a multi-site Australian HER2+ MBC registry. RESULTS: Of 333 HER2+ MBC patients, 171 (51%) had bone metastases at diagnosis, with a mean age of 58.1 years (range, 32-87). One hundred and thirty (76%) patients received a BMA, with 90 (69%) receiving denosumab and 40 (31%) receiving a bisphosphonate. Patients who received a BMA were more likely to have received concurrent first-line systemic anti-HER2 therapy (95% vs 83%; P = 0.04), to present with bone-only metastases at diagnosis (24% vs 7%; P = 0.02) and less likely to have visceral metastases (51% vs 71%; P = 0.03). Ten of 40 (25%) bisphosphonate patients and 45 of 90 (50%) denosumab patients received their BMA at the recommended 4-weekly interval. Prescribing intervals varied over time. Adverse events reported were consistent with clinical trial data. CONCLUSION: Three-quarters of Australian HER2+ MBC patients with bone metastases receive a BMA, often at different schedules than guidelines recommend. Further studies, including all MBC subtypes, are warranted to better understand clinicians' prescribing rationale and potential consequences of current prescribing practice on SRE incidence.

Drinking from the firehose - A clinician's perspective on the challenges of delivering biomarker-driven care in routine practice.

Countless biomarkers continue to be identified and analysed in the modern era of omics focused research, with innumerable articles purporting clinical utility and bolstering optimism for truly personalised cancer care. While many commentaries have expounded on the complexities of biomarker development, validation and reporting, the monumental challenge of integrating this research into clinical practice has to date received little attention. The challenges are multitude; variable and sometimes contradictory findings across studies for individual biomarkers, a rapidly evolving landscape with new biomarkers continually being presented and tendency to examine each biomarker in isolation. Here, using examples from colorectal cancer, we explore the difficulties for the practicing clinician in interpreting and integrating novel biomarkers. Here, we present the '4Cs' to interrogate the biomarker literature, including analysis of the credibility, consistency, completeness and context of the biomarker research, and suggest a framework to frame the literature moving forward.

Treatment and Outcomes of Oligometastatic Colorectal Cancer Limited to Lymph Node Metastases.

INTRODUCTION: The optimal management of isolated distant lymph node metastases (IDLNM) from a colorectal primary, is not clearly established. We aimed to analyze the outcomes of patients with IDLNM treated with systemic therapies plus locoregional therapy with curative intent versus systemic therapies with palliative intent. MATERIALS & METHODS: Clinical data were collected and reviewed from the Treatment of Recurrent and Advanced Colorectal Cancer registry, a prospective, comprehensive registry for metastatic colorectal cancer (mCRC) treated at multiple tertiary hospitals across Australia. Clinicopathological characteristics, treatment modalities and survival outcomes were analyzed in patients with IDLNM and compared to patients with disease at other sites. RESULTS: Of 3408 mCRC patients diagnosed 2009 to 2020, with median follow-up of 38.0 months, 93 (2.7%) were found to have IDLNM. Compared to mCRC at other sites, patients with IDLNM were younger (mean age: 62.1 vs. 65.6 years, P = .02), more likely to have metachronous disease (57.0% vs. 38.9%, P < .01), be KRAS wild-type (74.6% vs. 53.9%, P< .01) and BRAF mutant (12.9% vs. 6.2%, P = .01). Amongst mCRC patients with IDLNM, 24 (25.8%) received treatment with curative intent and had a significantly better overall median survival than those treated with palliative intent (73.5 months vs. 23.2 months, P = .01). These 24 patients had an overall median survival similar (62.7 months, P = .82) to patients with isolated liver or lung metastases also treated with curative intent. CONCLUSION: Curative treatment strategies (radiotherapy or surgery), with or without systemic therapy, should be considered for mCRC patients with IDLNM where appropriate as assessed by the multidisciplinary team.

Personalizing First-Line Systemic Therapy in Metastatic Colorectal Cancer: Is There a Role for Initial Low-Intensity Therapy in 2021 and Beyond? A Perspective From Members of the Australasian Gastrointestinal Trials Group.

Palliative chemotherapy is the cornerstone of treatment for the majority of patients with metastatic colorectal cancer, with the aim of increasing length and quality of life. Although guidelines outline the available treatment options in the first line, they provide limited guidance on choice and intensity of the chemotherapy backbone. Data from the TRIBE and TRIBE2 studies confirm a survival benefit with triplet FOLFOXIRI and bevacizumab, and this is a preferred option for younger patients with good performance status able to tolerate it. However, the relative benefit of a fluoropyrimidine doublet with oxaliplatin or irinotecan over single-agent fluoropyrimidine with or without a biologic is less certain; the available data demonstrate that single-agent fluoropyrimidine plus a biologic with planned sequencing of subsequent agents can produce similar overall survival outcomes with reduced toxicity. Our analysis of local real-world registry data suggests that this is an underutilized approach, particularly in younger and fitter patients. Established prognostic factors, including patient age, performance status, tumor sidedness, and biomarkers such as RAS/BRAF, are key in treatment selection; patients with left-sided RAS/BRAF wild-type disease or patients with low tumor bulk may be ideal for a less intensive regimen. Further studies are required to confirm the value of less-intensive regimens in the modern era, where the incorporation of biologic therapies has become routine and where non-chemotherapy options are emerging as viable options for molecularly defined patient subsets.

Circulating Tumour DNA as a Potential Cost-Effective Biomarker to Reduce Adjuvant Chemotherapy Overtreatment in Stage II Colorectal Cancer.

BACKGROUND AND OBJECTIVE: Substantial adjuvant chemotherapy (AC) overtreatment for stage II colorectal cancer results in a health and financial burden. Circulating tumour DNA (ctDNA) can improve patient selection for AC by detecting micro-metastatic disease. We estimated the health economic potential of ctDNA-guided AC for stage II colorectal cancer. METHODS: A cost-utility analysis was performed to compare ctDNA-guided AC to standard of care, where 22.6% of standard of care patients and all ctDNA-positive patients (8.7% of tested patients) received AC and all ctDNA-negative patients (91.3%) did not. A third preference-sensitive ctDNA strategy was included where 6.8% of ctDNA-negative patients would receive AC. A state-transition model was populated using data from a prospective cohort study and clinical registries. Health and economic outcomes were discounted at 5% over a lifetime horizon from a 2019 Australian payer perspective. Extensive scenario and probabilistic analyses quantified model uncertainty. RESULTS: Compared to standard of care, the ctDNA and preference-sensitive ctDNA strategies increased quality-adjusted life-years by 0.20 (95% confidence interval - 0.40 to 0.81) and 0.19 (- 0.40 to 0.78), and resulted in incremental costs of AUD - 4055 (- 16,853 to 8472) and AUD - 2284 (- 14,685 to 10,116), respectively. Circulating tumour DNA remained cost effective at a willingness to pay of AUD 20,000 per quality-adjusted life-year gained throughout most scenario analyses in which the proportion of ctDNA-positive patients cured by AC and compliance to a ctDNA-negative test results were decreased. CONCLUSIONS: Circulating tumour-guided AC is a potentially cost-effective strategy towards reducing overtreatment in stage II colorectal cancer. Results from ongoing randomised clinical studies will be important to reduce uncertainty in the estimates.

Can Social Media Be Used as a Community-Building and Support Tool among Jewish Women Impacted by Breast and Ovarian Cancer? An Evidence-Based Observational Report.

About 1 in 40 Ashkenazi Jewish women carry a deleterious mutation in BRCA1/2 genes, predisposing them to hereditary breast/ovarian cancer (HBOC). Thus, efforts to prevent and control HBOC in the US must include sufficient outreach and education campaigns within and across the Jewish community. Social media (SM) is utilized in public health campaigns focused on cancer, but very little is known about the efficacy of those efforts when directed toward Jewish women at risk for ("previvors") and affected by ("survivors") HBOC. Here, we report on outcomes of a targeted SM campaign for this population, as led by a national not-for-profit HBOC advocacy organization. Mixed-methods data were obtained from n = 393 members of the community, including n = 20 key informants, and analyzed for engagement and satisfaction with its SM campaign and HBOC resources. Message recipients identified the SM campaign as helpful/meaningful (82%), of 'newsworthy' value (78%), and actionable/navigable (71%): interviews revealed that women were more likely to engage with SM if/when it featured stories relevant to their personal cancer experiences. SM is a valuable public health education tool to address the comprehensive cancer control and prevention needs of those previving and surviving with HBOC, including high-risk Jewish women.

The Victorian Comprehensive Cancer Centre lung cancer clinical audit: collecting the UK National Lung Cancer Audit data from hospitals in Australia.

BACKGROUND: Clinical audit may improve practice in cancer service provision. The UK National Lung Cancer Audit (NLCA) collects data for all new cases of thoracic cancers. AIM: To collect similar data for our Victorian patients from six hospitals within the Victorian Comprehensive Cancer Centre and associated Western and Central Melbourne Integrated Cancer Service. METHODS: We conducted a retrospective audit of all newly diagnosed patients with lung cancer and mesothelioma in 2013 across the six Victorian Comprehensive Cancer Centre/Western and Central Melbourne Integrated Cancer Service hospitals. The objectives were to adapt the NLCA data set for use in the Australian context, to analyse the findings using descriptive statistics and to determine feasibility of implementing a routine, ongoing audit similar to that in the UK. Individual data items were adapted from the NLCA by an expert steering committee. Data were collated from the Victorian Cancer Registry, Victorian Admitted Episodes Dataset and individual hospital databases. Individual medical records were audited for missing data. RESULTS: Eight hundred and forty-five patients were diagnosed across the sites in 2013. Most were aged 65-80 (55%) and were male (62%). Most had non-small-cell lung cancer (81%) with 9% diagnosed with small cell lung cancer and 2% with mesothelioma. Data completeness varied significantly between fields. For those with higher levels of completeness, headline indicators of clinical care were comparable with NLCA data. The Victorian population seem to lack access to specialist lung cancer nurse services. CONCLUSION: Lung cancer care at participating hospitals appeared to be comparable with the UK in 2013. In future, prospective data collection should be harmonised across sites and correlated with survival outcomes. One area of concern was a lack of documented access to specialist nursing services.

Spatial updating in monkey superior colliculus in the absence of the forebrain commissures: dissociation between superficial and intermediate layers.

In previous studies, we demonstrated that the forebrain commissures are the primary pathway for remapping from one hemifield to the other. Nonetheless, remapping in lateral intraparietal cortex (LIP) across hemifield is still present in split brain monkeys. This finding indicates that a subcortical structure must contribute to remapping. The primary goal of the current study was to characterize remapping activity in the superior colliculus in intact and split brain monkeys. We recorded neurons in both the superficial and intermediate layers of the SC. We found that across-hemifield remapping was reduced in magnitude and delayed compared with within-hemifield remapping in the intermediate layers of the SC in split brain monkeys. These results mirror our previous findings in area LIP. In contrast, we found no difference in the magnitude or latency for within- compared with across-hemifield remapping in the superficial layers. At the behavioral level, we compared the performance of the monkeys on two conditions of a double-step task. When the second target remained within a single hemifield, performance remained accurate. When the second target had to be updated across hemifields, the split brain monkeys' performance was impaired. Remapping activity in the intermediate layers was correlated with the accuracy and latency of the second saccade during the across-hemifield trials. Remapping in the superficial layers was correlated with latency of the second saccade during the within- and across-hemifield trials. The differences between the layers suggest that different circuits underlie remapping in the superficial and intermediate layers of the superior colliculus.

Representation of the ipsilateral visual field by neurons in the macaque lateral intraparietal cortex depends on the forebrain commissures.

Our eyes are constantly moving, allowing us to attend to different visual objects in the environment. With each eye movement, a given object activates an entirely new set of visual neurons, yet we perceive a stable scene. One neural mechanism that may contribute to visual stability is remapping. Neurons in several brain regions respond to visual stimuli presented outside the receptive field when an eye movement brings the stimulated location into the receptive field. The stored representation of a visual stimulus is remapped, or updated, in conjunction with the saccade. Remapping depends on neurons being able to receive visual information from outside the classic receptive field. In previous studies, we asked whether remapping across hemifields depends on the forebrain commissures. We found that, when the forebrain commissures are transected, behavior dependent on accurate spatial updating is initially impaired but recovers over time. Moreover, neurons in lateral intraparietal cortex (LIP) continue to remap information across hemifields in the absence of the forebrain commissures. One possible explanation for the preserved across-hemifield remapping in split-brain animals is that neurons in a single hemisphere could represent visual information from both visual fields. In the present study, we measured receptive fields of LIP neurons in split-brain monkeys and compared them with receptive fields in intact monkeys. We found a small number of neurons with bilateral receptive fields in the intact monkeys. In contrast, we found no such neurons in the split-brain animals. We conclude that bilateral representations in area LIP following forebrain commissures transection cannot account for remapping across hemifields.

Dynamic circuitry for updating spatial representations. III. From neurons to behavior.

Each time the eyes move, the visual system must adjust internal representations to account for the accompanying shift in the retinal image. In the lateral intraparietal cortex (LIP), neurons update the spatial representations of salient stimuli when the eyes move. In previous experiments, we found that split-brain monkeys were impaired on double-step saccade sequences that required updating across visual hemifields, as compared to within hemifield. Here we describe a subsequent experiment to characterize the relationship between behavioral performance and neural activity in LIP in the split-brain monkey. We recorded from single LIP neurons while split-brain and intact monkeys performed two conditions of the double-step saccade task: one required across-hemifield updating and the other required within-hemifield updating. We found that, despite extensive experience with the task, the split-brain monkeys were significantly more accurate for within-hemifield than for across-hemifield sequences. In parallel, we found that population activity in LIP of the split-brain monkeys was significantly stronger for the within-hemifield than for the across-hemifield condition of the double-step task. In contrast, in the normal monkey, both the average behavioral performance and population activity showed no bias toward the within-hemifield condition. Finally, we found that the difference between within-hemifield and across-hemifield performance in the split-brain monkeys was reflected at the level of single-neuron activity in LIP. These findings indicate that remapping activity in area LIP is present in the split-brain monkey for the double-step task and covaries with spatial behavior on within-hemifield compared to across-hemifield sequences.

Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution.

Neuronal apoptosis inhibitory protein (NAIP, also known as BIRC1) is a member of the conserved inhibitor of apoptosis protein (IAP) family. Lineage-specific rearrangements and expansions of this locus have yielded different copy numbers among primates and rodents, with human retaining a single functional copy and mouse possessing several copies, depending on the strain. Roles for this gene in disease have been documented, but little is known about transcriptional regulation of NAIP. We show here that NAIP has multiple promoters sharing no similarity between human and rodents. Moreover, we demonstrate that multiple, domesticated long terminal repeats (LTRs) of endogenous retroviral elements provide NAIP promoter function in human, mouse, and rat. In human, an LTR serves as a tissue-specific promoter, active primarily in testis. However, in rodents, our evidence indicates that an ancestral LTR common to all rodent genes is the major, constitutive promoter for these genes, and that a second LTR found in two of the mouse genes is a minor promoter. Thus, independently acquired LTRs have assumed regulatory roles for orthologous genes, a remarkable evolutionary scenario. We also demonstrate that 5' flanking regions of IAP family genes as a group, in both human and mouse are enriched for LTR insertions compared to average genes. We propose several potential explanations for these findings, including a hypothesis that recruitment of LTRs near NAIP or other IAP genes may represent a host-cell adaptation to modulate apoptotic responses.