Disruption of the Orion molecular core 1 by wind from the massive star θ1 Orionis C.

Massive stars inject mechanical and radiative energy into the surrounding environment, which stirs it up, heats the gas, produces cloud and intercloud phases in the interstellar medium, and disrupts molecular clouds (the birth sites of new stars1,2). Stellar winds, supernova explosions and ionization by ultraviolet photons control the lifetimes of molecular clouds3-7. Theoretical studies predict that momentum injection by radiation should dominate that by stellar winds8, but this has been difficult to assess observationally. Velocity-resolved large-scale images in the fine-structure line of ionized carbon ([C II]) provide an observational diagnostic for the radiative energy input and the dynamics of the interstellar medium around massive stars. Here we report observations of a one-square-degree region (about 7 parsecs in diameter) of Orion molecular core 1-the region nearest to Earth that exhibits massive-star formation-at a resolution of 16 arcseconds (0.03 parsecs) in the [C II] line at 1.9 terahertz (158 micrometres). The results reveal that the stellar wind originating from the massive star θ1 Orionis C has swept up the surrounding material to create a 'bubble' roughly four parsecs in diameter with a 2,600-solar-mass shell, which is expanding at 13 kilometres per second. This finding demonstrates that the mechanical energy from the stellar wind is converted very efficiently into kinetic energy of the shell and causes more disruption of the Orion molecular core 1 than do photo-ionization and evaporation or future supernova explosions.

Genomic profiling of late-onset basal cell carcinomas from two brothers with nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genetic disorder. It is commonly caused by mutations in PTCH1 and chiefly characterized by multiple basal cell carcinomas (BCCs) developing prior to the age of 30 years. In rare cases, NBCCS presents with a late onset of BCC development. OBJECTIVE: To investigate BCC tumorigenesis in two brothers, who showed characteristic features of NBCCS but developed their first BCCs only after the age of 40 years. Two other siblings did not show signs of NBCCS. RESULTS: We obtained blood samples from four siblings and nine BCCs from the two brothers with NBCCS. Whole exome sequencing and RNA sequencing revealed loss of heterozygosity (LOH) of PTCH1 in eight out of nine tumours that consistently involved the same haplotype on chromosome 9. This haplotype contained a germinal splice site mutation in PTCH1 (NM_001083605:exon9:c.763-6C>A). Analysis of germline DNA confirmed segregation of this mutation with the disease. All BCCs harboured additional somatic loss-of-function (LoF) mutations in the remaining PTCH1 allele which are not typically seen in other cases of NBCCS. This suggests a hypomorphic nature of the germinal PTCH1 mutation in this family. Furthermore, all BCCs had a similar tumour mutational burden compared to BCCs of unrelated NBCCS patients while harbouring a higher number of damaging PTCH1 mutations. CONCLUSIONS: Our data suggest that a sequence of three genetic hits leads to the late development of BCCs in two brothers with NBCCS: a hypomorphic germline mutation, followed by somatic LOH and additional mutations that complete PTCH1 inactivation. These genetic events are in line with the late occurrence of the first BCC and with the higher number of damaging PTCH1 mutations compared to usual cases of NBCCS.

Risk Factors for De Novo Malignancy Following Lung Transplantation.

Risk factors for non-skin cancer de novo malignancy (DNM) after lung transplantation have yet to be identified. We queried the United Network for Organ Sharing database for all adult lung transplant patients between 1989 and 2012. Standardized incidence ratios (SIRs) were computed by comparing the data to Surveillance, Epidemiology, and End Results Program data after excluding skin squamous/basal cell carcinomas. We identified 18 093 adult lung transplant patients; median follow-up time was 1086 days (interquartile range 436-2070). DNMs occurred in 1306 patients, with incidences of 1.4%, 4.6%, and 7.9% at 1, 3, and 5 years, respectively. The overall cancer incidence was elevated compared with that of the general US population (SIR 3.26, 95% confidence interval [CI]: 2.95-3.60). The most common cancer types were lung cancer (26.2% of all malignancies, SIR 6.49, 95% CI: 5.04-8.45) and lymphoproliferative disease (20.0%, SIR 14.14, 95% CI: 9.45-22.04). Predictors of DNM following lung transplantation were age (hazard ratio [HR] 1.03, 95% CI: 1.02-1.05, p < 0.001), male gender (HR 1.20, 95% CI: 1.02-1.42, p = 0.03), disease etiology (not cystic fibrosis, idiopathic pulmonary fibrosis or interstitial lung disease, HR 0.59, 95% CI 0.37-0.97, p = 0.04) and single-lung transplantation (HR 1.64, 95% CI: 1.34-2.01, p < 0.001). Significant interactions between donor or recipient smoking and single-lung transplantation were noted. On multivariable survival analysis, DNMs were associated with an increased risk of mortality (HR 1.44, 95% CI: 1.10-1.88, p = 0.009).

Simulated Regionalization of Heart and Lung Transplantation in the United States.

We simulated the impact of regionalization of isolated heart and lung transplantation within United Network for Organ Sharing (UNOS) regions. Overall, 12 594 orthotopic heart transplantation (OHT) patients across 135 centers and 12 300 orthotopic lung transplantation (OLT) patients across 67 centers were included in the study. An algorithm was constructed that "closed" the lowest volume center in a region and referred its patients to the highest volume center. In the unadjusted analysis, referred patients were assigned the highest volume center's 1-year mortality rate, and the difference in deaths per region before and after closure was computed. An adjusted analysis was performed using multivariable logistic regression using recipient and donor variables. The primary outcome was the potential number of lives saved at 1 year after transplant. In adjusted OHT analysis, 10 lives were saved (95% confidence interval [CI] 9-11) after one center closure and 240 lives were saved (95% CI 209-272) after up to five center closures per region, with the latter resulting in 1624 total patient referrals (13.2% of OHT patients). For OLT, lives saved ranged from 29 (95% CI 26-32) after one center closure per region to 240 (95% CI 224-256) after up to five regional closures, but the latter resulted in 2999 referrals (24.4% of OLT patients). Increased referral distances would severely limit access to care for rural and resource-limited populations.

A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study.

BACKGROUND: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. PATIENTS AND METHODS: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo. Randomization was stratified by platinum-free interval (≤6 versus >6-12 months) and Gynecologic Oncology Group (GOG) performance status (0 versus 1). Treatment cycles were repeated every 28 days until disease progression. RESULTS: The addition of motolimod to PLD did not significantly improve overall survival (OS; log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no synergistic or unexpected serious toxicity. Most patients experienced adverse events of fatigue, anemia, nausea, decreased white blood cells, and constipation. In pre-specified subgroup analyses, motolimod-treated patients who experienced injection site reactions (ISR) had a lower risk of death compared with those who did not experience ISR. Additionally, pre-treatment in vitro responses of immune biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8 single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair genes, and autoantibody biomarkers did not correlate with OS or PFS. CONCLUSIONS: The addition of motolimod to PLD did not improve clinical outcomes compared with placebo. However, subset analyses identified statistically significant differences in the OS of motolimod-treated patients on the basis of ISR and in vitro immune responses. Collectively, these data may provide important clues for identifying patients for treatment with immunomodulatory agents in novel combinations and/or delivery approaches. TRIAL REGISTRATION: Clinicaltrials.gov, NCT 01666444.

Canine Nervous System Lymphoma Subtypes Display Characteristic Neuroanatomical Patterns.

Primary and secondary nervous system involvement occurs in 4% and 5%-12%, respectively, of all canine non-Hodgkin lymphomas. The recent new classification of canine malignant lymphomas, based on the human World Health Organization classification, has been endorsed with international acceptance. This histological and immunocytochemical classification provides a unique opportunity to study the histologic anatomic distribution patterns in the central and peripheral nervous system of these defined lymphoma subtypes. In this study, we studied a cohort of 37 dogs with lymphoma, which at necropsy had either primary (n = 1, 2.7%) or secondary (n = 36; 97.3%) neural involvement. These T- (n = 16; 43.2%) or B-cell (n = 21; 56.8%) lymphomas were further classified into 12 lymphoma subtypes, with predominant subtypes including peripheral T-cell lymphoma (PTCL) or diffuse large B-cell lymphoma (DLBCL), respectively. This systematic study identified 6 different anatomically based histologically defined patterns of lymphoma infiltration in the nervous system of dogs. Different and distinct combinations of anatomical patterns correlated with specific lymphoma subtypes. Lymphoma infiltration within the meningeal, perivascular, and periventricular compartments were characteristic of DLBCL, whereas peripheral nerve involvement was a frequent feature of PTCL. Similarly cell counts above 64 cells/µL in cerebrospinal samples correlated best with marked meningeal and periventricular lymphoma infiltration histologically. Prospective studies are needed in order to confirm the hypothesis that these combinations of histological neuroanatomic patterns reflect targeting of receptors specific for the lymphoma subtypes at these various sites.

Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma.

Immune checkpoint inhibitors such as ipilimumab and nivolumab improve survival in patients with advanced melanoma and are increasingly available to clinicians for use in the clinic. Their safety in organ transplant recipients is not well defined but published case reports describing treatment with ipilimumab have not been complicated by graft rejection. No cases of anti-programmed cell death protein 1 administration are reported in this group. We describe a case of acute graft rejection in a kidney transplant recipient after treatment with nivolumab, after progression on ipilimumab. Potential factors increasing the risk of graft rejection in this case are discussed, in particular the contribution of nivolumab.

Kidney Transplantation Significantly Improves Patient and Graft Survival Irrespective of BMI: A Cohort Study.

Obesity and end-stage renal disease (ESRD) are on the increase worldwide. Kidney transplantation is the treatment of choice for ESRD. However, obesity is considered a contraindication for transplantation. We investigated the effect of BMI on mortality in transplanted and patients remaining on the waiting list in the United Kingdom. We analyzed the UK Renal Registry (RR) and the National Health Service Blood and Transplant (NHSBT) Organ Donation and Transplantation data for patients listed from January 1, 2004 to December 31, 2010, with follow-up until December 31, 2011. Seventeen thousand six hundred eighty-one patients were listed during the study period, with BMI recorded for 13 526 (77%). One- and five-year patient survival was significantly better in all BMI bands (<18.5, 18.5-<25, 25-<30, 30-<35, 35-<40, and 40+kg/m(2) ) in the transplant group when compared to those who remained on the waiting list (p < 0.0001). The analyses were repeated excluding live donor transplants and the results were essentially the same. On analyses of patient survival with BMI as a continuous variable or using 5 kg weight bands, there was no cut-off observed in the higher BMI patients where there would be no benefit to transplantation. For transplanted patients (N = 8088), there was no difference in patient or graft survival between the defined BMI bands. Thus, irrespective of BMI, patient survival is improved if transplanted.

Meeting report: 3rd international transplant conference: how much risk can you take?

The 3rd International Transplant Conference took place on 31st October and 1st November 2014 at the University of Warwick, Coventry, UK. Key focal points of the meeting were the exploration of the molecular basis of antibody-antigen interactions and their relation to clinical practice and to share experiences and knowledge regarding strategies to transplant the 'high-risk' patient. In addition, lively debate sessions were hosted where controversial clinical and immunological themes were discussed by leading experts in the field.

Temporal and geographic clustering of polyomavirus-associated olfactory tumors in 10 free-ranging raccoons (Procyon lotor).

Reports of primary nervous system tumors in wild raccoons are extremely rare. Olfactory tumors were diagnosed postmortem in 9 free-ranging raccoons from 4 contiguous counties in California and 1 raccoon from Oregon within a 26-month period between 2010 and 2012. We describe the geographic and temporal features of these 10 cases, including the laboratory diagnostic investigations and the neuropathologic, immunohistochemical, and ultrastructural characteristics of these tumors in the affected animals. All 9 raccoons from California were found within a localized geographic region of the San Francisco Bay Area (within a 44.13-km radius). The tight temporal and geographic clustering and consistent anatomic location in the olfactory system of tumor types not previously described in raccoons (malignant peripheral nerve sheath tumors and undifferentiated sarcomas) strongly suggest either a common cause or a precipitating factor leading to induction or potentiation of neuro-oncogenesis and so prompted an extensive diagnostic investigation to explore possible oncogenic infectious and/or toxic causes. By a consensus polymerase chain reaction strategy, a novel, recently reported polyomavirus called raccoon polyomavirus was identified in all 10 tumors but not in the normal brain tissue from the affected animals, suggesting that the virus might play a role in neuro-oncogenesis. In addition, expression of the viral protein T antigen was detected in all tumors containing the viral sequences. We discuss the potential role of raccoon polyomavirus as an oncogenic virus.

Making a difference: 5 years of Cardiac Surgery Intersociety Alliance (CSIA).

Informed by the almost unimaginable unmet need for cardiac surgery in the developing regions of the world, leading surgeons, cardiologists, editors in chief of the major cardiothoracic journals as well as representatives of medical industry and government convened in December 2017 to address this unacceptable disparity in access to care. The ensuing "Cape Town Declaration" constituted a clarion call to cardiac surgical societies to jointly advocate the strengthening of sustainable, local cardiac surgical capacity in the developing world. The Cardiac Surgery Intersociety Alliance (CSIA) was thus created, comprising The Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery (AATS), the Asian Society for Cardiovascular and Thoracic Surgery (ASCVTS), the European Association for Cardio-Thoracic Surgery (EACTS) and the World Heart Federation (WHF). The guiding principle was advocacy for sustainable cardiac surgical capacity in low-income countries. As a first step, a global needs assessment confirmed rheumatic heart disease as the overwhelming pathology requiring cardiac surgery in these regions. Subsequently, CSIA published a request for proposals to support fledgling programmes that could demonstrate the backing by their governments and health care institution. Out of 11 applicants, and following an evaluation of the sites, including site visits to the 3 finalists, Mozambique and Rwanda were selected as the first Pilot Sites. Subsequently, a mentorship and training agreement was completed between Mozambique and the University of Cape Town, a middle-income country with a comparable burden of rheumatic heart disease. The agreement entails regular video calls between the heart teams, targeted training across all aspects of cardiac surgery, as well as on-site presence of mentoring teams for complex cases with the strict observance of 'assisting only'. In Rwanda, Team Heart, a US and Rwanda-based non-governmental organization (NGO) that has been performing cardiac surgery in Rwanda and helping to train the cardiac surgery workforce since 2008, has agreed to continue providing mentorship for the local team and to assist in the establishment of independent cardiac surgery with all that entails. This involves intermittent virtual conferences between Rwandan and US cardiologists for surgical case selection. Five years after CSIA was founded, its 'Seal of Approval' for the sustainability of endorsed programmes in Mozambique and Rwanda has resulted in higher case numbers, a stronger government commitment, significant upgrades of infrastructure, the nurturing of generous consumable donations by industry and the commencement of negotiations with global donors for major grants. Extending the CSIA Seal to additional deserving programmes could further align the international cardiac surgical community with the principle of local cardiac surgery capacity-building in developing countries.

Making a Difference: 5 Years of Cardiac Surgery Intersociety Alliance (CSIA).

Informed by the almost unimaginable unmet need for cardiac surgery in the developing regions of the world, leading surgeons, cardiologists, editors in chief of the major cardiothoracic journals as well as representatives of medical industry and government convened in December 2017 to address this unacceptable disparity in access to care. The ensuing "Cape Town Declaration" constituted a clarion call to cardiac surgical societies to jointly advocate the strengthening of sustainable, local cardiac surgical capacity in the developing world. The Cardiac Surgery Intersociety Alliance (CSIA) was thus created, comprising The Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery (AATS), the Asian Society for Cardiovascular and Thoracic Surgery (ASCVTS), the European Association for Cardio-Thoracic Surgery (EACTS) and the World Heart Federation (WHF). The guiding principle was advocacy for sustainable cardiac surgical capacity in low-income countries. As a first step, a global needs assessment confirmed rheumatic heart disease as the overwhelming pathology requiring cardiac surgery in these regions. Subsequently, CSIA published a request for proposals to support fledgling programs that could demonstrate the backing by their governments and health care institution. Out of 11 applicants, and following an evaluation of the sites, including site visits to the 3 finalists, Mozambique and Rwanda were selected as the first Pilot Sites. Subsequently, a mentorship and training agreement was completed between Mozambique and the University of Cape Town, a middle-income country with a comparable burden of rheumatic heart disease. The agreement entails regular video calls between the heart teams, targeted training across all aspects of cardiac surgery, as well as on-site presence of mentoring teams for complex cases with the strict observance of "assisting only." In Rwanda, Team Heart, a US and Rwanda-based non-governmental organization (NGO) that has been performing cardiac surgery in Rwanda and helping to train the cardiac surgery workforce since 2008, has agreed to continue providing mentorship for the local team and to assist in the establishment of independent cardiac surgery with all that entails. This involves intermittent virtual conferences between Rwandan and US cardiologists for surgical case selection. Five years after CSIA was founded, its "Seal of Approval" for the sustainability of endorsed programs in Mozambique and Rwanda has resulted in higher case numbers, a stronger government commitment, significant upgrades of infrastructure, the nurturing of generous consumable donations by industry and the commencement of negotiations with global donors for major grants. Extending the CSIA Seal to additional deserving programs could further align the international cardiac surgical community with the principle of local cardiac surgery capacity-building in developing countries.

Making a difference: 5 years of Cardiac Surgery Intersociety Alliance (CSIA).

Informed by the almost unimaginable unmet need for cardiac surgery in the developing regions of the world, leading surgeons, cardiologists, editors in chief of the major cardiothoracic journals as well as representatives of medical industry and government convened in December 2017 to address this unacceptable disparity in access to care. The ensuing "Cape Town Declaration" constituted a clarion call to cardiac surgical societies to jointly advocate the strengthening of sustainable, local cardiac surgical capacity in the developing world. The Cardiac Surgery Intersociety Alliance (CSIA) was thus created, comprising The Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery (AATS), the Asian Society for Cardiovascular and Thoracic Surgery (ASCVTS), the European Association for Cardio-Thoracic Surgery (EACTS) and the World Heart Federation (WHF). The guiding principle was advocacy for sustainable cardiac surgical capacity in low-income countries. As a first step, a global needs assessment confirmed rheumatic heart disease as the overwhelming pathology requiring cardiac surgery in these regions. Subsequently, CSIA published a request for proposals to support fledgling programs that could demonstrate the backing by their governments and health care institution. Out of 11 applicants, and following an evaluation of the sites, including site visits to the 3 finalists, Mozambique and Rwanda were selected as the first Pilot Sites. Subsequently, a mentorship and training agreement was completed between Mozambique and the University of Cape Town, a middle-income country with a comparable burden of rheumatic heart disease. The agreement entails regular video calls between the heart teams, targeted training across all aspects of cardiac surgery, as well as on-site presence of mentoring teams for complex cases with the strict observance of "assisting only." In Rwanda, Team Heart, a US and Rwanda-based nongovernmental organization (NGO) that has been performing cardiac surgery in Rwanda and helping to train the cardiac surgery workforce since 2008, has agreed to continue providing mentorship for the local team and to assist in the establishment of independent cardiac surgery with all that entails. This involves intermittent virtual conferences between Rwandan and US cardiologists for surgical case selection. Five years after CSIA was founded, its "Seal of Approval" for the sustainability of endorsed programs in Mozambique and Rwanda has resulted in higher case numbers, a stronger government commitment, significant upgrades of infrastructure, the nurturing of generous consumable donations by industry and the commencement of negotiations with global donors for major grants. Extending the CSIA Seal to additional deserving programs could further align the international cardiac surgical community with the principle of local cardiac surgery capacity-building in developing countries.

Making a difference: 5 years of Cardiac Surgery Intersociety Alliance (CSIA).

Informed by the almost unimaginable unmet need for cardiac surgery in the developing regions of the world, leading surgeons, cardiologists, editors in chief of the major cardiothoracic journals as well as representatives of medical industry and government convened in December 2017 to address this unacceptable disparity in access to care. The ensuing "Cape Town Declaration" constituted a clarion call to cardiac surgical societies to jointly advocate the strengthening of sustainable, local cardiac surgical capacity in the developing world. The Cardiac Surgery Intersociety Alliance (CSIA) was thus created, comprising The Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery (AATS), the Asian Society for Cardiovascular and Thoracic Surgery (ASCVTS), the European Association for Cardio-Thoracic Surgery (EACTS) and the World Heart Federation (WHF). The guiding principle was advocacy for sustainable cardiac surgical capacity in low-income countries.

Meeting report: 2nd international conference: antibody incompatible transplantation and transplant infectious disease.

The 2nd International Conference on Antibody Incompatible Transplantation and Transplant Infectious Disease took place at the University of Warwick on 23rd and 24th November 2012. The aims of the meeting were to discuss the pertinent clinical and laboratory issues surrounding antibody incompatible transplantation and to provide a contemporary analysis of transplant infectious disease. This report summarises the key points discussed at the meeting.

Optimising care and the patient experience for people living with dementia: The perceptions of radiography practitioners.

INTRODUCTION: Despite abundant literature on the diagnosis of dementia, limited research has explored the lived experiences by radiography practitioners when delivering care to people living with dementia (PLWD). This study explored the perceptions and compatibility of current professional guidance by both radiography practitioners and key stakeholders involved in developing the Society and College of Radiographers clinical practice guideline document for caring for people with dementia. METHODS: This was a two-stage qualitative multi-method study. Fifteen diagnostic and two therapeutic radiography practitioners from across the UK participated with three asynchronous online discussion forums. One core member and three members from the key stakeholder group participated with individual semi-structured interviews. Data analysis included narrative and thematic analysis. RESULTS: Participants from both stages identified enablers and barriers to providing person-centred care (PCC) to PLWD. Three superordinate themes were identified linked to (1) Challenges in delivering person-centred care to people living with dementia, (2) The need for role specific education and training, and (3) Partnership working with carers. Challenges in delivering care included time and resource pressures. The lack of dementia specific education compounded these difficulties. Care partners were seen as an asset to providing care. CONCLUSION: Providing PCC to meet the individual needs of PLWD can be challenging in practice. This is often due to time and resource implications. There were also issues with the identification of PLWD prior to their attendance in the department. Carers could help to alleviate some challenges. There is a need for profession specific education and dementia awareness training to support the provision of PCC to PLWD. IMPLICATIONS FOR PRACTICE: Dementia training needs to be specifically tailored for radiography practitioners to bridge the gap between guidelines and clinical practice rather than being generalised from other disciplines.

Specialized Thoracic Adapted Recovery Model for Thoracic Organ Recovery: a 15-Year Review.

BACKGROUND: To review outcomes from a regionalized heart and lung transplant service over a 15-year period. METHODS: Data on organ procurements made by the Specialized Thoracic Adapted Recovery (STAR) team. The STAR team staff recorded data from November 2, 2004 to June 30, 2020, were reviewed. RESULTS: The STAR teams recovered thoracic organs from 1118 donors between November 2004 and June 2020. The teams recovered 978 hearts, 823 bilateral lungs, 89 right lungs and 92 left lungs, and 8 heart and lung sets. A total of 79% of hearts and 76.1% of lungs were transplanted, whereas 2.5% of hearts and 5.1% of lungs were declined; the remainder were used for research, valves, or abandoned. A total of 47 transplantation centers received at least 1 heart, and 37 centers received at least 1 lung during this period. The 24-hour graft survival among organs recovered by STAR teams was 100% for lungs and 99% for hearts. CONCLUSIONS: A specialized regional thoracic organ procurement team may improve transplantation rates.

Large herbivore diversity slows sea ice-associated decline in arctic tundra diversity.

Biodiversity is declining globally in response to multiple human stressors, including climate forcing. Nonetheless, local diversity trends are inconsistent in some taxa, obscuring contributions of local processes to global patterns. Arctic tundra diversity, including plants, fungi, and lichens, declined during a 15-year experiment that combined warming with exclusion of large herbivores known to influence tundra vegetation composition. Tundra diversity declined regardless of experimental treatment, as background growing season temperatures rose with sea ice loss. However, diversity declined slower with large herbivores than without them. This difference was associated with an increase in effective diversity of large herbivores as formerly abundant caribou declined and muskoxen increased. Efforts that promote herbivore diversity, such as rewilding, may help mitigate impacts of warming on tundra diversity.

TP53 mutations in canine brain tumors.

The p53 tumor suppressor gene (TP53) is the most frequently altered gene in human cancer. Mutation of the gene has been shown to be an important mechanism of p53 pathway inactivation in a variety of human brain tumors, particularly those of astrocytic origin. Genomic DNA from a series of 37 glial and 51 nonglial canine brain tumors was sequenced to determine the frequency of TP53 gene mutations involving exons 3-9. Exonic mutations were found in 3 of 88 tumors (3.4%) and specifically in 1 of 18 astrocytic tumors (5.5%). This is markedly lower than that reported in comparable human tumors, suggesting that alternative mechanisms of p53 inactivation are likely to be present if p53 function contributes significantly to oncogenesis in canine brain tumors.