The Tumor Microenvironment: The Making of a Paradigm

What has been will be again, what has been done will be done again; there is nothing new under the su

Supernova remnants: the X-ray perspective

Supernova remnants are beautiful astronomical objects that are also of high scientific interest, because they provide insights into supernova explosion mechanisms, and because they are the likely sources of Galactic cosmic rays. X-ray observations are an important means to study these objects.And in particular the advances made in X-ray imaging spectroscopy over the last two decades has greatly increased our knowledge about supernova remnants. It has made it possible to map the products of fresh nucleosynthesis, and resulted in the identification of regions near shock fronts that emit X-ray synchrotron radiation. In this text all the relevant aspects of X-ray emission from supernova remnants are reviewed and put into the context of supernova explosion properties and the physics and evolution of supernova remnants. The first half of this review has a more tutorial style and discusses the basics of supernova remnant physics and thermal and non-thermal X-ray emission. The second half offers a review of the recent advances.The topics addressed there are core collapse and thermonuclear supernova remnants, SN 1987A, mature supernova remnants, mixed-morphology remnants, including a discussion of the recent finding of overionization in some of them, and finally X-ray synchrotron radiation and its consequences for particle acceleration and magnetic fields.Comment: Published in Astronomy and Astrophysics Reviews. This version has 2 column-layout. 78 pages, 42 figures. This replaced version has some minor language edits and several references have been correcte

Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor [see comments]

Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increased risk of graft- versus-host-disease (GVHD) from the large number of T cells infused. Eight patients with advanced malignancies received allogeneic PBSC transplants from genotypically HLA-identical sibling donors. All donors received 5 days of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 16 micrograms/kg/day) subcutaneously and were leukapheresed for 2 days. After treatment of the patient with total body irradiation and cyclophosphamide (n = 7) or etoposide, thiotepa, and cyclophosphamide (n = 1), PBSCs were infused immediately after collection and without modification. All patients received cyclosporine and either methotrexate (n = 6) or prednisone (n = 2) for GVHD prophylaxis, rhG-CSF was well tolerated with mild bone pain requiring acetaminophen occurring in two donors. All patients engrafted and in seven hematopoietic recovery was rapid, with 500 neutrophils/microL achieved by day 18 and 20,000 platelets/microL by day 12. Complete donor engraftment was documented by Y chromosome analysis in all four sex-mismatched donor-recipient pairs tested and by DNA analysis in two sex-matched pairs. One patient died on day 18 of veno-occlusive disease of the liver with engraftment but before chromosome analysis could be performed (results are pending in 1 patient). A second patient died of fungal infection 78 days after transplant. Grade 2 acute GVHD occurred in two patients and grade 3 GVHD occurred in one patient. One patient is 301 days from transplant in remission with chronic GVHD; the remaining five patients are alive and disease free 67 to 112 days after transplantation. Preliminary results indicate that allogeneic PBSCs mobilized by rhG-CSF can provide rapid hematologic recovery without an appreciably greater incidence of acute GVHD than would be expected with marrow. Further follow-up is required to determine the incidence of chronic GVHD and any potential beneficial effects on relapse after transplant.</jats:p

A new socioeconomic status measure for vaccine research in children using individual housing data: a population-based case-control study

Abstract Background We recently developed HOUSES, an individual housing-based socioeconomic status (SES) measurement for health disparities research. We assessed whether HOUSES was associated with risk of pertussis and pertussis vaccine up-to-date status in children. Methods The study utilized a previous population-based case-control study cohort assembled during the 2004–2005 pertussis outbreak. We collected data on pertussis vaccine status (up-to-date status) at the time of the index date. Using a z-score for housing value, actual square footage, and numbers of bedrooms and bathrooms, HOUSES was formulated in continuous variable and categorized into quartiles. Vaccine up-to-date status was compared among subjects with different SES as measured by HOUSES using a chi-square test and logistic regression models. Results Of the 391 eligible pediatric subjects (median age of 13.1 years with male sex of 55 %), 363 (93 %) were successfully geocoded to formulate HOUSES index. HOUSES was not associated with the risk of pertussis (p = 0.82). Pertussis vaccine up-to-date statuses were 79, 86, 83, and 94 % for children in the first (the lowest SES), second, third, and fourth quartiles of HOUSES, respectively (p = 0.03). HOUSES as a continuous variable was associated with pertussis vaccine up-to-date status (adjusted OR: 1.15 per increment of one unit of HOUSES, 95 % CI: 1.04–1.27, p = 0.008). Conclusion While HOUSES is not associated with the risk of pertussis, it predicts vaccine up-to-date status among children with different SES. HOUSES may be a useful tool for vaccine delivery research among children

Risk factors for development of long-term mood and anxiety disorder after pediatric traumatic brain injury: a population-based, birth cohort analysis

The objective of this study was to identify characteristics associated with an increased risk of anxiety and mood disorder prior to 25 years of age, in children who sustained a traumatic brain injury (TBI) prior to age 10. This population-based study identified 562 TBI cases from a 1976–1982 birth cohort in Olmsted County, Minnesota. TBI cases were manually confirmed and classified by injury severity. Separate Cox proportional hazards regression models were fit to estimate the association of TBI and secondary non-TBI related characteristics with the risk of a subsequent clinically determined anxiety or mood disorder. Multivariable-adjusted population attributable risk (PAR) estimates were calculated for TBI characteristics. Older age at initial TBI and extracranial injury at time of initial TBI were significantly associated with an increased risk of anxiety (adjusted HR [95% CI]: 1.33 [1.16, 1.52] per 1-year increase and 2.41 [1.26, 4.59]), respectively. Older age at initial TBI was significantly associated with an increased risk of a mood disorder (adjusted HR 1.17 [1.08–1.27]). In individuals sustaining a TBI prior to age 10, age at injury greater than 5 years old was the largest contributor to development of a mood or anxiety disorder.</p

Association of Perinatal Factors With Severe Obesity and Dyslipidemia in Adulthood

Background: Perinatal factors including gestational age, birthweight, size for gestational age, delivery route, maternal parity, maternal age, maternal education, socioeconomic status, race, and sex, are associated with the future risk of obesity and co-morbid conditions. This study evaluated the relationship of birthweight for gestational age and perinatal factors with severe obesity and dyslipidemia in adulthood. Methods: We conducted a population-based, retrospective birth cohort study of infants born to residents of Olmsted County, MN between 1976 and 1982. Outcomes were assessed after age 18 years until October 2020, including severe obesity (BMI ≥ 40 kg/m2) and dyslipidemia (total cholesterol ≥200 mg/dL, non-high density lipoprotein [non-HDL] cholesterol ≥145 mg/dL or HDL cholesterol &lt;40 mg/dL). We obtained mother’s age, education level, and parity as well as newborn sex, race, type of delivery, single/multiple birth, gestational age, and birthweight from birth certificate data. Individual-level socioeconomic status (SES) of the household at birth was determined with the HOUSES index. Results: Of 10 938 birth cohort subjects, 7394 had clinic visits after age 18 years and were included, with 2630 having severe obesity (n = 798) or dyslipidemia (n = 2357) as adults. In multivariable models, female sex, singleton birth, less maternal education, and lower SES defined by HOUSES were independently associated with an increased risk of severe obesity in adulthood. Non-white race, singleton birth, and lower birthweight were independently associated with adult dyslipidemia. Birthweight for gestational age was not associated with severe obesity or dyslipidemia. Conclusion: Perinatal factors were associated with both severe obesity and dyslipidemia in adulthood. Lower SES at birth was predictive of severe obesity in adulthood, highlighting the opportunity to investigate modifiable perinatal social determinants to reduce the risk of severe obesity. </jats:sec

Role of individual-housing–based socioeconomic status measure in relation to smoking status among late adolescents with asthma

PURPOSE: We aimed to assess whether smoking status among individuals in late adolescence (19-22 years) with asthma was associated with socioeconomic status (SES) defined by HOUSES, an individual housing based SES measure. METHODS: A population-based cross-sectional study was conducted among the 1988-1989 Olmsted County, Minnesota Birth Cohort, with physician-diagnosed asthma and that lived in the community during the study period (November 1, 2008-October 31, 2012). Using a z-score for housing value, actual square footage, and numbers of bedrooms and bathrooms, HOUSES was formulated and categorized into quartiles. Smoking status (both current and past smoker) was compared among subjects with different SES as measured by HOUSES using logistic regression, adjusting for age and sex. RESULTS: Among 289 eligible subjects, 287 (99%) were successfully geo-coded to real property data for HOUSES. Of the 257 subjects whose smoke exposure was recorded, 70 (27%) had smoking status. An inverse association was observed between HOUSES and smoking status after accounting for age, gender, and General Medical Exam status. (adjusted OR: 0.39, 95%CI: 0.18-0.87 for comparing highest vs. lowest HOUSES in quartile; overall p=0.02). CONCLUSIONS: A significant proportion of individuals with asthma in late adolescence were smokers during the study period, disproportionally affecting those with lower SES