The Long-Term Mortality Effects Associated with Exposure to Particles and NOx in the Malmö Diet and Cancer Cohort.

In this study, the long-term mortality effects associated with exposure to PM10 (particles with an aerodynamic diameter smaller than or equal to 10 µm), PM2.5 (particles with an aerodynamic diameter smaller than or equal to 2.5 µm), BC (black carbon), and NOx (nitrogen oxides) were analyzed in a cohort in southern Sweden during the period from 1991 to 2016. Participants (those residing in Malmö, Sweden, born between 1923 and 1950) were randomly recruited from 1991 to 1996. At enrollment, 30,438 participants underwent a health screening, which consisted of questionnaires about lifestyle and diet, a clinical examination, and blood sampling. Mortality data were retrieved from the Swedish National Cause of Death Register. The modeled concentrations of PM10, PM2.5, BC, and NOx at the cohort participants' home addresses were used to assess air pollution exposure. Cox proportional hazard models were used to estimate the associations between long-term exposure to PM10, PM2.5, BC, and NOx and the time until death among the participants during the period from 1991 to 2016. The hazard ratios (HRs) associated with an interquartile range (IQR) increase in each air pollutant were calculated based on the exposure lag windows of the same year (lag0), 1-5 years (lag1-5), and 6-10 years (lag6-10). Three models were used with varying adjustments for possible confounders including both single-pollutant estimates and two-pollutant estimates. With adjustments for all covariates, the HRs for PM10, PM2.5, BC, and NOx in the single-pollutant models at lag1-5 were 1.06 (95% CI: 1.02-1.11), 1.01 (95% CI: 0.95-1.08), 1.07 (95% CI: 1.04-1.11), and 1.11 (95% CI: 1.07-1.16) per IQR increase, respectively. The HRs, in most cases, decreased with the inclusion of a larger number of covariates in the models. The most robust associations were shown for NOx, with statistically significant positive HRs in all the models. An overall conclusion is that road traffic-related pollutants had a significant association with mortality in the cohort.

Exposure to long-term source-specific transportation noise and incident breast cancer: A pooled study of eight Nordic cohorts.

BACKGROUND: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. METHODS: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. RESULTS: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th-95th percentile) 5-year residential road traffic noise was 54.8 (40.0-67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2-65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99-1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96-1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99-1.18) for road traffic and 1.19 (0.95-1.49) for railway noise. CONCLUSIONS: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before conclusions regarding noise as a risk factor for breast cancer can be made.

Health impact assessment of road traffic noise exposure based on different densification scenarios in Malmö, Sweden.

While urbanization provides many opportunities to those arriving in thriving urban areas, a greater number of residents necessitates the expansion of housing and infrastructure. This is often achieved through densification, which can lead to increased noise, particularly through increased road traffic. A key challenge of promoting healthy urban planning is to understand potential health effects, especially on the local level. The aim of the present study is, therefore, to estimate and compare the health impacts of road traffic noise exposure for various urban densification scenarios within a neighborhood (Lorensborg) in Malmö, Sweden. The three scenarios include 1) Present-day, representing the study area as it is presently organized; 2) Planned municipal strategy (the city of Malmö's own densification plans) and 3) Health-centred, which involves major structural alterations and reflects an effort prioritize a health-centred approach. Noise was modelled using the Nordic prediction method for road traffic. Health outcomes included noise annoyance, adverse sleep disturbance, ischemic heart disease (IHD) incidence and mortality. Within all scenarios, a large proportion of the study population was exposed above the WHO's health-based guideline value (Lden 53 dB): >80% for Present-day and Planned municipal strategy scenarios, and almost 50% in the Health-centred scenario. Still, densifying Lorensborg (population ≈9,600) according to the Health-centred scenario could prevent 549 cases of highly annoyed, 193 cases of adverse sleep disturbance, 4.7 new cases of IHD (8.9% of total cases), and 1.5 deaths due to IHD (17.8% of IHD mortality) annually. The results demonstrated that it is possible to considerably lower the health impact with a more health-centred densification strategy. Important co-benefits for public and environmental health include air pollution reduction and green space creation, although their health effects were not quantified in the present study. Urban planning initiatives must be more ambitious in order to create healthy, sustainable cities.

Exposure to local, source-specific ambient air pollution during pregnancy and autism in children: a cohort study from southern Sweden.

Evidence of air pollution exposure, namely, ambient particulate matter (PM), during pregnancy and an increased risk of autism in children is growing; however, the unique PM sources that contribute to this association are currently unknown. The aim of the present study was to investigate local, source-specific ambient PM exposure during pregnancy and its associations with childhood autism, specifically, and autism spectrum disorders (ASD) as a group. A cohort of 40,245 singleton births from 2000 to 2009 in Scania, Sweden, was combined with data on locally emitted PM with an aerodynamic diameter < 2.5 µm (PM2.5). A flat, two-dimensional dispersion model was used to assess local PM2.5 concentrations (all-source PM2.5, small-scale residential heating- mainly wood burning, tailpipe exhaust, and vehicle wear-and-tear) at the mother's residential address during pregnancy. Associations were analyzed using binary logistic regression. Exposure to local PM2.5 during pregnancy from each of the investigated sources was associated with childhood autism in the fully adjusted models. For ASD, similar, but less pronounced, associations were found. The results add to existing evidence that exposure to air pollution during pregnancy may be associated with an increased risk of childhood autism. Further, these findings suggest that locally produced emissions from both residential wood burning and road traffic-related sources (tailpipe exhaust and vehicle wear-and-tear) contribute to this association.

An investigation of child health in relation to housing renovations for a disadvantaged immigrant population in Malmö, Sweden.

AIMS: The aim of the study was to describe child health in relation to housing renovations in more than 800 rental units, consisting of repairs of dilapidated kitchens and bathrooms, in the disadvantaged neighbourhood of Herrgården in Rosengård, Malmö, Sweden. METHODS: Data on housing conditions and self-reported health were collected during home visits to families living in Herrgården (building renovations area) and a comparison area (neighbouring Törnrosen, with generally better housing conditions). At baseline, 130 families with 359 children participated, while 51 families with 127 children participated at follow-up. All data were collected between 2010 and 2012. Additionally, regional register data on health-care usage/in- and outpatient contacts within the public health-care system between 2008 and 2013 were also collected for all 8715 children registered as living in the two areas. RESULTS: Self-reported health seemed to somewhat improve in both areas, with 74% versus 86% and 78% versus 88% reporting good or very good health in Herrgården and in the comparison area at baseline and follow-up, respectively. In Herrgården, crowdedness increased, while it decreased in the comparison area. The number of health-care contacts remained stable over time in Herrgården, while it decreased in the comparison area. CONCLUSIONS: Partial housing renovations did not seem to result in clear health improvements as measured with the indicators used in the present study. This could possibly be due to persisting health effects due to increased crowdedness or persisting poor housing conditions, as only kitchens and bathrooms were renovated.

Long-term residential exposure to source-specific particulate matter and incidence of diabetes mellitus - A cohort study in northern Sweden.

Diabetes mellitus (DM) incidence have been assessed in connection with air pollution exposure in several studies; however, few have investigated associations with source-specific local emissions. This study aims to estimate the risk of DM incidence associated with source-specific air pollution in a Swedish cohort with relatively low exposure. Individuals in the Västerbotten intervention programme cohort were followed until either a DM diagnosis or initiation of treatment with glucose-lowering medication occurred. Dispersion models with high spatial resolution were used to estimate annual mean concentrations of particulate matter (PM) with aerodynamic diameter ≤10 µm (PM10) and ≤2.5 µm (PM2.5) at individual addresses. Hazard ratios were estimated using Cox regression models in relation to moving averages 1-5 years preceding the outcome. During the study period, 1479 incident cases of DM were observed during 261,703 person-years of follow-up. Increased incidence of DM was observed in association with PM10 (4% [95% CI: -54-137%] per 10 µg/m3), PM10-traffic (2% [95% CI: -6-11%] per 1 µg/m3) and PM2.5-exhaust (11% [95% CI: -39-103%] per 1 µg/m3). A negative association was found for both PM2.5 (-18% [95% CI: -99-66%] per 5 µg/m3), but only in the 2nd exposure tertile (-10% [95% CI: -25-9%] compared to the first tertile), and PM2.5-woodburning (-30% [95% CI: -49-4%] per 1 µg/m3). In two-pollutant models including PM2.5-woodburning, there was an 11% [95% CI: -11-38%], 6% [95% CI: -16-34%], 13% [95% CI: -7-36%] and 17% [95% CI: 4-41%] higher risk in the 3rd tertile of PM10, PM2.5, PM10-traffic and PM2.5-exhaust, respectively, compared to the 1st. Although the results lacked in precision they are generally in line with the current evidence detailing particulate matter air pollution from traffic as an environmental risk factor for DM.

A novel stress-based intervention reduces cigarette use in non-treatment seeking smokers.

Tobacco use is the leading cause of preventable mortality worldwide. Since current smoking cessation aids show only modest efficacy, new interventions are needed. Given the evidence that stress is a potent trigger for smoking, the present randomized clinical trial tested whether stress could augment the effects of a memory updating (retrieval-extinction) intervention. Non-treatment seeking smokers (n = 76) were assigned to one of four conditions composed of either a stressful or non-stressful psychosocial challenge followed by either smoking or neutral cues. Ten minutes after this manipulation, all underwent a 60-minute extinction procedure during which they viewed smoking-related videos and images and manipulated smoking paraphernalia. Compared to participants who were not exposed to the laboratory stressor, the stressor-exposed groups exhibited greater psychophysiological responses during their intervention and greater decreases in cigarette use at two- and six-weeks follow-up independent of smoking cue exposure. Together, these findings suggest that the ability of stress to activate cigarette seeking processes can be exploited to decrease cigarette use. With replication, the stress-based intervention could become a novel strategy for decreasing cigarette use in non-treatment seeking smokers.Clinicaltrials.gov identifier: NCT04843969.

Estimated public health benefits of a low-emission zone in Malmö, Sweden.

Air pollution is one of the leading causes of morbidity and mortality worldwide. Low-emission zones (LEZ) have been increasingly implemented in cities throughout Europe as a measure to reduce the adverse health effects and premature deaths associated with traffic-related air pollution. In the present study, a health impact analysis was conducted to estimate the effect of a hypothetical LEZ on mortality and morbidity in Malmö, Sweden. Baseline health statistics were gathered from health registers and applied to each resident according to individual-level data on age and/or sex. Concentration-response parameters were derived from current epidemiological literature, specifically meta-analyses. A Gaussian dispersion model (AERMOD) combined with a detailed emission database was used to calculate NO2 emissions from traffic, which could be applied on an individual-level using data on each person's residential coordinates. The adjusted exposure scenario replaced all vehicles on municipal roads having Euro 5 or lower emission standards with Euro 6 equivalents. This LEZ would, on average, decrease NO2 concentrations by 13.4%, preventing an estimated 9-26 deaths in Malmö each year. Additionally, 12 respiratory disease hospitalizations, 8 childhood asthma cases, and 9 cases of hypertensive disorders of pregnancy were estimated to be avoided annually. These results suggest that LEZs can effectively improve air quality, reduce greenhouse gas emissions, and safeguard public health.

Prenatal Exposure to Locally Emitted Air Pollutants Is Associated with Birth Weight: An Administrative Cohort Study from Southern Sweden.

While prenatal exposure to ambient air pollution has been shown to be associated with reduced birth weight, there is substantial heterogeneity across studies, and few epidemiological studies have utilized source-specific exposure data. The aim of the present study was, therefore, to investigate the associations between local, source-specific exposure to fine particulate matter (PM2.5) during pregnancy and birth weight. An administrative cohort comprising 40,245 singleton births from 2000 to 2009 in Scania, Sweden, was combined with data on relevant covariates. Investigated sources of PM2.5 included all local sources together as well as tailpipe exhaust, vehicle wear-and-tear, and small-scale residential heating separately. The relationships between these exposures, represented as interquartile range (IQR) increases, and birth weight (continuous) and low birth weight (LBW; <2500 g) were analyzed in crude and adjusted models. Each local PM2.5 source investigated was associated with reduced birth weight; average decreases varied by source (12−34 g). Only small-scale residential heating was clearly associated with LBW (adjusted odds ratio: 1.14 (95% confidence interval: 1.04−1.26) per IQR increase). These results add to existing evidence that prenatal exposure to ambient air pollution disrupts fetal growth and suggest that PM2.5 from both vehicles and small-scale residential heating may reduce birth weight.

Ambient and indoor air pollution exposure and adverse birth outcomes in Adama, Ethiopia.

Air pollution poses a threat to human health, with pregnant women and their developing fetuses being particularly vulnerable. A high dual burden of ambient and indoor air pollution exposure has been identified in Ethiopia, but studies investigating their effects on adverse birth outcomes are currently lacking. This study explores the association between ambient air pollution (NOX and NO2) and indoor air pollution (cooking fuel type) and fetal and neonatal death in Adama, Ethiopia. A prospective cohort of mothers and their babies was used, into which pregnant women were recruited at their first antenatal visit (n = 2085) from November 2015 to February 2018. Previously developed land-use regression models were utilized to assess ambient concentrations of NOX and NO2 at the residential address, whereas data on cooking fuel type was derived from questionnaires. Birth outcome data was obtained from self-reported questionnaire responses during the participant's postnatal visit or by phone if an in-person meeting was not possible. Binary logistic regression was employed to assess associations within the final study population (n = 1616) using both univariate and multivariate models; the latter of which adjusted for age, education, parity, and HIV status. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were reported. Within the cohort, 69 instances of fetal death (n = 16 miscarriages; n = 53 stillbirths) and 16 cases of neonatal death were identified. The findings suggest a tendency towards an association between ambient NOX and NO2 exposure during pregnancy and an increased risk of fetal death overall as well as stillbirth, specifically. However, statistical significance was not observed. Results for indoor air pollution and neonatal death were inconclusive. As limited evidence on the effects of exposure to ambient air pollution on adverse birth outcomes exists in Sub-Saharan Africa and Ethiopia, additional studies with larger study populations should be conducted.

Factors associated with 60-day adherence to "safer supply" opioids prescribed under British Columbia's interim clinical guidance for health care providers to support people who use drugs during COVID-19 and the ongoing overdose emergency.

AIMS: In March 2020, British Columbia issued Risk Mitigation Guidance (RMG) to support prescribing of pharmaceutical alternatives to illicit drugs, in order to reduce risk for COVID-19, overdose, and withdrawal among people who use drugs. This study evaluated factors associated with 60-day adherence to novel opioid alternatives prescribed at an inner-city health centre in Victoria, Canada. METHODS: A chart review was conducted to collect data on sociodemographic information, medical histories, and follow-up services among all clients prescribed novel opioid alternatives from March 2020-August 2020 (n = 286). Bivariable and multivariable regression were used to identify independent and adjusted factors associated with 60-day adherence. RESULTS: Overall, 77% of 286 clients were still receiving opioids after 60 days of follow-up. Medications included hydromorphone (n = 274), sustained-release oral morphine (n = 2), and oxycodone (n = 9). The adjusted odds of 60-day adherence to novel opioid alternatives were significantly higher for those receiving a mental health medication (aOR = 3.49, 95%CI = 1.26, 11.00), a higher maximum daily dosage of RMG prescriptions (aOR = 1.03 per mg increase, 95%CI = 1.01, 1.04), and those with continuous receipt of OAT (aOR = 6.25, 95%CI = 2.67, 15.90). CONCLUSIONS: Higher dosages and co-prescription of mental health medications and OAT may help support better adherence to this form of prescriber-based "safer supply". Further work is needed to identify optimal prescribing practices and the longer term impacts of differing implementation scenarios.

Prehospital Echocardiogram Use in Identifying Massive Pulmonary Embolism in Unidentified Respiratory Failure.

Medical transport teams often handle cases of complex, critically ill patients and are in need of rapid, bedside assessments to guide clinical decision making. The use of point-of-care ultrasound (POCUS) as a diagnostic indicator has gained increased acceptance in emergency medicine. Ultrasound devices have become increasingly portable, and numerous studies have demonstrated that use in the prehospital setting is feasible, accurate, and can have a dramatic impact on the care of patients. In this case report, we highlight the use of handheld ultrasound in the identification of right heart dilation in an unstable patient with respiratory failure in a rural emergency department, concerning for massive pulmonary embolism. The patient was given thrombolytic therapy with dramatic clinical improvement, ultimately surviving transport to the intensive care unit at a nearby tertiary care center.

Health Impacts from Ambient Particle Exposure in Southern Sweden.

A health impact assessment (HIA) is an important tool for making informed decisions regarding the design and evaluation of environmental interventions. In this study, we performed a quantitative HIA for the population of Scania (1,247,993), the southernmost county in Sweden, in 2016. The impact of annual mean concentrations of particulate matter with an aerodynamic diameter <2.5 µm (PM2.5), modeled at their home residences for the year 2011, on mortality, asthma, dementia, autism spectrum disorders, preeclampsia and low birth weight (LBW) was explored. Concentration-response (C-R) functions were taken from epidemiological studies reporting meta-analyses when available, and otherwise from single epidemiological studies. The average level of PM2.5 experienced by the study population was 11.88 µg/m3. The PM2.5 exposure was estimated to cause 9-11% of cases of LBW and 6% of deaths from natural causes. Locally produced PM2.5 alone contributed to 2-9% of the cases of diseases and disorders investigated. Reducing concentrations to a maximum of 10 µg/m3 would, according to our estimations, reduce mortality by 3% and reduce cases of LBW by 2%. Further analyses of separate emission sources' distinct effects were also presented. Reduction of air pollution levels in the study area would, as expected, have a substantial effect on both mortality and adverse health outcomes. Reductions should be aimed for by local authorities and on national and even international levels.

Health Care Surrogacy Laws Do Not Adequately Address the Needs of Minors.

A couple and their five-year-old daughter are in a car accident. The parents are not expected to survive. The child is transported to a children's hospital, and urgent treatment decisions must be made. Whom should the attending physician approach to make decisions for the child? When such cases arise in, for example, the hospitals where we work, the social worker or chaplain is instructed to use the Illinois Health Care Surrogacy Act as a guidepost to identify a decision-maker. But in our state and the country overall, the limitations of such statutes leave hospital workers to make a judgment call among friends, family, and clergy who may come forward. While surrogate decision-making statutes comprehensively address surrogate decision-makers for adults, a patchwork of laws-permanency statutes, kinship provider statutes, standby guardianship statutes, and, in some cases, surrogate decision-making statutes-provide variable decision-making pathways for children.

Maternal Exposure to Ambient Air Pollution and Risk of Preeclampsia: A Population-Based Cohort Study in Scania, Sweden.

The aim of this study was to investigate the risk of developing preeclampsia (PE) associated with gestational exposure to ambient air pollutants in southern Sweden, a low-exposure area. We used a cohort of 43,688 singleton pregnancies and monthly mean exposure levels of black carbon (BC), local and total particulate matter (PM2.5 and PM10), and NOX at the maternal residential address estimated by Gaussian dispersion modeling from 2000 to 2009. Analyses were conducted using binary logistic regression. A subtype analysis for small-for-gestational age (SGA) was performed. All analyses were adjusted for obstetrical risk factors and socioeconomic predictors. There were 1286 (2.9%) PE cases in the analysis. An adjusted odds ratio (AOR) of 1.35 with a 95% confidence interval (CI) of 1.11-1.63 was found when comparing the lowest quartile of BC exposure to the highest quartile in the third trimester The AOR for PE associated with each 5 µg/m3 increase in locally emitted PM2.5 was 2.74 (95% CI: 1.68, 4.47) in the entire pregnancy. Similar patterns were observed for each 5 µg/m3 increment in locally emitted PM10. In pregnancies complicated by PE with SGA, the corresponding AOR for linear increases in BC was 3.48 (95% CI: 1.67, 7.27). In this low-level setting, maternal exposure to ambient air pollution during gestation was associated with the risk of developing PE. The associations seemed more pronounced in pregnancies with SGA complications, a finding that should be investigated further.

Surrogate Decision Making for Children: Who Should Decide?

OBJECTIVE: To identify caregivers' views on preferred surrogate decision makers for their children. STUDY DESIGN: A respondent-anonymous survey was distributed to a convenience sample of adults who accompanied a child to general and subspecialty pediatric care at 2 different institutions or were at the bedside of a child in the pediatric intensive care unit at a third institution in Chicago. RESULTS: We collected 462 valid surveys. The average age of the legal guardian and accompanying child was 36.8 years and 6.6 years, respectively. Most legal guardians designated "other parent with legal authority" as their first choice surrogate decision maker (70%). Respondent's sex, respondent's age, child's age, and child's ethnicity had no effect on first choice surrogate decision maker. "Other parent with legal authority" was less likely to be first choice surrogate if respondents had Medicaid insurance, less than a college degree, or lived in a non-nuclear household (P<.01 for all factors). The surrogacy ladder selected by 31% of legal guardians was "other parent with legal authority," "child's grandparent(s)," and "child's aunt(s) or uncle(s)." No other sequence received more than 10% designation. Study site had no effect on surrogate preference (P = .30). CONCLUSIONS: A surrogacy priority ladder for minors needs to include relatives who are often not included in state surrogacy statutes (eg, grandparents, aunts and uncles). The most popular surrogacy ladder will not be ideal for many families. Parents need to be informed and empowered to choose alternate surrogates, and documented preferences must be easily and widely accessible.

Connecting Air Pollution Exposure to Socioeconomic Status: A Cross-Sectional Study on Environmental Injustice among Pregnant Women in Scania, Sweden.

Environmental injustice, characterized by lower socioeconomic status (SES) persons being subjected to higher air pollution concentrations, was explored among pregnant women in Scania, Sweden. Understanding if the general reduction of air pollution recorded is enjoyed by all SES groups could illuminate existing inequalities and inform policy development. "Maternal Air Pollution in Southern Sweden", an epidemiological database, contains data for 48,777 pregnancies in Scanian hospital catchment areas and includes births from 1999-2009. SES predictors considered included education level, household disposable income, and birth country. A Gaussian dispersion model was used to model women's average NOX and PM2.5 exposure at home residence over the pregnancy period. Total concentrations were dichotomized into emission levels below/above respective Swedish Environmental Protection Agency (EPA) Clean Air objectives. The data were analyzed using binary logistic regression. A sensitivity analysis facilitated the investigation of associations' variation over time. Lower-SES women born outside Sweden were disproportionately exposed to higher pollutant concentrations. Odds of exposure to NOX above Swedish EPA objectives reduced over time, especially for low-SES persons. Environmental injustice exists in Scania, but it lessened with declining overall air pollution levels, implying that continued air quality improvement could help protect vulnerable populations and further reduce environmental inequalities.

Targeting the tumour vasculature: exploitation of low oxygenation and sensitivity to NOS inhibition by treatment with a hypoxic cytotoxin.

Many cancer research efforts focus on exploiting genetic-level features that may be targeted for therapy. Tissue-level features of the tumour microenvironment also represent useful therapeutic targets. Here we investigate the presence of low oxygen tension and sensitivity to NOS inhibition of tumour vasculature as potential tumour-specific features that may be targeted by hypoxic cytotoxins, a class of therapeutics currently under investigation. We have previously demonstrated that tirapazamine (TPZ) mediates central vascular dysfunction in tumours. TPZ is a hypoxic cytotoxin that is also a competitive inhibitor of NOS. Here we further investigated the vascular-targeting activity of TPZ by combining it with NOS inhibitor L-NNA, or with low oxygen content gas breathing. Tumours were analyzed via multiplex immunohistochemical staining that revealed irreversible loss of perfusion and enhanced tumour cell death when TPZ was combined with either low oxygen or a NOS inhibitor. Tumour growth rate was reduced by TPZ + NOS inhibition, and tumours previously resistant to TPZ-mediated vascular dysfunction were sensitized by low oxygen breathing. Additional mapping analysis suggests that tumours with reduced vascular-associated stroma may have greater sensitivity to these effects. These results indicate that poorly oxygenated tumour vessels, also being abnormally organized and with inadequate smooth muscle, may be successfully targeted for significant anti-cancer effects by inhibition of NOS and hypoxia-activated prodrug toxicity. This strategy illustrates a novel use of hypoxia-activated cytotoxic prodrugs as vascular targeting agents, and also represents a novel mechanism for targeting tumour vessels.

A survey of chaplains' roles in pediatric palliative care: integral members of the team.

To date, the field of health care chaplaincy has had little information about how pediatric palliative care (PPC) programs meet the spiritual needs of patients and families. We conducted a qualitative study consisting of surveys of 28 well-established PPC programs in the United States followed by interviews with medical directors and professional chaplains in 8 randomly selected programs among those surveyed. In this report, we describe the PPC chaplain activities, evidence regarding chaplain integration with the PPC team, and physician and chaplain perspectives on the chaplains' contributions. Chaplains described their work in terms of processes such as presence, while physicians emphasized outcomes of chaplains' care such as improved communication. Learning to translate what they do into the language of outcomes will help chaplains improve health care colleagues' understanding of chaplains' contributions to care for PPC patients and their families. In addition, future research should describe the spiritual needs and resources of PPC patients and families and examine the contribution chaplains make to improved outcomes for families and children facing life-limiting illnesses.

The role of professional chaplains on pediatric palliative care teams: perspectives from physicians and chaplains.

CONTEXT: Pediatric palliative care (PPC) specialists recognize spiritual care as integral to the services offered to seriously ill children and their families. Little is known about how PPC programs deliver spiritual care. OBJECTIVE: The goal of this pilot study was to begin to describe the role of professional chaplains in established PPC programs in children's hospitals in the United States. METHODS: In 2009 we surveyed 28 PPC programs to ascertain how spiritual care was provided. Of the 19 programs with staff chaplains who met additional study criteria, we randomly selected eight to study in detail. Based on interviews with the medical director and staff chaplain in these eight programs, we qualitatively delineated chaplains' roles in PPC. RESULTS: Twenty-four of the 28 surveyed programs (86%) reported having a staff chaplain on their clinical team. Among the 8 interviewed programs, there was considerable variation in how chaplains functioned as members of interdisciplinary teams. Despite these variations, physicians and chaplains agreed that chaplains address patients' and families' spiritual suffering, improve family-team communication, and provide rituals valued by patients, families, and staff. CONCLUSIONS: Our survey of these PPC programs found that spiritual care was typically provided by staff chaplains, and our interviews indicated that chaplains appeared to be well-integrated members of these teams. Further research is needed to evaluate how well the spiritual needs of patients, families, and staff are being met, and the organizational factors that support the delivery of spiritual care in children's hospitals.