Sub-City Scale Hourly Air Quality Forecasting by Combining Models, Satellite Observations, and Ground Measurements.

While multiple information sources exist concerning surface-level air pollution, no individual source simultaneously provides large-scale spatial coverage, fine spatial and temporal resolution, and high accuracy. It is, therefore, necessary to integrate multiple data sources, using the strengths of each source to compensate for the weaknesses of others. In this study, we propose a method incorporating outputs of NASA's GEOS Composition Forecasting model system with satellite information from the TROPOMI instrument and ground measurement data on surface concentrations. Although we use ground monitoring data from the Environmental Protection Agency network in the continental United States, the model and satellite data sources used have the potential to allow for global application. This method is demonstrated using surface measurements of nitrogen dioxide as a test case in regions surrounding five major US cities. The proposed method is assessed through cross-validation against withheld ground monitoring sites. In these assessments, the proposed method demonstrates major improvements over two baseline approaches which use ground-based measurements only. Results also indicate the potential for near-term updating of forecasts based on recent ground measurements.

Subclinical tuberculosis and adverse infant outcomes in pregnant women with HIV.

BACKGROUND: Tuberculosis (TB) in pregnant women with HIV is associated with adverse maternal and infant outcomes. Previous studies have described a substantial prevalence of subclinical TB in this group, but little is known about the impact of subclinical TB on maternal and pediatric outcomes.METHODS: The Tshepiso Study recruited 235 HIV-infected pregnant women with TB (and matched HIV-positive, TB-negative pregnant controls), in Soweto, South Africa, from 2011 to 2014. During enrolment screening, some women initially recruited as controls were subsequently diagnosed with prevalent TB. We therefore assessed the prevalence of subclinical TB, associated participant characteristics and outcomes.RESULTS: Of 162 women initially recruited as TB-negative controls, seven (4.3%) were found to have TB on sputum culture. All seven had negative WHO symptom screens, and six (86%) were smear-negative. Of their seven infants, one was diagnosed with TB, and three (43%) experienced complications compared to zero infants with TB and 11% experiencing complications in the control group of TB-negative mothers (P = 0.045).CONCLUSION: We discovered an appreciable prevalence of subclinical TB in HIV-infected pregnant women in Soweto, which had not been detected by screening algorithms based solely on symptoms. Infants of HIV-infected mothers with subclinical TB appear to have a higher risk of adverse outcomes than those of TB-negative mothers.

There Is High Sensitive and Specific Correlation Between Frozen and Permanent Sections in Renal Transplant Biopsies.

INTRODUCTION: Frozen sections have been used for evaluating tumors and margins during daily practice in pathology with high specificity and sensitivity (>90% for both indices both at national level and in our department). The correlation between frozen section tissue for immunofluorescent (IF) studies and permanent sections for light microscopy, along with electron microscopy, is critical for constructing a final renal pathology diagnosis. METHODS: We studied the correlation between the frozen sections for IF studies and separate fragments of tissue for permanent light microscopic sections in our renal transplant biopsies for purposes of quality control. Frozen sections for IF sections were compared with permanent sections for light microscopy in 122 renal transplant biopsies, using inflammation as the key criterion (63 with no inflammation and 59 with inflammation) to determine the correlation. RESULTS: There was high sensitivity (94.9%) and specificity (92.1%) for the correlation between the frozen section and permanent sections. CONCLUSIONS: Our data suggest that parts of renal transplant biopsy tissue dissected to freeze for IF studies and for light microscopy were highly correlated to ensure a high quality of renal tissue dissection for the final diagnosis in renal transplant biopsies.

Donor understandings of blood and the body in relation to more frequent donation.

BACKGROUND AND OBJECTIVES: The INTERVAL trial aimed to find the optimum frequency of blood donation to enhance blood supplies and maintain donor health. This not only requires biological knowledge, but also an appreciation of donor perspectives, and how their experiences and beliefs might be central if any changes are ever to be made. To address this, trial participants were interviewed about their ideas of blood and the body in relation to their experiences of increased donation frequency. MATERIALS AND METHODS: Thirty in depth face-to-face interviews conducted with blood donors participating in the trial. RESULTS: Three key themes emerged: ideas about how blood and iron reserves are replenished, and what people did to facilitate this; beliefs about physiological differences relating to age and gender; and practical issues that affected the experience of donation. Overall, participants interviewed welcomed more frequent donation, despite a range of pragmatic concerns. CONCLUSION: Despite some practical obstacles, increased donation frequency aligned with participant's ideas about bodily replenishment, the value of donation, and their identity as enduring blood donors. They therefore supported the idea of increasing frequency of donation, independently of the biomedical evidence from the trial itself.

Feasibility of BK Virus Real-Time PCR Testing in Renal Graft Biopsies With Negative SV40 Staining.

BACKGROUND: BK virus (BKV)-associated nephropathy (BKVAN) is often associated with renal graft dysfunction. When renal transplant recipients present with high clinical suspicion for BKVAN (high serum and urine BKV titer with graft dysfunction) but their graft biopsies stain negatively for BKV, non-correlated situations between the two tests often lead to a dilemma about how to treat them. METHODS: This retrospective investigation was conducted to determine how real-time quantitative PCR (qPCR) for BKV, routinely applied to serum and urine, could be helpful in identifying the existing BKV in biopsy tissue stained negatively for BKV. RESULTS: DNA was extracted from each specimen through the use of five 10-µm curls from the tissue block with use of the QIAamp DNA FFPE Tissue Kit (Qiagen), followed by BKV qPCR to determine copies of BKV/µg of biopsy tissue DNA. Group 1 (11 negative renal controls for BKV) demonstrated 0 to 9 BKV copies/µg DNA. Except for 3 focally staining cases showing low BKV, the remaining 10 positive renal controls in group 2 (13 positive transplant biopsies staining positively) demonstrated elevated BKV up to 160 million copies/µg DNA. Group 3 transplants (13 uncertain transplants with negative BKV staining but positive liquid BKV) were negative for BKV (0-12 copies/µg) in 4 of 13, had low BKV copies (36-346 copies/µg) in 5 of 13, and had high BKV copies (17,240-526,945 copies/µg) in 4 of 13 cases, through the use of qPCR. CONCLUSIONS: The data indicate that qPCR from paraffin-embedded tissue as a backup test is sensitive for ruling in/out BKV infection in renal transplant biopsies, particularly in uncertain cases.

Postpartum hemorrhage following vaginal delivery: risk factors and maternal outcomes.

OBJECTIVE: Limited understanding of risk factors exists for postpartum hemorrhage (PPH) post-vaginal delivery. The aim of this study was to identify risk factors for PPH post-vaginal delivery within a contemporary obstetric cohort. STUDY DESIGN: Retrospective case-control study. PPH was classified by an estimated blood loss ⩾500 ml. Risk factors for PPH were identified using univariable and multivariable logistic regression. We secondarily investigated maternal outcomes and medical and surgical interventions for PPH management. RESULTS: The study cohort comprised 159 cases and 318 controls. Compared with a second-stage duration <2 h, a second stage⩾3 h was associated with PPH (adjusted odds ratio=2.3; 95% CI=1.2 to 4.6). No other clinical or obstetric variables were identified as independent risk factors for PPH. Among cases, 4% received red blood cells and 1% required intensive care admission. CONCLUSION: Although PPH-related morbidity may be uncommon after vaginal delivery, PPH should be anticipated for women after a second stage ⩾3 h.

Cooking-related PM2.5 and acrolein measured in grocery stores and comparison with other retail types.

We measured particulate matter (PM), acrolein, and other indoor air contaminants in eight visits to grocery stores in California. Retail stores of other types (hardware, furniture, and apparel) were also sampled on additional visits. Based on tracer gas decay data, most stores had adequate ventilation according to minimum ventilation rate standards. Grocery stores had significantly higher concentrations of acrolein, fine and ultrafine PM, compared to other retail stores, likely attributable to cooking. Indoor concentrations of PM2.5 and acrolein exceeded health guidelines in all tested grocery stores. Acrolein emission rates to indoors in grocery stores had a mean estimate about 30 times higher than in other retail store types. About 80% of the indoor PM2.5 measured in grocery stores was emitted indoors, compared to only 20% for the other retail store types. Calculations suggest a substantial increase in outdoor air ventilation rate by a factor of three from current level is needed to reduce indoor acrolein concentrations. Alternatively, acrolein emission to indoors needs to be reduced 70% by better capturing of cooking exhaust. To maintain indoor PM2.5 below the California annual ambient standard of 12 µg/m(3) , grocery stores need to use air filters with an efficiency rating higher than the MERV 8 air filters commonly used today.

Augmented expression of MYC and/or MYCN protein defines highly aggressive MYC-driven neuroblastoma: a Children's Oncology Group study.

BACKGROUND: MYCN amplification with subsequent MYCN protein overexpression is a powerful indicator of poor prognosis of neuroblastoma patients. Little is known regarding the prognostic significance of the homologous MYC protein expression in neuroblastoma. METHODS: Immunostaining for MYCN and MYC protein was performed on 357 undifferentiated/poorly differentiated neuroblastomas. Results were analysed with other prognostic markers. RESULTS: Sixty-seven (19%) tumours were MYCN(+), 38 (11%) were MYC(+), and one(0.3%) had both proteins(+). MYCN(+) tumours and MYC(+) tumours were more likely diagnosed in children>18months with stage4-disease. MYCN(+) tumours were associated with amplified MYCN, Unfavourable Histology (UH), and High-MKI (Mitosis-Karyorrhexis Index). MYC(+) tumours were also frequently UH but not associated with MYCN amplification, and more likely to have low-/intermediate-MKI. Favourable Histology patients without MYC/MYCN expressions exhibited the best survival (N=167, 89.7±5.5% 3-year EFS, 97.0±3.2% 3-year OS), followed by UH patients without MYC/MYCN expressions (N=84, 63.1±13.6% 3-year EFS, 83.5±9.4% 3-year OS). MYCN(+)patients and MYC(+)patients had similar and significantly low (P<0.0001) survivals (46.2±12.0% 3-year EFS, 63.2±12.1% 3-year OS and 43.4±23.1% 3-year EFS, 63.5±19.2% 3-year OS, respectively). Notably, the prognostic impact imparted by MYC expression was independent from other markers. CONCLUSIONS: In this series, ∼30% of neuroblastomas had augmented MYCN or MYC expression with dismal survivals. Prospective study of MYC/MYCN protein expression signature as a new biomarker for high-risk neuroblastomas should be conducted.

Contaminant levels, source strengths, and ventilation rates in California retail stores.

UNLABELLED: This field study measured ventilation rates and indoor air quality in 21 visits to retail stores in California. Three types of stores, such as grocery, furniture/hardware stores, and apparel, were sampled. Ventilation rates measured using a tracer gas decay method exceeded the minimum requirement of California's Title 24 Standard in all but one store. Concentrations of volatile organic compounds (VOCs), ozone, and carbon dioxide measured indoors and outdoors were analyzed. Even though there was adequate ventilation according to standard, concentrations of formaldehyde and acetaldehyde exceeded the most stringent chronic health guidelines in many of the sampled stores. The whole-building emission rates of VOCs were estimated from the measured ventilation rates and the concentrations measured indoor and outdoor. Estimated formaldehyde emission rates suggest that retail stores would need to ventilate at levels far exceeding the current Title 24 requirement to lower indoor concentrations below California's stringent formaldehyde reference level. Given the high costs of providing ventilation, effective source control is an attractive alternative. PRACTICAL IMPLICATIONS: Field measurements suggest that California retail stores were well ventilated relative to the minimum ventilation rate requirement specified in the Building Energy Efficiency Standards Title 24. Concentrations of formaldehyde found in retail stores were low relative to levels found in homes but exceeded the most stringent chronic health guideline. Looking ahead, California is mandating zero energy commercial buildings by 2030. To reduce the energy use from building ventilation while maintaining or even lowering formaldehyde in retail stores, effective formaldehyde source control measures are vitally important.

The effects of an energy efficiency retrofit on indoor air quality.

To investigate the impacts of an energy efficiency retrofit, indoor air quality and resident health were evaluated at a low-income senior housing apartment complex in Phoenix, Arizona, before and after a green energy building renovation. Indoor and outdoor air quality sampling was carried out simultaneously with a questionnaire to characterize personal habits and general health of residents. Measured indoor formaldehyde levels before the building retrofit routinely exceeded reference exposure limits, but in the long-term follow-up sampling, indoor formaldehyde decreased for the entire study population by a statistically significant margin. Indoor PM levels were dominated by fine particles and showed a statistically significant decrease in the long-term follow-up sampling within certain resident subpopulations (i.e. residents who report smoking and residents who had lived longer at the apartment complex).

Cost-effectiveness of tuberculosis screening and isoniazid treatment in the TB/HIV in Rio (THRio) Study.

OBJECTIVE: To estimate the incremental cost-effectiveness of tuberculosis (TB) screening and isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV) infected adults in Rio de Janeiro, Brazil. DESIGN: We used decision analysis, populated by data from a cluster-randomized trial, to project the costs (in 2010 USD) and effectiveness (in disability-adjusted life years [DALYs] averted) of training health care workers to implement the tuberculin skin test (TST), followed by IPT for TST-positive patients with no evidence of active TB. This intervention was compared to a baseline of usual care. We used time horizons of 1 year for the intervention and 20 years for disease outcomes, with all future DALYs and medical costs discounted at 3% per year. RESULTS: Providing this intervention to 100 people would avert 1.14 discounted DALYs (1.57 undiscounted DALYs). The median estimated incremental cost-effectiveness ratio was $2273 (IQR $1779-$3135) per DALY averted, less than Brazil's 2010 per capita gross domestic product (GDP) of $11,700. Results were most sensitive to the cost of providing the training. CONCLUSION: Training health care workers to screen HIV-infected adults with TST and provide IPT to those with latent tuberculous infection can be considered cost-effective relative to the Brazilian GDP per capita.

Integrating cell-based and clinical genome-wide studies to identify genetic variants contributing to treatment failure in neuroblastoma patients.

High-risk neuroblastoma is an aggressive malignancy, with high rates of treatment failure. We evaluated genetic variants associated with in vitro sensitivity to two derivatives of cyclophosphamide for association with clinical response in a separate replication cohort of neuroblastoma patients (n = 2,709). To determine sensitivity, lymphoblastoid cell lines (LCLs) were exposed to increasing concentrations of 4-hydroperoxycyclophosphamide (4HC; n = 422) and phosphoramide mustard (PM; n = 428). Genome-wide association studies were performed to identify single-nucleotide polymorphisms (SNPs) associated with sensitivity to 4HC and PM. SNPs consistently associated with LCL sensitivity were analyzed for associations with event-free survival (EFS) in patients. Two linked SNPs, rs9908694 and rs1453560, were found to be associated with (i) sensitivity to PM in LCLs across populations and (ii) EFS in all patients (P = 0.01) and within the high-risk subset (P = 0.05). Our study highlights the value of cell-based models to identify candidate variants that may predict response to treatment in patients with cancer.

Acute tubular injury is an important component in type I acute antibody-mediated rejection.

BACKGROUND: "Acute tubular necrosis (ATN)-like" changes in type I acute antibody- mediated rejection (AAMR) have been proposed since 2005, but the presence of "ATN-like" injury in AAMR has not well been established. The aim of this study was to confirm the presence of acute tubular injury in type I AAMR, using the specific proximal tubular injury marker, kidney injury molecule-1 (KIM-1). DESIGN: The study included 3 groups of cases, namely, a negative control group (normal nontransplantation renal parenchyma as group 1, n = 11), a positive control group (transplant ATN with negative C4d staining as group 2, n = 12), and study cases (type 1 AAMR as group 3, n = 19). Biopsy specimens from all groups were stained immunohistochemically for KIM-1 (monoclonal antibody) and KIM-1 staining intensity in proximal tubules was graded from 0.5 to 3+. Clinical indices were also correlated and analyzed. RESULTS: Group 1 demonstrated significantly lower serum creatinine levels (1.02 ± 0.10 mg/dL) when compared with both group 2 and group 3. Both groups 2 and 3 showed similar serum creatinine levels (4.02 ± 0.59 mg/dL in group 2 and 3.24 ± 0.34 mg/dL in group 3). The negative control group demonstrated negative proximal tubule staining for KIM-1, whereas both groups 2 and 3 showed positive KIM-1 staining in proximal tubules (intensity ranging from 1+ to 3+ in group 2 and from 0.5 to 3+ in group 3). CONCLUSION: Our results, using KIM-1 immunohistochemistry, demonstrated that acute tubular injury is an important component of type I AAMR.

A pilot study of tandem high-dose chemotherapy with stem cell rescue as consolidation for high-risk neuroblastoma: Children's Oncology Group study ANBL00P1.

Increasing treatment intensity has improved outcomes for children with neuroblastoma. We performed a pilot study in the Children's Oncology Group to assess the feasibility and toxicity of a tandem myeloablative regimen without TBI supported by autologous CD34-selected peripheral blood stem cells. Forty-one patients with high-risk neuroblastoma were enrolled; eight patients did not receive any myeloablative consolidation procedure and seven received only one. Two patients out of 41 (4.9%) experienced transplant-related mortality. CD34 selection was discontinued after subjects were enrolled due to serious viral illness. From the time of study enrollment, the overall 3-year EFS and OS were 44.8 ± 9.6% and 59.2 ± 9.2% (N=41). These results demonstrate that tandem transplantation in the cooperative group setting is feasible and support a randomized comparison of single vs tandem myeloablative consolidation with PBSC support for high-risk neuroblastoma.

Quality of life among people treated for tuberculosis and human immunodeficiency virus in Rio de Janeiro, Brazil.

We measured quality of life (QOL) among individuals receiving treatment for human immunodeficiency virus (HIV; n = 45), active tuberculosis (TB; n = 44) and both TB and HIV (n = 9) in Rio de Janeiro, Brazil. Active treated TB was associated with lower physical health (absolute decrease of 0.95 standard deviation in summary score), but not mental health, among people being treated for HIV. Visual analogue scale scores were similar across all three populations, and corresponded closely to standard disability weights used in the literature. Among patients receiving treatment, those with HIV, active TB and both conditions together appear to have similar QOL.

Risk of cardiovascular disease in HIV, hepatitis C, or HIV/hepatitis C patients compared to the general population.

BACKGROUND: As a result of effective antiretroviral therapy HIV patients are living longer, and their risk of cardiovascular disease (CVD) is a growing concern. It remains unknown whether coinfection with hepatitis C (HCV) changes an HIV person's CVD risk, and how the risks compare to the general population. The objective of this study was to compare the Framingham Risk Score (FRS) and vascular age differences in persons with HIV, HCV or HIV/HCV disease to the general population. METHODS: HIV, HCV, and HIV/HCV patients with clinic visits between 2004 and 2009 were sampled from medical clinics in Rochester, NY. Uninfected persons were randomly selected from the National Health and Nutrition Examination Survey (NHANES), and individually matched on gender, race, and age. We stratified by infection group and conducted separate multivariable linear regression analyses between each infection group and the gender, race, and age matched participants from NHANES. RESULTS: Rochester patients (HIV = 239, HCV = 167, HIV/HCV = 182) were compared 3 : 1 with the NHANES participants. After controlling for weight, marital status, current pharmacotherapies and the matching variables of gender, race, and age, HIV/HCV patients had a 2% higher general FRS compared with the general population (p = 0.03), and vascular age differences that were 4.1 years greater (p = .01). HCV patients had a 2.4% higher general FRS than the general population (p < .001), and vascular age differences that were 4.4 years greater (p < .001). CVD risk was elevated but not significantly different between HIV patients and the general population. CONCLUSION: Cardiovascular disease risk is elevated among HIV/HCV and HCV infected persons compared with the general population.

Do Not Attempt Cardiopulmonary Resuscitation orders in acute medical settings: a qualitative study.

BACKGROUND: Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders have been shown to be independently associated with patients receiving fewer treatments, reduced admission to intensive care and worse outcomes even after accounting for known confounders. The mechanisms by which they influence practice have not previously been studied. OBJECTIVES: To present a rich qualitative description of the use of the DNACPR form in a hospital ward setting and explore what influence it has on the everyday care of patients. DESIGN: Multi-source qualitative study, primarily using direct observation and semi-structured interviews based on two acute wards in a typical middle-sized National Health Service hospital in UK. RESULTS: The study identified a range of ways in which DNACPR orders influence ward practice, beyond dictating whether or not cardiopulmonary resuscitation should be attempted. Five key themes encapsulate the range of potential impacts emerging from the data: the specific design and primacy of the form, matters relating to clinical decision making, staff reflections on how the form can affect care, staff concern over 'inappropriate' resuscitation, and discussions with patients/relatives about DNACPR decisions. Overall, it was found that while the DNACPR form is recognized as serving a useful purpose, its influence negatively permeated many aspects of clinical practice. CONCLUSION: DNACPR orders can act as unofficial 'stop' signs and can often signify the inappropriate end to clinical decision making and proactive care. Many clinicians were uncomfortable discussing DNACPR orders with patients and families. These findings help understand why patients with DNACPR orders have worse outcomes, as such they may inform improvements in resuscitation policies.

Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project.

BACKGROUND: In the INRG dataset, the hypothesis that any segmental chromosomal alteration might be of prognostic impact in neuroblastoma without MYCN amplification (MNA) was tested. METHODS: The presence of any segmental chromosomal alteration (chromosome 1p deletion, 11q deletion and/or chromosome 17q gain) defined a segmental genomic profile. Only tumours with a confirmed unaltered status for all three chromosome arms were considered as having no segmental chromosomal alterations. RESULTS: Among the 8800 patients in the INRG database, a genomic type could be attributed for 505 patients without MNA: 397 cases had a segmental genomic type, whereas 108 cases had an absence of any segmental alteration. A segmental genomic type was more frequent in patients >18 months and in stage 4 disease (P<0.0001). In univariate analysis, 11q deletion, 17q gain and a segmental genomic type were associated with a poorer event-free survival (EFS) (P<0.0001, P=0.0002 and P<0.0001, respectively). In multivariate analysis modelling EFS, the parameters age, stage and a segmental genomic type were retained in the model, whereas the individual genetic markers were not (P<0.0001 and RR=2.56; P=0.0002 and RR=1.8; P=0.01 and RR=1.7, respectively). CONCLUSION: A segmental genomic profile, rather than the single genetic markers, adds prognostic information to the clinical markers age and stage in neuroblastoma patients without MNA, underlining the importance of pangenomic studies.

Developing a programme for healthy growth and nutrition during infancy: understanding user perspectives.

BACKGROUND: Avoiding excess energy intake and rapid weight gain during infancy may be effective in preventing childhood obesity. We developed a programme for healthy growth and nutrition in formula milk-fed babies. The aim of this study was to understand users' perspectives about the programme and planned trial. METHODS: We conducted three focus group discussions (10 mothers) and nine individual interviews (seven health visitors, one midwife and one mother) discussing the programme materials and trial protocol. All sessions were transcribed verbatim and a thematic analysis was performed using the framework approach. RESULTS: Mothers reported receiving conflicting messages about infant feeding and were keen for consistent advice. They welcomed the support that the programme would offer to mothers who gave their babies formula milk, but some were sceptical about the feasibility of limiting formula milk quantities. They suggested that recommended quantities should be presented as general guidelines rather than rigid rules. Some mothers said that it was too early to intervene to prevent obesity, that babies could not be overfed and that the risks of formula milk feeding had been exaggerated. Because of the routine advice to feed on demand, babies were fed in response to crying, and crying was equated with 'hunger'. Some mothers said that growth was genetically determined so they ignored the growth charts. Health visitors used the growth charts to assess adequate weight gain rather than to identify excess weight gain. Health visitors said that mothers would need a lot of education and support to limit formula milk quantities. CONCLUSIONS: Efforts to prevent childhood obesity by avoiding excess weight gain during infancy have to address mothers' beliefs that babies cannot be overfed, that crying always signals hunger and that growth is determined by genes rather than nutrition. Mothers and healthcare providers have different motivations and understanding these are important in the development of any intervention.