CC16 polymorphisms in asthma, asthma subtypes, and asthma control in adults from the Agricultural Lung Health Study.

BACKGROUND: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects and is a potential early biomarker of lung damage. The CC16 single nucleotide polymorphism (SNP) rs3741240 risk allele (A) has been inconsistently linked to asthma; other tagging SNPs in the gene have not been explored. The aim was to determine whether CC16 tagging polymorphisms are associated with adult asthma, asthma subtypes or asthma control in the Agricultural Lung Health Study (ALHS). METHODS: The ALHS is an asthma case-control study nested in the Agricultural Health Study cohort. Asthma cases were individuals with current doctor diagnosed asthma, likely undiagnosed asthma, or asthma-COPD overlap defined by questionnaire. We also examined asthma subtypes and asthma control. Five CC16 tagging SNPs were imputed to 1000 Genomes Integrated phase 1 reference panel. Logistic regression was used to estimate associations between CC16 SNPs and asthma outcomes adjusted for covariates. RESULTS: The sample included 1120 asthma cases and 1926 controls of European ancestry, with a mean age of 63 years. The frequency of the risk genotype (AA) for rs3741240 was 12.5% (n = 382). CC16 rs3741240 was not associated with adult asthma outcomes. A tagging SNP in the CC16 gene, rs12270961 was associated with uncontrolled asthma (n = 208, ORadj= 1.4, 95% CI 1.0, 1.9; p = 0.03). CONCLUSION: This study, the largest study to investigate associations between CC16 tagging SNPs and asthma phenotypes in adults, did not confirm an association of rs3741240 with adult asthma. A tagging SNP in CC16 suggests a potential relationship with asthma control.

Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.

We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.

Net benefits of smallholder dairy cattle farms in Senegal can be significantly increased through the use of better dairy cattle breeds and improved management practices.

Senegal, located in West Africa, is an example of a low- to middle-income country where the government has prioritized improving livestock production self-sufficiency, with a strong focus on dairy. Among other initiatives, the use of exotic dairy cattle has been promoted, despite no evidence for the potential livelihood benefits (or otherwise) to smallholder farmers on adopting the new genetics. The current work fills this evidence gap by performing a farm-level economic study comparing the keeping of different breed and cross-breed types of dairy cattle under different management levels. Data for the study were obtained by monitoring 220 smallholder dairy cattle farms, with a combined cattle population of about 3,000 animals, over an almost 2-yr period. Findings of the study suggest that the most net-beneficial and cost-beneficial dairy cattle enterprise that could be used by the smallholder farmers was to keep crossbred indigenous zebu by exotic Bos taurus animals under management standards that are considered good compared with local standards. This dairy enterprise type was 7.4-fold more net beneficial and had a 1.4-fold more favorable cost-benefit ratio than the traditional system of keeping indigenous zebu animals under poor (low-input) management. Interestingly, the keeping of (near) pure B. taurus dairy cattle resulted in the highest milk yields and thus benefit from milk, but was not the most net beneficial due to the high costs of keeping these animals, particularly in terms of feed. We also found that increasing the management level of any of the breed or cross-breed types under consideration, including the indigenous zebu animals, resulted in an increased net benefit of 2.2- to 2.9-fold. Results of this economic analysis are discussed as part of a broader trade-off analysis, resulting in recommendations to strengthen the Senegal dairy sector. The combined intervention of improved dairy cattle genetics and management is considered a promising intervention to improve livelihoods of the rural poor as well as livestock production self-sufficiency for Senegal; some other system constraints are addressed.

Developing a questionnaire to assess the health effects of bioaerosols.

BACKGROUND: Bioaerosol exposure occurs in several industries including green waste recycling, poultry farming, grain, animal feed and cotton production. Whilst several studies have investigated exposure and health effects in compost workers, the best questions to ask about health are uncertain. AIMS: This study aimed to develop a questionnaire to assess health symptoms in compost workers. METHODS: A 46-item questionnaire to ascertain possible symptoms of occupational illness related to bioaerosol exposure in a cohort of UK industrial compost workers and delivery in an interviewer-led format. The reliability of the questionnaire was assessed using Cronbach's α. A principal component analysis (PCA) was conducted to condense the questionnaire for practical purposes. RESULTS: One hundred and eleven (89%) workers completed the questionnaire. All items showed very good reliability (Cronbach's α = 0.83). After removing perfectly correlated questions from the data set, the PCA was conducted on a reduced data set of 28 items to explore underlying themes. Nine components were identified that explained 77% of the total variation. Nine of the questions removed prior to PCA due to perfect correlation were reintroduced because they added clinical value. The final questionnaire therefore consisted of 37 items and retained very adequate reliability (Cronbach's α = 0.76). CONCLUSIONS: Our health questionnaire has demonstrated adequate reliability when used within this industrial composting workforce. Further applications may include health surveillance, investigating outbreaks of occupational disease or research. Future work should examine the predictive validity of the questionnaire in these settings.

Individual patient data analysis of tidal volumes used in three large randomized control trials involving patients with acute respiratory distress syndrome.

BACKGROUND.: The acute respiratory distress syndrome (ARDS) is a condition with a high mortality and morbidity. Mechanical ventilation prevents immediate mortality but may further damage patients' lungs. Low tidal volume lung-protective strategies have been shown to increase survival by reducing this iatrogenic damage. Current guidelines recommend tidal volumes of 6-8 ml kg -1 of predicted body weight. We used data from three large randomized controlled trials of treatments for ARDS to determine compliance with these recommendations. METHODS.: We used the tidal volume recorded at randomization for all patients in the OSCAR, HARP-2, and BALTI-2 studies. In addition, we used the ventilation data for control arm patients in OSCAR and all patients in HARP-2 at days 1 and 7 after randomization. RESULTS.: The three trials enrolled 1660 patients, with tidal volume data available at least at one time point in 1412 patients. Compliance with the 6-8 ml kg -1 recommendation for tidal volume ranged from 20 to 39% of patients across all time points in all three trials. CONCLUSION.: Poor compliance with the guidelines for tidal volume in patients with ARDS has been demonstrated before in case series, but not in clinical trials where the patient population is specifically selected against standard ARDS diagnostic criteria and the investigators were encouraged to use low tidal volumes. This study may indicate a need to improve implementation and compliance with protective lung ventilation.

Thirty-day postoperative mortality for endometrial carcinoma in England: a population-based study.

OBJECTIVE: To quantify trends in 30-day mortality following surgery for endometrial carcinoma in England, and investigate hospital- and geographical-level variations. DESIGN: Retrospective population-based observational study using cancer registration and Hospital Episodes Statistics data. SETTING: England. POPULATION: Women diagnosed with endometrial carcinoma (ICD10 C54-C55 excluding sarcomas and malignant mixed Mullerian tumours) between 2000 and 2009 who were treated surgically (n = 38 332). METHODS: Random effects logistic regression model of postoperative mortality rates, adjusting for patient- and/or tumour-level factors (namely age, income deprivation, year of diagnosis, FIGO stage and grade). Case-mix adjusted postoperative mortality rates for hospitals and cancer networks were derived from the model. Multiple imputation was used to account for missing stage and grade data. MAIN OUTCOME MEASURES: 30-day postoperative mortality rate. RESULTS: For 2000-2009, the percentage of women dying within 30 days of surgery for endometrial carcinoma was very low at 0.61% (235 deaths), and decreased from 0.70% in 2000-2001 to 0.48% in 2008-2009. Postoperative mortality rates were lower for laparoscopic surgery, and higher for older women, those with advanced stage disease and high-grade tumours. Crude and case-mix adjusted results indicated that one hospital had a higher postoperative mortality rate than expected. CONCLUSIONS: The postoperative mortality rate for endometrial carcinoma in England is low and has improved since 2000, with increasing use of laparoscopic surgery. Postoperative mortality rates differed by surgical approach, patient age, disease stage and tumour grade. Only one hospital had a higher postoperative mortality rate than expected after adjusting for patient case-mix. TWEETABLE ABSTRACT: More women with endometrial cancer but better 30-day survival after surgery since 2000.

Antibody response and risk factors for seropositivity in backyard poultry following mass vaccination against highly pathogenic avian influenza and Newcastle disease in Indonesia.

A large-scale mass vaccination campaign was carried out in Java, Indonesia in an attempt to control outbreaks of highly pathogenic avian influenza (HPAI) in backyard flocks and commercial smallholder poultry. Sero-monitoring was conducted in mass vaccination and control areas to assess the proportion of the target population with antibodies against HPAI and Newcastle disease (ND). There were four rounds of vaccination, and samples were collected after each round resulting in a total of 27 293 samples. Sampling was performed irrespective of vaccination status. In the mass vaccination areas, 20-45% of poultry sampled had a positive titre to H5 after each round of vaccination, compared to 2-3% in the control group. In the HPAI + ND vaccination group, 12-25% of the population had positive ND titres, compared to 5-13% in the areas without ND vaccination. The level of seropositivity varied by district, age of the bird, and species (ducks vs. chickens).

Three uncommon KEL alleles in one family with unusual Kell phenotypes explain a 35-year old conundrum.

BACKGROUND: Kell is a complex blood group system comprising 35 antigens. Kell antigens are absent from rare red cells of the Ko (null) phenotype and expressed only weakly in the Kmod phenotype. Molecular analysis of three uncommon KEL alleles elucidated the obscure pattern of inheritance of Kell antigens in one family. MATERIALS AND METHODS: Standard serological methods were employed. All exons, flanking intronic sequence and introns 15 and 16 of KEL were sequenced from genomic DNA. cDNA was obtained from erythroid cells cultured from progenitor cells isolated from peripheral blood. RESULTS: The Kmod propositus was heterozygous for two KEL mutations: c.2107G>A, p.Gly703Arg and a synonymous mutation, c.1719C>T, in the codon for p.573Gly. Sequencing of cDNA revealed that c.1719C>T caused skipping of exon 16, resulting in a silent allele. Her KEL:3,-4 brother was heterozygous for KEL*03/04 and c.1719C/T. CONCLUSION: A synonymous mutation caused complete exon skipping, despite being located 16 bases downstream of the 3' splice site, resulting in a null KEL allele. The combined effects of two mod alleles, one responsible for KEL3 expression and the other for p.Gly703Arg, were probably responsible for an unexpected KEL:3,-4 phenotype.

International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Cancun report (2012).

The International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems.

Vulval cancer incidence, mortality and survival in England: age-related trends.

OBJECTIVE: To explore the trends and age characteristics of vulval cancer incidence, mortality, survival and stage of disease. DESIGN: Retrospective population-based observational study based on cancer registry and Office for National Statistics data. SETTING: England. POPULATION: All women diagnosed with vulval cancer, defined by the site of the tumour (ICD-10 code C51). METHODS: Including all C51 cases, Poisson regression was used to test for trends in incidence and mortality rates, and generalised linear modelling was used to test for trends in relative survival. Excluding women with melanomas, basal cell carcinomas and Paget disease, stage was investigated as a percentage of staged data by age. MAIN OUTCOME MEASURES: Age-standardised incidence and mortality rates, relative survival rates and stage of disease at diagnosis. RESULTS: From 1990, there was a statistically significant increase in overall incidence (P = 0.018) and decrease in mortality (P < 0.001). In addition, there were statistically significant increases in overall survival (1-year, P < 0.001; 5-year, P < 0.001). However, from 1990, incidence increased in women aged 20-39 years (P = 0.002), 40-49 and 50-59 years (both P < 0.001) and 60-69 years (P = 0.030) and decreased in women aged 80 years and above (P < 0.001). There were statistically significant decreases in mortality in women aged ≥60 years (P < 0.001), and statistically significant increases in 1-year survival in women aged ≥40 years (P ≤ 0.047) and in 5-year survival in women aged 40-49 and ≥60 years (P ≤ 0.011). Stage patterns by age highlight diagnosis at an earlier stage in younger women and more advanced stage diagnosis in older women. CONCLUSION: Survival from vulval cancer has improved and mortality has decreased since 1990. The overall incidence of disease has increased as a result of more new diagnoses in the under 70-year age group.

Growth and temperature relationships for juvenile fish species in seagrass beds: implications of climate change.

The effect of water temperature on growth responses of three common seagrass fish species that co-occur as juveniles in the estuaries in Sydney (34° S) but have differing latitudinal ranges was measured: Pelates sexlineatus (subtropical to warm temperate: 27-35°S), Centropogon australis (primarily subtropical to warm temperate: 24-37°S) and Acanthaluteres spilomelanurus (warm to cool temperate: below 32°S). Replicate individuals of each species were acclimated over a 7 day period in one of three temperature treatments (control: 22°C, low: 18°C and high: 26°C) and their somatic growth was assessed within treatments over 10 days. Growth of all three species was affected by water temperature, with the highest growth of both northern species (P. sexlineatus and C. australis) at 22 and 26°C, whereas growth of the southern ranging species (A. spilomelanurus) was reduced at temperatures higher than 18°C, suggesting that predicted increase in estuarine water temperatures through climate change may change relative performance of seagrass fish assemblages.

Rural hospital mass casualty response to a terrorist shooting spree.

BACKGROUND: Civilian mass casualty incidents may occur infrequently and suddenly, and are caused by accidents, natural disasters or human terrorist incidents. Most reports deal with trauma centre management in large cities, and data from small local hospitals are scarce. A rural hospital response to a mass casualty incident caused by a terrorist shooting spree was evaluated. METHODS: An observational study was undertaken to evaluate the triage, diagnosis and management of all casualties received from the Utøya youth camp in Norway on 22 July 2011 by a local hospital, using data from the hospital's electronic records. Descriptive data are presented for patient demographics, injuries and patient flow. RESULTS: The shooting on Utøya youth camp left 69 people dead and 60 wounded. A rural hospital (Ringerike Hospital) triaged 35 patients, of whom 18 were admitted. During the main surge, the hospital triaged and treated 22 patients within 1 h, of whom 13 fulfilled the criteria for activating the hospital trauma team, including five with critical injuries (defined as an Injury Severity Score above 15). Ten computed tomography scans, two focused assessment with sonography for trauma (FAST) scans and 25 conventional X-rays were performed. During the first 24 h, ten surgical procedures were performed and four chest drains inserted. No patient died. CONCLUSION: Critical deviation from the major incident plan was needed, and future need for revision is deemed necessary based on the experience. Communication systems and the organization of radiological services proved to be most vulnerable.

The Association of Clinical Characteristics and Tumour Markers With Image-Defined Risk Factors in the Management of Neuroblastoma in South Africa.

AIMS: Image-defined risk factors (IDRFs) in neuroblastoma predict surgical complications and management outcomes. As there is a lack of data regarding the association of IDRFs with clinical and pathological factors, this study evaluated the prognostic value of IDRFs to predict neuroblastoma survival outcomes. MATERIALS AND METHODS: This was a retrospective study including 345 patients and reviewed diagnostic imaging for 20 IDRFs, pleural effusions and ascites. The IDRFs were grouped into five 'primary IDRFs' cohorts with vascular encasement, involvement of multiple body compartments, organ infiltration, airway obstruction and intraspinal extension. The association between clinical, histopathological and biological characteristics of neuroblastoma and management was evaluated. RESULTS: More patients without IDRFs had operations compared with patients with IDRFs, with a trend towards significance (64.4% versus 35.6%, P = 0.082). Patients with multiple compartment tumour involvement (P = 0.003) and organ infiltration (P < 0.001) had a higher risk of surgical complications. The 5-year overall survival of the group with more than one IDRF was 0.0% and those with pleural effusions or ascites 6.7%, associated with the worst outcome (P = 0.005). The total number of IDRFs was not predictive of the metastatic remission rate (P = 0.585) or overall survival (P = 0.142), with no conclusive association found between IDRF groups and clinical or biological markers. CONCLUSIONS: Patients with more than one IDRF had the shortest survival time, whereas those with pleural effusions and ascites at diagnosis had a poor outcome. Standardised reporting of IDRFs is crucial for predicting prognosis.

The obligation to say 'Thank you': heart transplant recipients' experience of writing to the donor family.

Transplant recipients are encouraged to write anonymous thank-you letters to the donor family. We prospectively explored heart transplant recipients' embodied responses to the 'obligation' to write a thank-you letter using audio/video-taped open-ended interviews (N = 27). Fifteen of the 19 participants, who wrote letters to the donor family, expressed or visually revealed significant distress about issues such as the obligation to write anonymously and the inadequacy of the 'thank-you'. Writing the thank-you letter is not a neutral experience for heart transplant recipients. Rethinking the obligatory practice regarding the thank-you letter and developing the necessary support for the recipient through this process is necessary.

A new blood group system, RHAG: three antigens resulting from amino acid substitutions in the Rh-associated glycoprotein.

BACKGROUND AND OBJECTIVES: Rh-associated glycoprotein (RhAG) is closely associated with the Rh proteins in the red cell membrane. Two high frequency antigens (Duclos and DSLK) and one low frequency antigen (Ol(a)) have serological characteristics suggestive of expression on RhAG. MATERIALS AND METHODS: RHAG was sequenced from the DNA of one Duclos-negative, one DSLK-negative, and two Ol(a+) individuals. Recombinant protein was expressed in HEK 293 cells. Protein models with RhAG subunits were constructed. RESULTS: The original Duclos-negative patient was homozygous for RHAG 316C>G, encoding Gln106Glu. HEK 293 cells expressing Gln106Glu mutant RhAG did not react with anti-Duclos. An individual with DSLK-negative red cells was homozygous for 490A>C, encoding Lys164Gln. Two Ol(a+) members of the original Norwegian family were heterozygous for 680C>T, encoding Ser227Leu. A Japanese donor with Rh(mod) phenotype had Ol(a+) red cells and was homozygous for 680C>T. CONCLUSION: The three red cell antigens encoded by RHAG form the RHAG blood group system: Duclos is RHAG1 (030001); Ol(a) is RHAG2 (030002); and DSLK is provisionally RHAG3 (030003).

Changes in lung cancer incidence in South Asians in Leicester, 1990-2005.

BACKGROUND: A previous study showed that lung cancer incidence in Leicester's South Asian (SA) population had increased between 1990 and 1999. We expanded the original data set to determine if this increase had continued in recent years. METHODS: All patients diagnosed with lung cancer in Leicester between 1990 and 2005 were identified. Ethnicity was assigned using Nam Pechan software, deprivation by Townsend score. Using Poisson regression, incidence rate ratios (IRRs) were calculated to assess variations in incidence by ethnicity, deprivation and period of diagnosis. RESULTS: Comparing patients diagnosed in 2000-2005 with those in 1990-1994, the risk of lung cancer increased in the SA men (IRR: 1.67 (95% CI: 0.99, 2.78)) whereas in the non-South Asian (NSA) men, it had fallen (IRR: 0.84 (95% CI: 0.76, 0.94)). Comparing patients diagnosed in 2000-2005 with those in 1995-1999 an increase continued in the SA men (IRR: 1.11 (95% CI: 0.71-1.74)). A significant rise was observed in the NSA women comparing those diagnosed from 2000-2005 to 1995-1999 (IRR: 1.16 (95% CI: 1.01, 1.33)). CONCLUSION: Lung cancer is an important public health issue amongst SAs in Leicester and has increased significantly since the early 1990s, with rates sustained in the more recent years of 2000-2005. Changes in the rates of lung cancer in SA and NSA populations are likely to be due to changing smoking habits.

Organic dust-induced lung injury and repair: Bi-directional regulation by TNFα and IL-10.

Exposure to organic dust increases chronic airway inflammatory disorders. Effective treatment strategies are lacking. It has been reported that hog barn dust extracts (HDE) induce TNFα through protein kinase C (PKC) activation and that lung inflammation is enhanced in scavenger receptor A (SRA/CD204) knockout (KO) mice following HDE. Because interleukin (IL)-10 production can limit excessive inflammation, it was hypothesized here that HDE-induced IL-10 would require CD204 to effect inflammatory responses. C57BL/6 wild-type (WT), SRA KO, and IL-10 KO mice were intranasally challenged daily for 8 days with HDE and subsequently rested for 3 days with/without recombinant IL-10 (rIL-10) treatment. Primary peritoneal macrophages (PM) and murine alveolar macrophages (MH-S cells) were treated in vitro with HDE, SRA ligand (fucoidan), rIL-10, and/or PKC isoform inhibitors. HDE induced in vivo lung IL-10 in WT, but not SRA KO mice, and similar trends were demonstrated in isolated PM from same treated mice. Lung lymphocyte aggregates and neutrophils were elevated in in vivo HDE-treated SRA and IL-10 KO mice after a 3-d recovery, and treatment during recovery with rIL-10 abrogated these responses. In vitro rIL-10 treatment reduced HDE-stimulated TNFα release in MH-S and WT PM. In SRA KO macrophages, there was reduced IL-10 and PKC zeta (ζ) activity and increased TNFα following in vitro HDE stimulation. Similarly, blocking SRA (24 hr fucoidan pre-treatment) resulted in enhanced HDE-stimulated macrophage TNFα and decreased IL-10 and PKCζ activation. PKCζ inhibitors blocked HDE-stimulated IL-10, but not TNFα. Collectively, HDE stimulates IL-10 by an SRA- and PKCζ-dependent mechanism to regulate TNFα. Enhancing resolution of dust-mediated lung inflammation through targeting IL-10 and/or SRA may represent new approaches to therapeutic interventions.

Genetic control of lactate dehydrogenase formation in the hagfish Eptatretus stoutii.

The isozyme patterns of lactate dehydrogenases of various tissues were studied on 51 hagfish by starch-gel electrophoresis. Nine lactate dehydrogenase phenotypes were encountered, suggesting the coexistence of two alleles at each of the two separate gene loci. There apparently was no interaction between the products of these two separate loci. Even the products of two alleles at the same locus were apparently incapable of forming hybrid molecules, an indication of the possible monomeric nature of each lactate dehydrogenase molecule.

A giant sauropod dinosaur from an Upper Cretaceous mangrove deposit in Egypt.

We describe a giant titanosaurid sauropod dinosaur discovered in coastal deposits in the Upper Cretaceous Bahariya Formation of Egypt, a unit that has produced three Tyrannosaurus-sized theropods and numerous other vertebrate taxa. Paralititan stromeri is the first tetrapod reported from Bahariya since 1935. Its 1.69-meter-long humerus is longer than that of any known Cretaceous sauropod. The autochthonous scavenged skeleton was preserved in mangrove deposits, raising the possibility that titanosaurids and their predators habitually entered such environments.