Changing attitudes to gender roles: A longitudinal analysis of ordinal response data from the British household panel study

This article examines changes in attitudes to gender roles in contemporary Britain by using a first-order Markov process in which cumulative transition probabilities are logistic functions of a set of personal and socioeconomic characteristics of respondents. The data are taken from the British Household Panel Study (BHPS). The attitudinal responses examined take the form of ordinal responses concerning gender roles in 1991 and 2003. The likelihood function is partitioned to make possible the use of existing software for estimating model parameters. For the BHPS data, it was found that, depending on the value of the response in 1991, a variety of factors were important determinants of attitudes to gender roles by 2003.

Nilotinib 300mg BID as frontline treatment of CML:Prospective analysis of the Xpert BCR-ABL Monitor system and significance of 3-month molecular response

Sixty patients with early chronic phase CML (ECPCML) received Nilotinib on a phase II study which included a comparison of the Xpert BCR-ABL Monitor™ PCR system with standardized (IS) BCR-ABL1 real-time quantitative PCR (RQ-PCR). 88% patients achieved MMR with 45% achieving MR4.5. At 3 months BCR-ABL1/ABL1 IS >1% and

Proteomic analysis reveals oxidative stress response as the main adaptative physiological mechanism in cows under different production systems

Three groups of cows representing three ranges of welfare in the production system were included in the study: two groups of Bruna dels Pirineus beef cattle maintained under different management systems (good and semiferal conditions) and a group of Alberes cows, a breed that lives in the mountains (hardest conditions).

In order to identify new stress/welfare biomarkers, serum from Bruna cows living in both environments was subjected to DIGE labelling, two-dimensional electrophoresis and MALDI-MS or ion trap MS. Identification was achieved for 15 proteins, which mainly belonged to three biological functions, the oxidative stress pathway (glutathione peroxidase (GPx) and paraoxonase (PON-1)), the acute phase protein family (Heremans Schmid glycoprotein alpha2 (α2-HSG)) and the complement system.

Biological validation included the Alberes breed. GPx and PON-1 were validated by an enzymatic assay and found to be higher and lower, respectively, in cows living in hard conditions. α2-HSG was validated by ELISA and found to be reduced in hard conditions. Other biomarkers of the redox status were also altered by living conditions: protein carbonyl content, superoxide dismutase (SOD) and glutathione reductase (GR).

Our results show that changes in the redox system are the main adaptation of cows living in challenging environmental conditions. This article is part of a Special Issue entitled: “Farm animal proteomics”.

Climate change response in Europe: What's the reality? Analysis of adaptation and mitigation plans from 200 urban areas in 11 countries

Urban areas are pivotal to global adaptation and mitigation efforts. But how do cities actually perform in terms of climate change response? This study sheds light on the state of urban climate change adaptation and mitigation planning across Europe. Europe is an excellent test case given its advanced environmental policies and high urbanization. We performed a detailed analysis of 200 large and medium-sized cities across 11 European countries and analysed the cities' climate change adaptation and mitigation plans. We investigate the regional distribution of plans, adaptation and mitigation foci and the extent to which planned greenhouse gas (GHG) reductions contribute to national and international climate objectives. To our knowledge, it is the first study of its kind as it does not rely on self-assessment (questionnaires or social surveys). Our results show that 35 % of European cities studied have no dedicated mitigation plan and 72 % have no adaptation plan. No city has an adaptation plan without a mitigation plan. One quarter of the cities have both an adaptation and a mitigation plan and set quantitative GHG reduction targets, but those vary extensively in scope and ambition. Furthermore, we show that if the planned actions within cities are nationally representative the 11 countries investigated would achieve a 37 % reduction in GHG emissions by 2050, translating into a 27 % reduction in GHG emissions for the EU as a whole. However, the actions would often be insufficient to reach national targets and fall short of the 80 % reduction in GHG emissions recommended to avoid global mean temperature rising by 2 °C above pre-industrial levels. © 2013 Springer Science+Business Media Dordrecht.

Efficacy response in CF patients treated with ivacaftor: Post-hoc analysis

Clinical studies in patients with cystic fibrosis and G551D-CFTR showed that the group treated with ivacaftor had improved clinical outcomes. To better understand the effect of ivacaftor therapy across the distribution of individual FEV1 responses, data from Phase 3 studies (STRIVE/ENVISION) were re-examined. In this post-hoc analysis of patients (n=209) who received 48 weeks of ivacaftor or placebo, patients were assigned to tertiles according to FEV1 response. These groups were then used to evaluate response (FEV1, sweat chloride, weight, CFQ-R, and pulmonary exacerbation). The number needed to treat (NNT) was calculated for specific thresholds for each outcome. Across all tertiles, numerical improvements in FEV1, sweat chloride, CFQ-R and the frequency of pulmonary exacerbations were observed in ivacaftor-treated patients: the treatment difference versus placebo was statistically significant for all outcomes in the upper tertile and for some outcomes in the lower and middle tertiles. The NNT for a≥5% improvement in %predicted FEV1 was 1.90, for a≥5% body weight increase was 5.74, and to prevent a pulmonary exacerbation was 3.85. This analysis suggests that the majority of patients with clinical characteristics similar to STRIVE/ENVISION patients have the potential to benefit from ivacaftor therapy.

Analysis of groundwater-level response to rainfall and recharge estimates in fractured hard rock aquifers, NW Ireland

Despite fractured hard rock aquifers underlying over 65% of Ireland, knowledge of key processes controlling groundwater recharge in these bedrock systems is inadequately constrained. In this study, we examined 19 groundwater-level hydrographs from two Irish hillslope sites underlain by hard rock aquifers. Water-level time-series in clustered monitoring wells completed at the subsoil, soil/bedrock interface, shallow and deep bedrocks were continuously monitored hourly over two hydrological years. Correlation methods were applied to investigate groundwater-level response to rainfall, as well as its seasonal variations. The results reveal that the direct groundwater recharge to the shallow and deep bedrocks on hillslope is very limited. Water-level variations within these geological units are likely dominated by slow flow rock matrix storage. The rapid responses to rainfall (⩽2 h) with little seasonal variations were observed to the monitoring wells installed at the subsoil and soil/bedrock interface, as well as those in the shallow or deep bedrocks at the base of the hillslope. This suggests that the direct recharge takes place within these units. An automated time-series procedure using the water-table fluctuation method was developed to estimate groundwater recharge from the water-level and rainfall data. Results show the annual recharge rates of 42–197 mm/yr in the subsoil and soil/bedrock interface, which represent 4–19% of the annual rainfall. Statistical analysis of the relationship between the rainfall intensity and water-table rise reveal that the low rainfall intensity group (⩽1 mm/h) has greater impact on the groundwater recharge rate than other groups (>1 mm/h). This study shows that the combination of the time-series analysis and the water-table fluctuation method could be an useful approach to investigate groundwater recharge in fractured hard rock aquifers in Ireland.

Fluid strategies and outcomes in patients with acute respiratory distress syndrome, systemic inflammatory response syndrome and sepsis: a protocol for a systematic review and meta-analysis

Background
Fluid administration to critically ill patients remains the subject of considerable controversy. While intravenous fluid given for resuscitation may be life-saving, a positive fluid balance over time is associated with worse outcomes in critical illness. The aim of this systematic review is to summarise the existing evidence regarding the relationship between fluid administration or balance and clinically important patient outcomes in critical illness.

Methods
We will search Medline, EMBASE, the Cochrane Central Register of Controlled Trials from 1980 to the present and key conference proceedings from 2009 to the present. We will include studies of critically ill adults and children with acute respiratory distress syndrome (ARDS), sepsis and systemic inflammatory response syndrome (SIRS). We will include randomised controlled trials comparing two or more fluid regimens of different volumes of fluid and observational studies reporting the relationship between volume of fluid administered or fluid balance and outcomes including mortality, lengths of intensive care unit and hospital stay and organ dysfunction. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. We will conduct a narrative and/or meta-analysis as appropriate.

Discussion
While fluid management has been extensively studied and discussed in the critical care literature, no systematic review has attempted to summarise the evidence for post-resuscitation fluid strategies in critical illness. Results of the proposed systematic review will inform practice and the design of future clinical trials.

Systematic review registration
PROSPERO CRD42013005608. (http://​www.​crd.​york.​ac.​uk/​PROSPERO/​)

Functional analysis of the ATM-p53-p21 pathway in the LRF CLL4 trial: blockade at the level of p21 is associated with short response duration.

PURPOSE: This study sought to establish whether functional analysis of the ATM-p53-p21 pathway adds to the information provided by currently available prognostic factors in patients with chronic lymphocytic leukemia (CLL) requiring frontline chemotherapy. EXPERIMENTAL DESIGN: Cryopreserved blood mononuclear cells from 278 patients entering the LRF CLL4 trial comparing chlorambucil, fludarabine, and fludarabine plus cyclophosphamide were analyzed for ATM-p53-p21 pathway defects using an ex vivo functional assay that uses ionizing radiation to activate ATM and flow cytometry to measure upregulation of p53 and p21 proteins. Clinical endpoints were compared between groups of patients defined by their pathway status. RESULTS: ATM-p53-p21 pathway defects of four different types (A, B, C, and D) were identified in 194 of 278 (70%) samples. The type A defect (high constitutive p53 expression combined with impaired p21 upregulation) and the type C defect (impaired p21 upregulation despite an intact p53 response) were each associated with short progression-free survival. The type A defect was associated with chemoresistance, whereas the type C defect was associated with early relapse. As expected, the type A defect was strongly associated with TP53 deletion/mutation. In contrast, the type C defect was not associated with any of the other prognostic factors examined, including TP53/ATM deletion, TP53 mutation, and IGHV mutational status. Detection of the type C defect added to the prognostic information provided by TP53/ATM deletion, TP53 mutation, and IGHV status. CONCLUSION: Our findings implicate blockade of the ATM-p53-p21 pathway at the level of p21 as a hitherto unrecognized determinant of early disease recurrence following successful cytoreduction.