Absorbent products for urinary/faecal incontinence: a comparative evaluation of key product designs

Background: The UK health service, nursing homes and public spend around £94 million per year on incontinence pads (absorbent products) to contain urine and/or faeces, but the research base for making informed choices between different product designs is very weak.Objectives: The aim of this trial was to compare the performance and cost-effectiveness of the key absorbent product designs to provide a more solid basis for guiding selection and purchase.A further aim was to carry out the first stage in the development of a quality of life instrument for measuring the impact of absorbent product use on users' lives.Design: The work involved three clinical trials focusing on the three biggest market sectors. Each trial had a similar crossover design in which each participant tested all products within their group in random order.Settings, participants and methods: In Trial 1, 85 women with light urinary incontinence living in the community tested three products from each of the four design categories available (total of 12 test products): disposable inserts (pads); menstrual pads; washable pants with integral pad; and washable inserts. In Trial 2a, 85 moderate/heavily incontinent adults (urinary or urinary/faecal) living in the community (49 men and 36 women) tested three (or two) products from each of the five design categories available (total of 14 test products): disposable inserts (with mesh pants); disposable diapers (nappies); disposable pull-ups (similar to toddlers' trainer pants); disposable T-shaped diapers (nappies with waist-band); and washable diapers. All products were provided in a daytime and a (mostly more absorbent) night-time variant. In these first two trials, the test products were selected on the basis of data from pilot studies. In Trial 2b, 100 moderate/heavily incontinent adults (urinary or urinary/faecal) living in 10 nursing homes (27 men and 73 women) evaluated one product from each of the four disposable design categories from Trial 2a. Products were selected on the basis of product performance in Trial 2a and, again, daytime and night-time variants were provided. The first phase of work to develop a quality of life tool for measuring the impact of using different pad designs was carried out by interviewing participants from Trials 1 and 2a.Outcome measures: Product performance was characterised using validated questionnaires, which asked the participants (in Trials 1 and 2a) or carers (all participants in Trial 2b, except for the few who could report for themselves) to evaluate various aspects of pad performance (leakage, ease of putting on, discreetness, etc.) using a five-point scale (very good–very poor) at the end of the week (or 2 weeks for Trial 2b) of product testing. In addition, participants/carers were asked to save individual used pads in bags for weighing and to indicate the severity of any leakage from them on a three-point scale (none, a little, a lot). These data were used to determine differences in leakage performance. Numbers of laundry items and pads used were recorded to estimate costs, and skin health changes were recorded by the participant or by the researchers (Trial 2b). At the end of testing, participants were interviewed and ranked their preferences (with and without costs), stated the acceptability of each design (highly acceptable–totally unacceptable) and recorded their overall opinion on a visual analogue scale (VAS) of 0–100 points (worst design–best design). This VAS score was used with product costs to estimate cost-effectiveness. In addition, a timed pad changing exercise was conducted with 10 women from Trial 2b to determine any differences between product designs.Results: Results presented are for statistically and clinically significant findings.<br/

The effects of cropping intensity and cropland expansion of Brazilian soybean production on green water flows

As land use change alters how green water is appropriated, cropland expansion is instrumental in re-allocating green water towards agriculture. Alongside cropland expansion, agricultural intensification practices modify crop water use and land and water productivity. Particularly, one form of agricultural intensification known as multi-cropping (the cultivation of a piece of land sequentially more than once a year) can result in greater agricultural output per unit of land, as well as more productive use of the available water throughout the annual rainfall cycle. We assess the influence of these two processes, cropland expansion and agricultural intensification, in agricultural green water use in Brazilian agriculture. We applied the biophysical crop model Environmental Policy Integrated Climate (EPIC) to estimate green water use for single and double cropping of soybean (Glycine max) and maize (Zea mays) in Brazil. The first part of our study analyses changes in soybean green water use and virtual water content nationwide between 1990 and 2013, and in a second part we look into the effect of double-cropping on water use for soybean and maize in the Brazilian states of Paraná and Mato Grosso between 2003 and 2013. The results show that cropland expansion plays a more prominent effect in green water use for production of soybean than intensification, and harvested area increase was responsible for the appropriation of an additional 95 km3 of green water in 2013 when compared to 1990, an increase of 155%. We estimate that an additional green water use of around 26 km3 related to second season maize was appropriated through increase of cropping frequency, and without expansion of cropland, in 2013 in the selected states. We discuss the importance of considering multi cropping practices when assessing green water sustainability, and the importance of differentiating green water appropriation through expansion and through cropping frequency changes

Low-Grade Serous Ovarian Cancer: Expert Consensus Report on the State of the Science

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care

Global Carbon Budget 2015

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates as well as consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuels and industry (E-FF) are based on energy statistics and cement production data, while emissions from land-use change (E-LUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (G(ATM)) is computed from the annual changes in concentration. The mean ocean CO2 sink (S-OCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in S-OCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (S-LAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO2, and land-cover change (some including nitrogen-carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as +/- 1 sigma, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (20052014), E-FF was 9.0 +/- 0.5 GtC yr(-1) E-LUC was 0.9 +/- 0.5 GtC yr(-1), GATM was 4.4 +/- 0.1 GtC yr(-1), S-OCEAN was 2.6 +/- 0.5 GtC yr(-1), and S LAND was 3.0 +/- 0.8 GtC yr(-1). For the year 2014 alone, E FF grew to 9.8 +/- 0.5 GtC yr(-1), 0.6% above 2013, continuing the growth trend in these emissions, albeit at a slower rate compared to the average growth of 2.2% yr(-1) that took place during 2005-2014. Also, for 2014, E-LUC was 1.1 +/- 0.5 GtC yr(-1), G(ATM) was 3.9 +/- 0.2 GtC yr(-1), S-OCEAN was 2.9 +/- 0.5 GtC yr(-1), and S-LAND was 4.1 +/- 0.9 GtC yr(-1). G(ATM) was lower in 2014 compared to the past decade (2005-2014), reflecting a larger S-LAND for that year. The global atmospheric CO2 concentration reached 397.15 +/- 0.10 ppm averaged over 2014. For 2015, preliminary data indicate that the growth in E-FF will be near or slightly below zero, with a projection of 0.6 [ range of 1.6 to C 0.5] %, based on national emissions projections for China and the USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the global economy for the rest of the world. From this projection of E-FF and assumed constant E LUC for 2015, cumulative emissions of CO2 will reach about 555 +/- 55 GtC (2035 +/- 205 GtCO(2)) for 1870-2015, about 75% from E FF and 25% from E LUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quere et al., 2015, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi: 10.3334/CDIAC/GCP_2015)

Lapatinib Induces Autophagy, Apoptosis and Megakaryocytic Differentiation in Chronic Myelogenous Leukemia K562 Cells

Lapatinib is an oral, small-molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptors (EGFR, or ErbB/Her) in solid tumors. Little is known about the effect of lapatinib on leukemia. Using human chronic myelogenous leukemia (CML) K562 cells as an experimental model, we found that lapatinib simultaneously induced morphological changes resembling apoptosis, autophagy, and megakaryocytic differentiation. Lapatinib-induced apoptosis was accompanied by a decrease in mitochondrial transmembrane potential and was attenuated by the pancaspase inhibitor z-VAD-fmk, indicating a mitochondria-mediated and caspase-dependent pathway. Lapatinib-induced autophagic cell death was verified by LC3-II conversion, and upregulation of Beclin-1. Further, autophagy inhibitor 3-methyladenine as well as autophagy-related proteins Beclin-1 (ATG6), ATG7, and ATG5 shRNA knockdown rescued the cells from lapatinib-induced growth inhibition. A moderate number of lapatinib-treated K562 cells exhibited features of megakaryocytic differentiation. In summary, lapatinib inhibited viability and induced multiple cellular events including apoptosis, autophagic cell death, and megakaryocytic differentiation in human CML K562 cells. This distinct activity of lapatinib against CML cells suggests potential for lapatinib as a therapeutic agent for treatment of CML. Further validation of lapatinib activity in vivo is warranted

Global Monthly Water Scarcity: Blue Water Footprints versus Blue Water Availability

Freshwater scarcity is a growing concern, placing considerable importance on the accuracy of indicators used to characterize and map water scarcity worldwide. We improve upon past efforts by using estimates of blue water footprints (consumptive use of ground- and surface water flows) rather than water withdrawals, accounting for the flows needed to sustain critical ecological functions and by considering monthly rather than annual values. We analyzed 405 river basins for the period 1996–2005. In 201 basins with 2.67 billion inhabitants there was severe water scarcity during at least one month of the year. The ecological and economic consequences of increasing degrees of water scarcity – as evidenced by the Rio Grande (Rio Bravo), Indus, and Murray-Darling River Basins – can include complete desiccation during dry seasons, decimation of aquatic biodiversity, and substantial economic disruption

Juvenile Facility Staff Contestations of Change

This article explores juvenile facility frontline staff members’ contestations of change to custodial practices aimed at reducing restraints, introducing trauma-informed practices, and downsizing juvenile facilities. Drawing from qualitative research about frontline staff members in a U.S. state undergoing reform, the article points to the ways that the reforms challenge staff members’ investments in behavioral control practices as a vehicle for achieving order and control in their everyday lives as workers. It also points to shifts in the broader political economy of punishment at the local, facility level, and the subsequent impact on staff member perceptions of order, control and criminality

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.

The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers\u27 tissue of origin