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Background: Aspirin use has been associated with reduced ovarian cancer risk, yet the underlying biological mechanisms are not fully understood. To gain mechanistic insights, we assessed the association between prediagnosis low and regular‐dose aspirin use and gene expression profiles in ovarian tumors. Methods: RNA sequencing was performed on high‐grade serous, poorly differentiated, and high‐grade endometrioid ovarian cancer tumors from the Nurses' Health Study (NHS), NHSII, and New England Case–Control Study (n = 92 cases for low, 153 cases for regular‐dose aspirin). Linear regression identified differentially expressed genes associated with aspirin use, adjusted for birth decade and cohort. False discovery rates (FDR) were used to account for multiple testing and gene set enrichment analysis was used to identify biological pathways. Results: No individual genes were significantly differentially expressed in ovarian tumors in low or regular‐dose aspirin users accounting for multiple comparisons. However, current versus never use of low‐dose aspirin was associated with upregulation of immune pathways (e.g., allograft rejection, FDR = 5.8 × 10−10; interferon‐gamma response, FDR = 2.0 × 10−4) and downregulation of estrogen response pathways (e.g., estrogen response late, FDR = 4.9 × 10−8). Ovarian tumors from current regular aspirin users versus never users were also associated with upregulation in interferon pathways (FDR <1.5 × 10−4) and downregulation of multiple extracellular matrix (ECM) architecture pathways (e.g., ECM organization, 4.7 × 10−8). Conclusion: Our results suggest low and regular‐dose aspirin may impair ovarian tumorigenesis in part via enhancing adaptive immune response and decreasing metastatic potential supporting the likely differential effects on ovarian carcinogenesis and progression by dose of aspirin. [ABSTRACT FROM AUTHOR]

Background: Cluster analysis is utilized frequently in scientific theory and applications to separate data into groups. A key assumption in many clustering algorithms is that the data was generated from a population consisting of multiple distinct clusters. Clusterability testing allows users to question the inherent assumption of latent cluster structure, a theoretical requirement for meaningful results in cluster analysis. Results: This paper proposes methods for clusterability testing designed for high-dimensional data by utilizing sparse principal component analysis. Type I error and power of the clusterability tests are evaluated using simulated data with different types of cluster structure in high dimensions. Empirical performance of the new methods is evaluated and compared with prior methods on gene expression, microarray, and shotgun proteomics data. Our methods had reasonably low Type I error and maintained power for many datasets with a variety of structures and dimensions. Cluster structure was not detectable in other datasets with spatially close clusters. Conclusion: This is the first analysis of clusterability testing on both simulated and real-world high-dimensional data. [ABSTRACT FROM AUTHOR]

Background: Greater ovulatory years is associated with increased ovarian cancer risk. Although ovulation leads to an acute pro-inflammatory local environment, how long-term exposure to ovulation impacts ovarian carcinogenesis is not fully understood. Thus, we examined the association between gene expression profiles of ovarian tumors and lifetime ovulatory years to enhance understanding of associated biological pathways. Methods: RNA sequencing data was generated on 234 invasive ovarian cancer tumors that were high-grade serous, poorly differentiated, or high-grade endometrioid from the Nurses' Health Study (NHS), NHSII, and the New England Case Control Study. We used linear regression to identify differentially expressed genes by estimated ovulatory years, adjusted for birth decade and cohort, overall and stratified by menopausal status at diagnosis. We used false discovery rates (FDR) to account for multiple testing. Gene set enrichment analysis (GSEA) with Cancer Hallmarks, KEGG, and Reactome databases was used to identify biological pathways associated with ovulatory years. Results: No individual genes were significantly differentially expressed by ovulatory years (FDR > 0.19). However, GSEA identified several pathways that were significantly associated with ovulatory years, including downregulation of pathways related to inflammation and proliferation (FDR < 1.0 × 10–5). Greater ovulatory years were more strongly associated with downregulation of genes related to proliferation (e.g., E2F targets, FDR = 1.53 × 10–24; G2M checkpoints, FDR = 3.50 × 10–22) among premenopausal versus postmenopausal women at diagnosis. The association of greater ovulatory years with downregulation of genes involved in inflammatory response such as interferon gamma response pathways (FDR = 7.81 × 10–17) was stronger in postmenopausal women. Conclusions: Our results provide novel insight into the biological pathways that link ovulatory years to ovarian carcinogenesis, which may lead to development of targeted prevention strategies for ovarian cancer. [ABSTRACT FROM AUTHOR]

During the current pandemic, forest loss in 2020 has dwarfed the devastation of the previous year. The scale of environmental crimes and aggression towards indigenous peoples and people of African-descendent has been a characteristic of the Bolsonaro administration in the Amazon region. As cases of COVID-19 rise daily in remote areas of the Amazon, a recent study indicates that indigenous lands that aren't formally demarcated are more vulnerable to intrusion and hence disease: indeed illegal loggers have emerged as a key vector of Covid-19 transmission in a region with Brazil's lowest number of intensive care units. The weakening of environmental protection in the Amazon has been systematic and a feature of the Brazilian shift from neo-liberalism to neo-developmentalism which can be characterised politically as neo-liberal authoritarianism. If Covid-19 also is now becoming a metaphor for the poisonous spread of neo-liberal globalisation, plunder and land grabs in the Brazilian rainforest can be seen to represent the most egregious of many egregious cases on the ground zero of neo-liberalism unchained. With the rise of Bolsonaro, we can see that the previous conjuncture characterised by the hegemony of PT and Lula was the exception to Brazil's long embrace of the caudillo going back to the 1930s. Even then, a look at the mechanism of Lula's rule raises questions as to precisely what changed under Lula when it came to the state and the rule of big capital. [ABSTRACT FROM AUTHOR]

Background: Factor VIIc, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) are cardiovascular disease (CVD) risk factors and are modulated, in part, by fat type and amount.Objective: We evaluated fat type and amount on the primary outcomes: factor VIIc, fibrinogen, and PAI-1.Methods: In the Dietary Effects on Lipoproteins and Thrombogenic Activity (DELTA) Trial, 2 controlled crossover feeding studies evaluated substituting carbohydrate or MUFAs for SFAs. Study 1: healthy participants (n = 103) were provided with (8 wk) an average American diet [AAD; designed to provide 37% of energy (%E) as fat, 16% SFA], a Step 1 diet (30%E fat, 9% SFA), and a diet low in SFA (Low-Sat; 26%E fat, 5% SFA). Study 2: participants (n = 85) at risk for CVD and metabolic syndrome (MetSyn) were provided with (7 wk) an AAD, a step 1 diet, and a high-MUFA diet (designed to provide 37%E fat, 8% SFA, 22% MUFA).Results: Study 1: compared with AAD, the Step 1 and Low-Sat diets decreased mean factor VIIc by 1.8% and 2.6% (overall P = 0.0001), increased mean fibrinogen by 1.2% and 2.8% (P = 0.0141), and increased mean square root PAI-1 by 0.0% and 6.0% (P = 0.0037), respectively. Study 2: compared with AAD, the Step 1 and high-MUFA diets decreased mean factor VIIc by 4.1% and 3.2% (overall P < 0.0001), increased mean fibrinogen by 3.9% and 1.5% (P = 0.0083), and increased mean square-root PAI-1 by 2.0% and 5.8% (P = 0.1319), respectively.Conclusions: Replacing SFA with carbohydrate decreased factor VIIc and increased fibrinogen in healthy and metabolically unhealthy individuals and also increased PAI-1 in healthy subjects. Replacing SFA with MUFA decreased factor VIIc and increased fibrinogen but less than carbohydrate. Our results indicate an uncertain effect of replacing SFA with carbohydrate or MUFA on cardiometabolic risk because of small changes in hemostatic factors and directionally different responses to decreasing SFA. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT00000538?term=NCT00000538&rank=1 as NCT00000538. [ABSTRACT FROM AUTHOR]

Summary: Glucocorticoids (GCs) are steroid hormones, which are essential for life. They are secreted by the adrenal cortex under the control of the hypothalamic‐pituitary‐adrenal (HPA) axis. Glucocorticoids are essential for the normal function of most organ systems and, in both, excess and deficiency can lead to significant adverse consequences. Adrenal insufficiency (AI) is a rare, life‐threatening disorder characterized by insufficient production of corticosteroid hormones. Primary AI is defined by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids despite normal or increased adrenocorticotropin hormone (ACTH). Secondary AI is adrenal hypofunction due to insufficient amount of ACTH produced by the pituitary gland. Conventional treatment of both primary and secondary adrenal insufficiencies involves lifelong glucocorticoid replacement therapy. The role of cortisol deficiency and the impact of hydrocortisone replacement on morbidity and mortality in this patient group are under increasing scrutiny. Established glucocorticoid replacement regimens do not completely mirror endogenous hormonal production, and their monitoring to ensure optimum therapy is hampered by the lack of reliable biomarkers of hormone sufficiency. A further confounding issue is the tissue‐specific regulation of glucocorticoid through the two isozymes of 11β‐hydroxysteroid dehydrogenase (11β‐HSD) with research focusing on the role of this prereceptor regulation in the development of adverse metabolic features in patients. This review defines the factors influencing glucocorticoid action in patients with adrenal insufficiency receiving glucocorticoid therapy. [ABSTRACT FROM AUTHOR]

Background: Symptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings are not known. We characterized these patient-reported outcomes (PROs) among HCV-infected patients and explored associations with sociodemographic, liver disease, and psychiatric/substance abuse variables. Methods and findings: PROP UP is a large US multicenter observational study that enrolled 1,600 patients with chronic HCV in 2016–2017. Data collected prior to initiating DAA therapy assessed the following PROs: number of medical comorbidities; neuropsychiatric, somatic, gastrointestinal symptoms (PROMIS surveys); overall symptom burden (Memorial Symptom Assessment Scale); and functional well-being (HCV-PRO). Candidate predictors included liver disease markers and patient-reported sociodemographic, psychiatric, and alcohol/drug use features. Predictive models were explored using a random selection of 700 participants; models were then validated with data from the remaining 900 participants. The cohort was 55% male, 39% non-white, 48% had cirrhosis (12% with advanced cirrhosis); 52% were disabled or unemployed; 63% were on public health insurance or uninsured; and over 40% had markers of psychiatric illness. The median number of medical comorbidities was 4 (range: 0–15), with sleep disorders, chronic pain, diabetes, joint pain and muscle aches being present in 20–50%. Fatigue, sleep disturbance, pain and neuropsychiatric symptoms were present in over 60% and gastrointestinal symptoms in 40–50%. In multivariable validation models, the strongest and most frequent predictors of worse PROs were disability, unemployment, and use of psychiatric medications, while liver markers generally were not. Conclusions: This large multi-center cohort study provides a comprehensive and contemporary assessment of the symptom burden and comorbid medical conditions in patients with HCV treated in real world settings. Pain, fatigue, and sleep disturbance were common and often severe. Sociodemographic and psychiatric markers were the most robust predictors of PROs. Future research that includes a rapidly changing population of HCV-infected individuals needs to evaluate how DAA therapy affects PROs and elucidate which symptoms resolve with viral eradication. Trial registration: (Clinicaltrial.gov: ). [ABSTRACT FROM AUTHOR]

Background: Microsoft Excel automatically converts certain gene symbols, database accessions, and other alphanumeric text into dates, scientific notation, and other numerical representations. These conversions lead to subsequent, irreversible, corruption of the imported text. A recent survey of popular genomic literature estimates that one-fifth of all papers with supplementary gene lists suffer from this issue. Results: Here, we present an open-source tool, Escape Excel, which prevents these erroneous conversions by generating an escaped text file that can be safely imported into Excel. Escape Excel is implemented in a variety of formats (), including a command line based Perl script, a Windows-only Excel Add-In, an OS X drag-and-drop application, a simple web-server, and as a Galaxy web environment interface. Test server implementations are accessible as a Galaxy interface () and simple non-Galaxy web server (). Conclusions: Escape Excel detects and escapes a wide variety of problematic text strings so that they are not erroneously converted into other representations upon importation into Excel. Examples of problematic strings include date-like strings, time-like strings, leading zeroes in front of numbers, and long numeric and alphanumeric identifiers that should not be automatically converted into scientific notation. It is hoped that greater awareness of these potential data corruption issues, together with diligent escaping of text files prior to importation into Excel, will help to reduce the amount of Excel-corrupted data in scientific analyses and publications. [ABSTRACT FROM AUTHOR]

Political commitment linked to robust research is seen as a major challenge amongst progressive researchers. Many suggest that one way forward is to engage with those being researched in novel and participative ways so that a democratic spirit is sustained. The preferred methodology is 'participatory action research' (PAR). The paper begins with an outline of PAR and its attraction for balancing political commitment with valueneutrality in research. It then discusses the importance, purpose and radicalness of what we interpret as a 'left-radical' methodology for making alliances with those excluded in myriad ways. The paper subsequently insists on the need to understand the limitations of PAR used by those working from within the neo-liberal academy. We insist that its utility depends upon context, feasibility and desirability. Without this awareness, and without connecting with a broader understanding of the notion of organic and committed intellectuals, then PAR (still a relatively unused research practice) becomes practically limited if not merely symbolic. First, PAR is not inherently democratic - it has radical usage but it is a methodology subject to various social appropriations. Second, when used by left-radical researchers, PAR should be emancipatory; however, it is not the only or the best way to engage with people outside the academy. Third, while some of us working within the academy have been fortunate to use PAR, there are constraints due to the rise of the neo-liberal university. [ABSTRACT FROM AUTHOR]

DC–DC power converters such as buck converters are susceptible to degradation and failure due to operating under conditions of electrical stress and variable power sources in power conversion applications, such as electric vehicles and renewable energy. Some key components such as electrolytic capacitors degrade over time due to evaporation of the electrolyte. In this paper, a model-observer based scheme is proposed to monitor the states of Buck converters and to estimate their component parameters, such as capacitance and inductance. First, a diagnosis observer is proposed, and the generated residual vectors are applied for fault detection and isolation. Second, component condition parameters, such as capacitance and inductance are reconstructed using another novel observer with adaptive feedback law. Additionally, the observer structures and their theoretical performance are analyzed and proven. In contrast to existing reliability approaches applied in buck converters, the proposed scheme performs online-estimation for key parameters. Finally, buck converters in conventional dc–dc step-down and photovoltaic applications are investigated to test and validate the effectiveness of the proposed scheme in both simulation and laboratory experiments. Results demonstrate the feasibility, performance, and superiority of the proposed component parameter estimation scheme. [ABSTRACT FROM AUTHOR]

The argument of the moral economy of mines claims to illuminate the consent and associational power of mineworkers, and thereby the real foundation of social exchanges between management and black mineworkers. Our collection of life histories shows how the moral economy was fragile and its codes not widely accepted. As a tool of analysis it does not include certain facets of the workers’ experience, feeling and human essence. The moral–economic relationship was conducive to surplus extraction by eliminating the non-conformist but industrious or sick workers in the labour system. It contributed to morbid sexual and emotional ways of life. The life histories further reveal how the rank-and-file generally endorsed and participated in what Moodie depicts as a positive class compromise struck between management and the workers’ union from the 1980s to the 1990s. It brought to them conditions for a regular family life and ‘advancing humanity’. This notwithstanding, our narrators found that the norm of apartheid gave way to that of discrimination and differentiation between black workers. Management replaced white ‘boss-ism’ by economism and a corporatist model of labour–management relationship. It engendered the spirit of new ways to secure opportunity. [ABSTRACT FROM AUTHOR]

In ‘The Ideology of Modernism’, Georg Lukács accused Beckett, alongside other Modernists, of having turned away from the political function of literature. This article seeks to challenge such a view of Beckett as an apolitical writer. With reference to two works in different forms – the stage-play Catastrophe (1982) and the short prose work Company (1980) – it is argued that the more social form of the theatre might fail in its attempts to protest against prevailing social and political conditions. In contrast, the work of the prose, in its relation to the Bildungsroman, is seen as political precisely in its adherence to an asocial conception of man. [ABSTRACT FROM PUBLISHER]

Labor time, as a dimension of South African mining labor history, has been ignored, both conceptually and historically. This article remedies this yawning gap by presenting primary and secondary evidence which demonstrates the centrality of labor time in South African gold mines since the discovery of gold in 1886. To this end, labor time is traced in two ways. Part I tracks industrial working time by tracing the length of the working day and week. Part II tracks the ever-increasing length of the African migrant labor contract. While industrial working hours remain remarkably stable for almost a century, the migrant labor contract systematically increases over a similar period. These two measures of labor time eventually coincide when the migrant labor system dissolves and black African workers take annual leave together with their compatriots across the racial divide. The explanation for the mining industry’s long struggle to bothmaintainrelatively long working hours and increasinglymaximizethe length of the migrant labor contract is construed ascompletingthe received wisdom of Harold Wolpe's much celebrated and criticized `cheap- labor' thesis. (Wolpe, “Capitalism and Cheap Labor Power.”) [ABSTRACT FROM PUBLISHER]

We present an analysis of spectral and spatial data of Mira obtained by the Cassini spacecraft, which not only observed the star's spectra over a broad range of near-infrared wavelengths, but was also able to obtain high-resolution spatial information by watching the star pass behind Saturn's rings. The observed spectral range of 1-5 microns reveals the stellar atmosphere in the crucial water-bands which are unavailable to terrestrial observers, and the simultaneous spatial sampling allows the origin of spectral features to be located in the stellar environment. Models are fitted to the data, revealing the spectral and spatial structure of molecular layers surrounding the star. High-resolution imagery is recovered revealing the layered and asymmetric nature of the stellar atmosphere. The observational data set is also used to confront the state-of-theart cool opacity-sampling dynamic extended atmosphere models of Mira variables through a detailed spectral and spatial comparison, revealing in general a good agreement with some specific departures corresponding to particular spectral features. [ABSTRACT FROM AUTHOR]

This article presents an historical overview of the occupation of rock drillers in South African mines. It is argued that the critical productive role this occupation plays in the underground production process must be central to understanding why the rock drill operators (RDOs) initiated a major strike wave on South African platinum mines in 2012, what transpired at Marikana in August of that year and the 2014 industry-wide strike. Long established as an elite within the mining industry, the RDOs negotiated directly with management over the past 30 years beyond the ambit of representational politics. However, the migrant labour status, deplorable living conditions and memories of past struggles intersect with the impact of their working conditions underground. This article suggests that the historically identifiable objective location of these workers in production serves as the material basis for their political subjectivity. [ABSTRACT FROM AUTHOR]

We performed a pilot proteogenomic study to compare lung adenocarcinoma to lung squamous cell carcinoma using quantitative proteomics (6-plex TMT) combined with a customized Affymetrix GeneChip. Using MaxQuant software, we identified 51,001 unique peptides that mapped to 7,241 unique proteins and from these identified 6,373 genes with matching protein expression for further analysis. We found a minor correlation between gene expression and protein expression; both datasets were able to independently recapitulate known differences between the adenocarcinoma and squamous cell carcinoma subtypes. We found 565 proteins and 629 genes to be differentially expressed between adenocarcinoma and squamous cell carcinoma, with 113 of these consistently differentially expressed at both the gene and protein levels. We then compared our results to published adenocarcinoma versus squamous cell carcinoma proteomic data that we also processed with MaxQuant. We selected two proteins consistently overexpressed in squamous cell carcinoma in all studies, MCT1 (SLC16A1) and GLUT1 (SLC2A1), for further investigation. We found differential expression of these same proteins at the gene level in our study as well as in other public gene expression datasets. These findings combined with survival analysis of public datasets suggest that MCT1 and GLUT1 may be potential prognostic markers in adenocarcinoma and druggable targets in squamous cell carcinoma. Data are available via ProteomeXchange with identifier PXD002622. [ABSTRACT FROM AUTHOR]

This article alludes to historical evidence that traces working time arrangements in South African mining since 1886. It does so by very briefly summarising detailed narratives of both working hours (which remain remarkably stable) since 1911 and the length of the migrant labour contract (which progressively lengthens) until the collapse of the controls of the migrant labour supply system in the 1980s. At this point the labour contract aligns with the annual cycle of industrial working time. It is argued here that because labour time has been ignored in scholarly historical analyses, there is no explanation why long working hours are required in mining. The reason is that theretentionof labour in production underground is foundational to and of greater explanatory import in understanding the role of the mining industry than itsacquisition. This view challenges the received wisdom that the exploitation of mine labour is chiefly accounted for in terms of cheap wages for black mineworkers. Labour time, a concept defined at the outset of this article, is asserted as the missing explanatory variable necessary for understanding the developmental trajectory of mining in South Africa, both historically and in the contemporary period. [ABSTRACT FROM PUBLISHER]

This article examines the rise of the Independent Workers Union (IWU) in Ireland, North and South, in relation to the bifurcation of trade unionism on the Island, from 1900 until the demise of the so-called Celtic tiger in the early years of the twenty-first century. It is argued that two competing ideological and political trajectories defined the major divisions in the Irish labour movement and where given added impetus with the formation of two separate states after 1920. One tradition was committed to an idea of a progressive British empire, while the other was born of a movement linking together trade union, class and national autonomy. A trade union with a long history and recent past, the IWU represents a labour movement formation whose tradition extends the latter: it is committed to developing forms of opposition to state and capital. If more subdued since the partition of the island, this tradition was reignited with the implosion of Social Partnership in the South and the rise of the new sectarianism in the North. Neoliberalism, with its consequent assault upon labour and its various institutions more broadly, provided additional impetus to the creation of the IWU in 2004. The article also assesses its various alternative union and community organising strategies. [ABSTRACT FROM PUBLISHER]

Our aim was to study the effects and safety of cantharidin in the treatment of molluscum contagiosum (MC), we conducted a prospective, double-blinded, placebo-controlled, randomized clinical trial to evaluate the safety and efficacy of topical cantharidin for treatment of pediatric MC in an academic ambulatory care center. Twenty-nine children aged 5-10 with a diagnosis of MC were enrolled to receive treatment with cantharidin or placebo. The main outcome measure was complete clearance of all molluscum lesions. In contrast to previous retrospective observational studies, the performance of cantharidin treatment over 2 months was not substantially better than the performance of placebo. The scope of follow-up was limited to five visits over 2 months of treatment. A longer follow-up period might have captured a greater effect of cantharidin. Over a 2 month period, the magnitude of the cantharidin treatment effects in the target population are, at best, not large. This study provided objective unbiased estimates of the magnitude of cantharidin treatment effects and provided important prospective safety data. Our subjects experienced minimal side effects when treated with cantharidin. [ABSTRACT FROM AUTHOR]

This paper examines warehouse workers' experiences of the labour process and employment relations in an ambient food distribution depot governed by a labour management system described as lean logistics. Lean logistics is seen by the sector as an aid to, and necessary development of, the globalisation of the sector's supply chain (global commodity chain). The focus is on how the restructuring of work as a result of lean logistics and the consequent imposition of a supermarket Taylorist work culture led to the demise of an industrial workplace culture and a dramatic deterioration in pay and working conditions. The latter included an increase in the scope and intensity of management control of labour. [ABSTRACT FROM PUBLISHER]

Many investigators sample a site or watershed only once and use that sample to characterize the location (e.g., indices of biotic integrity studies). Using real-world fish assemblages, we investigated the adequacy of using a single sample, site, or season to characterize the fish community at a site or watershed. We sampled twelve sites from the Little Choctawhatchee River watershed (416 km2) by electrofishing six times at each location over 18 months ( n = 72). We estimated species richness at each site during each season and for the entire watershed using the Chao 2 estimator. We used these estimates to determine how many samples at the local level and how many sites at the watershed level were needed. Additionally, we determined the proportion of species found after 1-6 samples. Our results showed that to observe 80-100% of species, 5.6-47.4 samples, respectively, were needed at the local level over six seasons, 8.4-86.9 sites, respectively, were needed at the watershed level over a single season, and 9-70 samples, respectively, were needed for the entire watershed over six seasons. At the local level, we found a mean of 50-83% of the estimated species with 1-6 samples over six seasons. At the watershed level, we found a mean of 37%) (SD = 3) with one sample and 76% (SD = 6) after six samples over one season. Our results indicate that in general a minimum of 5 samples is needed to detect at least 80% of the species present at the local (site) level, and a minimum of 8 sites is needed in watersheds of approximately 400-450 km2. [ABSTRACT FROM AUTHOR]

Background Hormonal status influences haemostatic factors including fibrinogen, factor VII and plasminogen activator inhibitor ( PAI-1), and concentrations differ among men, premenopausal and postmenopausal women. This study examines how phases of the menstrual cycle influence variability of fibrinogen, factor VII and PAI-1. Design We studied 103 subjects (39 premenopausal women, 18 postmenopausal women and 46 men) during three, randomized, 8-week energy- and nutrient-controlled experimental diets in the Dietary Effects on Lipids and Thrombogenic Activity ( DELTA) Study. Fasting blood samples were collected weekly during the last 4 weeks of each diet period, and haemostatic factors were quantified. Two linear mixed-effects models were used for fibrinogen, factor VII and PAI-1: one to estimate and compare group-specific components of variance, and the other to estimate additional fixed effects representing cyclical functions of day of menstrual cycle in premenopausal women. Results Systematic cyclical variation with day of menstrual cycle was observed for fibrinogen ( P < 0·0001), factor VII ( P = 0·0012) and PAI-1 ( P = 0·0024) in premenopausal women. However, the amplitude of cycling was small relative to the total magnitude of intra-individual variability. In addition, the intra-individual variance and corresponding coefficient of variation observed in premenopausal women did not differ from postmenopausal women and men. Conclusions The variability in haemostatic factors in premenopausal women is no greater than for postmenopausal women or men. Consequently, premenopausal women can be included in studies investigating haemostatic factor responses without controlling for stage of menstrual cycle. [ABSTRACT FROM AUTHOR]

This article explains why rock drill operators (RDOs) initiated the 2012 strike wave in South African mining. It does so by sketching the history of the specific industrial occupation of rock drilling over a century, describing its central role in the mining labour process and discussing a case study undertaken in 2005 after a strike by over 400 RDOs. It argues that due to the centrality and stability of the machine rock drill, resulting from stalled mechanisation at the rock face, the continued presence of large numbers of rock drillers and other underground workers are still required to mine both gold and platinum. The consequence is a mass-based mining working class reminiscent of early industrial capitalism. This, the argument goes, is the basis of the objective social power recently wielded by the RDOs. For these reasons rock drillers have consequently been singled out for differential treatment by mining companies for over a century. The contemporary evidence for this is the case study of the struggle of a group of RDOs whose independent workers’ committees have been traced back to 1985. When the RDOs went out on a series of strikes in 1999 and 2004, the parallels with the 2012 strike wave in mining are notable. When analysed from the perspective of their historical point-of-production struggles in the labour process, the reasons why the RDOs were at the forefront of the strike wave in 2012 are explained. A fuller explanation of the strike wave, its underlying causes and the ensuing political events, it is argued, must begin by understanding the occupation of the rock driller, the source of their social power and their history of struggle. [ABSTRACT FROM PUBLISHER]

Background: Child maltreatment (CM) is a pervasive public health problem and there is a critical need for brief, effective, scalable prevention programs. Problematic parent-child relationships lie at the heart of CM. Parents who maltreat their children are more likely to have punitive parenting styles characterized by high rates of negative interaction and ineffective discipline strategies with over-reliance on punishment. Thus, parenting interventions that strengthen parent-child relationships, teach positive discipline techniques, decrease harsh parenting, and decrease child behavioral problems hold promise as CM prevention strategies. Challenges in engaging parents, particularly low-income and minority parents, and a lack of knowledge regarding effective implementation strategies, however, have greatly limited the reach and impact of parenting interventions. Child Adult Relationship Enhancement in Primary Care (PriCARE)/Criando Niños con CARIÑO is a 6-session group parenting intervention that holds promise in addressing these challenges because PriCARE/CARIÑO was (1) developed and iteratively adapted with input from racially and ethnically diverse families, including low-income families and (2) designed specifically for implementation in primary care with inclusion of strategies to align with usual care workflow to increase uptake and retention. Methods: This study is a multicenter randomized controlled trial with two parallel arms. Children, 2–6 years old with Medicaid/CHIP/no insurance, and their English- and Spanish-speaking caregivers recruited from pediatric primary care clinics in Philadelphia and North Carolina will be enrolled. Caregivers assigned to the intervention regimen will attend PriCARE/CARIÑO and receive usual care. Caregivers assigned to the control regimen will receive usual care only. The primary outcome is occurrence of an investigation for CM by child protective services during the 48 months following completion of the intervention. In addition, scores for CM risk, child behavior problems, harsh and neglectful parenting behaviors, caregiver stress, and caregiver-child interactions will be assessed as secondary outcome measures and for investigation of possible mechanisms of intervention-induced change. We will also identify PriCARE/CARIÑO implementation factors that may be barriers and facilitators to intervention referrals, enrollment, and attendance. Discussion: By evaluating proximal outcomes in addition to the distal outcome of CM, this study, the largest CM prevention trial with individual randomization, will help elucidate mechanisms of change and advance the science of CM prevention. This study will also gather critical information on factors influencing successful implementation and how to optimize intervention referrals, enrollment, and attendance to inform future dissemination and practical applications. Trial registration: This trial was registered on ClinicalTrials.gov (NCT05233150) on February 1, 2022, prior to enrolling subjects. [ABSTRACT FROM AUTHOR]

Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment. Plasma exosomes were isolated from CRPC (n = 10), NSCLC (n = 14), and healthy controls (n = 10) using three different methods: size exclusion chromatography (SEC), lectin binding, and T-cell immunoglobulin domain and mucin domain-containing protein 4 (TIM4) binding. Molecular profiles were determined by mass spectrometry of extracted exosome fractions. Enrichment analysis of uniquely detected molecules was performed for each method with MetaboAnalyst. The exosome enrichment index (EEI) scores methods based on top differential molecules between patient groups. The lipidomic analysis detected 949 lipids using exosomes from SEC, followed by 246 from lectin binding and 226 from TIM4 binding. The detectable metabolites showed SEC identifying 191 while lectin binding and TIM4 binding identified 100 and 107, respectively. When comparing uniquely detected molecules, different methods showed preferential enrichment of different sets of molecules with SEC enriching the greatest diversity. Compared to controls, SEC identified 28 lipids showing significant difference in NSCLC, while only 1 metabolite in NSCLC and 5 metabolites in CRPC were considered statistically significant (FDR < 0.1). Neither lectin-binding- nor TIM4-binding-derived exosome lipids or metabolites demonstrated significant differences between patient groups. We observed the highest EEI from SEC in lipids (NSCLC: 871.33) which was also noted in metabolites. These results support that the size exclusion method of exosome extraction implemented by SBI captures more heterogeneous exosome populations. In contrast, lectin-binding and TIM4-binding methods bind surface glycans or phosphatidylserine moieties of the exosomes. Overall, these findings suggest that specific isolation methods select subpopulations which may significantly impact cancer biomarker discovery. [ABSTRACT FROM AUTHOR]

Background: Early initiation of reperfusion therapy in ST-segment elevation myocardial infarction im-proves outcome. Prehospital thrombolysis (PHT) is 1 strategy to deliver earlier reperfusion. Objective: The goal of this study was to discuss the pros and cons of PHT and to describe the implemen-tation of a program of PHT in the Hunter Region of Australia. Methods: Recent literature on PHT was reviewed to present a critical assessment of the evidence to support PHT. Different models of PHT are presented including the experience of the introduction of the Hunter program. Results: Meta-analyses of clinical trials and regis-tries have shown that PHT significantly decreases the time to thrombolysis, with reduction in the incidence of cardiogenic shock and a trend to a mortality benefit. The STREAM study reinforces current policy, which favors primary percutaneous coronary inter-vention (PCI) over thrombolysis, providing that PCI can be performed within an appropriate time interval; emphasizes that timely thrombolysis linked to an early invasive strategy provides an equivalent outcome when timely primary PCI is not possible; and supports other published experience that early-rescue PCI can be performed safely after administration of PHT. Although PHT can be implemented by trained para-medics working with on-board physicians, the Hunter Region has successfully used paramedics and ECG telemetry in consultation with hospital-based physi-cians. When the time to open the artery is ≤90 minutes, primary PCI is preferred. When the time to open the artery is > 90 minutes, PHT with immediate transport postthrombolysis to a PCI-capable hospital is feasible and effective. Conclusions: PHT delivered by trained paramedics with telemetery backup to assist ECG interpretation is feasible and delivers the prospect of early reperfusion. [ABSTRACT FROM AUTHOR]

The Little Choctawhatchee River watershed is currently affected by effluents from wastewater treatment plants and may be subject to impoundment as a water supply reservoir. We used historical data from the literature and the results of recent surveys (2006--2008) to assess past and current patterns of the diversity of mussels, crayfishes, and fishes throughout the river basin in order to gain information about the past and potential future effects of degraded water and habitat quality to the fauna of this region. Our results suggest that mussel assemblages have declined dramatically from historical levels, with only three of the eleven historically recorded species found. Several state-listed mussel species and candidates for federal protection formerly present are now believed extirpated from the watershed. Fish and crayfish collections during 2006--2008 were more diverse (52 and 6 species) than historical records indicated (39 and 3 species). This increased diversity was probably due to a more concentrated sampling effort in the current study than in the past. Future impoundment may cause further and possibly drastic changes to the remaining freshwater faunal diversity. [ABSTRACT FROM AUTHOR]

Context: A statistical model that accurately predicts human forced expiratory volume in one second (FEV1) response to ozone exposure has been identified and proposed as the foundation for future risk assessments for ambient ozone. We believe that the assumptions about intra-subject variability in the published model can be improved and hypothesize that more realistic assumptions will improve the fit of the model and the accuracy of risk assessments based on the model. Objective: Identify alternate assumptions about intra-subject variability and compare goodness-of-fit for models with various variability structures. Materials and methods: Models were fit to an existing data set using a statistical program for fitting nonlinear mixed models. Goodness-of-fit was assessed using Akaike's Information Criteria (AIC) and visual examination of graphical figures showing observed and predicted values. Results: The AIC indicated that a model that assumed intra-subject variability was related to the magnitude of individual response fit the data better than a model that assumes intra-subject variability is constant across individuals and exposures (the original model). This finding was consistent with the variability of observed responses for filtered air exposures and for exposures predicted to be below the threshold for response. Conclusion: An ozone exposure-response model that assumes intra-subject variability increases with individual mean FEV1 response appears to fit the data better than one that assumes constant variability. [ABSTRACT FROM AUTHOR]

Pleurobema strodeanum (Fuzzy Pigtoe), is listed as threatened under the Endangered Species Act. The purpose of this study was to estimate growth rate, morphometric ratios, and ages for this species. One hundred and sixty-one P. strodeanum were originally tagged and measured in 2004 at Eightmile Creek, Walton County, FL. In 2011, 28 of those 161 were recovered and re-measured. Growth-rate percentages were determined based on length, width, height, and volume. Age was estimated using the von Bertalanffy growth equation. Results indicate that over a period of seven years, P. strodeanum grew 0.48 mm/year (SD = 0.14) in length. The age estimations in this study ranged from 48.7 to 74.5 years. The growth constant (K) was 0.018 per year, and the asymptotic length (L∞) was 71.97 mm. Natural history data such as these will be useful in understanding the basic biology of P. strodeanum and may assist in successful mussel management. [ABSTRACT FROM AUTHOR]

Rock drill operators on the platinum belt in the North West province of South Africa initiated a strike wave in 2012, which led to the well-known events at Marikana in August of that year. The role of workers' committees featured prominently. Less well known is that rock drill operators 'committees go back thirty years and negotiated directly with mine management. Their actions impacted on intra-working class relations, with rock drill operators consequently having had an ambiguous relationship with trade unions on the mines of which they were members. This article discusses the central role of the rock drill operators' committee on one mine shaft in 2005, following the strike of over 400 rock drill operators in late 2004 which led to their dismissal, though eventually they were reemployed. In detailing the aftermath of that strike, the paper traces the existence of the rock drill operator committee on this shaft and how they were compelled to engage in an unusual productivity deal resulting in intensified work efforts. The account demonstrates how the objective power of the rock drill operators derives from their central role in the mining production labour process. The paper argues that if the 2012 strike wave, Marikana and the recent tumult on the platinum mines - as well as its future - are to be better understood and explained, the character, role and struggles of the rock drill operators and their long-standing and occupationally distinct independent worker committees need to assume the focus of analysis. [ABSTRACT FROM AUTHOR]

Context: A human exposure-response (E-R) model previously demonstrated to accurately predict population mean FEV1 response to ozone exposure has been proposed as the foundation for future risk assessments for ambient ozone. Objective: Fit the original and related models to a larger data set with a wider range of exposure conditions and assess agreement between observed and population mean predicted values. Materials and methods: Existing individual E-R data for 23 human controlled ozone exposure studies with a wide range of concentrations, activity levels, and exposure patterns have been obtained. The data were fit to the original model and to a version of the model that contains a threshold below which no response occurs using a statistical program for fitting nonlinear mixed models. Results: Mean predicted FEV1 responses and the predicted proportions of individuals experiencing FEV1 responses greater than 10, 15, and 20% were found to be in agreement with observed responses across a wide range of exposure conditions for both models. The threshold model, however, provided a better fit to the data than the original, particularly at the lowest levels of exposure. Conclusion: The models identified in this manuscript predict population FEV1 response characteristics for 18-35-year-old individuals exposed to ozone over a wide range of conditions and represent a substantial improvement over earlier E-R models. Because of its better fit to the data, particularly at low levels of exposure, the threshold model is likely to provide more accurate estimates of risk in future risk assessments of ozone-induced FEV1 effects. [ABSTRACT FROM AUTHOR]

Abstract: The literature concerning the relationship between polychlorinated biphenyl (PCB) exposure and Intelligence (IQ) is not entirely consistent. Two studies showed inverse associations between PCBs and IQ in cohorts of children whose mothers consumed Great Lakes fish contaminated with PCBs and other organochlorines (Jacobson & Jacobson 1996; Stewart et al. 2008). Another study from the general US population, where women were exposed to background levels of PCBs, showed no association between PCBs and IQ (Gray et al. 2005). The current report examines two potential sources of inconsistency across studies: 1) confounding with non-PCB organochlorines [Hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and Mirex]; and 2) the presence of negative confounding (i.e., suppressor variables). The former could confound PCBs and lead to spurious associations (Type I errors), while the latter could suppress PCB associations and obscure true associations (Type II errors). These issues were explored through the analysis of associations between placental levels of organochlorines and IQ in children at 9 and 11years of age in the Oswego study. Neither DDE nor mirex was related to lower IQ at either age; PCBs predicted lower IQ at both ages; and hexachlorobenzene (HCB) appeared as a significant predictor of IQ at the 11-year assessment. However, analysis of the IQ data set as a whole showed that both PCBs and HCB predicted lower IQ in a generally independent fashion. There was, however, overlap in the variance in some cases, and the pattern of findings between the two was remarkably similar. These results may provide some evidence for the potential involvement of non-PCB organochlorines in the Oswego study. To explore negative confounding, we analyzed the relationships between PCB exposure and demographic variables as well as the unadjusted and adjusted relationships between PCB and IQ. Results revealed that placental PCB levels were associated with older mothers who were more educated and came from higher socioeconomic strata. Due to this fact, unadjusted relationships between PCBs and IQ appeared null or slightly positive. After control for confounders, several significant negative associations between PCBs and IQ were revealed. These data might suggest that inadequate control for confounders in PCB studies, where negative confounding is present, may bias results toward the null (Type II error) rather than spurious associations (Type I error). This pattern of confounding with PCB exposure in the Oswego study also has implications for the assessment of risk. The most highly exposed children came from families with somewhat higher socioeconomic status, and tended to score in the average to above-average range, well above IQ scores that are considered “at risk.” Further, such children were exposed prenatally to PCBs through maternal consumption of PCB-contaminated Great Lakes fish in the early 1990s, when PCB levels were higher than today. [Copyright &y& Elsevier]

Over the last thirty years, there never has been a more confused doctrine than the current "duty of reasonable care" faced by transportation brokers, third-party logistics companies and shippers as they select carriers for transport. The confusion in what was once reasonable and well understood law has been fueled by a perfect storm of judicial reasoning with misplaced reference to faulty empirical data, the complete failure of the Federal Motor Carrier Safety Administration (FMCSA) to properly assess carrier safety worthiness, a feeding frenzy by the plaintiffs' bar and apathy by many in the industry. The purpose of this commentary is to examine how this uncertainty developed, to identify some of the more glaring issues that must be addressed, and to give some possible guidance as to how the industry, FMCSA and courts should proceed to clarify the duty of a broker in complying with "reasonable care" in selecting carriers. [ABSTRACT FROM AUTHOR]

This study observed agonistic interactions and contests between size-matched form I vs. form I, form II vs. form II, and form I vs. form II males to establish baseline dominance orders and behavioral dynamics for Procambarus suttkusi (Choctawhatchee Crayfish). Three types of initiation behaviors, or attacks, were observed during each interaction: ambivalent contact, claw raise, and lunge. Feeding competition studies were also performed to assess the relationship between the winners of the agonistic interactions and feeding contests. Only form I vs. form I contests showed a decline in the number of interactions observed over time, but the duration of each individual agonistic interaction declined for all three types of behaviors during the thirty-minute recording period. Winners and losers did not preferentially use the same initiation behaviors as used in other studies. Previous studies also documented form I dominating form II males, but form I males did not dominate form II males in the present study. Winners of the agonistic contests won significantly more feeding contests. The results of the current study suggested that behavioral dynamics and form dominance may be species specific and that careful consideration of size differences are necessary in order to examine form dominance. [ABSTRACT FROM AUTHOR]

Habitats provide food sources, cover, concealment, and a place to reproduce; thus, habitat selection is an important aspect of an organism's ecology. The objectives of this study were to investigate habitat preferences of crayfish and to determine if there was habitat partitioning among different species of crayfish in wadeable streams. Data were collected while collecting crayfish at 50 sites throughout southeastern Alabama. Data collected along with species and relative abundance were: sex, stream position, type of instream cover, and type of substrate. The 3 dominant aquatic species found in the study area were Procambarus suttkusi (Choctawhatchee Crayfish), P. versutus (Sly Crayfish), and Cambarus graysoni (Twospot Crayfish). These 3 species were most often found in woody debris, on sandy substrate, and in stream runs. In addition, there was a significant difference in abundance in pools where P. suttkusi was found alone and where P. suttkusi was found along with other crayfish species. In contrast to other reported studies, these 3 crayfish species appeared to have no preference among habitat types, but were found in the habitat most available. This result may be due to the limited habitat found in the sandy-bottomed streams of the southeastern coastal plains, and their lack of variety in cover and substrates. [ABSTRACT FROM AUTHOR]

Alabama has at least 83 species of native crayfish reported, more than any other state in the United States. Information associated with crayfish distribution, life history, and ecological importance in Alabama is extremely limited. The objective of this research is to determine the presence and relative abundance of crayfish species in the southeastern coastal plain of Alabama. Crayfish were collected at 50 sites within the Choctawhatchee River, Pea River, Yellow River, and Patsaliga Creek watersheds by electrofishing and hand excavation. Twelve crayfish taxa were collected, with 10 successfully identified to species. Procambarus suttkusi (Choctawhatchee Crayfish) was found at 40 sites and was the most widespread and abundant of the aquatic species. Procambarus versutus (Sly Crayfish) and Cambarus graysoni (Twospot Crayfish) were also found to be common aquatic species. Cambarus (Tubericambarus) sp. B was the most abundant primary burrower, and C. (Lacunicambarus) sp. B was a common burrower. Species with less than 10 individuals collected were considered rare and were as follows: Procambarus acutus (White River Crawfish), P. okaloosae (Okaloosa Crayfish), C. latimanus (Variable Crayfish), C. ludovicianus (Painted Devil Crayfish), and C. striatus (Ambiguous Crayfish). [ABSTRACT FROM AUTHOR]

Abstract: Background: The Cavidi viral load assay and the ultra-sensitive p24 antigen assay (Up24 Ag) have been suggested as more feasible alternatives to PCR-based HIV viral load assays for use in monitoring patients infected with HIV-1 in resource-limited settings. Objectives: To describe the performance of the Cavidi ExaVir Load™ assay (version 2.0) and two versions of the Up24 antigen assay and to characterize their agreement with the Roche Monitor HIV-1 RNA assay (version 1.5). Study design: Observational study using a convenience sample of 342 plasma specimens from 108 patients enrolled in two ACTG clinical trials to evaluate the performance characteristics of the Up24 Ag assay using two different lysis buffers and the Cavidi ExaVir Load™ assay. Results: In analysis of agreement with the Roche assay, the Cavidi assay demonstrated superiority to the Up24 Ag assays in accuracy and precision, as well as sensitivity, specificity, and positive and negative predictive values for HIV-1 RNA ≥400, ≥1000 and ≥5000copies/mL. Logistic performance curves indicated that the Cavidi assay was superior to the Up24 assays for viral loads greater than 650copies/mL. Conclusions: The results suggest that the Cavidi ExaVir Load assay could be used for monitoring HIV-1 viral load in resource-limited settings. [ABSTRACT FROM AUTHOR]

Two case studies suggest the restructuring of labour time in South African mining is indissolubly linked with work reorganisation. This results in organisational complexity by virtue of a plethora of production and social issues requiring attention, and alluded to in this article. Two primary forms of temporal restructuring are identified: the first option, continuous operations, is preferred by the industry and marks the lengthening and absolute extension of aggregate social labour time. It extends labour time to its maximum temporal limit, disrupting established patterns of social life. This option represents a retrogressive social development and is resisted by organised labour. The second option, a five-day working week, is preferred by labour organisations and marks the shortening and relative intensification of labour time expenditure. It results in the rhythms of working-time remaining more regular, maintaining established patterns of social life. This option represents a progressive social development, yet is resisted by mining capital. When changing working-time arrangements, the adoption of mining capital's preference results in the social impact of continuous working-time schedules coming to the fore. The adoption of organised labour's preference results in issues of control over the labour process coming to the fore when reducing working hours. [ABSTRACT FROM AUTHOR]

Abstract: Due to its impact upon health and the economy, the mechanisms that contribute to the pathogenesis of obesity and the metabolic syndrome are under intense scrutiny. In addition to understanding the pathogenesis of disease it is important to design and trial novel therapies. Patients with cortisol excess, Cushing''s syndrome, have a phenotype similar to that of the metabolic syndrome and as a result there is much interest the manipulation of glucocorticoid (GC) action as a therapeutic strategy. Intracellular GC levels are regulated by 11β-hydroxysteriod dehydrogenase (11β-HSD1) which converts inactive cortisone to cortisol, thereby increasing local GC action. There is an abundance of data implicating 11β-HSD1 in the pathogenesis of obesity, type 2 diabetes and the metabolic syndrome and 11β-HSD1 is an attractive therapeutic target. Selective 11β-HSD1 inhibitors, which do not act upon 11β-HSD2 (which inactivates cortisol to cortisone) are in development. So far studies have primarily been carried out in rodents, with results showing improvements in metabolic profile. Data are now beginning to emerge from human studies and the results are promising. [Copyright &y& Elsevier]

Real-time thermal management of electrical machines relies on sufficiently accurate indicators of internal temperature. One indicator of temperature in a permanent-magnet synchronous motor (PMSM) is the stator winding resistance. Detection of PMSM winding resistance in the literature has been made on machines with relatively high resistances, where the resistive voltage vector is significant under load. This paper describes two techniques, which can be applied to detect the winding resistance, through “angle” and “magnitude” current injection. Two further methods are described, which discriminate injected current and voltages from motoring currents and voltages: “unipolar” and “bipolar” separation. These enable the resistance to be determined, and hence the winding temperature in permanent-magnet machines. These methods can be applied under load, and in a manner that does not disturb motor torque or speed. The method distinguishes between changes in the electromotive force constant and the resistive voltage. This paper introduces the techniques, while a companion paper covers the application of one of the methods to a PMSM drive system. [ABSTRACT FROM PUBLISHER]

The main purpose of this study was to evaluate the ability of a human exposure-response model, which describes ozone-induced changes in forced expiratory volume in 1 second (FEV1) across a wide range of dynamic exposure conditions, to predict responses in independent data. We first conducted an n-fold cross-validation of the model using samples of the original EPA data from which the model was developed. We then identified seven more recently published studies with controlled exposures to a wide range of ozone exposure patterns relevant to the current ambient ozone health standard and used the model to calculate the mean predicted responses for the exposure conditions of the individual studies that we compared to the mean observed responses reported in these studies. The n-fold cross-validation indicated good internal agreement between mean predicted and mean observed responses in the original data used to develop the model. The model accurately captured the patterns of response in each of the seven independent studies with a tendency to overpredict the observed responses by about 1 percentage point of FEV1 decrement on average. We conclude that the model is currently capable of predicting human FEV1 responses across a wide range of dynamic exposure conditions and anticipate further improvements in predictions with the addition of low-concentration exposure data. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including novel electrical power systems, energy vectors, and electrical power generation systems.

19-nor-progesterone (19-nor-P) has the characteristics of a potent mineralocorticoid in adrenalectomized or salt-loaded rats and is capable of causing hypertension. In human placenta, progesterone is converted to 19-hydroxy-progesterone, a precursor of 19-nor-P. In some states of pregnancy hypertension, 19-nor-P may inhibit renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), thus allowing cortisol to bind to the mineralocorticoid receptor (MR). Therefore, we investigated the ability of 19-nor-P to inhibit human 11β-HSD2. Fetal kidney cells (HEK 293) were transfected with human 11β-HSD2 and incubated with increasing concentrations of 19-nor-P, labelled and unlabelled cortisol. Steroids were extracted, separated by TLC, and radioactivity was measured using a TLC scanner. 19-nor-P treatment did not significantly reduce 11β-HSD2 activity (430 to 300 pmol/mg protein/h) in the range of tested concentrations. In conclusion, 19-nor-P did not inhibit human 11β-HSD2 and seems not to be involved in human hypertension. Nevertheless, 19-nor-P may be converted by extra-adrenal tissues into 19-nor-deoxycorticosterone (DOC) or 19-nor-corticosterone, which are potent mineralocorticoids and may be involved in the pathogenesis of hypertension during pregnancy. [ABSTRACT FROM AUTHOR]