Homecare Worker Organizing in California: An Analysis of a Successful Strategy

This paper examines the challenges facing California homecare workers in their historic struggle to unionize from the 1980s through the 90s. Three inter-related components were critical to their ultimate success: 1) grassroots organizing, 2) changing policy at the state and county level and 3) working in coalition with groups of senior and disabled care recipients. Now that the union repre-sents more than 100,000 workers, consolidation of those victories involves challenges such as developing leadership among the new membership and strengthening the labor-consumer coalition that will be critical to further improvements in homecare services and working conditions. This campaign has already had significant impact on the structure of this emerging workforce, and will have long-term effects on social policy for care of the elderly and dis-abled. The economic and political influence of American labor unions hassuffered greatly over the past several decades, and one reason for this has been a steadily declining rate of union membership. Union members currently make up 13.5 % of the workforce, which compares to a high of 35 % in 1954. In 1995, the AFL-CIO launched a program to reverse this trend by prioritizing organizing of the unorganized, and encouraging af-filiated unions to spend at least 30 % of their budget on organizing. How-ever, in spite of significant efforts by some unions to recruit new mem-bers, union density has continued to decline (Bureau of Labor Statistics

A cluster randomized trial evaluating electronic prescribing in an ambulatory care setting

<p>Abstract</p> <p>Background</p> <p>Medication errors, adverse drug events and potential adverse drug events are common and serious in terms of the harms and costs that they impose on the health system and those who use it. Errors resulting in preventable adverse drug events have been shown to occur most often at the stages of ordering and administration. This paper describes the protocol for a pragmatic trial of electronic prescribing to reduce prescription error. The trial was designed to overcome the limitations associated with traditional study design.</p> <p>Design</p> <p>This study was designed as a 65-week, cluster randomized, parallel study.</p> <p>Methods</p> <p>The trial was conducted within ambulatory outpatient clinics in an academic tertiary care centre in Ontario, Canada. The electronic prescribing software for the study is a Canadian electronic prescribing software package which provides physician prescription entry with decision support at the point of care. Using a handheld computer (PDA) the physician selects medications using an error minimising menu-based pick list from a comprehensive drug database, create specific prescription instructions and then transmit the prescription directly and electronically to a participating pharmacy via facsimile or to the physician's printer using local area wireless technology. The unit of allocation and randomization is by 'week', i.e. the system is "on" or "off" according to the randomization scheme and the unit of analysis is the prescription, with adjustment for clustering of patients within practitioners.</p> <p>Discussion</p> <p>This paper describes the protocol for a pragmatic cluster randomized trial of point-of-care electronic prescribing, which was specifically designed to overcome the limitations associated with traditional study design.</p> <p>Trial Registration</p> <p>This trial has been registered with clinicaltrials.gov (ID: NCT00252395)</p

Land Governance and Inclusive business in Agriculture: Advancing the Debate

This paper reviews the state of the global debate on the idea of inclusive agricultural investments by assessing, and makes an original contribution by interrogating the core features of inclusive business relations in Agriculture. Based on an assessment of areas of agreement in what ‘inclusiveness’ in agribusiness means to different business, civil society and development agency stakeholders is considered to mean, drawn from the policy literature in a series of interviews, five “pillars” of inclusive agribusiness are identified: effective arrangements for farmer representation, fair value chain relations, respect for land rights and agreement on tenure relations, employment creation and respect for labour rights, and contributions to food security. A literature review of crop and market characteristics identified four key variables that influence business configurations in different sectors (crop characteristics, scope for mechanisation, capital investment requirements, and market destinations and conditions) to develop a simple typology of value chain types: perishables linked to distant markets; labour intensive, hard-to-mechanise crops with high perishability and bulk; and labour intensive crops with high perishability and bulk that can be fully mechanised. Each of these value chain types was then examined in relation to the five dimensions of inclusiveness through literature based case studies of specific commodity sectors and geographies, respectively: high value horticulture in East Africa and the Andes; oil palm in Southeast Asia and Colombia, and sugarcane in eastern and southern Africa. Significantly, the analysis finds that without an understanding of how crop and value chain characteristics and market trends shape opportunities and constraints in specific geographies and commodity sectors it is difficult to advance inclusiveness in agribusiness or develop effective public policy. Inclusiveness is found not to be inherent in specific types of business models, such as large plantations, outgrower schemes or contract farming, but rather a matter of degree, dependent on context, the crops and commodities n question and the outcomes for different social groups. These outcomes are affected by trade-offs amongst the different pillars of inclusiveness and how they are managed. Large plantations may create employment but also pose risks to local community land rights and food security. Labour intensive crops that are hard to mechanise encourage firms to engage smallholder suppliers, but the quality and terms of engagement are highly variable. Drives to increase efficiency can undermine inclusiveness and market restructuring have raised the bar for smallholder participation. Where small farmers have secure control over land resources companies have greater incentives to work with them, and as control over land has a bearing on all five dimensions of inclusiveness, land governance is a key area for attention in promoting greater social and economic inclusion in agriculture. The paper offers an original and rigorous approach to understanding inclusiveness in agribusiness by focussing on the processes and terms through which small scale farming communities are incorporated and the distributive outcomes of specific productive arrangements in different value chains. It has been welcomed within development agencies and the investment community as providing a fresh analytical perspective and a framework for advancing social and economic inclusion in agribusiness investment in practice

Human Cytomegalovirus Long Non-coding RNA1.2 Suppresses Extracellular Release of the Pro-inflammatory Cytokine IL-6 by Blocking NF-κB Activation.

Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides that are not translated into functional proteins. Cellular lncRNAs have been shown to act as regulators by interacting with target nucleic acids or proteins and modulating their activities. We investigated the role of RNA1.2, which is one of four major lncRNAs expressed by human cytomegalovirus (HCMV), by comparing the properties of parental virus in vitro with those of deletion mutants lacking either most of the RNA1.2 gene or only the TATA element of the promoter. In comparison with parental virus, these mutants exhibited no growth defects and minimal differences in viral gene expression in human fibroblasts. In contrast, 76 cellular genes were consistently up- or down-regulated by the mutants at both the RNA and protein levels at 72 h after infection. Differential expression of the gene most highly upregulated by the mutants (Tumor protein p63-regulated gene 1-like protein; TPRG1L) was confirmed at both levels by RT-PCR and immunoblotting. Consistent with the known ability of TPRG1L to upregulate IL-6 expression via NF-κB stimulation, RNA1.2 mutant-infected fibroblasts were observed to upregulate IL-6 in addition to TPRG1L. Comparable surface expression of TNF receptors and responsiveness to TNF-α in cells infected by the parental and mutant viruses indicated that activation of signaling by TNF-α is not involved in upregulation of IL-6 by the mutants. In contrast, inhibition of NF-κB activity and knockdown of TPRG1L expression reduced the extracellular release of IL-6 by RNA1.2 mutant-infected cells, thus demonstrating that upregulation of TPRG1L activates NF-κB. The levels of MCP-1 and CXCL1 transcripts were also increased in RNA1.2 mutant-infected cells, further demonstrating the presence of active NF-κB signaling. These results suggest that RNA1.2 plays a role in manipulating intrinsic NF-κB-dependent cytokine and chemokine release during HCMV infection, thereby impacting downstream immune responses

Tolerogenic dendritic cells protect against acute kidney injury

Ischemia reperfusion injury is a common precipitant of acute kidney injury that occurs following disrupted perfusion to the kidney. This includes blood loss and hemodynamic shock, as well as during retrieval for deceased donor kidney transplantation. Acute kidney injury is associated with adverse long-term clinical outcomes and requires effective interventions that can modify the disease process. Immunomodulatory cell therapies such as tolerogenic dendritic cells remain a promising tool, and here we tested the hypothesis that adoptively transferred tolerogenic dendritic cells can limit kidney injury. The phenotypic and genomic signatures of bone marrow–derived syngeneic or allogeneic, Vitamin-D3/IL-10–conditioned tolerogenic dendritic cells were assessed. These cells were characterized by high PD-L1:CD86, elevated IL-10, restricted IL-12p70 secretion and a suppressed transcriptomic inflammatory profile. When infused systemically, these cells successfully abrogated kidney injury without modifying infiltrating inflammatory cell populations. They also provided protection against ischemia reperfusion injury in mice pre-treated with liposomal clodronate, suggesting the process was regulated by live, rather than reprocessed cells. Co-culture experiments and spatial transcriptomic analysis confirmed reduced kidney tubular epithelial cell injury. Thus, our data provide strong evidence that peri-operatively administered tolerogenic dendritic cells have the ability to protect against acute kidney injury and warrants further exploration as a therapeutic option. This technology may provide a clinical advantage for bench-to-bedside translation to affect patient outcomes

Genomic surveillance of Escherichia coli and Klebsiella spp. in hospital sink drains and patients

Escherichia coli and Klebsiella spp. are important human pathogens that cause a wide spectrum of clinical disease. In healthcare settings, sinks and other wastewater sites have been shown to be reservoirs of antimicrobial-resistant E. coli and Klebsiella spp., particularly in the context of outbreaks of resistant strains amongst patients. Without focusing exclusively on resistance markers or a clinical outbreak, we demonstrate that many hospital sink drains are abundantly and persistently colonised with diverse populations of E. coli, Klebsiella pneumoniae and Klebsiella oxytoca, including both antimicrobial-resistant and susceptible strains. Using whole genome sequencing (WGS) of 439 isolates, we show that environmental bacterial populations are largely structured by ward and sink, with only a handful of lineages, such as E. coli ST635, being widely distributed, suggesting different prevailing ecologies which may vary as a result of different inputs and selection pressures. WGS of 46 contemporaneous patient isolates identified one (2%; 95% CI 0.05-11%) E. coli urine infection-associated isolate with high similarity to a prior sink isolate, suggesting that sinks may contribute to up to 10% of infections caused by these organisms in patients on the ward over the same timeframe. Using metagenomics from 20 sink-timepoints, we show that sinks also harbour many clinically relevant antimicrobial resistance genes including blaCTX-M, blaSHV and mcr, and may act as niches for the exchange and amplification of these genes. Our study reinforces the potential role of sinks in contributing to Enterobacterales infection and antimicrobial resistance in hospital patients, something that could be amenable to intervention

Human cytomegalovirus RNA2.7 is required for upregulating multiple cellular genes to promote cell motility and viral spread late in lytic infection

Long non-coding RNAs are frequently associated with broad modulation of gene expression and thus provide the cell with the ability to synchronize entire metabolic processes. We used transcriptomic approaches to investigate whether the most abundant human cytomegalovirus-encoded lncRNA, RNA2.7, has this characteristic. By comparing cells infected with wild-type virus (WT) with cells infected with RNA2.7 deletion mutants, RNA2.7 was implicated in regulating a large number of cellular genes late in lytic infection. Pathway analysis indicated that &gt;100 of these genes are associated with promoting cell movement, and the ten most highly regulated of these were validated in further experiments. Morphological analysis and live cell tracking of WT- and RNA2.7 mutant-infected cells indicated that RNA2.7 is involved in promoting the movement and detachment of infected cells late in infection, and plaque assays using sparse cell monolayers indicated that RNA2.7 is also involved in promoting cell-to-cell spread of virus. Consistent with the observation that upregulated mRNAs are relatively A+U-rich, which is a trait associated with transcript instability, and that they are also enriched in motifs associated with mRNA instability, transcriptional inhibition experiments on WT- and RNA2.7 mutant-infected cells showed that four upregulated transcripts were longer-lived in the presence of RNA2.7. These findings demonstrate that RNA2.7 is required for promoting cell movement and viral spread late in infection and suggest that this may be due to general stabilization of A+U-rich transcripts

IMI - Myopia Genetics Report

The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary of current genetic findings and defines the direction where development is needed. We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes. To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed. This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery