Constructing public-private partnerships to undermine the public interest: critical discourse analysis of Working Together published by the International Alliance for Responsible Drinking.

BACKGROUND: The global burden of alcohol harm has increased and is forecast to grow further without effective policy implementation. Public-private partnerships aiming to address global health, and other societal challenges, are a burgeoning feature of neoliberal governance. Rhetorically distancing themselves from tobacco, the major alcohol companies are committed to tackling 'harmful drinking' and have created a distinct type of public relations organization for this purpose. The activities of such organizations are increasingly recognized as an impediment to the implementation of policies to reduce alcohol harm, including in low- and middle-income countries where markets are expanding. METHODS: The approach of critical discourse analysis is used to examine the discursive tactics and strategies used in Working Together; a 'toolkit' published by the key global level alcohol industry public relations organization, the International Alliance for Responsible Drinking (IARD). This study considers how it works discursively to set the terms of, and overcome skepticism about partnerships, to define aims and position various actors by constructing their roles. The construction of prospective partners provides insights into the alcohol industry itself. RESULTS: The toolkit operates as an ideological resource for forming public-private partnerships across the world based on the accumulated know-how of the major companies through IARD. This allows the largest alcohol companies to exercise leadership of the industry, while remaining off-stage. The toolkit relies on a form of rhetorical work which creates distance from obvious corporate interests and the harms caused to population health and society. This is accomplished by working against evidence-informed population level approaches, and thus avoiding policies that will make any significant difference to overall alcohol harm. Unspecific "complexity" affords opportunity for preferred types of "actions", and "partnership" provides opportunity to gain credibility by association, further minimizing the likelihood of any material harm being reduced. CONCLUSIONS: The toolkit is designed to not only legitimate the inclusion of alcohol industry actors as initiating 'partners', but also assigns them roles as managers of a set of carefully constructed relationships. This vision of public-private partnership reproduces the hegemonic narrative that has successfully blocked policy advances for decades and led to growing alcohol harm globally.

Alcohol policy framing in South Africa during the early stages of COVID-19: using extraordinary times to make an argument for a new normal.

INTRODUCTION: Public health and alcohol industry actors compete to frame alcohol policy problems and solutions. Little is known about how sudden shifts in the political context provide moments for policy actors to re-frame alcohol-related issues. South Africa's temporary bans on alcohol sales during the COVID-19 pandemic offered an opportunity to study this phenomenon. METHODS: We identified Professor Charles Parry from the South African Medical Research Council as a key policy actor. Parry uses a Twitter account primarily to comment on alcohol-related issues in South Africa. We harvested his tweets posted from March 18 to August 31, 2020, coinciding with the first two alcohol sales bans. We conducted a thematic analysis of the tweets to understand how Parry framed alcohol policy evidence and issues during these 'extraordinary times.' RESULTS: Parry underlined the extent of alcohol-related harm during 'normal times' with scientific evidence and contested industry actors' efforts to re-frame relevant evidence in a coherent and well-constructed argument. Parry used the temporary sales restrictions to highlight the magnitude of the health and social harms resulting from alcohol consumption, particularly trauma, rather than the COVID-19 transmission risks. Parry portrayed the sales ban as a policy learning opportunity (or 'experiment') for South Africa and beyond. CONCLUSIONS: Crisis conditions can provide new openings for public health (and industry) actors to make salient particular features of alcohol and alcohol policy evidence.

Structure, self-assembly, and properties of a truncated reflectin variant.

Naturally occurring and recombinant protein-based materials are frequently employed for the study of fundamental biological processes and are often leveraged for applications in areas as diverse as electronics, optics, bioengineering, medicine, and even fashion. Within this context, unique structural proteins known as reflectins have recently attracted substantial attention due to their key roles in the fascinating color-changing capabilities of cephalopods and their technological potential as biophotonic and bioelectronic materials. However, progress toward understanding reflectins has been hindered by their atypical aromatic and charged residue-enriched sequences, extreme sensitivities to subtle changes in environmental conditions, and well-known propensities for aggregation. Herein, we elucidate the structure of a reflectin variant at the molecular level, demonstrate a straightforward mechanical agitation-based methodology for controlling this variant's hierarchical assembly, and establish a direct correlation between the protein's structural characteristics and intrinsic optical properties. Altogether, our findings address multiple challenges associated with the development of reflectins as materials, furnish molecular-level insight into the mechanistic underpinnings of cephalopod skin cells' color-changing functionalities, and may inform new research directions across biochemistry, cellular biology, bioengineering, and optics.

Circulating tumor and invasive cell expression profiling predicts effective therapy in pancreatic cancer.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) remains a refractory disease; however, modern cytotoxic chemotherapeutics can induce tumor regression and extend life. A blood-based, pharmacogenomic, chemosensitivity assay using gene expression profiling of circulating tumor and invasive cells (CTICs) to predict treatment response was previously developed. The combination regimen of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel (G/nab-P) are established frontline approaches for treating advanced PDAC; however, there are no validated biomarkers for treatment selection. A similar unmet need exists for choosing second-line therapy. METHODS: The chemosensitivity assay was evaluated in metastatic PDAC patients presenting for frontline treatment. A prospective study enrolled patients (n = 70) before receiving either FOLFIRINOX or G/nab-P at a 1:1 ratio. Six milliliters of peripheral blood was collected at baseline and at time of disease progression. CTICs were isolated, gene-expression profiling was performed, and the assay was used to predict effective and ineffective chemotherapeutic agents. Treating physicians were blinded to the assay prediction results. RESULTS: Patients receiving an effective regimen as predicted by the chemosensitivity assay experienced significantly longer median progression-free survival (mPFS; 7.8 months vs. 4.2 months; hazard ratio [HR], 0.35; p = .0002) and median overall survival (mOS; 21.0 months vs. 9.7 months; HR, 0.40; p = .005), compared with an ineffective regimen. Assay prediction for effective second-line therapy was explored. The entire study cohort experienced favorable outcomes compared with historical controls, 7.1-month mPFS and 12.3-month mOS. CONCLUSIONS: Chemosensitivity assay profiling is a promising tool for guiding therapy in advanced PDAC. Further prospective validation is under way (clinicaltrials.gov NCT03033927).

In search of optimal resilience ratios: Differential influences of neurobehavioral factors contributing to stress-resilience spectra.

The ability to adapt to stressful circumstances, known as emotional resilience, is a key factor in the maintenance of mental health. Several individual biomarkers of the stress response (e.g., corticosterone) that influence an animal's position along the continuum that ranges from adaptive allostasis to maladaptive allostatic load have been identified. Extending beyond specific biomarkers of stress responses, however, it is also important to consider stress-related responses relative to other relevant responses for a thorough understanding of the underpinnings of adaptive allostasis. In this review, behavioral, neurobiological, developmental and genomic variables are considered in the context of emotional resilience [e.g., explore/exploit behavioral tendencies; DHEA/CORT ratios and relative proportions of protein-coding/nonprotein-coding (transposable) genomic elements]. As complex and multifaceted relationships between pertinent allostasis biomediators are identified, translational applications for optimal resilience are more likely to emerge as effective therapeutic strategies.

Early experience alters developmental trajectory of central oxytocin systems involved in hypothalamic-pituitary-adrenal axis regulation in Long-Evans rats.

Oxytocin is important for postnatal developmental experiences for mothers, infants, and transactions between them. Oxytocin is also implicated in adult affiliative behaviors, including social buffering of stress. There is evidence for connections between early life experience and adult oxytocin system functioning, but effects of early experience on behavioral, endocrine, and neurophysiological outcomes related to adult social buffering are not well explored. We use a limited bedding and nesting (LBN) material paradigm as an environmental disruption of early experiences and assessed central oxytocin systems in brain regions related to hypothalamic-pituitary-adrenal (HPA) axis regulation (paraventricular nucleus of the hypothalamus, amygdala, hippocampus). We also assessed developmentally-appropriate social behaviors and HPA reactivity during social buffering testing in adulthood. LBN litters had larger huddles and more pups visible compared to control litters during the first two weeks of life. LBN also altered the developmental trajectory of oxytocin-expressing cells and oxytocin receptor cells, with increases in oxytocin receptor cells at P15 in LBN pups. By adulthood, LBN females had more and LBN males had fewer oxytocin and oxytocin receptor cells in these areas compared to sex-matched controls. Adult LBN females, but not LBN males, had behavioral changes during social interaction and social buffering testing. The sex-specific effects of early experience on central oxytocin systems and social behavior may contribute to female resilience to early life adversity.

Measuring and assessing the competencies of preceptors in health professions: a systematic scoping review.

BACKGROUND: In healthcare, preceptors act as a role model and supervisor, thereby facilitating the socialisation and development of the preceptee into a professional fit to practice. To ensure a consistent approach to every preceptorship experience, preceptor competencies should be measured or assessed to ensure that the desired outcomes are achieved. Defining these would ensure quality management and could inform development of an preceptor competency framework. This review aimed to evaluate the evidence for preceptor competencies and assessment in health professions. METHODS: This study followed the PRISMA ScR scoping review guidelines. A database search was conducted in Embase, Medline, CINAHL and IPA in 2019. Articles were included if they defined criteria for competency, measured or assessed competency, or described performance indicators of preceptors. A modified GRADE CERQual approach and CASP quality assessment were used to appraise identified competencies, performance indicators and confidence in evidence. RESULTS: Forty one studies identified 17 evidence-based competencies, of which 11 had an associated performance indicator. The competency of preceptors was most commonly measured using a preceptee completed survey (moderate to high confidence as per CERQual), followed by preceptor self-assessment, and peer-assessment. Preceptee outcomes as a measure of preceptor performance had good but limited evidence. CONCLUSIONS: Competencies with defined performance indicators allow for effective measurement and may be modifiable with training. To measure preceptor competency, the preceptor perspective, as well as peer and preceptee assessment is recommended. These findings can provide the basis for a common preceptor competency framework in health professions.

Novel Bioinformatics Approach Identifies Transcriptional Profiles of Lineage-Specific Transposable Elements at Distinct Loci in the Human Dorsolateral Prefrontal Cortex.

Expression of transposable elements (TE) is transiently activated during human preimplantation embryogenesis in a developmental stage- and cell type-specific manner and TE-mediated epigenetic regulation is intrinsically wired in developmental genetic networks in human embryos and embryonic stem cells. However, there are no systematic studies devoted to a comprehensive analysis of the TE transcriptome in human adult organs and tissues, including human neural tissues. To investigate TE expression in the human Dorsolateral Prefrontal Cortex (DLPFC), we developed and validated a straightforward analytical approach to chart quantitative genome-wide expression profiles of all annotated TE loci based on unambiguous mapping of discrete TE-encoded transcripts using a de novo assembly strategy. To initially evaluate the potential regulatory impact of DLPFC-expressed TE, we adopted a comparative evolutionary genomics approach across humans, primates, and rodents to document conservation patterns, lineage-specificity, and colocalizations with transcription factor binding sites mapped within primate- and human-specific TE. We identified 654,665 transcripts expressed from 477,507 distinct loci of different TE classes and families, the majority of which appear to have originated from primate-specific sequences. We discovered 4,687 human-specific and transcriptionally active TEs in DLPFC, of which the prominent majority (80.2%) appears spliced. Our analyses revealed significant associations of DLPFC-expressed TE with primate- and human-specific transcription factor binding sites, suggesting potential cross-talks of concordant regulatory functions. We identified 1,689 TEs differentially expressed in the DLPFC of Schizophrenia patients, a majority of which is located within introns of 1,137 protein-coding genes. Our findings imply that identified DLPFC-expressed TEs may affect human brain structures and functions following different evolutionary trajectories. On one side, hundreds of thousands of TEs maintained a remarkably high conservation for ∼8 My of primates' evolution, suggesting that they are likely conveying evolutionary-constrained primate-specific regulatory functions. In parallel, thousands of transcriptionally active human-specific TE loci emerged more recently, suggesting that they could be relevant for human-specific behavioral or cognitive functions.

Transposons, stress and the functions of the deep genome.

The brain is responsible for both recognition and adaptation to stressful stimuli. Many molecular mechanisms have been implicated in this response including those governing neuronal plasticity, neurogenesis and, changes gene expression. Far less is known regarding effects of stress on the deep genome. In the hippocampus, stress appears to regulate expression of non-coding elements of the genome as well as the chromatin permissive for their transcription. Specifically, hippocampal retrotransposon (RT) elements are regulated by acute stress via the accumulation of the repressive H3K9me3 mark at RT loci. Further, corticosteroids appear to induce changes in heterochromatin status as well as RT expression in both adrenalectomized animal and rat cell culture models. Dysregulation of RT expression is predicted to result in functional deficits in affected brain areas. More broadly, however, transposons may have a variety of adaptive functions. As techniques improve to probe the deep genome, this approach to understanding stress neurobiology has the potential to yield insights into environment and genome interactions that may contribute to the physiology underlying a number of stress-related mental health disorders.

Bioinformatics: indispensable, yet hidden in plain sight?

BACKGROUND: Bioinformatics has multitudinous identities, organisational alignments and disciplinary links. This variety allows bioinformaticians and bioinformatic work to contribute to much (if not most) of life science research in profound ways. The multitude of bioinformatic work also translates into a multitude of credit-distribution arrangements, apparently dismissing that work. RESULTS: We report on the epistemic and social arrangements that characterise the relationship between bioinformatics and life science. We describe, in sociological terms, the character, power and future of bioinformatic work. The character of bioinformatic work is such that its cultural, institutional and technical structures allow for it to be black-boxed easily. The result is that bioinformatic expertise and contributions travel easily and quickly, yet remain largely uncredited. The power of bioinformatic work is shaped by its dependency on life science work, which combined with the black-boxed character of bioinformatic expertise further contributes to situating bioinformatics on the periphery of the life sciences. Finally, the imagined futures of bioinformatic work suggest that bioinformatics will become ever more indispensable without necessarily becoming more visible, forcing bioinformaticians into difficult professional and career choices. CONCLUSIONS: Bioinformatic expertise and labour is epistemically central but often institutionally peripheral. In part, this is a result of the ways in which the character, power distribution and potential futures of bioinformatics are constituted. However, alternative paths can be imagined.

Anxiety and Epigenetics.

Anxiety disorders are highly prevalent psychiatric disorders often comorbid with depression and substance abuse. Twin studies have shown that anxiety disorders are moderately heritable. Yet, genome-wide association studies (GWASs) have failed to identify gene(s) significantly associated with diagnosis suggesting a strong role for environmental factors and the epigenome. A number of anxiety disorder subtypes are considered "stress related." A large focus of research has been on the epigenetic and anxiety-like behavioral consequences of stress. Animal models of anxiety-related disorders have provided strong evidence for the role of stress on the epigenetic control of the hypothalamic-pituitary-adrenal (HPA) axis and of stress-responsive brain regions. Neuroepigenetics may continue to explain individual variation in susceptibility to environmental perturbations and consequently anxious behavior. Behavioral and pharmacological interventions aimed at targeting epigenetic marks associated with anxiety may prove fruitful in developing treatments.

Length-Independent Charge Transport in Chimeric Molecular Wires.

Advanced molecular electronic components remain vital for the next generation of miniaturized integrated circuits. Thus, much research effort has been devoted to the discovery of lossless molecular wires, for which the charge transport rate or conductivity is not attenuated with length in the tunneling regime. Herein, we report the synthesis and electrochemical interrogation of DNA-like molecular wires. We determine that the rate of electron transfer through these constructs is independent of their length and propose a plausible mechanism to explain our findings. The reported approach holds relevance for the development of high-performance molecular electronic components and the fundamental study of charge transport phenomena in organic semiconductors.

Ophthalmic Procedures for Treatment of Advanced Ocular Surface Diseases.

Dry eye disease and other ocular surface diseases are complex multifactorial disorders often characterized by ocular surface inflammatory changes, instability of the tear film, and functional vision impairment. Recent research has led to new concepts regarding diagnosis and management, and therapeutic interventions now include ocular lubricants, secretagogues, topical and systemic anti-inflammatory and immunosuppressive agents, tear preservation, and, for advanced cases, a variety of surgical approaches. This review considers contemporary procedures for treatment of advanced ocular surface diseases, including thermal and electrocautery of the lacrimal puncta, lid surgeries such as tarsorrhaphy, and multiple procedures to protect the exposed or compromised ocular surface.

Novel superficial temporal artery access route for middle meningeal artery embolization and treatment of chronic subdural hematoma.

We describe the use of direct superficial temporal artery puncture to access the left middle meningeal artery for embolization of a recurrent chronic subdural hematoma in a patient with a type A aortic dissection, involving the origin of the left common carotid artery which precluded conventional access from a radial or femoral approach.

Managing Disruption: A Case Study of Boundary Work around Alcohol Industry Sponsored Scientific Interventions.

OBJECTIVES: Following recent work examining alcohol industry involvements in science, this is a case study that examines the ways in which the alcohol research community engages in 'boundary work' - in which scientists define and defend the demarcation between their community of knowledge makers and others, justifying their claim to legitimacy and authority - in response to alcohol industry-sponsored interventions. The case here involves an economist who disputes the research consensus positions and policy recommendations of the field, having been funded by the key global alcohol industry political organization. METHODS: We examine the 'functional' statements of both sides of this issue to show the ways in which the scientific and policy consensus of the field is disputed. Three examples of the responses of the alcohol research community, presenting different types of response, are interrogated. RESULTS: In late-career and retirement, this economist published extensively in alcohol and health economics journals within the peer-reviewed literature on two key topics in alcohol policy; pricing/taxation measures and advertising restrictions. These commentaries, reviews and correspondence propose alternative policies favored by the alcohol industry which are at odds with the alcohol public health evidence-base. The three examples examined of 'boundary work' performed by alcohol public health researchers illustrate the variety of ways in which the legitimacy of these interventions has been questioned; on technical grounds, on explicitly normative grounds, and as a body of work as a whole. DISCUSSION: Interventions in the scientific literature create important resources for alcohol industry actors to oppose alcohol policy measures globally. The alcohol research field may benefit from discussion about how to respond to these kinds of interventions.

The international center for alcohol policies (ICAP) book series: a key resource globally for alcohol industry political strategies.

This study examines the functions and purposes of the International Center for Alcohol Policies (ICAP) book series, published by Routledge between 1998 and 2010. The books were authored by invited academics, ICAP staffers, and alcohol industry representatives.The key data source for this paper was the framing material - forewords, introductions, conclusions - of the books. A thematic analysis positioned the contents with regard to ongoing alcohol research and public health policy issues.This was a project to 'shift the paradigm'. ICAP frames alcohol policy choices in ways which direct policy attention to sub-groups rather than the population level. Population-level approaches are caricatured as 'ideological'. The concept of 'balance' is prominent and is employed in multiple ways. Business interests are elided and industry involvement in policy making is promoted on scientific grounds. The intellectual programme is lent credibility by leading scientists and the imprimatur of an academic publisher.While this attempt to change the paradigm in alcohol science has failed, ineffective alcohol policies remain common, uninformed by scientific evidence on how harms at the societal level may be reduced. The ICAP book series continues to serve its function as a resource to support the status quo in respect of alcohol policy.

Physical therapists' use of telehealth in older adults within the home health setting: a scoping review protocol.

OBJECTIVES: The objective of this scoping review is to summarize the available information on types of telehealth services provided to older adults when physical therapy is involved in their delivery of care. Methods of clinical assessment and outcomes will also be identified. INTRODUCTION: Information on telerehabilitation interventions for older adults is lacking, yet older individuals can greatly benefit from person-centered care within a home setting. Hence, it is important to synthesize the literature pertaining to telehealth and physical therapy to identify gaps and key implications. INCLUSION CRITERIA: This review will consider studies that include adults who are 65 years of age or older, who receive telehealth services within their home, and have a physical therapist involved. Quantitative, qualitative, and gray literature will be included in this review. There will be no language limits. METHODS: A 3-step search strategy will be followed, in line with the JBI methodology for scoping reviews. Databases to be searched will include JBI Evidence Synthesis , Cochrane Database of Systematic Reviews, MEDLINE (Ovid), CINAHL (EBSCOhost), PRIMO, PubMed Central, PsycINFO (Ovid), LWW Nursing/Medical Journals (Ovid), and OpenGrey. Data will be extracted by 2 independent reviewers. The results will be synthesized, charted, and mapped and the findings will be presented in a peer-reviewed journal. REVIEW REGISTRATION: Open Science Framework https://osf.io/9kyus/.

From the tobacco industry's uses of science for public relations purposes to the alcohol industry: Tobacco industry documents study.

INTRODUCTION: Associates for Research in Substances of Enjoyment (ARISE) was formed by tobacco companies in the late 1980s designed to counter public health policy development. This study examines the alcohol content of ARISE and the contribution of ARISE to alcohol industry activities in a key period in the globalisation of the alcohol industry, generating insights into the inter-relationships between the tobacco and alcohol industries in their involvements in policy-oriented science. METHODS: We systematically searched the UCSF Truth Tobacco Documents Library for information about ARISE, alcohol and the alcohol industry. This material was supplemented with an analysis of the contributions by ARISE associates to one volume in the International Center for Alcohol Policies (ICAP) book series on alcohol and pleasure. RESULTS: ARISE placed nicotine alongside caffeine, chocolate and other foods, and alcohol as treats which brought pleasure and other benefits. Alcohol was thus intrinsic to the ARISE project for the tobacco industry. This study shows that at a formative moment in the mid-1990s the major alcohol companies took advantage of the intellectual inheritance and personnel provided by the tobacco industry when establishing ICAP. Key to this was an ICAP conference that resulted in Alcohol and pleasure: A health perspective (1999). DISCUSSION AND CONCLUSIONS: Not only did ARISE use alcohol to play a supporting role in a sophisticated tobacco industry strategy, the alcohol industry engaged with ARISE as part of its own strategy. This shows the importance of careful attention to corporate activities on the fringes of peer-reviewed science.

Why we need a Public Understanding of Social Science.

Who is licensed to make knowledge claims about society? A more diffuse group of individuals are afforded the status of legitimate speakers on society in the public sphere than is the case when the questions relate to the expertise of the natural sciences. We draw on the concept of the 'locus of legitimate interpretation' and the sensibilities of Collins and Evans' Studies of Expertise and Experience programme to help make sense of these issues. The social sciences are not the natural sciences, and one key difference is their relationship with publics. The social sciences are intrinsically entangled, at both the level of the research question and the research subject/object, with public knowledge, the knowledges of publics and public interests. We therefore outline what these differences might mean for a serious, distinct and purposive Public Understanding of Social Science programme and how this differs from current work in the Public Understanding of Science.

B2 SINE RNA as a novel regulator of glucocorticoid receptor transcriptional activity.

Glucocorticoids are a key component to the cellular response to stress. Glucocorticoids act via glucocorticoid receptors found ubiquitously in the brain and body. Glucocorticoid receptors can bind to response elements throughout the genome to elicit changes in transcription, an adaptation observed at the cellular level. Yet, the transcriptional changes as a consequence of glucocorticoid receptor activation are variable across brain regions, stress conditions and recurrent bouts of glucocorticoid exposure. Here we describe a non-coding RNA, B2 SINE, which is regulated by glucocorticoids and can in turn regulate glucocorticoid receptor transcriptional activity. We show that activated glucocorticoid receptors interact directly with B2 SINE RNA via a decoy response element contained within the transcript sequence and alter receptor binding to response elements in the genome and, subsequently, changes in loci expression.