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This article discusses the role of 'artworks' produced by women with breast cancer in the context of breast cancer activism. We argue that such works play a key role in making visible and collective the ideological issues surrounding this disease. They do this through their potential for anchoring social practices relating to its treatment and what might be done about it (Klawiter 2004, Swidler 2001). The article focuses upon the work of two women artists diagnosed with breast cancer - the British photographer Jo Spence, and Martha Hall, an American who made artist's books. We examine specific works from these collections, and the context of their production. In this way we show how and why artworks are important in establishing visual and discursive space related to social practices associated with disease regimes, and how they provide emancipatory potential for women living with breast cancer. We argue that artworks work through and on bodies to enable a redemptive and emancipatory potential. As mediators of representations of illness, they deserve attention from sociologists researching social movements, the sharing of illness experience and strategies for survival. [ABSTRACT FROM AUTHOR]

Heart failure is one of the most common diagnoses of the elderly in the United States. The nursing literature has demonstrated that nursing interventions aimed at effective discharge planning and appropriate self-care activities can improve outcomes for patients hospitalized with heart failure. The purpose of this research was to identify, through retrospective medical record review, the discharge instruction related to self-weight monitoring provided to a sample of heart failure patients. The patients in the sample were 65 years and older with an ICD-9 diagnostic code of heart failure upon discharge from an acute care hospital in the Midwest. Results demonstrated the lack of nursing attentiveness to teaching self-monitoring weight gain to heart failure patients while hospitalized and the need for more comprehensive planning for appropriate discharge referrals. Suggestions are made for expanding documentation tools to improve nursing discharge planning and case management to ensure that the patient or caregiver is able to carry out self-care activities at home. [ABSTRACT FROM AUTHOR]

The purpose of this research was to describe the characteristics of nurses who perform telephonic care quality assessment, or utilization review, prior to, concurrent with, and after medical interventions and hospitalizations. It compares these nurses demographically to nurses employed in other settings, discusses the nurses' perceptions of the nature of their work, examines assertions that utilization review is a nursing activity, and documents the nurses' education and training for ethical decision-making. Implications for nursing care quality are discussed. [ABSTRACT FROM AUTHOR]

Medical sociologists have much to gain by bringing in global health. In this article, I make the case for expanding our field by furthering sociological perspectives on global health. I reflect on my career, the influence of scholar-activist mentors, and my contributions to the development of scholarship about medicalization, narrative, and global health in medical sociology. First, I focus on medicalization, its relationship to biomedicalization and pharmaceuticalization, and critiques of the medicalization of global health. Second, I analyze the narrative turn in studies of illness experiences and the inclusion of visual materials as an integral part of narrative studies of illness. Third, I explore global health and show examples of bodies of knowledge that medical sociologists are building. Although I present each as a distinct area, my discussion illustrates how the three areas are intertwined and how my contributions to each traverse and build connections among them.

Puromycin-sensitive aminopeptidases have long been implicated in cell-cycle regulation, but the mechanism remains unknown. Here we show that mutations in the gene encoding the C. elegans puromycin-sensitive aminopeptidase, PAM-1 , cause chromosome segregation defects and an elongated mitosis in the one-cell embryo. Depleting a known regulator of the spindle assembly checkpoint (SAC), MDF-2 (MAD2 in humans), restores normal mitotic timing to pam-1 mutants but exacerbates the chromosome segregation defects. Thus, PAM-1 is required for proper attachment of chromosomes to the mitotic spindle and its absence triggers the SAC., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Aims and Objectives: This paper describes the development of a SBHC with an innovative model of care that grew out of a partnership between a public-school district and a university nursing programme in the midwestern region of the United States., Background and Purpose: Persistent barriers to health and health care experienced by youth are well documented. School-based health centres (SBHCs) can improve educational and health outcomes, positively impacting health equity. Academic systems are positioned to address health care needs of the school-aged population, yet educators face challenges of accessing quality learning placements for students and faculty practice sites., Methods: A community-based collaborative methodology guided the planning phases that were driven by priority needs identified by families and stakeholders. With the mission of "partnering with students, families, and communities in the promotion of health and wellness through engagement in practice, education, and research," an ongoing dialogue over a two-year period led to articulating a vision, designing a plan and implementing a nurse-managed SBHC. The Standards for Reporting Qualitative Research (SRQR) checklist was considered in the preparation of this paper., Results: In three years, this SBHC has addressed and identified priority needs and served individual youth and families. The SBHC provides opportunities for the faculty to fulfil a practice requirement for certification and accreditation. Nursing students engage with youth and families in health education and health promotion while strengthening their technical and relational skills. Family nurse practitioner students gain valuable clinical experience. Faculty with expertise in family nursing guide family assessments, support family resiliency and direct therapeutic conversations with family units., Conclusion: SBHCs serve youth, families, and community. This academic-practice partnership has the added benefit of providing faculty practice opportunities and nursing student experiential learning., Relevance to Clinical Practice: SHBCs provide practice opportunities that address needs in individuals, families, and communities. Partnerships should be considered at academic nursing programmes to support their needs and fulfil commitments to address health equity gaps., (© 2022 John Wiley & Sons Ltd.)

The ZFP36 family of RNA-binding proteins acts post-transcriptionally to repress translation and promote RNA decay. Studies of genes and pathways regulated by the ZFP36 family in CD4 + T cells have focussed largely on cytokines, but their impact on metabolic reprogramming and differentiation is unclear. Using CD4 + T cells lacking Zfp36 and Zfp36l1, we combined the quantification of mRNA transcription, stability, abundance and translation with crosslinking immunoprecipitation and metabolic profiling to determine how they regulate T cell metabolism and differentiation. Our results suggest that ZFP36 and ZFP36L1 act directly to limit the expression of genes driving anabolic processes by two distinct routes: by targeting transcription factors and by targeting transcripts encoding rate-limiting enzymes. These enzymes span numerous metabolic pathways including glycolysis, one-carbon metabolism and glutaminolysis. Direct binding and repression of transcripts encoding glutamine transporter SLC38A2 correlated with increased cellular glutamine content in ZFP36/ZFP36L1-deficient T cells. Increased conversion of glutamine to α-ketoglutarate in these cells was consistent with direct binding of ZFP36/ZFP36L1 to Gls (encoding glutaminase) and Glud1 (encoding glutamate dehydrogenase). We propose that ZFP36 and ZFP36L1 as well as glutamine and α-ketoglutarate are limiting factors for the acquisition of the cytotoxic CD4 + T cell fate. Our data implicate ZFP36 and ZFP36L1 in limiting glutamine anaplerosis and differentiation of activated CD4 + T cells, likely mediated by direct binding to transcripts of critical genes that drive these processes., (© 2022. The Author(s).)

Neuropeptides (NPs), a unique class of neuronal signaling molecules, participate in a variety of physiological processes and diseases. Quantitative measurements of NPs provide valuable information regarding how these molecules are differentially regulated in a multitude of neurological, metabolic, and mental disorders. Mass spectrometry (MS) has evolved to become a powerful technique for measuring trace levels of NPs in complex biological tissues and individual cells using both targeted and exploratory approaches. There are inherent challenges to measuring NPs, including their wide endogenous concentration range, transport and postmortem degradation, complex sample matrices, and statistical processing of MS data required for accurate NP quantitation. This review highlights techniques developed to address these challenges and presents an overview of quantitative MS-based measurement approaches for NPs, including the incorporation of separation methods for high-throughput analysis, MS imaging for spatial measurements, and methods for NP quantitation in single neurons.

CD8 + T cell differentiation into effector cells is initiated early after antigen encounter by signals from the T cell antigen receptor and costimulatory molecules. The molecular mechanisms that establish the timing and rate of differentiation however are not defined. Here we show that the RNA binding proteins (RBP) ZFP36 and ZFP36L1 limit the rate of differentiation of activated naïve CD8 + T cells and the potency of the resulting cytotoxic lymphocytes. The RBP function in an early and short temporal window to enforce dependency on costimulation via CD28 for full T cell activation and effector differentiation by directly binding mRNA of NF-κB, Irf8 and Notch1 transcription factors and cytokines, including Il2. Their absence in T cells, or the adoptive transfer of small numbers of CD8 + T cells lacking the RBP, promotes resilience to influenza A virus infection without immunopathology. These findings highlight ZFP36 and ZFP36L1 as nodes for the integration of the early T cell activation signals controlling the speed and quality of the CD8 + T cell response., (© 2022. The Author(s).)

Microfluidic and mass spectrometry (MS) methods are widely used to sample and probe the chemical composition of biological systems to elucidate chemical correlates of their healthy and disease states. Though matrix-assisted laser desorption/ionization-mass spectrometry (MALDI)-MS has been hyphenated to droplet microfluidics for offline analyses, the effects of parameters related to droplet generation, such as the type of oil phase used, have been understudied. To characterize these effects, five different oil phases were tested in droplet microfluidics for producing samples for MALDI-MS analysis. Picoliter to nanoliter aqueous droplets containing 0.1 to 100 mM γ-aminobutyric acid (GABA) and inorganic salts were generated inside a polydimethylsiloxane microfluidic chip and deposited onto a conductive glass slide. Optical microscopy, Raman spectroscopy, and MALDI-mass spectrometry imaging (MSI) of the droplet samples and surrounding areas revealed patterns of solvent and oil evaporation and analyte deposition. Optical microscopy detected the presence of salt crystals in 50-100 μm diameter dried droplets, and Raman and MSI were used to correlate GABA signals to the visible droplet footprints. MALDI-MS analyses revealed that droplets prepared in the presence of octanol oil led to the poorest detectability of GABA, whereas the oil phases containing FC-40 provided the best detectability; GABA signal was localized to the footprint of 65 pL droplets with a limit of detection of 23 amol. The effect of the surfactant perfluorooctanol on analyte detection was also investigated., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

This commentary evaluates the contributions to this special issue through a feminist lens. It reviews the field of ignorance studies and two distinguishable areas in the field: undone science and ignorance/non-knowledge. It points to ways in which the articles in this special issue engage with the social production of ignorance. It explores feminist roots of ignorance studies, including feminist ignorance epistemologies, identifies strengths and gaps in ignorance studies, and suggests possible lines of future work., (© 2021 The Author.)

The germinal centre (GC) is required for the generation of high affinity antibodies and immunological memory. Here we show that the RNA binding protein HuR has an essential function in GC B cells to sustain the GC response. In its absence, the GC reaction and production of high-affinity antibody is severely impaired. Mechanistically, HuR affects the transcriptome qualitatively and quantitatively. The expression and splicing patterns of hundreds of genes are altered in the absence of HuR. Among these genes, HuR is required for the expression of Myc and a Myc-dependent transcriptional program that controls GC B cell proliferation and Ig somatic hypermutation. Additionally, HuR regulates the splicing and abundance of mRNAs required for entry into and transition through the S phase of the cell cycle, and it modulates a gene signature associated with DNA deamination protecting GC B cells from DNA damage and cell death., (© 2021. The Author(s).)

In this paper we propose a new category of International Medical Graduates (IMGs) who are forced to leave their home countries: "refugee physicians." In US social science scholarship, IMGs are divided into US citizen IMG (USIMG) and non-US citizen IMG (non-USIMG). For purposes of US medical licensure qualifications and recordkeeping, US- and non-USIMGs are lumped together. These categorizations are too blunt to demonstrate important differences among non-USIMGs. The category of "refugee physicians" distinguishes non-USIMGs who are forced to flee their homelands from other IMGs. We define and develop this category based on qualitative in-depth interviews conducted in 2019 with 28 non-USIMGs who fled to the US within the past 15 years. Using narrative analysis, we constructed "flight biographies," storied chronological events and experiences, for each physician. The flight biographies highlight the medical and political contexts in which they were forced to flee and are situated in the US. Two representative cases demonstrate how and why lumping refugee physicians together with other IMGs obscures the constraints and challenges that set them apart from the other IMG categories. First, the term refugee physician focuses attention on how physicians are located among forcibly displaced people worldwide, including their distinct relationships to their home countries, transit countries in which some of them seek sanctuary, and the US, where some requested asylum and others have been resettled. Second, because refugee is an umbrella term that blends categories of law, policy, social science, and everyday usage it encompasses a wide variety of lived experiences along a continuum of compulsion to leave. Finally, refugee physician illuminates the group's distinct relationship to medical licensure and brings into focus structural barriers that impede their goal of gaining a US medical license., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cell migration relies on coordinated activity of chemotactic and guidance receptors. Here, we report a specific role for the RNA-binding protein ZFP36L1 in limiting the abundance of molecules involved in the homing of antibody-secreting cells (ASCs) to the bone marrow (BM). In the absence of ZFP36L1, ASCs build up in the spleen and the liver and show diminished accumulation in the BM. ZFP36L1 facilitates migration by directly regulating G protein-coupled receptor kinase 2 (GRK2) and the integrin chains α4 and β1 in splenic ASCs. Expression of CXCR4 and of the integrins α4 and β1 is differentially regulated on ASCs produced at the early and late stages of the immune response. Consequently, deletion of the Zfp36l1 gene has a stronger effect on BM accumulation of high-affinity ASCs formed late in the response. Thus, ZFP36L1 is an integral part of the regulatory network controlling gene expression during ASC homing., Competing Interests: Disclosures: M. Turner reported funding from Cancer Research Technology, financial compensation from Wellcome as an interview panel member, and consultancy from Roche. None of these involve or are related to the work in this study. No other disclosures were reported., (© 2020 Saveliev et al.)

The administration of an oral probiotic has been demonstrated to impact oral microbial diversity in humans but has not been examined in canines. The objective of this study was to test the hypothesis that oral probiotic administration would impact the oral microbiota of canines compared to control. Working canines in training ( n = 13) were assigned to Test or Control groups and acclimated to one of three commercially available study diets utilizing common protein sources (Purina Pro Plan Savor lamb, Purina Pro Plan Sport chicken, Purina Pro Plan Focus salmon) for a minimum of 30 days prior to initiation of the study. Following acclimation, dogs in the Test group began a daily regimen of oral probiotic (Fortiflora® Purina, St. Louis, MO) top-dressed on their midday feeding. Control dogs received their midday feeding with no probiotic. All dogs were sampled once weekly via oral pediatric swabs across the 7-week study. Next generation sequencing (Illumina, MiSeq) was utilized to develop microbial profiles specific to treatment, diet, and time. Bacterial composition was dominated by eight phyla (Proteobacteria 43.8%, Bacteroidetes 22.5%, Firmicutes 18.9%, Actinobacteria 6.1%, Fusobacteria 3.6%, Gracilibacteria 2.1%, SR1 Absconditabacteria 1.5%, and Saccharibacteria 1.3%) representing more than 99% of the relative abundance of the microbial composition. Probiotic administration failed to impact relative abundance at any taxonomic level ( P > 0.05). Similarly, no effect on the oral microbiota was measured for diet ( P > 0.05). Comparison using a Jaccard Index demonstrate a consistent microbial profile over the 7-week study with no impact evidenced by study week ( P = 0.19). The data also revealed a profile of ubiquitous taxa that were present across all dogs and all samples regardless of breed, sex, diet, treatment or other factors. These genera include Actinomyces, Corynebacterium, Capnocytophaga, Flavobacterium, Gemella, Abiotrophia, Streptococcus, and Frederiksenia . These data demonstrate the stability of canine oral microbiota over time., (Copyright © 2020 Bell, Nash, Zanghi, Otto and Perry.)

The brain consists of organized ensembles of cells that exhibit distinct morphologies, cellular connectivity, and dynamic biochemistries that control the executive functions of an organism. However, the relationships between chemical heterogeneity, cell function, and phenotype are not always understood. Recent advancements in matrix-assisted laser desorption/ionization mass spectrometry have enabled the high-throughput, multiplexed chemical analysis of single cells, capable of resolving hundreds of molecules in each mass spectrum. We developed a machine learning workflow to classify single cells according to their mass spectra based on cell groups of interest (GOI), e.g., neurons vs astrocytes. Three data sets from various cell groups were acquired on three different mass spectrometer platforms representing thousands of individual cell spectra that were collected and used to validate the single cell classification workflow. The trained models achieved >80% classification accuracy and were subjected to the recently developed instance-based model interpretation framework, SHapley Additive exPlanations (SHAP), which locally assigns feature importance for each single-cell spectrum. SHAP values were used for both local and global interpretations of our data sets, preserving the chemical heterogeneity uncovered by the single-cell analysis while offering the ability to perform supervised analysis. The top contributing mass features to each of the GOI were ranked and selected using mean absolute SHAP values, highlighting the features that are specific to the defined GOI. Our approach provides insight into discriminating the chemical profiles of the single cells through interpretable machine learning, facilitating downstream analysis and validation.

This article describes a collaboration among a group of university faculty, undergraduate students, local governments, local residents, and U.S. Army staff to address long-standing concerns about the environmental health effects of an Army ammunition plant. The authors describe community-responsive scientific pilot studies that examined potential environmental contamination and a related undergraduate research course that documented residents' concerns, contextualized those concerns, and developed recommendations. We make a case for the value of resource-intensive university-community partnerships that promote the production of knowledge through collaborations across disciplinary paradigms (natural/physical sciences, social sciences, health sciences, and humanities) in response to questions raised by local residents. Our experience also suggests that enacting this type of research through a university class may help promote researchers' adoption of "epistemological pluralism", and thereby facilitate the movement of a study from being "multidisciplinary" to "transdisciplinary".

This case series describes the clinical courses of 3 juvenile Yucatan miniature swine ( Sus scrofa ) that experienced a suspected anaphylactic reaction to ketamine hydrochloride during premedication for protocol-related surgery. All 3 swine rapidly developed diffuse erythema shortly after injection with ketamine-containing drug combinations. Clinical signs ranged from tachycardia and erythema alone to tachycardia and erythema followed by respiratory and cardiac arrest. Ketamine was considered the most likely cause of these reactions because it was the only agent in the premedication sedation combination that was used in all 3 swine. Subsequent intradermal skin testing confirmed this suspicion. With supportive care measures and standard medical interventions for anaphylaxis, all 3 animals recovered well and went on to be successful experimental subjects when an alternative anesthetic regimen that did not contain ketamine was used. To our knowledge, this report is the first description of a suspected adverse ketamine reaction of this type in swine despite the widespread use of the drug in this species. Ketamine anaphylaxis is rare in people, but the few cases described presented with symptoms similar to the clinical signs seen in the pigs in this report. In addition to highlighting a potential adverse drug reaction to ketamine in swine, this case series demonstrates the value of emergency preparedness for even the most routine of procedures.

C cell hyperplasia is considered a precursor lesion for hereditary forms of medullary thyroid carcinoma. It has therefore been suggested as a morphological marker to distinguish hereditary from sporadic medullary thyroid carcinoma and to triage genetic testing in resource poor settings. However, numerous definitions for C cell hyperplasia have been suggested, and there is surprisingly little data regarding the number of C cells present in thyroid glands removed for conditions other than medullary carcinoma. We therefore sought to investigate the specificity of different criteria for C cell hyperplasia. We examined the number of C cells and solid cell nests (ultimobranchial body remnants) present in 118 completion thyroidectomy specimens from patients without medullary carcinoma and with no risk factors for MEN2. Morphological review was performed on all H&E-stained slides, and immunohistochemistry for calcitonin was performed on one block from each case. Solid cell nests were found in 4 (3.3%) of thyroids. Increased numbers of C cells sufficient to fulfil criteria for C cell hyperplasia were found in 5 (4.2%) to 36 (30.5%) cases depending on the criteria used. We conclude that large numbers of C cells are commonly found in thyroids not associated with medullary carcinoma. Therefore, regardless of which criteria are used, the presence of C cell hyperplasia is not a specific marker for hereditary medullary thyroid carcinoma.

US hospitals have developed a variety of strategies to meet federal requirements and provide culturally and linguistically appropriate health care for people who report limited English proficiency. A key strategy is the use of healthcare interpreters who may be physically present in the room or in the room via telephone or video conference. This paper analyzes the contingent and unstable combinations of heterogeneous human and nonhuman elements that form and disperse during visits to the hospital when healthcare interpreters are used. It draws its analysis from 9 months of fieldwork in 2012 that included following 69 adult immigrant and refugee patients in one hospital in Maine and observing encounters with interpreters and clinic staff. It introduces the concept of interpreter assemblage to make sense of the transnational mixes of people, technologies, and ideas that bring multilingual hospital care to life and give it a character of its own., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In the Medical Research Council (MRC) Myeloma IX trial (ISRCTN684564111) patients were randomised to sodium clodronate or zoledronic acid and induction treatment: cyclophosphamide, vincristine, doxorubicin and dexamethasone (CVAD) or cyclophosphamide, thalidomide and dexamethasone (CTD) followed by autologous stem cell transplant (ASCT) in the intensive pathway; attenuated CTD or melphalan and prednisolone (MP) in the non-intensive pathway. Subsequent randomisation allocated patients to either thalidomide or observation. The European Organisation for Research and Treatment of Cancer (EORTC) quality of life (QoL) questionnaires, QLQ-C30 and QLQ-MY24, were administered at baseline, 3, 6 and 12 months and annually thereafter, enabling the effect of sequential treatment on patient-reported health-related QoL (HR-QoL) to be investigated. The protocol specified four subscales of interest: Pain, Fatigue, Global Health Status/Quality of Life and Physical Functioning at 3, 6 and 12 months that were compared using linear models. The intensive pathway showed significant differences in favour of CTD for Fatigue at 3 months and Physical Functioning at 12 months. The non-intensive pathway and maintenance phase reported significant differences at 3 months; Pain (improved with attenuated CTD) and Global Health status/Quality of Life (improved with observation). The improved outcomes in MRC Myeloma IX were accompanied by some beneficial and few detrimental effects on HR-QoL., (© 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd and British Society for Haematology.)

Memory T cells are critical for the immune response to recurring infections. Their instantaneous reactivity to pathogens is empowered by the persistent expression of cytokine-encoding mRNAs. How the translation of proteins from pre-formed cytokine-encoding mRNAs is prevented in the absence of infection has remained unclear. Here we found that protein production in memory T cells was blocked via a 3' untranslated region (3' UTR)-mediated process. Germline deletion of AU-rich elements (AREs) in the Ifng-3' UTR led to chronic cytokine production in memory T cells. This aberrant protein production did not result from increased expression and/or half-life of the mRNA. Instead, AREs blocked the recruitment of cytokine-encoding mRNA to ribosomes; this block depended on the ARE-binding protein ZFP36L2. Thus, AREs mediate repression of translation in mouse and human memory T cells by preventing undesirable protein production from pre-formed cytokine-encoding mRNAs in the absence of infection.

Antibody affinity maturation occurs in germinal centers (GCs), where B cells cycle between the light zone (LZ) and the dark zone. In the LZ, GC B cells bearing immunoglobulins with the highest affinity for antigen receive positive selection signals from helper T cells, which promotes their rapid proliferation. Here we found that the RNA-binding protein PTBP1 was needed for the progression of GC B cells through late S phase of the cell cycle and for affinity maturation. PTBP1 was required for proper expression of the c-MYC-dependent gene program induced in GC B cells receiving T cell help and directly regulated the alternative splicing and abundance of transcripts that are increased during positive selection to promote proliferation.

This article is part of a hospital ethnography that investigates healthcare architecture as an aspect of an increasingly large, complex, and urgent global health issue: caring for refugees and other immigrants. It argues that hospitals are nodes in transnational social networks of immigrant and refugee patients that form assemblages of human and non-human objects. These assemblages co-produce place-specific hospital care in different hospital spaces. Place-specific tensions and power dynamics arise when refugees and immigrants come into contact with these biomedical spaces. The argument is developed by analysing waiting rooms and exam rooms in two outpatient clinics in one US hospital. The article draws its analysis from 9 months of fieldwork in 2012 that included following 69 adult immigrant and refugee patients and observing their encounters with interpreters and clinic staff. Its inclusion of a transnational dimension for understanding place-specific hospital care adds conceptual and empirical depth to the study of how place matters in 21st century hospitals., (© 2018 Foundation for the Sociology of Health & Illness.)

RNA-binding proteins of the ZFP36 family are best known for inhibiting the expression of cytokines through binding to AU-rich elements in the 3' untranslated region and promoting mRNA decay. Here we identified an indispensable role for ZFP36L1 as the regulator of a post-transcriptional hub that determined the identity of marginal-zone B cells by promoting their proper localization and survival. ZFP36L1 controlled a gene-expression program related to signaling, cell adhesion and locomotion; it achieved this in part by limiting expression of the transcription factors KLF2 and IRF8, which are known to enforce the follicular B cell phenotype. These mechanisms emphasize the importance of integrating transcriptional and post-transcriptional processes by RNA-binding proteins for maintaining cellular identity among closely related cell types.

The rise in popularity of electronic cigarettes and the associated new legislation concerning e-liquids has created a requirement for a rapid method for determining the nicotine content of e-liquids in the field, ideally at the point of sale. Here we have developed a rapid method based on surface-enhanced Raman spectroscopy (SERS) with Au colloids and an isotope-labeled nicotine (d 4 -nicotine) internal standard for the measurement/quantification of samples which contain 10s of mg mL -1 nicotine in a complex viscous matrix. This method is novel within the area of SERS because it uses high dilution (ca. 4000×) in the sample preparation which dilutes out the effects of the viscous glycerin/glycerol medium and any flavouring or colouring agents present but still allows for very accurate calibration with high reproducibility. This is possible because the nicotine concentration in the e-liquids (≤24 mg mL -1 ) is of several orders of magnitude above the working range of the SERS measurement. This method has been tested using a portable Raman spectrometer and a very large set of 42 commercial e-liquids to check that there is no matrix interference associated with different manufacturers/flavourings/colouring agents etc. Finally, as an alternative to determining the nicotine concentration by measuring peak heights in the spectra, the concentration was also estimated by comparing the sample spectra with those of a set of standard samples which were prepared at known concentrations and held in a spectral library file in the spectrometer. This simple approach allows the concentration to be estimated without any complex data analysis and lends itself readily to a handheld Raman system which is typically designed to carry out library searching using the internal software for materials identification. Library searching against standards correctly classified 41 of the 42 test liquids as belonging to the correct concentration group. This high dilution SERS approach is suitable for the analysis of sample types that have reasonably high concentrations of analytes but suffer from matrix problems, and it therefore has broad potential for applications across food, pharmaceutical and nutraceutical areas.

2D arrays of metal nanoparticles formed at liquid-liquid interfaces have been fixed in situ to a thin polymer support to create freestanding large (cm 2 ) composite films where the particles remain exposed rather than being trapped within the polymer. Applications of these flexible robust 2D nanoparticle arrays as sensors, thin film conductors, antimicrobial coatings, and dip-in catalysts are shown., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Highly swellable polymer films doped with Ag nanoparticle aggregates (poly-SERS films) have been used to record very high signal : noise ratio, reproducible surface-enhanced (resonance) Raman (SER(R)S) spectra of in situ dried ink lines and their constituent dyes using both 633 and 785 nm excitation. These allowed the chemical origins of differences in the SERRS spectra of different inks to be determined. Initial investigation of pure samples of the 10 most common blue dyes showed that the dyes which had very similar chemical structures such as Patent Blue V and Patent Blue VF (which differ only by a single OH group) gave SERRS spectra in which the only indications that the dye structure had been changed were small differences in peak positions or relative intensities of the bands. SERRS studies of 13 gel pen inks were consistent with this observation. In some cases inks from different types of pens could be distinguished even though they were dominated by a single dye such as Victoria Blue B (Zebra Surari) or Victoria Blue BO (Pilot Acroball) because their predominant dye did not appear in other inks. Conversely, identical spectra were also recorded from different types of pens (Pilot G7, Zebra Z-grip) because they all had the same dominant Brilliant Blue G dye. Finally, some of the inks contained mixtures of dyes which could be separated by TLC and removed from the plate before being analysed with the same poly-SERS films. For example, the Pentel EnerGel ink pen was found to give TLC spots corresponding to Erioglaucine and Brilliant Blue G. Overall, this study has shown that the spectral differences between different inks which are based on chemically similar, but nonetheless distinct dyes, are extremely small, so very close matches between SERRS spectra are required for confident identification. Poly-SERS substrates can routinely provide the very stringent reproducibility and sensitivity levels required. This, coupled with the awareness of the reasons underlying the observed differences between similarly coloured inks allows a more confident assessment of the evidential value of inks SERS and should underpin adoption of this approach as a routine method for the forensic examination of inks.

Two-dimensional metal nanoparticle arrays are normally constructed at liquid-oil interfaces by modifying the surfaces of the constituent nanoparticles so that they self-assemble. Here we present a general and facile new approach for promoting such interfacial assembly without any surface modification. The method use salts that have hydrophobic ions of opposite charge to the nanoparticles, which sit in the oil layer and thus reduce the Coulombic repulsion between the particles in the organic phase, allowing the particles to sit in close proximity to each other at the interface. The advantage of this method is that because it does not require the surface of the particles to be modified it allows nonmetallic particles including TiO2 and SiO2 to be assembled into dense interfacial layers using the same procedure as is used for metallic particles. This opens up a route to a new family of nanostructured functional materials.

Surface-enhanced Raman measurements of <1 μL analyte/colloid meso-droplets on superhydrophobic wires with hydrophilic tips allowed dipicolinic acid, a spore biomarker for Bacillus anthracis (anthrax), to be detected at 10(-6) mol dm(-3). This is equivalent to 18 spores, significantly below the infective dose of 10(4) spores and 2 orders of magnitude better than previous measurements.

Surface-enhanced Raman spectroscopy (SERS) is now widely used as a rapid and inexpensive tool for chemical/biochemical analysis. The method can give enormous increases in the intensities of the Raman signals of low-concentration molecular targets if they are adsorbed on suitable enhancing substrates, which are typically composed of nanostructured Ag or Au. However, the features of SERS that allow it to be used as a chemical sensor also mean that it can be used as a powerful probe of the surface chemistry of any nanostructured material that can provide SERS enhancement. This is important because it is the surface chemistry that controls how these materials interact with their local environment and, in real applications, this interaction can be more important than more commonly measured properties such as morphology or plasmonic absorption. Here, the opportunity that this approach to SERS provides is illustrated with examples where the surface chemistry is both characterized and controlled in order to create functional nanomaterials., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Context: Hamstring musculotendinous stiffness (MTS) is associated with lower-extremity injury risk (ie, hamstring strain, anterior cruciate ligament injury) and is commonly assessed using the damped oscillatory technique. However, despite a preponderance of studies that measure MTS reliably in laboratory settings, there are no valid clinical measurement tools. A valid clinical measurement technique is needed to assess MTS and permit identification of individuals at heightened risk of injury and track rehabilitation progress., Objective: To determine the validity and reliability of the Myotonometer for measuring active hamstring MTS., Design: Descriptive laboratory study., Setting: Laboratory., Participants: 33 healthy participants (15 men, age 21.33 ± 2.94 y, height 172.03 ± 16.36 cm, mass 74.21 ± 16.36 kg)., Main Outcome Measures: Hamstring MTS was assessed using the damped oscillatory technique and the Myotonometer. Intraclass correlations were used to determine the intrasession, intersession, and interrater reliability of the Myotonometer. Criterion validity was assessed via Pearson product-moment correlation between MTS measures obtained from the Myotonometer and from the damped oscillatory technique., Results: The Myotonometer demonstrated good intrasession (ICC3,1 = .807) and interrater reliability (ICC2,k = .830) and moderate intersession reliability (ICC2,k = .693). However, it did not provide a valid measurement of MTS compared with the damped oscillatory technique (r = .346, P = .061)., Conclusions: The Myotonometer does not provide a valid measure of active hamstring MTS. Although the Myotonometer does not measure active MTS, it possesses good reliability and portability and could be used clinically to measure tissue compliance, muscle tone, or spasticity associated with multiple musculoskeletal disorders. Future research should focus on portable and clinically applicable tools to measure active hamstring MTS in efforts to prevent and monitor injuries.

Raman analysis of dilute aqueous solutions is normally prevented by their low signal levels. A very general method to increase the concentration to detectable levels is to evaporate droplets of the sample to dryness, creating solid deposits which are then Raman probed. Here, superhydrophobic (SHP) wires with hydrophilic tips have been used as supports for drying droplets, which have the advantage that the residue is automatically deposited at the tip. The SHP wires were readily prepared in minutes using electroless galvanic deposition of Ag onto copper wires followed by modification with a polyfluorothiol (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-1-decanethiol, HDFT). Cutting the coated wires with a scalpel revealed hydrophilic tips which could support droplets whose maximum size was determined by the wire diameter. Typically, 230 μm wires were used to support 0.6 μL droplets. Evaporation of dilute melamine droplets gave solid deposits which could be observed by scanning electron microscopy (SEM) and Raman spectroscopy. The limit of detection for melamine using a two stage evaporation procedure was 1 × 10(-6) mol dm(-3). The physical appearance of dried droplets of sucrose and glucose showed that the samples retained significant amounts of water, even under high vacuum. Nonetheless, the Raman detection limits of sucrose and glucose were 5 × 10(-4) and 2.5 × 10(-3) mol dm(-3), respectively, which is similar to the sensitivity reported for surface-enhanced Raman spectroscopy (SERS) detection of glucose. It was also possible to quantify the two sugars in mixtures at concentrations which were similar to those found in human blood through multivariate analysis.

Large (10 × 10 cm) sheets of surface-enhanced Raman spectroscopy (SERS) active polymer have been prepared by stabilising metal nanoparticle aggregates within dry hydroxyethylcellulose (HEC) films. In these films the aggregates are protected by the polymer matrix during storage but in use they are released when aqueous analyte droplets cause the films to swell to their gel form. The fact that these "Poly-SERS" films can be prepared in bulk but then cut to size and stored in air before use means that they provide a cost effective and convenient method for routine SERS analysis. Here we have tested both Ag and Au Poly-SERS films for use in point-of-care monitoring of therapeutic drugs, using phenytoin as the test compound. Phenytoin in water could readily be detected using Ag Poly-SERS films but dissolving the compound in phosphate buffered saline (PBS) to mimic body fluid samples caused loss of the drug signal due to competition for metal surface sites from Cl(-) ions in the buffer solution. However, with Au Poly-SERS films there was no detectable interference from Cl(-) and these materials allowed phenytoin to be detected at 1.8 mg L(-1), even in PBS. The target range of detection of phenytoin in therapeutic drug monitoring is 10-20 mg L(-1). With the Au Poly-SERS films, the absolute signal generated by a given concentration of phenytoin was lower for the films than for the parent colloid but the SERS signals were still high enough to be used for therapeutic monitoring, so the cost in sensitivity for moving from simple aqueous colloids to films is not so large that it outweighs the advantages which the films bring for practical applications, in particular their ease of use and long shelf life., (Copyright © 2016 Elsevier B.V. All rights reserved.)