Starting antidepressant use: a qualitative synthesis of UK and Australian data

Objective To explore people's experiences of starting antidepressant treatment. Design Qualitative interpretive approach combining thematic analysis with constant comparison. Relevant coding reports from the original studies (generated using NVivo) relating to initial experiences of antidepressants were explored in further detail, focusing on the ways in which participants discussed their experiences of taking or being prescribed an antidepressant for the first time. Participants 108 men and women aged 22–84 who had taken antidepressants for depression. Setting Respondents recruited throughout the UK during 2003–2004 and 2008 and 2012–2013 and in Australia during 2010–2011. Results People expressed a wide range of feelings about initiating antidepressant use. People's attitudes towards starting antidepressant use were shaped by stereotypes and stigmas related to perceived drug dependency and potentially extreme side effects. Anxieties were expressed about starting use, and about how long the antidepressant might begin to take effect, how much it might help or hinder them, and about what to expect in the initial weeks. People worried about the possibility of experiencing adverse effects and implications for their senses of self. Where people felt they had not been given sufficient time during their consultation information or support to take the medicines, the uncertainty could be particularly unsettling and impact on their ongoing views on and use of antidepressants as a viable treatment option. Conclusions Our paper is the first to explore in-depth patient existential concerns about start of antidepressant use using multicountry data. People need additional support when they make decisions about starting antidepressants. Health professionals can use our findings to better understand and explore with patients’ their concerns before their patients start antidepressants. These insights are key to supporting patients, many of whom feel intimidated by the prospect of taking antidepressants, especially during the uncertain first few weeks of treatment

Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases.

One major hurdle to the success of adoptive T-cell therapy is the identification of antigens that permit effective targeting of tumors in the absence of toxicities to essential organs. Previous work has demonstrated that T cells engineered to express chimeric antigen receptors (CAR-T cells) targeting the murine homolog of the colorectal cancer antigen GUCY2C treat established colorectal cancer metastases, without toxicity to the normal GUCY2C-expressing intestinal epithelium, reflecting structural compartmentalization of endogenous GUCY2C to apical membranes comprising the intestinal lumen. Here, we examined the utility of a human-specific, GUCY2C-directed single-chain variable fragment as the basis for a CAR construct targeting human GUCY2C-expressing metastases. Human GUCY2C-targeted murine CAR-T cells promoted antigen-dependent T-cell activation quantified by activation marker upregulation, cytokine production, and killing of GUCY2C-expressing, but not GUCY2C-deficient, cancer cells in vitro. GUCY2C CAR-T cells provided long-term protection against lung metastases of murine colorectal cancer cells engineered to express human GUCY2C in a syngeneic mouse model. GUCY2C murine CAR-T cells recognized and killed human colorectal cancer cells endogenously expressing GUCY2C, providing durable survival in a human xenograft model in immunodeficient mice. Thus, we have identified a human GUCY2C-specific CAR-T cell therapy approach that may be developed for the treatment of GUCY2C-expressing metastatic colorectal cancer

The Mass-Size Relation from Clouds to Cores. I. A new Probe of Structure in Molecular Clouds

We use a new contour-based map analysis technique to measure the mass and size of molecular cloud fragments continuously over a wide range of spatial scales (0.05 < r / pc < 10), i.e., from the scale of dense cores to those of entire clouds. The present paper presents the method via a detailed exploration of the Perseus Molecular Cloud. Dust extinction and emission data are combined to yield reliable scale-dependent measurements of mass. This scale-independent analysis approach is useful for several reasons. First, it provides a more comprehensive characterization of a map (i.e., not biased towards a particular spatial scale). Such a lack of bias is extremely useful for the joint analysis of many data sets taken with different spatial resolution. This includes comparisons between different cloud complexes. Second, the multi-scale mass-size data constitutes a unique resource to derive slopes of mass-size laws (via power-law fits). Such slopes provide singular constraints on large-scale density gradients in clouds.Comment: accepted to ApJ; references updated in new versio

Turbulence driven by outflow-blown cavities in the molecular cloud of NGC 1333

Outflows from young stellar objects have been identified as a possible source of turbulence in molecular clouds. To investigate the relationship between outflows, cloud dynamics and turbulence, we compare the kinematics of the molecular gas associated with NGC 1333, traced in 13CO(1-0), with the distribution of young stellar objects (YSOs) within. We find a velocity dispersion of ~ 1-1.6 km/s in 13CO that does not significantly vary across the cloud, and is uncorrelated with the number of nearby young stellar outflows identified from optical and submillimeter observations. However, from velocity channel maps we identify about 20 cavities or depressions in the 13CO intensity of scales > 0.1-0.2 pc and velocity widths 1-3 km/s. The cavities exhibit limb brightened rims in both individual velocity channel maps and position velocity diagrams, suggesting that they are slowly expanding. We interpret these cavities to be remnants of past YSO outflow activity: If these cavities are presently empty, they would fill in on time scales of a million years. This can exceed the lifetime of a YSO outflow phase, or the transit time of the central star through the cavity, explaining the the absence of any clear correlation between the cavities and YSO outflows. We find that the momentum and energy deposition associated with the expansion of the cavities is sufficient to power the turbulence in the cloud. In this way we conclude that the cavities are an important intermediary step between the conversion of YSO outflow energy and momentum into cloud turbulent motions.Comment: Accepted for publication in ApJ. Check out http://astro.pas.rochester.edu/~aquillen/coolpics.html for channel map and PosVel movies of N133

Spitzer characterisation of dust in an anomalous emission region: the Perseus cloud

Anomalous microwave emission is known to exist in the Perseus cloud. One of the most promising candidates to explain this excess of emission is electric dipole radiation from rapidly rotating very small dust grains, commonly referred to as spinning dust. Photometric data obtained with the Spitzer Space Telescope have been reprocessed and used in conjunction with the dust emission model DUSTEM to characterise the properties of the dust within the cloud. This analysis has allowed us to constrain spatial variations in the strength of the interstellar radiation field ($\chi_\mathrm{ISRF}$), the mass abundances of the PAHs and VSGs relative to the BGs (Y$_\mathrm{PAH}$ and Y$_\mathrm{VSG}$), the column density of hydrogen (N$_\mathrm{H}$) and the equilibrium dust temperature (T$_\mathrm{dust}$). The parameter maps of Y$_\mathrm{PAH}$, Y$_\mathrm{VSG}$ and $\chi_\mathrm{ISRF}$ are the first of their kind to be produced for the Perseus cloud, and we used these maps to investigate the physical conditions in which anomalous emission is observed. We find that in regions of anomalous emission the strength of the ISRF, and consequently the equilibrium temperature of the dust, is enhanced while there is no significant variation in the abundances of the PAHs and the VSGs or the column density of hydrogen. We interpret these results as an indication that the enhancement in $\chi_\mathrm{ISRF}$ might be affecting the properties of the small stochastically heated dust grains resulting in an increase in the spinning dust emission observed at 33 GHz. This is the first time that such an investigation has been performed, and we believe that this type of analysis creates a new perspective in the field of anomalous emission studies, and represents a powerful new tool for constraining spinning dust models.Comment: 13 pages, 9 figures, accepted for publication in MNRA

Exploring the lived experience of Long Covid in black and minority ethnic groups in the UK: Protocol for qualitative interviews and art-based methods

Some people experience prolonged symptoms following an acute COVID-19 infection including fatigue, chest pain and breathlessness, headache and cognitive impairment. When symptoms persist for over 12 weeks following the initial infection, and are not explained by an alternative diagnosis, the term post-COVID-19 syndrome is used, or the patient-defined term of Long Covid. Understanding the lived experiences of Long Covid is crucial to supporting its management. However, research on patient experiences of Long Covid is currently not ethnically diverse enough. The study aim is to explore the lived experience of Long Covid, using qualitative interviews and art-based methods, among people from ethnically diverse backgrounds (in the UK), to better understand wider systems of support and healthcare support needs. Co-created artwork will be used to build on the interview findings. A purposive sampling strategy will be used to gain diverse experiences of Long Covid, sampling by demographics, geographic locations and experiences of Long Covid. Individuals (aged >18 years) from Black and ethnic minority backgrounds, who self-report Long Covid symptoms, will be invited to take part in a semi-structured interview. Interviews will be analysed thematically. A sub-sample of participants will be invited to co-create visual artwork to further explore shared narratives of Long Covid, enhance storytelling and increase understanding about the condition. A patient advisory group, representing diversity in ethnicity and experiences of Long Covid, will inform all research stages. Stakeholder workshops with healthcare professionals and persons, systems or networks important to people’s management of Long Covid, will advise on the integration of findings to inform management of Long Covid. The study will use patient narratives from people from diverse ethnic backgrounds, to raise awareness of Long Covid and help inform management of Long Covid and how wider social systems and networks may inform better healthcare service access and experiences

Pyruvate Oxidase of \u3ci\u3eStreptococcus pneumoniae\u3c/i\u3e Contributes to Penumolysin Release

Background Streptococcus pneumoniae is one of the leading causes of community acquired pneumonia and acute otitis media. Certain aspects of S. pneumoniae’s virulence are dependent upon expression and release of the protein toxin pneumolysin (PLY) and upon the activity of the peroxide-producing enzyme, pyruvate oxidase (SpxB). We investigated the possible synergy of these two proteins and identified that release of PLY is enhanced by expression of SpxB prior to stationary phase growth. Results Mutants lacking the \u3c\u3espxB gene were defective in PLY release and complementation of spxB restored PLY release. This was demonstrated by cytotoxic effects of sterile filtered supernatants upon epithelial cells and red blood cells. Additionally, peroxide production appeared to contribute to the mechanism of PLY release since a significant correlation was found between peroxide production and PLY release among a panel of clinical isolates. Exogenous addition of H2O2 failed to induce PLY release and catalase supplementation prevented PLY release in some strains, indicating peroxide may exert its effect intracellularly or in a strain-dependent manner. SpxB expression did not trigger bacterial cell death or LytA-dependent autolysis, but did predispose cells to deoxycholate lysis. Conclusions Here we demonstrate a novel link between spxB expression and PLY release. These findings link liberation of PLY toxin to oxygen availability and pneumococcal metabolism

Depression at Work, Authenticity in Question: Experiencing, Concealing and Revealing

Australia and the UK have both introduced policies to protect employees who experience mental illness, including depression. However, a better understanding of the issues workers face (e.g. sense of moral failure) is needed for the provision of appropriate and beneficial support. We analysed 73 interviews from the UK and Australia where narratives of depression and work intersected. Participants encountered difficulties in being (and performing as if) ‘authentic’ at work, with depression contributing to confusions about the self. The diffuse post-1960s imperative to ‘be yourself’ is experienced in conflicting ways: While some participants sought support from managers and colleagues (e.g. sick leave, back to work plans), many others put on a façade in an attempt to perform the ‘well’ and ‘authentic’ employee. We outline the contradictory forces at play for participants when authenticity and visibility are expected, yet moral imperatives to be good (healthy) employees are normative

Consensus: a framework for evaluation of uncertain gene variants in laboratory test reporting

Accurate interpretation of gene testing is a key component in customizing patient therapy. Where confirming evidence for a gene variant is lacking, computational prediction may be employed. A standardized framework, however, does not yet exist for quantitative evaluation of disease association for uncertain or novel gene variants in an objective manner. Here, complementary predictors for missense gene variants were incorporated into a weighted Consensus framework that includes calculated reference intervals from known disease outcomes. Data visualization for clinical reporting is also discussed

Constraints on the Polarization of the Anomalous Microwave Emission in the Perseus Molecular Complex from 7-year WMAP data

We have used the seven year Wilkinson Microwave Anisotropy Probe (WMAP) data in order to update the measurements of the intensity signal in the G159.6-18.5 region within the Perseus Molecular Complex, and to set constraints on the polarization level of the anomalous microwave emission in the frequency range where this emission is dominant. At 23, 33 and 41 GHz, we obtain upper limits on the fractional linear polarization of 1.0, 1.8 and 2.7% respectively (with a 95 per cent confidence level). These measurements rule out a significant number of models based on magnetic dipole emission of grains that consist of a simple domain (Draine & Lazarian 1999) as responsible of the anomalous emission. When combining our results with the measurement obtained with the COSMOSOMAS experiment at 11 GHz (Battistelli et al. 2006), we find consistency with the predictions of the electric dipole and resonance relaxation theory (Lazarian & Draine 2000) at this frequency range.Comment: 14 pages, 7 figures, ApJ submitte