Assimilation to the Unmarked

Steel, JC ORCiD: 0000-0003-3608-7542Intravitreal injection of recombinant adeno-associated virus (AAV) might be an alternative approach for retinal gene therapy for certain applications. Although the jelly-like substance consists mainly of water, anti-viral antibodies against various viruses such as HIV or HSV have been observed in the human vitreous and anti-AAV neutralising antibodies (NAbs) in rhesus macaque vitreous have also been detected. In this study, the human vitreous humour was obtained from 70 post mortem unpaired eye cups and 10 paired eye cups from the Queensland Eye Bank. The transduction efficiency of 1-3 · 108 vcg of recombinant AAV-2, -5, -6 and -8 expressing secreted nanoluciferase was measured following transduction of ARPE-19 and Cos-7 cells at vitreous humour dilutions from 1:2 to 1:10 000. At vitreous humour dilution of 1:2, a reduction in transduction of over 50% was observed for AAV2 in 50.5% of samples and for AAV6 in 66.2% of samples. Only 23.2% of tested samples showed similar reduction in transduction efficiency for AAV5, and for AAV8 only 2.5% of samples inhibited transduction by 50% at 1:2 dilution. Differences in serum antibody levels have been previously observed in a similar Australian population, but low transduction inhibition at vitreous humour dilutions of 1:100 suggests that the concentration of NAbs within the vitreous humour is lower than in human serum. In addition, this study also reported an increase in transduction efficiency for AAV8 at highest vitreous humour concentrations, supporting previous reports that human albumin can increase AAV transduction but only in some serotypes

Patient-reported outcome measures for acne: a mixed-methods validation study (acne PROMs).

OBJECTIVES: To examine the acceptability and validity of two patient-reported outcome measures (PROMs) for adult acne, comparing them to the validated Acne-specific Quality of Life (Acne-QoL) measure. DESIGN: Mixed-methods validation study. SETTING: Participants were recruited by (1) mail-out through primary care if they had ever consulted for acne and received a prescription for acne treatment within the last 6 months, (2) opportunistically in secondary care and (3) poster advertisement in community venues. PARTICIPANTS: 221 (204 quantitative and 17 qualitative) participants with acne, aged 18-50 years. OUTCOME MEASURES: Quantitative sub-study participants completed Acne-QoL, Skindex-16 and Comprehensive Acne Quality of Life Scale (CompAQ) at baseline, 24 hours and 6 weeks. Qualitative sub-study participants took part in cognitive think-aloud interviews, while completing the same measures. Transcribed audio recordings were analysed using inductive thematic analysis. RESULTS: Quantitative analyses suggested high internal consistency (Cronbach's alpha 0.74-0.96) and reliability (intraclass correlation coefficient values 0.88-0.97) for both questionnaires. Both scales showed floor effects on some subdomains. Skindex-16 and CompAQ showed good evidence of construct validity when compared with Acne-QoL with Spearman's correlation coefficients 0.54-0.81, and good repeatability over 24 hours.Qualitative data uncovered wide-ranging views regarding usability and acceptability. Interviewees held strong but differing views about layout, question/response wording, redundant/similar questions and guidance notes. Similarly, interviewees differed in perceptions of acceptability of the different scales, particularly on relatability of questions and emotive reactions to scales. CONCLUSIONS: All PROMs performed well in statistical analyses. No PROM showed superior usability and acceptability in the qualitative study. Any PROM should be acceptable for further research in adult acne but researchers should consider the different domains and whether they will measure only facial or facial and trunk acne before making a selection. A new PROM or further evaluation of novel PROMs may be beneficial

Systematic review of clinical practice guidelines for acne vulgaris published between January 2017 and July 2021

Background: Acne is very common, can cause considerable negative impact on quality of life and there is increasing concern over the use of long courses of oral antibiotics for this condition. Objectives: (1) To critically appraise reporting in acne guidelines and compare this with previous systematic review of acne guidelines. (2) Examine acne treatment guidance on pre-specified acne treatments of interest and compare between acne guidelines. Methods: Searches for new or updated guidelines were carried out in MEDLINE, Embase, Google Scholar, LILACS from 1 January 2017 to 31 July 2021, supplemented by searching a guideline-specific depository and checking for updates to guidelines included in previous review. We included guidelines, consensus statements or care protocols on the medical treatment of acne vulgaris in adults and/or children and excluded those that focused on a single intervention or subgroup of acne, regional adaptations of guidelines or guidelines included in previous review. AGREE II checklist was applied to critically appraise reporting of guidelines. Results were synthesised narratively. Results: Of 807 abstracts identified nine guidelines were identified that were eligible for inclusion. All guidelines had AGREE II scores above average in at least one domain and reporting was substantially improved compared to the systematic review of acne carried out 5 years previously. There was consensus between guidelines on the key role of topical treatments as first-line acne treatment and most recommended continuing topical treatments as maintenance therapy. There was considerable variation between guidelines on classification of severity, indications for commencing oral antibiotics and on maximum duration of oral antibiotics. However, there was consensus on the need for co-prescription of a non-antibiotic topical treatment when using oral antibiotics. There were notable differences on recommendations regarding provision of information for patients on how to use topical treatments or how to mitigate against side effects. Conclusions: Substantial differences in classification of acne severity hampered comparisons between guidelines. Although development and reporting of guidelines has improved over the past 5 years, differences in key recommendations remain, possibly reflecting uncertainties in the underlying evidence base. Differences between guidelines could have substantial implications for prevalence of antibiotic prescribing for acne

Using stakeholder insights to enhance engagement in PhD professional development

There is increasing awareness of the need for pre- and post-doctoral professional development and career guidance, however many academic institutions are only beginning to build out these functional roles. As a graduate career educator, accessing vast silos and resources at a university and with industry-partners can be daunting, yet collaboration and network development are crucial to the success of any career and professional development office. To better inform and direct these efforts, forty-five stakeholders external and internal to academic institutions were identified and interviewed to gather perspectives on topics critical to career development offices. Using a stakeholder engagement visualization tool developed by the authors, strengths and weaknesses can be assessed. General themes from interviews with internal and external stakeholders are discussed to provide various stakeholder subgroup perspectives to help prepare for successful interactions. Benefits include increased engagement and opportunities to collaborate, and to build or expand graduate career development offices

Political mobilisation by minorities in Britain: negative feedback of ‘race relations'?

This article uses a political opportunity approach to study the relationship of minority groups to the political community in Britain. The main argument is that the British race relations approach established in the 1960s had an important effect that still shapes the patterns of political contention by different minority groups today. Original data on political claims-making by minorities demonstrate that British 'racialised' cultural pluralism has structured an inequality of opportunities for the two main groups, African-Caribbeans and Indian subcontinent minorities. African-Caribbeans mobilise along racial lines, use a strongly assimilative 'black' identity, conventional action forms, and target state institutions with demands for justice that are framed within the recognised framework of race relations. Conversely, a high proportion of the Indian subcontinent minority mobilisation is by Muslim groups, a non-assimilative religious identity. These are autonomously organised, but largely make public demands for extending the principle of racial equality to their non-racial group. Within the Indian subcontinent minorities, the relative absence of mobilisation by Indian, Sikh and Hindu minorities, who have achieved much better levels of socio-economic success than Pakistani and Bangladeshi Muslims, suggests that there is also a strong socioeconomic basis for shared experiences and grievances as Muslims in Britain. This relativises the notion that Muslim mobilisation is Britain is purely an expression of the right for cultural difference per se, and sees it as a product of the paradoxes of British race relations

White Matter Integrity and Processing Speed in Sickle Cell Anemia

Objective The purpose of this retrospective cross-sectional study was to investigate whether changes in white matter integrity are related to slower processing speed in sickle cell anemia. Methods Thirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8–37 years) underwent cognitive assessment using the Wechsler scales and 3-tesla MRI. Tract-based spatial statistics analyses of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed. Results Processing speed index (PSI) was lower in patients than controls by 9.34 points (95% confi- dence interval: 4.635–14.855, p = 0.0003). Full Scale IQ was lower by 4.14 scaled points (95% confidence interval: −1.066 to 9.551, p = 0.1), but this difference was abolished when PSI was included as a covariate (p = 0.18). There were no differences in cognition between patients with and without silent cerebral infarction, and both groups had lower PSI than controls (both p < 0.001). In patients, arterial oxygen content, socioeconomic status, age, and male sex were identified as predictors of PSI, and correlations were found between PSI and DTI scalars (fractional anisotropy r = 0.614, p < 0.00001; r = −0.457, p < 0.00001; mean diffusivity r = −0.341, p = 0.0016; radial diffusivity r = −0.457, p < 0.00001) and NODDI parameters (intracellular volume fraction r = 0.364, p = 0.0007) in widespread regions. Conclusion Our results extend previous reports of impairment that is independent of presence of infarction and may worsen with age. We identify processing speed as a vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide evidence that reduced processing speed is related to the integrity of normal-appearing white matter using microstructure parameters from DTI and NODDI

Time evolution, cyclic solutions and geometric phases for the generalized time-dependent harmonic oscillator

The generalized time-dependent harmonic oscillator is studied. Though several approaches to the solution of this model have been available, yet a new approach is presented here, which is very suitable for the study of cyclic solutions and geometric phases. In this approach, finding the time evolution operator for the Schr\"odinger equation is reduced to solving an ordinary differential equation for a c-number vector which moves on a hyperboloid in a three-dimensional space. Cyclic solutions do not exist for all time intervals. A necessary and sufficient condition for the existence of cyclic solutions is given. There may exist some particular time interval in which all solutions with definite parity, or even all solutions, are cyclic. Criterions for the appearance of such cases are given. The known relation that the nonadiabatic geometric phase for a cyclic solution is proportional to the classical Hannay angle is reestablished. However, this is valid only for special cyclic solutions. For more general ones, the nonadiabatic geometric phase may contain an extra term. Several cases with relatively simple Hamiltonians are solved and discussed in detail. Cyclic solutions exist in most cases. The pattern of the motion, say, finite or infinite, can not be simply determined by the nature of the Hamiltonian (elliptic or hyperbolic, etc.). For a Hamiltonian with a definite nature, the motion can changes from one pattern to another, that is, some kind of phase transition may occur, if some parameter in the Hamiltonian goes through some critical value.Comment: revtex4, 28 pages, no figur

It’s time: Generation and temporality in psychoanalytic feminism

In this paper I examine some key aspects of defining one’s generation: transmitting values to younger generations in a way that makes sense to them; cultivating a psychic flexibility that allows us to welcome the future and be prepared for the unexpected whilst not succumbing to the fear of social, political and economic precarity; thinking of generation as both our collective moment in time and as generative potential; reaffirming the value of communication and sharing experience; and maintaining a dialogue between psychoanalytic feminism and other strands of feminist philosophy

Fluorescence characterization of clinically-important bacteria

Healthcare-associated infections (HCAI/HAI) represent a substantial threat to patient health during hospitalization and incur billions of dollars additional cost for subsequent treatment. One promising method for the detection of bacterial contamination in a clinical setting before an HAI outbreak occurs is to exploit native fluorescence of cellular molecules for a hand-held, rapid-sweep surveillance instrument. Previous studies have shown fluorescence-based detection to be sensitive and effective for food-borne and environmental microorganisms, and even to be able to distinguish between cell types, but this powerful technique has not yet been deployed on the macroscale for the primary surveillance of contamination in healthcare facilities to prevent HAI. Here we report experimental data for the specification and design of such a fluorescence-based detection instrument. We have characterized the complete fluorescence response of eleven clinically-relevant bacteria by generating excitation-emission matrices (EEMs) over broad wavelength ranges. Furthermore, a number of surfaces and items of equipment commonly present on a ward, and potentially responsible for pathogen transfer, have been analyzed for potential issues of background fluorescence masking the signal from contaminant bacteria. These include bedside handrails, nurse call button, blood pressure cuff and ward computer keyboard, as well as disinfectant cleaning products and microfiber cloth. All examined bacterial strains exhibited a distinctive double-peak fluorescence feature associated with tryptophan with no other cellular fluorophore detected. Thus, this fluorescence survey found that an emission peak of 340nm, from an excitation source at 280nm, was the cellular fluorescence signal to target for detection of bacterial contamination. The majority of materials analysed offer a spectral window through which bacterial contamination could indeed be detected. A few instances were found of potential problems of background fluorescence masking that of bacteria, but in the case of the microfiber cleaning cloth, imaging techniques could morphologically distinguish between stray strands and bacterial contamination