Navigating new sexual partnerships in midlife: a socioecological perspective on factors shaping STI risk perceptions and practices

OBJECTIVE: Despite increases in STIs among those over 40, little is known about the social context of STI transmission among people experiencing relationship transition in midlife, and few sexual health promotion initiatives are targeted at this group. This study sought to identify factors shaping STI risk perceptions and practices among midlife individuals either contemplating or having sex with new partners following the end of a long-term relationship. METHODS: Participants were purposively selected from respondents to Britain's third National Survey of Sexual Attitudes and Lifestyles, using three eligibility criteria: aged 40-59, reported experience of the end of a marital or cohabiting relationship with an opposite-sex partner in the past 5 years, and willingness to participate in a qualitative interview. Qualitative data were generated via face-to-face interviews with 10 women and 9 men and analysed inductively using thematic analysis, with themes then organised using a socioecological framework. RESULTS: Participants' accounts of new sexual partnerships in midlife indicate that STI risk perceptions and practices are shaped by factors operating at multiple levels across the socioecological arena (individual, partnership, peers and communities, societal). Constraints on, and resources for, the navigation of sexual safety include self-perceived STI risk rooted in past rather than present circumstances; legacies of mistrust within former relationships; intersecting gender-age dynamics in negotiation of risk prevention strategies with new partners; peers and younger relatives' influences on understandings of sexual risk and safety; postrelationship change in social networks that increase or mitigate vulnerability to sexual risk; age-related barriers to accessing condoms; and disconnection from safer sex messaging and services culturally coded as for the young. CONCLUSIONS: Improving sexual health among midlife adults requires age-sensitive interventions designed to address multilevel constraints, and harness positive influences, on the navigation of sexual safety at this stage of life

NRF2 Mediates Therapeutic Resistance to Chemoradiation in Colorectal Cancer through a Metabolic Switch

Radiation resistance is a significant clinical problem in rectal cancer treatment, the mechanisms of which are poorly understood. NRF2 signalling is known to contribute to chemo/radioresistance in some cancers, but its role in therapeutic resistance in colorectal cancer (CRC) is unexplored. Using siRNA and CRiSPR/Cas9 isogenic CRC cell lines, we investigated the effect of the knockdown and upregulation of the NRF2 pathway on chemo-radiosensitivity. Poly (A) enriched RNA sequencing and geneset enrichment analysis (GSEA) were carried out on both sensitive and resistant cell models for mechanistic insights. Finally, a cohort of rectal patient samples was profiled to understand the clinical relevance of NRF2 signalling. Radioresistant cell lines were significantly radiosensitised by siRNA knockdown (SW1463, SER10 1.22, ANOVA p < 0.0001; HT55, SER10 1.17, ANOVA p < 0.01), but not the (already) radiosensitive HCT116. The constitutive activation of NRF2 via a CRISPR Cas9 NFE2L2 mutation, E79K, induced radioresistance in HCT116 (SER10 0.71, ANOVA, p < 0.0001). GSEA demonstrated significant opposing metabolic dependencies in NRF2 signalling, specifically, the downregulation of amino acid and protein synthesis with low levels of NRF2 and upregulation with over expression. In a clinical cohort of 127 rectal patients, using a validated mRNA signature, higher baseline NRF2 signalling was associated with incomplete responses to radiation higher final neoadjuvant rectal (NAR) score (OR 1.34, 95% C.I. 1.01–1.80, LRT p-value = 0.023), where high NAR indicates poor radiation response and poor long-term prognosis. This is the first demonstration of NRF2-mediated radiation resistance in colorectal cancer. NRF2 appears to regulate crucial metabolic pathways, which could be exploited for therapeutic interventions

An interactive health communication application for supporting parents managing childhood long-term conditions: outcomes of a randomized controlled feasibility trial

Background: Families living with chronic or long-term conditions such as chronic kidney disease (CKD), stages 3-5, face multiple challenges and respond to these challenges in various ways. Some families adapt well while others struggle, and family response to a condition is closely related to outcome. With families and professionals, we developed a novel condition-specific interactive health communication app to improve parents’ management ability—the online parent information and support (OPIS) program. OPIS consists of a comprehensive mix of clinical caregiving and psychosocial information and support. Objective: The purpose of this study was to (1) assess feasibility of a future full-scale randomized controlled trial (RCT) of OPIS in terms of recruitment and retention, data collection procedures, and psychometric performance of the study measures in the target population, and (2) investigate trends in change in outcome measures in a small-scale RCT in parents of children with CKD stages 3-5. Methods: Parents were recruited from a pediatric nephrology clinic and randomly assigned to one of two treatment groups: usual support for home-based clinical caregiving (control) or usual support plus password-protected access to OPIS for 20 weeks (intervention). Both groups completed study measures at study entry and exit. We assessed feasibility descriptively in terms of recruitment and retention rates overall; assessed recruitment, retention, and uptake of the intervention between groups; and compared family condition management, empowerment to deliver care, and fathers’ involvement between groups. Results: We recruited 55 parents of 39 children (42% of eligible families). Of those, about three-quarters of intervention group parents (19/26, 73%) and control group parents (22/29, 76%) were retained through completion of 20-week data collection. The overall retention rate was 41/55 (75%). The 41 parents completing the trial were asked to respond to the same 10 questionnaire scales at both baseline and 20 weeks later; 10 scores were missing at baseline and nine were missing at 20 weeks. Site user statistics provided evidence that all intervention group parents accessed OPIS. Analysis found that intervention group parents showed a greater improvement in perceived competence to manage their child’s condition compared to control group parents: adjusted mean Family Management Measure (FaMM) Condition Management Ability Scale intervention group 44.5 versus control group 41.9, difference 2.6, 95% CI -1.6 to 6.7. Differences between the groups in the FaMM Family Life Difficulty Scale (39.9 vs 36.3, difference 3.7, 95% CI -4.9 to 12.2) appeared to agree with a qualitative observation that OPIS helped parents achieve understanding and maintain awareness of the impact of their child’s condition. Conclusions: A full-scale RCT of the effectiveness of OPIS is feasible. OPIS has the potential to beneficially affect self-reported outcomes, including parents’ perceived competence to manage home-based clinical care for children with CKD stage 3-5. Our design and methodology can be transferred to the management of other childhood conditions. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 84283190; http://www.controlled-trials.com/ISRCTN84283190 (Archived by WebCite at http://www.webcitation.org/6TuPdrXTF)

Scale Invariance and Nonlinear Patterns of Human Activity

We investigate if known extrinsic and intrinsic factors fully account for the complex features observed in recordings of human activity as measured from forearm motion in subjects undergoing their regular daily routine. We demonstrate that the apparently random forearm motion possesses previously unrecognized dynamic patterns characterized by fractal and nonlinear dynamics. These patterns are unaffected by changes in the average activity level, and persist when the same subjects undergo time-isolation laboratory experiments designed to account for the circadian phase and to control the known extrinsic factors. We attribute these patterns to a novel intrinsic multi-scale dynamic regulation of human activity.Comment: 4 pages, three figure

Temperature controlled motion of an antiferromagnet- ferromagnet interface within a dopant-graded FeRh epilayer

Chemically ordered B2 FeRh exhibits a remarkable antiferromagnetic-ferromagnetic phase transition that is first order. It thus shows phase coexistence, usually by proceeding though nucleation at random defect sites followed by propagation of phase boundary domain walls. The transition occurs at a temperature that can be varied by doping other metals onto the Rh site. We have taken advantage of this to yield control over the transition process by preparing an epilayer with oppositely directed doping gradients of Pd and Ir throughout its height, yielding a gradual transition that occurs between 350 K and 500 K. As the sample is heated, a horizontal antiferromagnetic-ferromagnetic phase boundary domain wall moves gradually up through the layer, its position controlled by the temperature. This mobile magnetic domain wall affects the magnetisation and resistivity of the layer in a way that can be controlled, and hence exploited, for novel device applications

P-ANCA vasculitic neuropathy with 12-year latency between onset of neuropathy and systemic symptoms

BACKGROUND: The differential diagnosis of chronic progressive multifocal asymmetric neuropathies is challenging. Vasculitic neuropathies, multifocal forms of chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathies, and asymmetric lower motor neuron disorders are important considerations. CASE PRESENTATION: We report a patient with an unusually long 12-year course of nonsystemic vasculitic neuropathy prior to the development of systemic manifestations. CONCLUSION: We discuss some of the difficulties involved in the diagnosis of chronic progressive multifocal asymmetric neuropathies

Transforming Post-Secondary Education in Mathematics

In this manuscript, I introduce and describe the work of mathematicians and mathematics educators in the group Transforming Post-Secondary Education in Mathematics (TPSE Math or TPSE, pronounced "tipsy", for short). TPSE aims to coordinate and drive constructive change in education in the mathematical sciences at two-year colleges, four-year colleges, and universities across the nation. It seeks to build on the successes of the entire mathematical sciences community. This manuscript reviews the events that led to the founding of TPSE Math and articulates its vision and mission. In its first phase with national events, TPSE found broad consensus with the mathematical sciences community on the challenges facing the community. Learning from educational transformations experiences in other scientific fields, and with the support of the Mathematical Advisory Group of 34 mathematical sciences department chairs and leaders, TPSE moves into a second phase focused on action. This is a snapshot in time, and TPSE's ongoing activities will continue to be documented and disseminated. The piece concludes with a reflection of the impact that my involvement in this work has had on my career.Comment: 17 page

Online Sexual Partner Seeking as a Social Practice: Qualitative Evidence from the 4(th) British National Survey of Sexual Attitudes and Lifestyles (Natsal-4)

Once perceived as a means for those unsuccessful at traditional dating, online dating has become normalized as a way to seek sexual or romantic partners. In 2019, we interviewed 40 British adults on the role of digital technologies in their sexual lives; this paper draws on the accounts of 22 who had used such technologies for seeking partners. We analyzed qualitative accounts of online partner seeking as a social practice, drawing on a sample diverse in age, gender and sexual orientation, and informed by sexual script and social practice theory. Our theoretically informed analysis emphasized the multiple meanings and goals involved, the affordances of the technology and individuals’ skills. Our study provided several novel contributions. Young heterosexual people commonly used general social media, rather than dating apps, to meet partners; meeting partners often involved complex interplays between online and offline networks and encounters. Risks were defined not merely in relation to “risky others” but in terms of one’s own actions or attitudes. Participants deployed various skills in minimizing harms such as non-consensual sharing of intimate images, and used self-care skills such as setting limits to engagement

The prismatic Sigma 3 (10-10) twin bounday in alpha-Al2O3 investigated by density functional theory and transmission electron microscopy

The microscopic structure of a prismatic $\Sigma 3$ $(10\bar{1}0)$ twin boundary in \aal2o3 is characterized theoretically by ab-initio local-density-functional theory, and experimentally by spatial-resolution electron energy-loss spectroscopy in a scanning transmission electron microscope (STEM), measuring energy-loss near-edge structures (ELNES) of the oxygen $K$-ionization edge. Theoretically, two distinct microscopic variants for this twin interface with low interface energies are derived and analysed. Experimentally, it is demonstrated that the spatial and energetical resolutions of present high-performance STEM instruments are insufficient to discriminate the subtle differences of the two proposed interface variants. It is predicted that for the currently developed next generation of analytical electron microscopes the prismatic twin interface will provide a promising benchmark case to demonstrate the achievement of ELNES with spatial resolution of individual atom columns

Robust aircraft conceptual design using automatic differentiation in Matlab

The need for robust optimisation in aircraft conceptual design, for which the design parameters are assumed stochastic, is introduced. We highlight two approaches, first-order method of moments and Sigma-Point reduced quadrature, to estimate the mean and variance of the design’s outputs. The method of moments requires the design model’s differentiation and here, since the model is implemented in Matlab, is performed using the AD tool MAD. Gradient-based constrained optimisation of the stochastic model is shown to be more efficient using AD-obtained gradients than finite-differencing. A post-optimality analysis, performed using ADenabled third-order method of moments and Monte-Carlo analysis, confirms the attractiveness of the Sigma-Point technique for uncertainty propagation