Ensuring the Stability of the Genome: DNA Damage Checkpoints

The cellular response to DNA damage is vital for the cell�s ability to maintain genomic integrity. Checkpoint signalling pathways, which induce a cell cycle arrest in response to DNA damage, are an essential component of this process. This is reflected by the functional conservation of these pathways in all eukaryotes from yeast to mammalian cells. This review will examine the cellular response to DNA damage throughout the cell cycle. A key component of the DNA damage response is checkpoint signalling, which monitors the state of the genome prior to DNA replication (G1/S) and chromosome segregation (G2/M). Checkpoint signalling in model systems including mice, Xenopus laevis, Drosophila melanogaster, and the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have been useful in elucidating these pathways in mammalian cells. An examination of this research, with emphasis on the function of checkpoint proteins, their relationship to DNA repair, and their involvement in oncogenesis is undertaken here

Perceptions of barriers to career progression for academic women in stem

Gender equity in academia is a long-standing struggle. Although common to all disciplines, the impacts of bias and stereotypes are particularly pronounced in science, technology, engineering and mathematics (STEM) disciplines. This paper explores what barriers exist for the career progression of women in academia in STEM disciplines in order to identify key issues and potential solutions. In particular, we were interested in how women perceive the barriers affecting their careers in comparison to their male colleagues. Fourteen focus groups with female-identifying academics showed that there were core barriers to career progression, which spanned countries, disciplines and career stages. Entrenched biases, stereotypes, double standards, bullying and harassment all nega-tively impact women’s confidence and sense of belonging. Women also face an additional biological burden, often being pushed to choose between having children or a career. Participants felt that their experiences as STEM academics were noticeably different to those of their male colleagues, where many of the commonly occurring barriers for women were simply non-issues for men. The results of this study indicate that some of these barriers can be overcome through networks, mentoring and allies. Addressing these barriers requires a reshaping of the gendered norms that currently limit progress to equity and inclusion

Perceptions of stereotypes applied to women who publicly communicate their STEM work

Gender biases and stereotypes are prevalent in science, technology, engineering and mathematics (STEM) fields, which can create obstacles for the attraction, retention and progression of girls and women to STEM studies and careers. There are many initiatives which are used to attempt to address these biases and stereotypes, including the use of visible role models. This study explores the perceptions of the stereotypes applied to female STEM professionals who publicly speak about their work in both academic and non-academic settings. Using workshops with over 300 participants, predominantly female STEM professionals, from over 25 different cultural backgrounds, the results showed women who publicly communicate their work are likely to be stereotyped as 'bitchy', 'bossy', and 'emotional' - often by their own gender. These findings suggest that women may be in a more vulnerable position when communicating publicly about their work, which could have implications for them participating fully in their careers. It may also have implications for programs which use role models to address prevailing STEM stereotypes. Systematic cultural and institutional change is needed in STEM fields to address the underlying bias and negative stereotypes facing women. However, it should be ensured that the intended solutions to facilitate this change are not compounding the problem

Observations of a mode transition in a hydrogen hollow cathode discharge using phase resolved optical emission spectroscopy

Two distinct operational modes are observed in a radio frequency (rf) low pressure hydrogen hollow cathode discharge. The mode transition is characterised by a change in total light emission and differing expansion structures. An intensified CCD camera is used to make phase resolved images of Balmer α emission from the discharge. The low emission mode is consistent with a typical γ discharge, and appears to be driven by secondary electrons ejected from the cathode surface. The bright mode displays characteristics common to an inductive discharge, including increased optical emission, power factor, and temperature of the H2 gas. The bright mode precipitates the formation of a stationary shock in the expansion, observed as a dark region adjacent to the source-chamber interface.This research was partially funded by the Australian Research Council Discovery Project (DP1096653)

One size does not fit all: gender implications for the design of outcomes, evaluation and assessment of science communication programs

As science communication programs grow worldwide, effective evaluation and assessment metrics lag. While there is no consensus on evaluation protocols specifically for science communication training, there is agreement on elements of effective training: listening, empathy, and knowing your audience - core tenets of improvisation. We designed an evaluation protocol, tested over three years, based on validated and newly developed scales for an improvisation-based communication training at the Alan Alda Center for Communicating Science. Initial results suggest that 'knowing your audience' should apply to training providers as they design and evaluate their curriculum, and gender may be a key influence on outcomes

The Effects of Walking or Walking-with-Poles Training on Tissue Oxygenation in Patients with Peripheral Arterial Disease

This randomized trial proposed to determine if there were differences in calf muscle StO(2) parameters in patients before and after 12 weeks of a traditional walking or walking-with-poles exercise program. Data were collected on 85 patients who were randomized to a traditional walking program (n = 40) or walking-with-poles program (n = 45) of exercise training. Patients walked for 3 times weekly for 12 weeks. Seventy-one patients completed both the baseline and the 12-week follow-up progressive treadmill tests (n = 36 traditional walking and n = 35 walking-with-poles). Using the near-infrared spectroscopy measures, StO(2) was measured prior to, during, and after exercise. At baseline, calf muscle oxygenation decreased from 56 ± 17% prior to the treadmill test to 16 ± 18% at peak exercise. The time elapsed prior to reaching nadir StO(2) values increased more in the traditional walking group when compared to the walking-with-poles group. Likewise, absolute walking time increased more in the traditional walking group than in the walking-with-poles group. Tissue oxygenation decline during treadmill testing was less for patients assigned to a 12-week traditional walking program when compared to those assigned to a 12-week walking-with-poles program. In conclusion, the 12-week traditional walking program was superior to walking-with-poles in improving tissue deoxygenation in patients with PAD

Strengthening midwifery in response to global climate change to protect maternal and newborn health

In this editorial, we argue that midwives should focus on climate change, a link which has been underexplored

Lentiviral Vector Delivery of Human Interleukin-7 (hIL-7) to Human Immune System (HIS) Mice Expands T Lymphocyte Populations

Genetically modified mice carrying engrafted human tissues provide useful models to study human cell biology in physiologically relevant contexts. However, there remain several obstacles limiting the compatibility of human cells within their mouse hosts. Among these is inadequate cross-reactvitiy between certain mouse cytokines and human cellular receptors, depriving the graft of important survival and growth signals. To circumvent this problem, we utilized a lentivirus-based delivery system to express physiologically relevant levels of human interleukin-7 (hIL-7) in Rag2-/-γc-/- mice following a single intravenous injection. hIL-7 promoted homeostatic proliferation of both adoptively transferred and endogenously generated T-cells in Rag2-/-γc-/- Human Immune System (HIS) mice. Interestingly, we found that hIL-7 increased T lymphocyte numbers in the spleens of HIV infected HIS mice without affecting viral load. Taken together, our study unveils a versatile approach to deliver human cytokines to HIS mice, to both improve engraftment and determine the impact of cytokines on human diseases

Efficacy and mechanism of sub-sensory sacral (optimised) neuromodulation in adults with faecal incontinence:Study protocol for a randomised controlled trial

Background: Faecal incontinence (FI) is a substantial health problem with a prevalence of approximately 8% in community-dwelling populations. Sacral neuromodulation (SNM) is considered the first-line surgical treatment option in adults with FI in whom conservative therapies have failed. The clinical efficacy of SNM has never been rigorously determined in a trial setting and the underlying mechanism of action remains unclear. Methods/design: The design encompasses a multicentre, randomised, double-blind crossover trial and cohort follow-up study. Ninety participants will be randomised to one of two groups (SNM/SHAM or SHAM/SNM) in an allocation ratio of 1:1. The main inclusion criteria will be adults aged 18-75 years meeting Rome III and ICI definitions of FI, who have failed non-surgical treatments to the UK standard, who have a minimum of eight FI episodes in a 4-week screening period, and who are clinically suitable for SNM. The primary objective is to estimate the clinical efficacy of sub-sensory SNM vs. SHAM at 32 weeks based on the primary outcome of frequency of FI episodes using a 4-week paper diary, using mixed Poisson regression analysis on the intention-to-treat principle. The study is powered (0.9) to detect a 30% reduction in frequency of FI episodes between sub-sensory SNM and SHAM stimulation over a 32-week crossover period. Secondary objectives include: measurement of established and new clinical outcomes after 1 year of therapy using new (2017 published) optimised therapy (with standardised SNM-lead placement); validation of new electronic outcome measures (events) and a device to record them, and identification of potential biological effects of SNM on underlying anorectal afferent neuronal pathophysiology (hypothesis: SNM leads to increased frequency of perceived transient anal sphincter relaxations; improved conscious sensation of defaecatory urge and cortical/subcortical changes in afferent responses to anorectal electrical stimulation (main techniques: high-resolution anorectal manometry and magnetoencephalography). Discussion: This trial will determine clinical effect size for sub-sensory chronic electrical stimulation of the sacral innervation. It will provide experimental evidence of modifiable afferent neurophysiology that may aid future patient selection as well as a basic understanding of the pathophysiology of FI

A team effort in Nepal: experiences from managing a large COVID-19 rehabilitation hospital outbreak

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic