Single-stranded DNA-binding protein hSSB1 is critical for genomic stability

Single-strand DNA (ssDNA)-binding proteins (SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair1. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand-exchange proteins, activating transcription and mediating protein–protein interactions. In eukaryotes, the major SSB, replication protein A (RPA), is a heterotrimer1. Here we describe a second human SSB (hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell-cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S-phase cells and hSSB1 deficiency does not influence S-phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse endpoints in the cellular DNA damage response.

Plantar enthesopathy : thickening of the enthesis is correlated with energy dissipation of the plantar fat pad during walking

Background: The enthesis of the plantar fascia is thought to play an important role in stress dissipation. However, the potential link between entheseal thickening characteristic of enthesopathy and the stress-dissipating properties of the intervening plantar fat pad have not been investigated. Purpose: This study was conducted to identify whether plantar fat pad mechanics explain variance in the thickness of the fascial enthesis in individuals with and without plantar enthesopathy. Study Design: Case-control study; Level of evidence, 3. Methods: The study population consisted of 9 patients with unilateral plantar enthesopathy and 9 asymptomatic, individually matched controls. The thickness of the enthesis of the symptomatic, asymptomatic, and a matched control limb was acquired using high-resolution ultrasound. The compressive strain of the plantar fat pad during walking was estimated from dynamic lateral radiographs acquired with a multifunction fluoroscopy unit. Peak compressive stress was simultaneously acquired via a pressure platform. Principal viscoelastic parameters were estimated from subsequent stress-strain curves. Results: The symptomatic fascial enthesis (6.7 ± 2.0 mm) was significantly thicker than the asymptomatic enthesis (4.2 ± 0.4 mm), which in turn was thicker than the enthesis (3.3 ± 0.4 mm) of control limbs (P < .05). There was no significant difference in the mean thickness, peak stress, peak strain, or secant modulus of the plantar fat pad between limbs. However, the energy dissipated by the fat pad during loading and unloading was significantly lower in the symptomatic limb (0.55 ± 0.17) when compared with asymptomatic (0.69 ± 0.13) and control (0.70 ± 0.09) limbs (P < .05). The sonographic thickness of the enthesis was correlated with the energy dissipation ratio of the plantar fat pad (r = .72, P < .05), but only in the symptomatic limb. Conclusion: The energy-dissipating properties of the plantar fat pad are associated with the sonograpic appearance of the enthesis in symptomatic limbs, providing a previously unidentified link between the mechanical behavior of the plantar fat pad and enthesopathy.

The influence of platform walking on BRT station bus dwell time estimation

The common approach to estimate bus dwell time at a BRT station platform is to apply the traditional dwell time methodology derived for suburban bus stops. Current dwell time models are sensitive towards bus type, fare collection policy along with the number of boarding and alighting passengers. However, they fall short in accounting for the effects of passenger/s walking on a relatively longer BRT station platform. Analysis presented in this paper shows that the average walking time of a passenger at BRT platform is 10 times more than that of bus stop. The requirement of walking to the bus entry door at the BRT station platform may lead to the bus experiencing a higher dwell time. This paper presents a theory for a BRT network which explains the loss of station capacity during peak period operation. It also highlights shortcomings of present available bus dwell time models suggested for the analysis of BRT operation.

Changes in resting and walking energy expenditure and walking speed during pregnancy in obese women

Background Energy conserving processes reported in undernourished women during pregnancy are a recognised strategy to provide energy required to support fetal development. Women who are obese before conceiving arguably have sufficient fat stores to support the energy demands of pregnancy without the need to provoke energy conserving mechanisms. Objective We tested the hypothesis that obese women would demonstrate behavioural adaptation (i.e. decrease in self-selected walking (SSW) speed) but not metabolic compensation (i.e. decrease in resting metabolic rate (RMR) or metabolic cost of walking) during gestation. Design RMR, SSW speed, metabolic cost of walking, and anthropometry were measured in 23 women (BMI: 33.6 ± 2.5 kg/m2; 31 ± 4 years) at approximately weeks 15 (wk 15) and 30 (wk 30) of gestation. RMR was also measured in two cohorts of non-pregnant controls matched for age, weight and height of the pregnant cohort at wk 15 (N=23) and wk 30 (N=23). Results GWG varied widely (11.3 ± 5.4 kg) and 52% of women gained more weight than is recommended. RMR increased significantly by an average 177 ± 176 kcal/d (11±12%; P<0.0001); however the within-group variability was large. Both the metabolic cost of walking and SSW speed decreased significantly (P<0.01). While RMR increased in >80% of the cohort, the net oxygen cost of walking decreased in the same proportion of women. Conclusions While the increase in RMR was greater than was explained by weight gain, there was evidence of both behavioural and biological compensation in the metabolic cost of walking in obese women during gestation.

Walking with another : rural nurses' experiences of mentoring

The aim of this constructivist grounded theory study was to explore rural nurses' experiences of mentoring. Mentoring is often proposed as a solution to the problem of nursing workforce shortages. The global problem of workforce for nurses can be defined using the parameters of recruitment and retention rates, 'problems' with which result in staff shortages, particularly of experienced nurses. Constructivist grounded theory has its foundations in relativism and an appreciation of the multiple truths and realities of subjectivism. Seven Australian rural nurses were interviewed. To ensure data saturation of particular categories and the fit of tentative theoretical conceptualisations, two participants were interviewed twice with no new codes identified from the subsequent interviews. Cultivating and growing new or novice rural nurses was the core category which conceptualised a two-part process consisting of getting to know a stranger and walking with another. Supportive relationships such as mentoring were found to be an existing, integral part of experienced rural nurses' practice - initiated by living and working in the same community. In this grounded theory, cultivating and growing is conceptualised as the core category. A two-part process was identified - getting to know a stranger and walking with another. This paper examines one of these subcategories, walking with another, relating the ways in which experienced rural nurses walk with another by firstly keeping things in perspective for new or novice rural nurses, and secondly using a particular form of language called nurse chat. For experienced rural nurses, mentoring in this way delivers a number of different outcomes with various nurses. Because it is a part of the experienced rural nurse's practice on an ongoing basis, individual mentoring relationships do not provide an end in relation to this nurse's experiences of mentoring, rather they are part of an ongoing experience. Creating supportive environments that include developing relationships such as mentoring is a potential solution to local staffing needs that does not require intensive resources. Experienced nurses engaged in clinical practice have the potential to cultivate and grow new or novice nurses - many already do so. Recognising their role and providing support as well as development opportunities will bring about a cycle of mentoring within the workplace. © 2008 Sage Publications.

The influence of conformity and group identity on drink walking intentions : comparing intentions to drink walk across risky pedestrian crossing scenarios

Despite the dangers associated with drink walking, limited research is currently available regarding the factors which influence individuals to engage in this risky behaviour. This study examined the influence of psychosocial factors upon individuals’ intentions to drink walk across four experimental scenarios (and a control condition). Specifically, a 2 × 2 repeated measures design was utilised in which all of the scenarios incorporated a risky pedestrian crossing situation (i.e., a pedestrian crossing against a red man signal) but differed according to the level of group identity (i.e., low/strangers and high/friends) and conformity (low and high). Individuals were assessed for their intentions to drink walk within each of these different scenarios. Undergraduate students (N = 151), aged 17–30 years, completed a questionnaire. Overall, most of the study's hypotheses were supported with individuals reporting the highest intentions to drink walk when in the presence of friends (i.e., high group identity) and their friends were said to be also crossing against the red man signal (i.e., high conformity). The findings may have significant implications for the design of countermeasures to reduce drink walking. For instance, the current findings would suggest that potentially effective strategies may be to promote resilience to peer influence as well as highlight the negative consequences associated with following the behaviour of other intoxicated pedestrians who are crossing against a red signal.

Walking when intoxicated : an investigation of the factors which influence individuals' drink walking intentions

Annually, in Australia, 10-15% of all road-related fatalities involve pedestrians. Of those pedestrians fatally injured, approximately 45% were walking while intoxicated or 'drink walking'. Drink walking is increasing in prevalence and younger persons may be especially prone to engage in this behaviour and, thus, are at heightened risk of being injured or killed. Presently, limited research is available regarding the factors which influence individuals to drink walk. This study explored young people's (17-25 years) intentions to drink walk, using an extended Theory of Planned Behaviour (TPB). Participants (N = 215), completed a self-report questionnaire which assessed the standard TPB constructs (attitude, subjective norm, perceived behavioural control) as well as the extended constructs of risk perception, anticipated regret, and past behaviour. It was hypothesised that the standard TPB constructs would significantly predict individuals' reported intentions to drink walk and that the additional constructs would predict intentions over and above the TPB constructs. The TPB variables significantly predicted 63.2% of the variance in individuals' reported intentions to drink walk, and the additional variables, combined, explained a further 6.1% of the variance. Of the additional constructs, anticipated regret and past behaviour, but not risk perception, were significant predictors of drink walking intentions. As one of the first studies to provide a theoretically-based investigation of factors influencing individuals' drink walking intentions, the current study's findings have potentially significant implications for understanding young people's decisions to drink walk and the design of future countermeasures to ultimately reduce this behaviour.

Simple classification of walking activities using commodity smart phones

People interact with mobile computing devices everywhere, while sitting, walking, running or even driving. Adapting the interface to suit these contexts is important, thus this paper proposes a simple human activity classification system. Our approach uses a vector magnitude recognition technique to detect and classify when a person is stationary (or not walking), casually walking, or jogging, without any prior training. The user study has confirmed the accuracy.

Safety, feasibility and effects of an individualised walking intervention for women undergoing chemotherapy for ovarian cancer : a pilot study

Background: Exercise interventions during adjuvant cancer therapy have been shown to increase functional capacity, relieve fatigue and distress and may assist rates of chemotherapy completion. These studies have been limited to breast, gastric and mixed cancer groups and it is not yet known if a similar intervention is even feasible among women with ovarian cancer. We aimed to assess safety, feasibility and potential effect of a walking intervention in women undergoing chemotherapy for ovarian cancer. Methods: Women newly diagnosed with ovarian cancer were recruited to participate in an individualised walking intervention throughout chemotherapy and were assessed pre-and post-intervention. Feasibility measures included session adherence, compliance with exercise physiologist prescribed walking targets and self-reported program acceptability. Changes in objective physical functioning (6 minute walk test), self-reported distress (Hospital Anxiety and Depression Scale), symptoms (Memorial Symptom Assessment Scale - Physical) and quality of life (Functional Assessment of Cancer Therapy - Ovarian) were calculated, and chemotherapy completion and adverse intervention effects recorded. Results: Seventeen women were enrolled (63% recruitment rate). Mean age was 60 years (SD = 8 years), 88% were diagnosed with FIGO stage III or IV disease, 14 women underwent adjuvant and three neo-adjuvant chemotherapy. On average, women adhered to > 80% of their intervention sessions and complied with 76% of their walking targets, with the majority walking four days a week at moderate intensity for 30 minutes per session. Meaningful improvements were found in physical functioning, physical symptoms, physical well-being and ovarian cancerspecific quality of life. Most women (76%) completed ≥85% of their planned chemotherapy dose. There were no withdrawals or serious adverse events and all women reported the program as being helpful. Conclusions: These positive preliminary results suggest that this walking intervention for women receiving chemotherapy for ovarian cancer is safe, feasible and acceptable and could be used in development of future work. Trial registration: ACTRN12609000252213