Proactive monitoring of pediatric hemodialysis vascular access: Effects of ultrasound dilution on thrombosis rates

Proactive monitoring of pediatric hemodialysis vascular access: Effects of ultrasound dilution on thrombosis rates.BackgroundHemodialysis vascular access thrombosis (VAT) is a significant cause of morbidity for hemodialysis patients and results, in part, from decreased access flow potentially caused by venous outflow stenosis. We have previously shown ultrasound dilution (UD) to be a practical and reliable predictor of venous outflow in children receiving hemodialysis.MethodsThe current study is the first to our knowledge to assess the impact of a proactive UD monitoring program upon VAT in pediatric patients. Nine patients experienced 18 VAT over the two-year study. Mean values for variables potentially associated with VAT were compared to values from a size-matched seven patient group without VAT during the study period. VAT rates were compared between the year-before (pre-UD era) and year-after (UD era) UD was initiated. During the latter half of the UD era (rapid referral period), patients with VA flow rate (QAcorr) <650 mL/min/1.73 m2 were referred for balloon angioplasty within 48 hours.ResultsMean QAcorr was lower for patients with subsequent VAT (562 ± 290 mL/min/1.73 m2) versus patients without VAT (1005 ± 372 mL/min/1.73 m2; P = 0.02). The VAT rate was significantly lower in the UD era (4.1 VAT/100 patient-months) versus the pre-UD era (11.0 VAT/100 patient-months; P = 0.03). The decrease in VAT rates was caused predominantly in the rapid referral period, where the VAT rate dropped to 0.96 VAT/100 patient-months (P < 0.001). Cost of vascular access management was 65% higher ($1264 vs.$765/patient-month) in the pre-UD era, reflecting the increased cost for treatment of VAT.ConclusionsMonthly QAcorr <650 mL/min/1.73 m2 is predictive of imminent VAT in children receiving hemodialysis. Prompt referral for angioplasty of VA with QAcorr <650 mL/min/1.73 m2 leads to decreased VAT rates in children

An Intersectional Lifecourse Lens and Participatory Methods as the Foundations for Co-Designing with and for Minoritised Older Adults

The design of digital technologies for older adults is often premised on deficit models of ageing that position older people as a homogenous group and as passive users of technology, with an overwhelming focus on meeting practical needs in older age. In response, a growing number of scholars in HCI and Science and Technology Studies (STS) are engaging with processes of co-design that situate older adults as experts in their own lives and as central to the design process. These scholars highlight how an essential first phase of co-design is understanding and foregrounding the lifeworlds, experiences and expertise of older adults. This paper responds to these calls, alongside the lack of consideration of minoritised older adults in co-design. It draws on the empirical findings from the first phase of the Connecting Through Culture As We Age project, which places twenty minoritised older adults who identify as disabled, and/or racially and/or socio-economically minoritised, at the centre of a digital innovation process. Through a case study approach, we focus on two of the minoritised older adults involved, to demonstrate the value of bringing together participatory methods with an interdisciplinary lifecourse lens. We highlight the power of this approach for understanding minoritised older adults’ relationships with technology, as shaped by experiences across the lifecourse, for building relationships, and ensuring their agency and voice underpin the co-design process

Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation

Rationale: Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation. Objectives: We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice. Methods: Male mice received paroxetine (10 mg/kg/day, s.c.) for 12 days, then were swapped to saline injections for a 13 day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system. Results Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24 h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation. Conclusions: This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms

Numerical calculation of strong-field laser-atom interaction: An approach with perfect reflection-free radiation boundary conditions

The time-dependent, single-particle Schrodinger equation with a finite-range potential is solved numerically on a three-dimensional spherical domain. In order to correctly account for outgoing waves, perfect reflection-free radiation boundary conditions are used on the surface of a sphere. These are computationally most effective if the particle wavefunction is expanded in the set of spherical harmonics and computations are performed in the Kramers-Henneberger accelerated frame. The method allows one to solve the full ionization dynamics in intense laser fields within a small region of atomic dimensions

Gelsolin Plays a Role in the Actin Polymerization Complex of Hair Cell Stereocilia

A complex of proteins scaffolded by the PDZ protein, whirlin, reside at the stereocilia tip and are critical for stereocilia development and elongation. We have shown that in outer hair cells (OHCs) whirlin is part of a larger complex involving the MAGUK protein, p55, and protein 4.1R. Whirlin interacts with p55 which is expressed exclusively in outer hair cells (OHC) in both the long stereocilia that make up the stereocilia bundle proper as well as surrounding shorter microvilli that will eventually regress. In erythrocytes, p55 forms a tripartite complex with protein 4.1R and glycophorin C promoting the assembly of actin filaments and the interaction of whirlin with p55 indicates that it plays a similar role in OHC stereocilia. However, the components directly involved in actin filament regulation in stereocilia are unknown. We have investigated additional components of the whirlin interactome by identifying interacting partners to p55. We show that the actin capping and severing protein, gelsolin, is a part of the whirlin complex. Gelsolin is detected in OHC where it localizes to the tips of the shorter rows but not to the longest row of stereocilia and the pattern of localisation at the apical hair cell surface is strikingly similar to p55. Like p55, gelsolin is ablated in the whirler and shaker2 mutants. Moreover, in a gelsolin mutant, stereocilia in the apex of the cochlea become long and straggly indicating defects in the regulation of stereocilia elongation. The identification of gelsolin provides for the first time a link between the whirlin scaffolding protein complex involved in stereocilia elongation and a known actin regulatory molecule

Multi-parameter flow cytometry and cell sorting reveal extensive physiological heterogeneity in Bacillus cereus batch cultures.

Based on two staining protocols, DiOC6(3)/ propidium iodide (PI) and RedoxSensor Green (an indicator of bacterial reductase activity)/PI, multiparameter flow cytometry and cell sorting has identified at least four distinguishable physiological states during batch cultures of Bacillus cereus. Furthermore, dependent on the position in the growth curve, single cells gave rise to varying numbers of colonies when sorted individually onto nutrient agar plates. These growing colonies derived from a single cell had widely different lag phases, inferred fromdifferences in colony size.This further highlights the complex population dynamics of bacterial monocultures and further demonstrates that individual bacterial cells in a culture respond in markedly dissimilar ways to the environment, resulting in a physiologically heterogenous and dynamic population

Infant sleep and anxiety disorders in early childhood: Findings from an Australian pregnancy cohort study

Emphasis on continuous infant sleep overnight may be driven by parental concern of risk to child mental health outcomes. The Mercy Pregnancy and Emotional Wellbeing Study (MPEWS) examined whether infant sleep at 6 and 12 months postpartum predicts anxiety disorders at 2–4 years, and whether this is moderated by maternal depression, active physical comforting (APC) or maternal cognitions about infant sleep. Data included 349 women and infants. Infant sleep was measured using the Brief Infant Sleep Questionnaire and child anxiety disorders by the Preschool Age Psychiatric Assessment. The risk of developing generalised anxiety or social phobia disorders at 3–4 years was reduced by 42% (p = 0.001) and 31% (p = 0.001), respectively, for a one standard deviation increase in total sleep at 12 months. No other infant sleep outcomes were associated. Maternal depression, APC and cognitions about infant sleep did not significantly moderate these relationships. Focus may need to be on total infant sleep, rather than when sleep is achieved. Highlights: To assess whether infant sleep outcomes (i.e., frequency of nocturnal wakes; nocturnal wakefulness and total sleep per day) at 6 and 12 months predict early childhood anxiety disorders at 3–4 years of age. Maternally reported infant sleep outcomes were not associated with the risk of developing early childhood anxiety disorders at 3–4 years. It may be total infant sleep, irrespective of when sleep occurs or night waking and, independently, active physical comforting that requires further investigation

Heparanase 2, mutated in urofacial syndrome, mediates peripheral neural development in Xenopus

Urofacial syndrome (UFS; previously Ochoa syndrome) is an autosomal recessive disease characterized by incomplete bladder emptying during micturition. This is associated with a dyssynergia in which the urethral walls contract at the same time as the detrusor smooth muscle in the body of the bladder. UFS is also characterized by an abnormal facial expression upon smiling, and bilateral weakness in the distribution of the facial nerve has been reported. Biallelic mutations in HPSE2 occur in UFS. This gene encodes heparanase 2, a protein which inhibits the activity of heparanase. Here, we demonstrate, for the first time, an in vivo developmental role for heparanase 2. We identified the Xenopus orthologue of heparanase 2 and showed that the protein is localized to the embryonic ventrolateral neural tube where motor neurons arise. Morpholino-induced loss of heparanase 2 caused embryonic skeletal muscle paralysis, and morphant motor neurons had aberrant morphology including less linear paths and less compactly-bundled axons than normal. Biochemical analyses demonstrated that loss of heparanase 2 led to upregulation of fibroblast growth factor 2/phosphorylated extracellular signal-related kinase signalling and to alterations in levels of transcripts encoding neural- and muscle-associated molecules. Thus, a key role of heparanase 2 is to buffer growth factor signalling in motor neuron development. These results shed light on the pathogenic mechanisms underpinning the clinical features of UFS and support the contention that congenital peripheral neuropathy is a key feature of this disorder