Somatosympathetic Vasoconstrictor Reflexes in Human Spinal Cord Injury: Responses to Innocuous and Noxious Sensory Stimulation below Lesion

It is known that the sudden increases in blood pressure associated with autonomic dysreflexia in people with spinal cord injury (SCI) are due to a spinally mediated reflex activation of sympathetic vasoconstrictor neurons supplying skeletal muscle and the gut. Apart from visceral inputs, such as those originating from a distended bladder, there is a prevailing opinion that autonomic dysreflexia can be triggered by noxious stimulation below the lesion. However, do noxious inputs really cause an increase in blood pressure in SCI? Using microelectrodes inserted into a peripheral nerve to record sympathetic nerve activity we had previously shown that selective stimulation of small-diameter afferents in muscle or skin, induced by bolus injection of hypertonic saline into the tibialis anterior muscle or the overlying skin, evokes a sustained increase in muscle sympathetic nerve activity and blood pressure and a transient increase in skin sympathetic nerve activity and decrease in skin blood flow in able-bodied subjects. We postulated that these sympathetic responses would be exaggerated in SCI, with a purely noxious stimulus causing long-lasting increases in blood pressure and long-lasting decreases in skin blood flow. Surprisingly, though, we found that intramuscular or subcutaneous injection of hypertonic saline into the leg caused negligible changes in these parameters. Conversely, weak electrical stimulation over the abdominal wall, which in able-bodied subjects is not painful and activates large-diameter cutaneous afferents, caused a marked increase in blood pressure in SCI but not in able-bodied subjects. This suggests that it is activation of large-diameter somatic afferents, not small-diameter afferents, that triggers increases in sympathetic outflow in SCI. Whether the responses to activation of large-diameter afferents reflect plastic changes in the spinal cord in SCI is unknown

Composite nature of fresh skin revealed during compression

Biological systems are subjected to moderate-to-high strain rates in blast-type traumatic injuries. An improved understanding of the responses of cells and tissues to extreme mechanical stresses could improve mitigation and post-injury treatment strategies. A key aim of this research is to create biologically meaningful injury models of soft tissues. Here the authors examine the material and cellular properties of freshly harvested porcine skin in compression. The data presented suggest that fresh skin differentially responds low to moderate strain rates as a composite rather than that of a homogeneous polymer. The implications of this work are discussed in terms of creating improved analytical models to describe the material properties of fresh skin. The Centre for Blast Injury Studies acknowledges The Royal British Legion for its support, as well as Imperial College London. The Institute of Shock Physics acknowledges the support of the Atomic Weapon Establishment, Aldermaston, UK and Imperial College London.This is the accepted manuscript. The final version is available at http://www.icevirtuallibrary.com/content/article/10.1680/bbn.14.00028

Interactions among multiple stressors vary with exposure duration and biological response

Coastal ecosystems are exposed to multiple anthropogenic stressors. Effective management actions would be better informed from generalized predictions of the individual, combined and interactive effects of multiple stressors; however, few generalities are shared across different meta-analyses. Using an experimental study, we present an approach for analysing regression-based designs with generalized additive models that allowed us to capture nonlinear effects of exposure duration and stressor intensity and access interactions among stressors. We tested the approach on a globally distributed marine diatom, using 72 h photosynthesis and growth assays to quantify the individual and combined effects of three common water quality stressors; photosystem II-inhibiting herbicide exposure, dissolved inorganic nitrogen (DIN) enrichment and reduced light (due to excess suspended sediment). Exposure to DIN and reduced light generally resulted in additivity, while exposure to diuron and reduced light resulted in additive, antagonistic or synergistic interactions, depending on the stressor intensity, exposure period and biological response. We thus find the context of experimental studies to be a primary driver of interactions. The experimental and modelling approaches used here bridge the gap between two-way designs and regression-based studies, which provides a way forward to identify generalities in multiple stressor interactions

Physician decision making in selection of second-line treatments in immune thrombocytopenia in children.

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians

Motivational interviewing for screening and feedback and encouraging lifestyle changes to reduce relative weight in 4-8 year old children: design of the MInT study

<p>Abstract</p> <p>Background</p> <p>Because parental recognition of overweight in young children is poor, we need to determine how best to inform parents that their child is overweight in a way that enhances their acceptance and supports motivation for positive change. This study will assess 1) whether weight feedback delivered using motivational interviewing increases parental acceptance of their child's weight status and enhances motivation for behaviour change, and 2) whether a family-based individualised lifestyle intervention, delivered primarily by a MInT mentor with limited support from "expert" consultants in psychology, nutrition and physical activity, can improve weight outcomes after 12 and 24 months in young overweight children, compared with usual care.</p> <p>Methods/Design</p> <p>1500 children aged 4-8 years will be screened for overweight (height, weight, waist, blood pressure, body composition). Parents will complete questionnaires on feeding practices, physical activity, diet, parenting, motivation for healthy lifestyles, and demographics. Parents of children classified as overweight (BMI ≥ CDC 85^th) will receive feedback about the results using Motivational interviewing or Usual care. Parental responses to feedback will be assessed two weeks later and participants will be invited into the intervention. Additional baseline measurements (accelerometry, diet, quality of life, child behaviour) will be collected and families will be randomised to Tailored package or Usual care. Parents in the Usual care condition will meet once with an advisor who will offer general advice regarding healthy eating and activity. Parents in the Tailored package condition will attend a single session with an "expert team" (MInT mentor, dietitian, physical activity advisor, clinical psychologist) to identify current challenges for the family, develop tailored goals for change, and plan behavioural strategies that best suit each family. The mentor will continue to provide support to the family via telephone and in-person consultations, decreasing in frequency over the two-year intervention. Outcome measures will be obtained at baseline, 12 and 24 months.</p> <p>Discussion</p> <p>This trial offers a unique opportunity to identify effective ways of providing feedback to parents about their child's weight status and to assess the efficacy of a supportive, individualised early intervention to improve weight outcomes in young children.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry ACTRN12609000749202</p

Discovery and Early Evolution of ASASSN-19bt, the First TDE Detected by TESS

We present the discovery and early evolution of ASASSN-19bt, a tidal disruption event (TDE) discovered by the All-Sky Automated Survey for Supernovae (ASAS-SN) at a distance of $d\simeq115$ Mpc and the first TDE to be detected by TESS. As the TDE is located in the TESS Continuous Viewing Zone, our dataset includes 30-minute cadence observations starting on 2018 July 25, and we precisely measure that the TDE begins to brighten $\sim8.3$ days before its discovery. Our dataset also includes 18 epochs of Swift UVOT and XRT observations, 2 epochs of XMM-Newton observations, 13 spectroscopic observations, and ground data from the Las Cumbres Observatory telescope network, spanning from 32 days before peak through 37 days after peak. ASASSN-19bt thus has the most detailed pre-peak dataset for any TDE. The TESS light curve indicates that the transient began to brighten on 2019 January 21.6 and that for the first 15 days its rise was consistent with a flux $\propto t^2$ power-law model. The optical/UV emission is well-fit by a blackbody SED, and ASASSN-19bt exhibits an early spike in its luminosity and temperature roughly 32 rest-frame days before peak and spanning up to 14 days that has not been seen in other TDEs, possibly because UV observations were not triggered early enough to detect it. It peaked on 2019 March 04.9 at a luminosity of $L\simeq1.3\times10^{44}$ ergs s$^{-1}$ and radiated $E\simeq3.2\times10^{50}$ ergs during the 41-day rise to peak. X-ray observations after peak indicate a softening of the hard X-ray emission prior to peak, reminiscent of the hard/soft states in X-ray binaries.Comment: 23 pages, 14 figures, 5 tables. A machine-readable table containing the host-subtracted photometry presented in this manuscript is included as an ancillary fil