Sympathetic nervous system (SNS)-mediated peripheral vasoconstriction plays a key role in initial maintenance of blood pressure during rapid-onset asphyxia in the mammalian fetus, but it is ...attenuated after the first few minutes. It is unclear whether the SNS response is sustained during the brief, but frequently repeated, episodes of asphyxia characteristic of labor. In the present study, 14 fetal sheep at 0.85 of gestation received either chemical sympathectomy with 6-hydroxydopamine (6-OHDA; n = 7) or sham injection (control; n = 7), followed 4-5 days later by repeated 2-min episodes of complete umbilical cord occlusion every 5 min for up to 4 h or until mean arterial blood pressure (MAP) fell to <20 mmHg for two successive occlusions. In controls, umbilical cord occlusions were associated with a rapid initial fall in fetal heart rate (FHR) and femoral blood flow (FBF), with initial hypertension, followed by progressive development of hypotension during ongoing occlusions. Sympathectomy was associated with attenuation of the initial rise in MAP during umbilical cord occlusion, and after the onset of hypotension, a markedly more rapid fall of MAP to the nadir, with a correspondingly slower fall in FBF (P < 0.05). In contrast, MAP and FHR between successive occlusions were higher after sympathectomy (P < 0.05). There was no significant difference in the number of occlusions before terminal hypotension (6-OHDA; 16.1 ± 2.2 vs. control; 18.7 ± 2.3). These data show that SNS activity provides ongoing support for fetal MAP during prolonged exposure to brief repeated asphyxia.
Objective To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management.Design ...Multicentre, parallel group, observer blind, randomised controlled trial. Setting 39 UK hospitals, recruiting from June 2009 to November 2012.Participants 121 patients (73 women, mean age 54 years) with clinician diagnosed pyoderma gangrenosum. Clinical diagnosis was revised in nine participants after randomisation, leaving 112 participants in the analysis set (59 ciclosporin; 53 prednisolone).Intervention Oral prednisolone 0.75 mg/kg/day compared with ciclosporin 4 mg/kg/day, to a maximum dose of 75 and 400 mg/day, respectively.Main outcome measures The primary outcome was speed of healing over six weeks, captured using digital images and assessed by blinded investigators. Secondary outcomes were time to healing, global treatment response, resolution of inflammation, self reported pain, quality of life, number of treatment failures, adverse reactions, and time to recurrence. Outcomes were assessed at baseline and six weeks and when the ulcer had healed (to a maximum of six months).Results Of the 112 participants, 108 had complete primary outcome data at baseline and six weeks (57 ciclosporin; 51 prednisolone). Groups were balanced at baseline. The mean (SD) speed of healing at six weeks was −0.21 (1.00) cm2/day in the ciclosporin group compared with −0.14 (0.42) cm2/day in the prednisolone group. The adjusted mean difference showed no between group difference (0.003 cm2/day, 95% confidence interval −0.20 to 0.21; P=0.97). By six months, ulcers had healed in 28/59 (47%) participants in the ciclosporin group compared with 25/53 (47%) in the prednisolone group. In those with healed ulcers, eight (30%) receiving ciclosporin and seven (28%) receiving prednisolone had a recurrence. Adverse reactions were similar for the two groups (68% ciclosporin and 66% prednisolone), but serious adverse reactions, especially infections, were more common in the prednisolone group.Conclusion Prednisolone and ciclosporin did not differ across a range of objective and patient reported outcomes. Treatment decisions for individual patients may be guided by the different side effect profiles of the two drugs and patient preference. Trial registration Current Controlled Trials ISRCTN35898459.
Although pain itself induces negative affect, the removal (or offset) of pain induces a powerful state of relief. Despite being implicated in a wide range of psychological and behavioral phenomena, ...relief remains a poorly understood emotion. In particular, some theorists associate relief with increased positive affect, whereas others associate relief with diminished negative affect. In the present study, we examined the affective nature of relief in a pain-offset paradigm with psychophysiological measures that were specific to negative valence (startle eyeblink reactivity) and positive valence (startle postauricular reactivity). Results revealed that pain offset simultaneously stimulates positive affect and diminishes negative affect for at least several seconds. Results also indicated that pain intensity differentially affects the positive and negative valence aspects of relief.These findings clarify the affective nature of relief and provide insight into why people engage in both normal and abnormal behaviors associated with relief.
Abstract Objective The purpose of this study is to review the available literature that describes forces of the most commonly used chiropractic techniques for children. Methods Review of the ...English-language literature using search terms Chiropract* and technique, protocol, or approach in databases PubMed, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine, and Index to Chiropractic Literature and direct contact with authors of articles and book chapters. Results Eleven articles that discussed the 7 most commonly used pediatric chiropractic techniques and the forces applied were identified. Chiropractic techniques reviewed described forces that were modified based on the age of the patient. Force data for mechanically assisted devices were varied, with the minimum force settings for some devices outside the age-specific safe range recommended in the literature when not modified in some way. Conclusion This review found that technique selection and application by chiropractors treating infants and young children are typically modified in force and speed to suit the age and development of the child.
Abstract Fusion crusts form during the atmospheric entry heating of meteorites and preserve a record of the conditions that occurred during deceleration in the atmosphere. The fusion crust of the ...Winchcombe meteorite closely resembles that of other stony meteorites, and in particular CM2 chondrites, since it is dominated by olivine phenocrysts set in a glassy mesostasis with magnetite, and is highly vesicular. Dehydration cracks are unusually abundant in Winchcombe. Failure of this weak layer is an additional ablation mechanism to produce large numbers of particles during deceleration, consistent with the observation of pulses of plasma in videos of the Winchcombe fireball. Calving events might provide an observable phenomenon related to meteorites that are particularly susceptible to dehydration. Oscillatory zoning is observed within olivine phenocrysts in the fusion crust, in contrast to other meteorites, perhaps owing to temperature fluctuations resulting from calving events. Magnetite monolayers are found in the crust, and have also not been previously reported, and form discontinuous strata. These features grade into magnetite rims formed on the external surface of the crust and suggest the trapping of surface magnetite by collapse of melt. Magnetite monolayers may be a feature of meteorites that undergo significant degassing. Silicate warts with dendritic textures were observed and are suggested to be droplets ablated from another stone in the shower. They, therefore, represent the first evidence for intershower transfer of ablation materials and are consistent with the other evidence in the Winchcombe meteorite for unusually intense gas loss and ablation, despite its low entry velocity.
Agricultural expansion is a primary driver of biodiversity decline in forested regions of the tropics. Consequently, it is important to understand the conservation value of remnant forests in ...production landscapes. In a tropical landscape dominated by oil palm (Elaeis guineensis), we characterized faunal communities across eight taxa occurring within riparian forest buffers, which are legally protected alongside rivers, and compared them to nearby recovering logged forest. Buffer width was the main predictor of species richness and abundance, with widths of 40–100 m on each side of the river supporting broadly equivalent levels of biodiversity as compared to logged forest. However, width responses varied markedly among taxa, and buffers often lacked forest‐dependent species. Much wider buffers than are currently mandated are needed to safeguard most species. The largest biodiversity gains are achieved by increasing relatively narrow buffers. To provide optimal conservation outcomes in tropical production landscapes, we encourage policy makers to prescribe width requirements for key taxa and different landscape contexts.
Mass spectrometry is an important analytical technique
within the field of atmospheric chemistry. Owing to advances in
instrumentation, particularly with regards to mass-resolving power and
...instrument response factors (sensitivities), hundreds of different
mass-to-charge (m/z) signals are routinely measured. This large number of
detected ions creates challenges for data visualization. Furthermore,
assignment of chemical formulas to these ions is time consuming and
increases in difficulty at the higher m/z ranges. Here, we describe generalized
Kendrick analysis (GKA) to facilitate the visualization and peak
identification processes for typical atmospheric organic (and to some extent
inorganic) compounds. GKA is closely related to resolution-enhanced Kendrick
mass defect analysis (REKMD), which introduces a tunable integer into the
Kendrick equation that effectively contracts or expands the mass scale. A
characteristic of all Kendrick analysis methods is that these changes
maintain the horizontal alignment of ion series related by integer multiples
of the chosen base unit. Compared to traditional Kendrick analysis, GKA and
REKMD use a tunable parameter (“scaling factor”) to alter the mass defect
spacing between different homologue ion series. As a result, the entire mass
defect range (−0.5 to 0.5) is more effectively used simplifying data
visualization and facilitating chemical formula assignment. We describe the
mechanism of this transformation and discuss base unit and scaling factor
selections appropriate for compounds typically found in atmospheric
measurements. We present an open-source graphical user interface (GUI) for
calculating and visualizing GKA results within the Igor Pro environment.
Manual interpretation of variants remains rate limiting in precision oncology. The increasing scale and complexity of molecular data generated from comprehensive sequencing of cancer samples requires ...advanced interpretative platforms as precision oncology expands beyond individual patients to entire populations. To address this unmet need, we introduce a Platform for Oncogenomic Reporting and Interpretation (PORI), comprising an analytic framework that facilitates the interpretation and reporting of somatic variants in cancer. PORI integrates reporting and graph knowledge base tools combined with support for manual curation at the reporting stage. PORI represents an open-source platform alternative to commercial reporting solutions suitable for comprehensive genomic data sets in precision oncology. We demonstrate the utility of PORI by matching 9,961 pan-cancer genome atlas tumours to the graph knowledge base, calculating therapeutically informative alterations, and making available reports describing select individual samples.
Clinical trial managers play a vital role in the design and conduct of clinical trials in the UK. There is a current recruitment and retention crisis for this specialist role due to a complex set of ...factors, most likely to have come to a head due to the COVID-19 pandemic. Academic clinical trial units and departments are struggling to recruit trial managers to vacant positions, and multiple influences are affecting the retention of this highly skilled workforce. Without tackling this issue, we face major challenges in the delivery on the Department of Health and Social Care's Future of UK Clinical Research Delivery implementation plan. This article, led by a leading network of and for UK Trial Managers, presents some of the issues and ways in which national stakeholders may be able to address this.
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