Breeding and Selecting Corals Resilient to Global Warming.

Selective breeding of resilient organisms is an emerging topic in marine conservation. It can help us predict how species will adapt in the future and how we can help restore struggling populations effectively in the present. Scleractinian corals represent a potential tractable model system given their widescale phenotypic plasticity across fitness-related traits and a reproductive life history based on mass synchronized spawning. Here, I explore the justification for breeding in corals, identify underutilized pathways of acclimation, and highlight avenues for quantitative targeted breeding from the coral host and symbiont perspective. Specifically, the facilitation of enhanced heat tolerance by targeted breeding of plasticity mechanisms is underutilized. Evidence from theoretical genetics identifies potential pitfalls, including inattention to physical and genetic characteristics of the receiving environment. Three criteria for breeding emerge from this synthesis: selection from warm, variable reefs that have survived disturbance. This information will be essential to protect what we have and restore what we can.

Predictive models for the selection of thermally tolerant corals based on offspring survival.

Finding coral reefs resilient to climate warming is challenging given the large spatial scale of reef ecosystems. Methods are needed to predict the location of corals with heritable tolerance to high temperatures. Here, we combine Great Barrier Reef-scale remote sensing with breeding experiments that estimate larval and juvenile coral survival under exposure to high temperatures. Using reproductive corals collected from the northern and central Great Barrier Reef, we develop forecasting models to locate reefs harbouring corals capable of producing offspring with increased heat tolerance of an additional 3.4° heating weeks (~3 °C). Our findings predict hundreds of reefs (~7.5%) may be home to corals that have high and heritable heat-tolerance in habitats with high daily and annual temperature ranges and historically variable heat stress. The locations identified represent targets for protection and consideration as a source of corals for use in restoration of degraded reefs given their potential to resist climate change impacts and repopulate reefs with tolerant offspring.

Daily physical activity and sleep in veterans: the role of insomnia severity.

Physical activity (PA) is suggested as an easily accessible adjunctive lifestyle intervention for insomnia. It is not clear if PA is equally beneficial across different levels of insomnia severity. The current study examined the relationship between daily PA (steps) and sleep (duration, efficiency, and quality) across the spectrum of insomnia severity. Multilevel models estimated day-to-night relationships between PA and sleep, and if insomnia severity moderated these relationships. Days with greater PA were associated with nights with longer sleep duration. This was moderated by insomnia severity; PA was associated with longer sleep that night in participants with mild insomnia and associated with less sleep in those with severe insomnia. PA was not associated with sleep efficiency or quality. PA is potentially an easily accessible and impactful intervention to promote sleep duration in participants who are experiencing less severe sleep disturbance. More complex, resource-intensive interventions may be needed as insomnia severity increases.

Assessing the role of historical temperature regime and algal symbionts on the heat tolerance of coral juveniles.

The rate of coral reef degradation from climate change is accelerating and, as a consequence, a number of interventions to increase coral resilience and accelerate recovery are under consideration. Acropora spathulata coral colonies that survived mass bleaching in 2016 and 2017 were sourced from a bleaching-impacted and warmer northern reef on the Great Barrier Reef (GBR). These individuals were reproductively crossed with colonies collected from a recently bleached but historically cooler central GBR reef to produce pure and crossbred offspring groups (warm-warm, warm-cool and cool-warm). We tested whether corals from the warmer reef produced more thermally tolerant hybrid and purebred offspring compared with crosses produced with colonies sourced from the cooler reef and whether different symbiont taxa affect heat tolerance. Juveniles were infected with Symbiodinium tridacnidorum, Cladocopium goreaui and Durusdinium trenchii and survival, bleaching and growth were assessed at 27.5°C and 31°C. The contribution of host genetic background and symbiont identity varied across fitness traits. Offspring with either both or one parent from the northern population exhibited a 13- to 26-fold increase in survival odds relative to all other treatments where survival probability was significantly influenced by familial cross identity at 31°C but not 27.5°C (Kaplan-Meier P=0.001 versus 0.2). If in symbiosis with D. trenchii, a warm sire and cool dam provided the best odds of juvenile survival. Bleaching was predominantly driven by Symbiodiniaceae treatment, where juveniles hosting D. trenchii bleached significantly less than the other treatments at 31°C. The greatest overall fold-benefits in growth and survival at 31°C occurred in having at least one warm dam and in symbiosis with D. trenchii Juveniles associated with D. trenchii grew the most at 31°C, but at 27.5°C, growth was fastest in juveniles associated with C. goreaui In conclusion, selective breeding with warmer GBR corals in combination with algal symbiont manipulation can assist in increasing thermal tolerance on cooler but warming reefs. Such interventions have the potential to improve coral fitness in warming oceans.This article has an associated First Person interview with the first author of the paper.

In vitro release of fentanyl from transdermal patches in gastric and intestinal fluid.

CONTEXT. Fentanyl patches are intended for transdermal use to treat pain. However, these patches have been abused by ingestion, offering a unique mode of drug delivery with unknown drug release characteristics. OBJECTIVES. In vitro fentanyl release from patches in simulated gastric and intestinal fluid was evaluated. MATERIALS AND METHODS. Ten 75 mcg/hr fentanyl transdermal patches (Mylan Pharmaceuticals Inc., Morgantown, WV), simulated gastric fluid without enzymes, and USP simulated intestinal fluid (Ricca Chemical Company, Arlington, TX) were obtained. Each fentanyl patch was placed into either 100 mL of simulated gastric fluid or 100 mL of simulated intestinal fluid. Flasks were agitated at 24 rpm while incubated at 36.8°C. Fluid was sampled at time zero and 5, 15, 30, 60, 120, and 180 min after submersion. Fentanyl was assayed using ultra performance liquid chromatography coupled with tandem mass spectrometry (AIT Laboratories, Indianapolis, IN). RESULTS. An average of 239 mcg and 1,962 mcg of fentanyl was released into gastric fluid and 338 mcg and 3,139 mcg into intestinal fluid in 5 min and 3 h, respectively. An average of 26% and 41% of 7.65 mg of fentanyl contained within the 75 mcg/hr patch was released into gastric and intestinal fluid in 3 h, respectively (p = 0.169, Student's t-test). DISCUSSION. Our results demonstrate fentanyl release within 5 min of submersion. CONCLUSION. These results help support the potential rapid onset of clinical compromise reported and are relevant to the design of future pharmacokinetic studies of fentanyl release from transdermal patches.

Immune mechanisms and the impact of the disrupted lung microbiome in chronic bacterial lung infection and bronchiectasis.

Recent studies analysing immunogenetics and immune mechanisms controlling susceptibility to chronic bacterial infection in bronchiectasis implicate dysregulated immunity in conjunction with chronic bacterial infection. Bronchiectasis is a structural pathological end-point with many causes and disease associations. In about half of cases it is termed idiopathic, because it is of unknown aetiology. Bronchiectasis is proposed to result from a 'vicious cycle' of chronic bacterial infection and dysregulated inflammation. Paradoxically, both immune deficiency and excess immunity, either in the form of autoimmunity or excessive inflammatory activation, can predispose to disease. It appears to be a part of the spectrum of inflammatory, autoimmune and atopic conditions that have increased in prevalence through the 20th century, attributed variously to the hygiene hypothesis or the 'missing microbiota'. Immunogenetic studies showing a strong association with human leucocyte antigen (HLA)-Cw*03 and HLA-C group 1 homozygosity and combinational analysis of HLA-C and killer immunoglobulin-like receptors (KIR) genes suggests a shift towards activation of natural killer (NK) cells leading to lung damage. The association with HLA-DR1, DQ5 implicates a role for CD4 T cells, possibly operating through influence on susceptibility to specific pathogens. We hypothesize that disruption of the lung microbial ecosystem, by infection, inflammation and/or antibiotic therapy, creates a disturbed, simplified, microbial community ('disrupted microbiota') with downstream consequences for immune function. These events, acting with excessive NK cell activation, create a highly inflammatory lung environment that, in turn, permits the further establishment and maintenance of chronic infection dominated by microbial pathogens. This review discusses the implication of these concepts for the development of therapeutic interventions.

Autologous non-myeloablative haematopoietic stem cell transplantation for refractory systemic vasculitis.

OBJECTIVE: For patients with systemic vasculitis (SV) refractory to conventional therapy, new treatment strategies aimed at aggressive induction of remission and relapse prevention are being sought. We herein report our single-centre experience in treating four patients with refractory SV employing non-myeloablative autologous haematopoietic stem cell transplantation (HSCT). METHODS: Four patients with refractory SV (two with neurovascular Behcet disease, one with neurovascular Sjögren syndrome, and one with Wegener granulomatosis) were involved in an Institutional Review Board (IRB) and US Food and Drug Administration (FDA) approved phase I clinical trial of high dose chemotherapy and autologous HSCT. Peripheral blood stem cells were mobilised with cyclophosphamide (Cy) and granulocyte-colony stimulating factor (G-CSF). Conditioning regimen consisted of Cy 200 mg/kg and rabbit anti-thymocyte globulin 5.5 mg/kg intravenously (iv). RESULTS: All four patients tolerated HSCT well without transplant related mortality or any significant toxicity. At median follow-up of 28 (range 22-36) months all patients were alive. Three patients (one with Behcet disease, one with Sjögren syndrome, and one with Wegener granulomatosis) entered a sustained remission at 6, 6 and 24 months, respectively, after transplant. They had significant decrease in disease activity and disease or treatment related damage, as measured by the Birmingham Vasculitis Activity Score and Vasculitis Damage Index, respectively. All three patients who achieved remission discontinued immunosuppressive therapy at the time of transplant and have not required treatment since. One patient with Behcet disease and positive for human leukocyte antigen (HLA)-B51 has not improved after HSCT. CONCLUSION: We suggest non-myeloablative autologous HSCT is an alternative therapy for select patients with SV refractory to conventional immunosuppressive therapies.

Autologous hematopoietic stem cell transplantation in systemic lupus erythematosus patients with cardiac dysfunction: feasibility and reversibility of ventricular and valvular dysfunction with transplant-induced remission.

Patients with cardiac dysfunction may be at increased risk of cardiac toxicity when undergoing hematopoietic stem cell transplantation (HSCT), which may preclude them from receiving this therapy. Cardiac dysfunction is, however, common in systemic lupus erythematosus (SLE) patients. While autologous HSCT (auto-HSCT) has been performed increasingly for SLE, its impact on cardiac function has not previously been evaluated. We, therefore, performed a retrospective analysis of SLE patients who had undergone auto-HSCT in our center to determine the prevalence of significant cardiac involvement, and the impact of transplantation on this. The records of 55 patients were reviewed, of which 13 were found to have abnormal cardiac findings on pre-transplant two-dimensional echocardiography or multi-gated acquisition scan: impaired left ventricular ejection fraction (LVEF) (n = 6), pulmonary hypertension (n = 5), mitral valve dysfunction (n = 3) and large pericardial effusion (n = 1). At a median follow-up of 24 months (8-105 months), there were no transplant-related or cardiac deaths. With transplant-induced disease remission, all patients with impaired LVEF remained stable or improved; while three with symptomatic mitral valve disease similarly improved. Elevated pulmonary pressures paralleled activity of underlying lupus. These data suggest that auto-HSCT is feasible in selected patients with lupus-related cardiac dysfunction, and with control of disease activity, may improve.

Mobilization, harvesting and selection of peripheral blood stem cells in patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation.

Peripheral blood stem cells (PBSC) were mobilized in 130 patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation using cyclophosphamide 2 g/m(2) and either granulocyte colony-stimulating factor (G-CSF) 5 mcg/kg/day (for systemic lupus erythematosus (SLE) and secondary progressive multiple sclerosis, SPMS) or G-CSF 10 mcg/kg/day (for relapsing remitting multiple sclerosis (RRMS), Crohn's disease (CD), systemic sclerosis (SSc), and other immune-mediated disorders). Mobilization-related mortality was 0.8% (one of 130) secondary to infection. Circulating peripheral blood (PB) CD34(+) cells/microl differed significantly by disease. Collected CD34(+) cells/kg/apheresis and overall collection efficiency was significantly better using Spectra apheresis device compared to the Fenwall CS3000 instrument. Patients with SLE and RRMS achieved the lowest and the highest CD34(+) cell yields, respectively. Ex vivo CD34(+) cell selection employing Isolex 300iv2.5 apparatus was significantly more efficient compared to CEPRATE CS device. Circulating PB CD34(+) cells/microl correlated positively with initial CD34(+) cells/kg/apheresis and enriched product CD34(+) cells/kg. Mean WBC and platelet engraftment (ANC>0.5 x 10(9)/l and platelet count >20 x 10(9)/l) occurred on days 9 and 11, respectively. Infused CD34(+) cell/kg dose showed significant direct correlation with faster white blood cell (WBC) and platelet engraftment. When adjusted for CD34(+) cell/kg dose, patients treated with a myeloablative regimen had significantly slower WBC and platelet recovery compared to non-myeloablative regimens.

Continuous measurement of BRSI in chronic fatigue syndrome.

This paper discusses the development of a system to measure continuous cardiac baroreceptor measurement during a 45-minute 70-degree head-up tilt (HUT) of five groups of subjects suffering the following: chronic fatigue syndrome (CFS), CFS with fibromyalgia (CFS-FM), CFS with postural orthostatic tachycardia syndrome (CFS-POTS), controls with POTS (CON-POTS), and controls (CON). The duration of the test was 56-minutes, which included a five-minute supine baseline, a 45-minute HUT and a six-minute recovery period. The system was developed in LabView, and can provide a comparative time analyses of weighted BRSI averages. Baroreflex effectiveness index (BEI) was also investigated over the course of lags 0, 1 and 2 as well as an assessment of overall BEI performance between groups.

Hematopoietic stem cell transplantation for systemic sclerosis with rapid improvement in skin scores: is neoangiogenesis occurring?

Systemic sclerosis (SSc) is presumed to be an immune-mediated vasculopathy of unknown etiology. SSc is unresponsive to most immune-modulating therapies except for intravenous cyclophosphamide, which is reported to demonstrate some benefit. We, therefore, dose-escalated cyclophosphamide to 200 mg/kg and added rabbit ATG 7.5 mg/kg along with infusion of unselected hematopoietic stem cells to minimize the cytopenic interval. Engraftment occurred rapidly (day 8) with minimal unexpected toxicity, no infections, and unexpectedly rapid improvement in the modified Rodnan Skin Score.

Application of a direct flow cytometric erythrocyte immunofluorescence assay in dogs with immune-mediated hemolytic anemia and comparison to the direct antiglobulin test.

A direct flow cytometric erythrocyte immunofluorescence assay (FC) was developed and compared with the direct antiglobulin test (DAT) for detection of erythrocyte-bound immunoglobulin (IgG and IgM) and complement (C3) in dogs with immune-mediated hemolytic anemia (IMHA). Tests were performed on erythrocytes from 13 healthy nonanemic dogs and from 13 anemic dogs with IMHA. The FC and DAT were negative for erythrocyte-bound immunoglobulin in all healthy dogs. The FC was negative for erythrocyte-bound C3 in 12 healthy dogs and positive in 1 healthy dog, and the DAT was negative for C3 in all healthy dogs. Of the 13 IMHA dogs tested for erythrocyte-bound IgG, 12 were positive using the FC and 7 were positive using the DAT. Sensitivity for the detection of erythrocyte-bound IgG in the 26 dogs was 92% for FC and 53% for DAT. Specificity for detection of erythrocyte bound IgG for FC and DAT was 100%. The addition of IgM and/ or C3 did not increase the sensitivity for FC or DAT. In this group of dogs, the FC provided a more rapid, cost-effective, sensitive, objective method to quantitate erythrocyte-bound immunoglobulin and/or complement compared with the currently used DAT.

Gastric myoelectrical and autonomic cardiac reactivity to laboratory stressors.

We evaluated the effects of two laboratory stressors (speech preparation and isometric handgrip) on gastric myoelectrical and autonomic cardiac activity, and the extent to which autonomic responses to these stressors and somatization predict reports of motion sickness during exposure to a rotating optokinetic drum. Both stressors prompted a decrease in preejection period (PEP) and respiratory sinus arrhythmia (RSA), and an increase in a dysrhythmic pattern of gastric myoelectrical activity, termed gastric tachyarrhythmia. Stressor-induced decreases in RSA and higher somatization scores predicted increased reports of motion sickness during drum rotation. These results demonstrate that laboratory stressors concurrently affect gastric myoelectrical activity and autonomic control of the heart, and that stressor-induced decreases in RSA and higher levels of somatization predict motion sickness susceptibility.

Feeling your body or feeling badly: evidence for the limited validity of the Somatosensory Amplification Scale as an index of somatic sensitivity.

OBJECTIVE: The Somatosensory Amplification Scale (SSAS) purports to measure the extent to which individuals are sensitive to their bodies. The present study examined the psychometric properties of the SSAS in two studies with university students. METHODS: Participants completed the SSAS, various cross-sectional measures of somatic and psychological distress, longitudinal measures of somatic symptoms, daily hassles and mood, and participated in a heartbeat detection task (Study 2 only). RESULTS: The SSAS was correlated with cross-sectional measures of somatic symptom reporting, but not with somatic symptoms reported on a daily basis nor with an index of interoceptive sensitivity. The SSAS was also correlated with several indices of general distress including anxious and depressive symptoms, daily hassles, and negative emotionality. CONCLUSION: Taken together, the results suggest that the SSAS is more likely an index of negative emotionality and general distress than a valid measure of somatic sensitivity per se.

Autonomic origins of a nonsignal stimulus-elicited bradycardia and its habituation in humans.

The purposes of the present study were to determine the autonomic origins of a bradycardiac response to a moderate intensity nonsignal auditory stimulus and the changes in autonomic cardiac control of this response as a function of habituation. Pure tone stimuli were repeatedly presented to participants while phasic changes in heart period (HP), preejection period (PEP), and respiratory sinus arrhythmia (RSA) were observed. Tone stimuli initially elicited an increase in HP, an increase in RSA, and a decrease in PEP, suggesting a coactivation of the parasympathetic and sympathetic inputs mediating changes in the bradycardiac HP response. As expected, HP responses habituated with repeated presentations of the tones. PEP and RSA responses, however, demonstrated different habituation rates than HP. These data demonstrate that cardiodeceleratory responses to nonsignal stimuli can arise from changes in activity of both autonomic divisions and document the importance of considering the autonomic origins of habituating cardiac responses in order to fully understand the process of response habituation.

Management of hospital outbreaks of gastro-enteritis due to small roundstructured viruses.

Small round structured viruses (SRSVs, Norwalk-like viruses, NLVs) are the most common cause of outbreaks of gastro-enteritis in hospitals and also cause outbreaks in other settings such as schools, hotels, nursing homes and cruise ships. Hospital outbreaks often lead to ward closure and major disruption in hospital activity. Outbreaks usually affect both patients and staff, sometimes with attack rates in excess of 50%. For this reason, staff shortages can be severe, particularly if several wards are involved at the same time. SRSVs may be spread by several routes: faecal-oral; vomiting/aerosols; food and water. Viruses may be introduced into the ward environment by any of these routes and then propagated by person-to-person spread. In an outbreak setting, the diagnosis can usually be made rapidly and confidently on clinical and epidemiological grounds, particularly if vomiting is a prominent symptom. By the time an SRSV outbreak has been recognized at ward level, most susceptible individuals will have been exposed to the virus and infection control efforts must prioritize the prevention of spread of infection to other clinical areas bycontainment of infected/exposed individuals (especially the prevention of patient and staff movements to other areas), hand-hygiene and effective environmental decontamination. This report of the Public Health Laboratory Service Viral Gastro-enteritis Working Group reviews the epidemiology of outbreaks of infection due to SRSVs and makes recommendations for their management in the hospital setting. The basic principles which underpin these recommendations will also be applicable to the management of some community-based institutional outbreaks.

Cardiovascular reactivity during hypnosis and hypnotic susceptibility: three studies of heart rate variability.

This paper was designed to examine the relationship between hypnotic susceptibility and cardiovascular measures, especially parasympathetic activity, in 3 separate studies. In these studies, neither heart rate nor heart rate variability differed between the high and low hypnotically susceptible individuals at the initial baseline. Furthermore, in the first study, experimental tasks designed to elicit differential sympathetic and parasympathetic cardiac responses demonstrated no interaction with hypnotic susceptibility. Overall, these 3 studies suggest that hypnotic susceptibility in itself is not associated with parasympathetic aspects of either basal cardiac states or cardiac responses. In addition, a hypnotic induction itself did not differentially influence parasympathetic activity for the high versus low susceptible individuals.

A voice-enabled, structured medical reporting system.

Kurzweil Applied Intelligence received a research grant from the National Institute of Standards and Technology (NIST) Advanced Technology Program to develop a prototype voice-enabled, structured medical reporting system. In typical usage, the physician dictates to the system, which then uses automatic speech recognition and medical knowledge bases to produce a structured report. This report can then be formatted and viewed on a computer screen, stored in databases of patient information, transmitted to other systems, used to support outcome studies, or viewed on a Web browser. The output reports are structured according to two standard, platform-independent formats: SGML and CORBA. These formats represent the data in a way that can be read by both computers and humans, and efficiently communicated to a wide range of databases and communications protocols.