Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure

Rationale: In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO2 and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited. Objectives: We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance “strength”) rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects. Methods: In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2 stimulation. Measurements and Main Results: Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain—consequent to increased chemosensitivity and delay—the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = −0.68) oscillations (P < 0.001 for all, both groups combined). Conclusions: Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population

Marine plastics threaten giant Atlantic Marine Protected Areas.

There has been a recent shift in global perception of plastics in the environment, resulting in a call for greater action. Science and the popular media have highlighted plastic as an increasing stressor [1,2]. Efforts have been made to confer protected status to some remote locations, forming some of the world's largest Marine Protected Areas, including several UK overseas territories. We assessed plastic at these remote Atlantic Marine Protected Areas, surveying the shore, sea surface, water column and seabed, and found drastic changes from 2013-2018. Working from the RRS James Clark Ross at Ascension, St. Helena, Tristan da Cunha, Gough and the Falkland Islands (Figure 1A), we showed that marine debris on beaches has increased more than 10 fold in the past decade. Sea surface plastics have also increased, with in-water plastics occurring at densities of 0.1 items m-3; plastics on seabeds were observed at ≤ 0.01 items m-2. For the first time, beach densities of plastics at remote South Atlantic sites approached those at industrialised North Atlantic sites. This increase even occurs hundreds of meters down on seamounts. We also investigated plastic incidence in 2,243 animals (comprising 26 species) across remote South Atlantic oceanic food webs, ranging from plankton to seabirds. We found that plastics had been ingested by primary consumers (zooplankton) to top predators (seabirds) at high rates. These findings suggest that MPA status will not mitigate the threat of plastic proliferation to this rich, unique and threatened biodiversity

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

Climate Mitigation through Biological Conservation: Extensive and Valuable Blue Carbon Natural Capital in Tristan da Cunha’s Giant Marine Protected Zone

Carbon-rich habitats can provide powerful climate mitigation if meaningful protection is put in place. We attempted to quantify this around the Tristan da Cunha archipelago Marine Protected Area. Its shallows (&lt;1000 m depth) are varied and productive. The 5.4 km2 of kelp stores ~60 tonnes of carbon (tC) and may export ~240 tC into surrounding depths. In deep-waters we analysed seabed data collected from three research cruises, including seabed mapping, camera imagery, seabed oceanography and benthic samples from mini-Agassiz trawl. Rich biological assemblages on seamounts significantly differed to the islands and carbon storage had complex drivers. We estimate ~2.3 million tC are stored in benthic biodiversity of waters &lt;1000 m, which includes &gt;0.22 million tC that can be sequestered (the proportion of the carbon captured that is expected to become buried in sediment or locked away in skeletal tissue for at least 100 years). Much of this carbon is captured by cold-water coral reefs as a mixture of inorganic (largely calcium carbonate) and organic compounds. As part of its 2020 Marine Protection Strategy, these deep-water reef systems are now protected by a full bottom-trawling ban throughout Tristan da Cunha and representative no take areas on its seamounts. This small United Kingdom Overseas Territory’s reef systems represent approximately 0.8 Mt CO2 equivalent sequestered carbon; valued at &gt;£24 Million GBP (at the UN shadow price of carbon). Annual productivity of this protected standing stock generates an estimated £3 million worth of sequestered carbon a year, making it an unrecognized and potentially major component of the economy of small island nations like Tristan da Cunha. Conservation of near intact habitats are expected to provide strong climate and biodiversity returns, which are exemplified by this MPA.</jats:p

Endoscopic resection of giant lipoma mimicking colonic neoplasm initially presenting with massive haemorrhage: a case report

Lipomas of the colon are benign tumors that rarely occur. Their size ranges from 2 mm to several cm. They are usually asymptomatic but occasionally they present with clinical manifestations depending on tumor size, localization and complications, which often lead to diagnostic difficulty. A 40-year-old man presented with massive rectal haemorrhage. During colonoscopy a giant polyp of over 50 mm in its bigger diameter, with a thick stalk of 2 cm, located in the transverse colon, was revealed. Endoscopic resection was performed with success. Histologic examination demonstrated a giant lipoma. In this report discussion over endoscopic resection of colonic lipomas mimicking neoplasms is also performed

Cryptic Speciation in Brazilian Epiperipatus (Onychophora: Peripatidae) Reveals an Underestimated Diversity among the Peripatid Velvet Worms

Taxonomical studies of the neotropical Peripatidae (Onychophora, velvet worms) have proven difficult, due to intraspecific variation and uniformity of morphological characters across this onychophoran subgroup. We therefore used molecular approaches, in addition to morphological methods, to explore the diversity of Epiperipatus from the Minas Gerais State of Brazil.Our analyses revealed three new species. While Epiperipatus diadenoproctussp. nov. can be distinguished from E. adenocryptussp. nov. and E. paurognostussp. nov. based on morphology and specific nucleotide positions in the mitochondrial cytochrome c oxidase subunit I (COI) and small ribosomal subunit RNA gene sequences (12S rRNA), anatomical differences between the two latter species are not evident. However, our phylogenetic analyses of molecular data suggest that they are cryptic species, with high Bayesian posterior probabilities and bootstrap and Bremer support values for each species clade. The sister group relationship of E. adenocryptussp. nov. and E. paurognostussp. nov. in our analyses correlates with the remarkable morphological similarity of these two species. To assess the species status of the new species, we performed a statistical parsimony network analysis based on 582 base pairs of the COI gene in our specimens, with the connection probability set to 95%. Our findings revealed no connections between groups of haplotypes, which have been recognized as allopatric lineages in our phylogenetic analyses, thus supporting our suggestion that they are separate species.Our findings suggest high cryptic species diversity and endemism among the neotropical Peripatidae and demonstrate that the combination of morphological and molecular approaches is helpful for clarifying the taxonomy and species diversity of this apparently large and diverse onychophoran group

Construct validation of the Health Utilities Index and the Child Health Questionnaire in children undergoing cancer chemotherapy

The objective of this study was to evaluate the construct validity of two questionnaire-based measures of health-related quality of life (HRQL) in children undergoing cancer chemotherapy: the Health Utilities Index (HUI) and the Child Health Questionnaire (CHQ). Subjects were children hospitalised for chemotherapy. To examine construct validity: (1) a priori expected relations between CHQ concepts and HUI attributes were examined; (2) HUI and CHQ summary scores were compared to visual analogue scale (VAS) scores. Ease of completion was rated using a 5-point categorical scale and completion time was recorded. A total of 36 subjects were included. The maximum score was seen in 15 (47%) of HUI3 assessments. As predicted, CHQ body pain was moderately correlated with HUI3 pain (r=0.51), CHQ physical functioning was moderately correlated with HUI2 mobility (r=0.58) and CHQ mental health was moderately correlated with HUI2 emotion (r=0.53). Only the CHQ psychosocial subscale (and not HUI) was correlated with VAS (r=0.44). The CHQ and the HUI were both easy to use. The HUI questionnaires required less time to complete (mean=3.1, s.d.=1 min) compared with CHQ (mean=13.1, s.d.=3.4 min, P<0.0001). In conclusion, HUI and CHQ demonstrated construct validity in children undergoing cancer chemotherapy. The Health Utilities Index is subject to a ceiling effect whereas CHQ requires more time to complete

Infrastructural support to promote farmer adoption of improved technologies.

The paper considers the factors responsible for technology adoption and suggests the infrastructures needed to hasten adoption. Case studies from Bangladesh are used to illustrate the beneficial effects of some of the infrastructural support systems on technology adoption

Comparing administrative and survey data for ascertaining cases of irritable bowel syndrome: a population-based investigation

<p>Abstract</p> <p>Background</p> <p>Administrative and survey data are two key data sources for population-based research about chronic disease. The objectives of this methodological paper are to: (1) estimate agreement between the two data sources for irritable bowel syndrome (IBS) and compare the results to those for inflammatory bowel disease (IBD); (2) compare the frequency of IBS-related diagnoses in administrative data for survey respondents with and without self-reported IBS, and (3) estimate IBS prevalence from both sources.</p> <p>Methods</p> <p>This retrospective cohort study used linked administrative and health survey data for 5,134 adults from the province of Manitoba, Canada. Diagnoses in hospital and physician administrative data were investigated for respondents with self-reported IBS, IBD, and no bowel disorder. Agreement between survey and administrative data was estimated using the κ statistic. The χ²statistic tested the association between the frequency of IBS-related diagnoses and self-reported IBS. Crude, sex-specific, and age-specific IBS prevalence estimates were calculated from both sources.</p> <p>Results</p> <p>Overall, 3.0% of the cohort had self-reported IBS, 0.8% had self-reported IBD, and 95.3% reported no bowel disorder. Agreement was poor to fair for IBS and substantially higher for IBD. The most frequent IBS-related diagnoses among the cohort were anxiety disorders (34.4%), symptoms of the abdomen and pelvis (26.9%), and diverticulitis of the intestine (10.6%). Crude IBS prevalence estimates from both sources were lower than those reported previously.</p> <p>Conclusions</p> <p>Poor agreement between administrative and survey data for IBS may account for differences in the results of health services and outcomes research using these sources. Further research is needed to identify the optimal method(s) to ascertain IBS cases in both data sources.</p