A hypothesis-generating study to evaluate platelet activity in diabetics with chronic kidney disease

Background It is well described that diabetes mellitus is a hypercoagulable state. It is also known that patients with renal dysfunction have impaired platelet aggregation and function. It is not well described how renal dysfunction affects the hypercoagulability associated with diabetes. This post-hoc sub-group analysis compares platelet function, clot structure and thrombin generation time at baseline, and following enoxaparin exposure in three groups of subjects. Methods 30 total subjects were evaluated in the three groups: Group I: normal controls (n = 10), Group II: subjects with renal dysfunction but without diabetes (n = 13), and Group III: subjects with concomitant diabetes and renal dysfunction (n = 7). For each subject, platelet contractile force (PCF), clot elastic modulus (CEM) and thrombin generation time (TGT) were simultaneously measured in whole blood at baseline, and following increasing enoxaparin antifactor Xa activity exposure. The group means for each parameter were determined and compared using one-way analysis of variance, with post-hoc Tukey-Kramer test. Results At baseline, subjects in Group III (diabetics with concomitant renal dysfunction) display significantly enhanced platelet activity, as measured by PCF (p = 0.003) and CEM (p = 0.03), relative to the non-diabetic Groups I and II. Subjects in Group II (renal dysfunction without diabetes) had significantly prolonged TGT values relative to controls when the antifactor Xa activity concentration reached 0.5 (p = 0.007), 1.0 (p = 0.005) and 3.0 IU/mL (p \u3c 0.0001), respectively. There were no differences between Group II and Group III with respect to TGT at these antifactor Xa activity concentrations. When the antifactor Xa activity concentration reached 3.0 IU/mL, Groups II and III formed significantly less rigid blood clots (CEM p = 0.003) and also trended toward reduced PCF (p = 0.06) relative to Group I. Conclusion This hypothesis-generating sub-group analysis suggests that at baseline, patients with concomitant diabetes and renal dysfunction have significantly enhanced platelet activity (PCF), and form more rigid blood clots (CEM) compared to controls and subjects with renal dysfunction but no diabetes. This may suggest that the presence of renal dysfunction does not ameliorate the hypercoagulable state associated with diabetes. Secondly, it appears that subjects with renal dysfunction but without diabetes have an enhanced response to enoxaparin relative to controls

Keck/Palomar Cosmic Web Imagers (KCWI/PCWI) Reveal an Enormous Lyα\alpha Nebula in an Extremely Overdense QSO Pair Field at z=2.45z=2.45

Enormous Ly$\alpha$ nebulae (ELANe) represent the extrema of Ly$\alpha$ nebulosities. They have detected extents of $>200$ kpc in Ly$\alpha$ and Ly$\alpha$ luminosities $>10^{44}$ erg s$^{-1}$. The ELAN population is an ideal laboratory to study the interactions between galaxies and the intergalactic/circumgalactic medium (IGM/CGM) given their brightness and sizes. The current sample size of ELANe is still very small, and the few $z\approx2$ ELANe discovered to date are all associated with local overdensities of active galactic nuclei (AGNs). Inspired by these results, we have initiated a survey of ELANe associated with QSO pairs using the Palomar and Keck Cosmic Web Imagers (PCWI/KCWI). In this letter, we present our first result: the discovery of ELAN0101+0201 associated with a QSO pair at $z=2.45$. Our PCWI discovery data shows that, above a 2-$\sigma$ surface brightness of $1.2\times10^{-17}$ \sbunit, the end-to-end size of ELAN0101+0201 is $\gtrsim 232$ kpc. We have conducted follow-up observations using KCWI, resolving multiple Ly$\alpha$ emitting sources within the rectangular field-of-view of $\approx 130\times165$ projected kpc$^2$, and obtaining their emission line profiles at high signal-to-noise ratios. Combining both KCWI and PCWI, our observations confirm that ELAN0101+0201 resides in an extremely overdense environment. Our observations further support that a large amount of cool ($T\sim10^4$K) gas could exist in massive halos (M$\gtrsim10^{13}$M$_\odot$) at $z\approx2$. Future observations on a larger sample of similar systems will provide statistics of how cool gas is distributed in massive overdensities at high-redshift and strongly constrain the evolution of the intracluster medium (ICM).Comment: Submitted to Astrophysical Journal Letter, 9 pages, 4 figures, Comments Welcom

Systemic central venous oxygen saturation is associated with clot strength during traumatic hemorrhagic shock: A preclinical observational model

<p>Abstract</p> <p>Background</p> <p>Clot strength by Thrombelastography (TEG) is associated with mortality during trauma and has been linked to severity of tissue hypoperfusion. However, the optimal method for monitoring this important relationship remains undefined. We hypothesize that oxygen transport measurements will be associated with clot strength during traumatic shock, and test this hypothesis using a swine model of controlled traumatic shock.</p> <p>Methods</p> <p>N = 33 swine were subjected to femur fracture and hemorrhagic shock by controlled arterial bleeding to a predetermined level of oxygen debt measured by continuous indirect calorimetry. Hemodynamics, oxygen consumption, systemic central venous oxygenation (ScvO₂), base excess, lactate, and clot maximal amplitude by TEG (TEG-MA) as clot strength were measured at baseline and again when oxygen debt = 80 ml/kg during shock. Oxygen transport and metabolic markers of tissue perfusion were then evaluated for significant associations with TEG-MA. Forward stepwise selection was then used to create regression models identifying the strongest associations between oxygen transport and TEG-MA independent of other known determinants of clot strength.</p> <p>Results</p> <p>Multiple markers of tissue perfusion, oxygen transport, and TEG-MA were all significantly altered during shock compared to baseline measurements (p < 0.05). However, only ScvO₂demonstrated a strong bivariate association with TEG-MA measured during shock (R = 0.7, p < 0.001). ScvO₂measured during shock was also selected by forward stepwise selection as an important covariate in linear regression models of TEG-MA after adjusting for the covariates fibrinogen, pH, platelet count, and hematocrit (Whole model R²= 0.99, p ≤ 0.032).</p> <p>Conclusions</p> <p>Among multiple measurements of oxygen transport, only ScvO₂was found to retain a significant association with TEG-MA during shock after adjusting for multiple covariates. ScvO₂should be further studied for its utility as a clinical marker of both tissue hypoxia and clot formation during traumatic shock.</p

Resilience-Focused HIV Care to Promote Psychological Well-Being During COVID-19 and Other Catastrophes

The COVID-19 pandemic has adversely affected people with HIV due to disruptions in prevention and care services, economic impacts, and social isolation. These stressors have contributed to worse physical health, HIV treatment outcomes, and psychological wellness. Psychological sequelae associated with COVID-19 threaten the overall well-being of people with HIV and efforts to end the HIV epidemic. Resilience is a known mediator of health disparities and can improve psychological wellness and behavioral health outcomes along the HIV Continuum of Care. Though resilience is often organically developed in individuals as a result of overcoming adversity, it may be fostered through multi-level internal and external resourcing (at psychological, interpersonal, spiritual, and community/neighborhood levels). In this Perspective, resilience-focused HIV care is defined as a model of care in which providers promote optimum health for people with HIV by facilitating multi-level resourcing to buffer the effects of adversity and foster well-being. Adoption of resilience-focused HIV care may help providers better promote well-being among people living with HIV during this time of increased psychological stress and help prepare systems of care for future catastrophes. Informed by the literature, we constructed a set of core principles and considerations for successful adoption and sustainability of resilience-focused HIV care. Our definition of resilience-focused HIV care marks a novel contribution to the knowledge base and responds to the call for a multidimensional definition of resilience as part of HIV research

Succession of physiological stages hallmarks the transcriptomic response of the&nbsp;fungus Aspergillus niger to lignocellulose.

BackgroundUnderstanding how fungi degrade lignocellulose is a cornerstone of improving renewables-based biotechnology, in particular for the production of hydrolytic enzymes. Considerable progress has been made in investigating fungal degradation during time-points where CAZyme expression peaks. However, a robust understanding of the fungal survival strategies over its life time on lignocellulose is thereby missed. Here we aimed to uncover the physiological responses of the biotechnological workhorse and enzyme producer Aspergillus niger over its life time to six substrates important for biofuel production.ResultsWe analysed the response of A. niger to the feedstock Miscanthus and compared it with our previous study on wheat straw, alone or in combination with hydrothermal or ionic liquid feedstock pretreatments. Conserved (substrate-independent) metabolic responses as well as those affected by pretreatment and feedstock were identified via multivariate analysis of genome-wide transcriptomics combined with targeted transcript and protein analyses and mapping to a metabolic model. Initial exposure to all substrates increased fatty acid beta-oxidation and lipid metabolism transcripts. In a strain carrying a deletion of the ortholog of the Aspergillus nidulans fatty acid beta-oxidation transcriptional regulator farA, there was a reduction in expression of selected lignocellulose degradative CAZyme-encoding genes suggesting that beta-oxidation contributes to adaptation to lignocellulose. Mannan degradation expression was wheat straw feedstock-dependent and pectin degradation was higher on the untreated substrates. In the later life stages, known and novel secondary metabolite gene clusters were activated, which are of high interest due to their potential to synthesize bioactive compounds.ConclusionIn this study, which includes the first transcriptional response of Aspergilli to Miscanthus, we highlighted that life time as well as substrate composition and structure (via variations in pretreatment and feedstock) influence the fungal responses to lignocellulose. We also demonstrated that the fungal response contains physiological stages that are conserved across substrates and are typically found outside of the conditions with high CAZyme expression, as exemplified by the stages that are dominated by lipid and secondary metabolism

The argument of the broken pane: Suffragette consumerism and newspapers

Within the cut-throat world of newspaper advertising the newspapers of Britain's Women's Social and Political Union (WSPU) Votes for Women and the Suffragette managed to achieve a balance that has often proved to be an impossible challenge for social movement press—namely the maintenance of a highly political stance whilst simultaneously exploiting the market system with advertising and merchandising. When the militant papers advocated window smashing of West End stores in 1912–1913, the companies who were the target still took advertisements. Why? What was the relationship between news values, militant violence and advertising income? ‘Do-it-yourself’ journalism operated within a context of ethical consumerism and promotionally orientated militancy. This resulted in newspaper connections between politics, commerce and a distinct market profile, evident in the customisation of advertising, retailer dialogue with militants and longer-term loyalty—symptomatic of a wider trend towards newspaper commercialism during this period

Viabilitas Probiotik Asal Fermentasi Maggot (Hermetia illucens) terhadap Suhu dan Lama Waktu Penyimpanan: Viability of Probiotics from Fermented Maggot (Hermetia illucens) on Temperature and Storage Time

This study aimed to analyze the viability of probiotics from maggot fermentation under environmental influence i.e., temperature and storage time. The experimental design was a factorial completely randomized design (CRD) using storage time and temperature as factors with 4 replications. The storage time was 3 months with monthly observations while the storage temperatures observed were 4°C, 28°C, 38°C and 48°C. The parameters were physical quality, microbial population, total titrated acid (TTA), and antimicrobial activity. The results showed that probiotics from maggot fermentation were dominated by lactic acid bacteria. The pH of probiotics increased and physical quality changes occured during storage. The yeast and actinomycete populations were not found during month 2 and month 3, respectively, while the population of Bacillus sp. decreased. There was an interaction between storage time and temperature on the population of lactic acid bacteria and TTA. Another interaction was found in the antimicrobial activity produced by probiotics/antibiotics and storage temperature in the third month of storage. Storage time and temperature influenced the physical quality of probiotics, the population of lactic acid bacteria and TTA, while the inhibition zone was influenced by the probiotic/antibiotic solution and storage temperature. It can be concluded that the highest viability of fermented maggot probiotics (LAB) was obtained in the 1st month at a temperature of 38℃. Key words:&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; maggot fermentation, probiotics, storage time, temperature, viabilit

Tarmo: A Framework for Parallelized Bounded Model Checking

This paper investigates approaches to parallelizing Bounded Model Checking (BMC) for shared memory environments as well as for clusters of workstations. We present a generic framework for parallelized BMC named Tarmo. Our framework can be used with any incremental SAT encoding for BMC but for the results in this paper we use only the current state-of-the-art encoding for full PLTL. Using this encoding allows us to check both safety and liveness properties, contrary to an earlier work on distributing BMC that is limited to safety properties only. Despite our focus on BMC after it has been translated to SAT, existing distributed SAT solvers are not well suited for our application. This is because solving a BMC problem is not solving a set of independent SAT instances but rather involves solving multiple related SAT instances, encoded incrementally, where the satisfiability of each instance corresponds to the existence of a counterexample of a specific length. Our framework includes a generic architecture for a shared clause database that allows easy clause sharing between SAT solver threads solving various such instances. We present extensive experimental results obtained with multiple variants of our Tarmo implementation. Our shared memory variants have a significantly better performance than conventional single threaded approaches, which is a result that many users can benefit from as multi-core and multi-processor technology is widely available. Furthermore we demonstrate that our framework can be deployed in a typical cluster of workstations, where several multi-core machines are connected by a network