The Association Between Rate and Severity of Exacerbations in Chronic Obstructive Pulmonary Disease: An Application of a Joint Frailty-Logistic Model.

Exacerbations are a hallmark of chronic obstructive pulmonary disease (COPD). Evidence suggests the presence of substantial between-individual variability (heterogeneity) in exacerbation rates. The question of whether individuals vary in their tendency towards experiencing severe (versus mild) exacerbations, or whether there is an association between exacerbation rate and severity, has not yet been studied. We used data from the MACRO Study, a 1-year randomized trial of the use of azithromycin for prevention of COPD exacerbations (United States and Canada, 2006-2010; n = 1,107, mean age = 65.2 years, 59.1% male). A parametric frailty model was combined with a logistic regression model, with bivariate random effects capturing heterogeneity in rate and severity. The average rate of exacerbation was 1.53 episodes/year, with 95% of subjects having a model-estimated rate of 0.47-4.22 episodes/year. The overall ratio of severe exacerbations to total exacerbations was 0.22, with 95% of subjects having a model-estimated ratio of 0.04-0.60. We did not confirm an association between exacerbation rate and severity (P = 0.099). A unified model, implemented in standard software, could estimate joint heterogeneity in COPD exacerbation rate and severity and can have applications in similar contexts where inference on event time and intensity is considered. We provide SAS code (SAS Institute, Inc., Cary, North Carolina) and a simulated data set to facilitate further uses of this method

Mouse models for preeclampsia: disruption of redox-regulated signaling

The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

Temporal and Spatial Beam Shaping in LPBF for Fine and Porous Ti-Alloy Structures for Regenerative Fuel Cell Applications

Laser Powder Bed Fusion (LPBF) presents itself as a potential method to produce thin porous structures, which have numerous applications in the medical and energy industries, due to its in-process pore formation capabilities. Particularly, regenerative fuel cells, which are capable of both producing and storing energy through the use of hydrogen-based electrochemical fuel cell and electrolysers, respectively, can benefit from the LPBF-induced porosity for it porous layer components in the electrode. Numerous studies have reported that process parameters, such as laser power, scan speed and hatch spacing, are key factors affecting the formation of pores in LPBF material due to their control over the energy density and melt pool formation during the build. Contemporary fibre lasers offer novel temporal and spatial beam shaping capabilities. Temporal laser control means that the laser can use pulsed wave (PW) or single point exposure (SPE), and spatial beam shaping refers to variations in the intensity distribution of the laser, which can be modulated from Gaussian to ring shape via the use of multi-core fibers. These have seldom been studied in combination with LPBF. Therefore, the aim of this study was to utilise temporal and spatial beam shaping in LPBF to produce thin porous structures. To do this, PW and SPE laser temporal strategies were utilised and the duty cycle (which relates the on and off time of the laser) was varied between 50% and 100%. Beam shape indexes 0 (Gaussian), 3 and 6 (ring) were also investigated alongside more standard LPBF process parameters such as laser power and scan speed to manufacture thin porous walls, as well as fine struts. The thinnest wall obtained was 130 μm thick, while the smallest strut had a diameter of 168 μm. The duty cycle had a clear effect on the porosity of thin walls, where a duty cycle of 50% produced the highest number of porous walls and had the highest porosity due to its ability to control the intensity of the energy density during the LPBF process. The different beam shape indexes corresponded to different spatial distribution of the power density, and hence, modifying the temperature distribution in the meltpool during the laser material interaction. Beam shape index 6 (corresponding to a ring mode with lower peak irradiance) created more porous specimens and smaller meltpool sizes, with respect to its beam size. Overall, this study showed that temporal and spatial control of the beam (through duty cycle and beam shape index) are powerful tools which can control the distribution and intensity of the energy density during the LPBF process to produce thin porous structures for energy applications

Automated Segmentation of Nanoparticles in BF TEM Images by U-Net Binarization and Branch and Bound

Transmission electron microscopy (TEM) provides information about Inorganic nanoparticles that no other method is able to deliver. Yet, a major task when studying Inorganic nanoparticles using TEM is the automated analysis of the images, i.e. segmentation of individual nanoparticles. The current state-of-the-art methods generally rely on binarization routines that require parameterization, and on methods to segment the overlapping nanoparticles (NPs) using highly idealized nanoparticle shape models. It is unclear, however, that there is any way to determine the best set of parameters providing an optimal segmentation, given the great diversity of NPs characteristics, such as shape and size, that may be encountered. Towards remedying these barriers, this paper introduces a method for segmentation of NPs in Bright Field (BF) TEM images. The proposed method involves three main steps: binarization, contour evidence extraction, and contour estimation. For the binarization, a model based on the U-Net architecture is trained to convert an input image into its binarized version. The contour evidence extraction starts by recovering contour segments from a binarized image using concave contour points detection. The contour segments which belong to the same nanoparticle are grouped in the segment grouping step. The grouping is formulated as a combinatorial optimization problem and solved using the well-known branch and bound algorithm. Finally, the full contours of the NPs are estimated by an ellipse. The experiments on a real-world dataset consisting of 150 BF TEM images containing approximately 2,700 NPs show that the proposed method outperforms five current state-of-art approaches in the overlapping NPs segmentation.Post-print / Final draf

The prevalence and control of lungworms of pastoral ruminants in Iran:The prevalence and control of lungworms of pastoral rumi-nants in Iran

Lungworms of the genera Dictyocaulus, Muellerius, Protostrongylus, and Cystocaulus are common helminths of domestic and wild ruminants with substantial veterinary and economic importance. Several studies have assessed the presence and prevalence of lungworm infections in ruminants in Iran. This report compiles the available scientific information about the occurrence of lungworms in domestic and wild ruminants in Iran between 1931 and June 2022 to give an insight into their epidemiology, and where possible to describe drug treatment efficacy. For this purpose, national and international scientific databases were searched. Overall, 54 publications comprising 33 articles in peer-reviewed journals, 8 conference papers, and 13 dissertations were evaluated regarding prevalence data; and an additional 4 peer-reviewed articles were evaluated regarding drug efficacy. Seven species of lungworms, namely Dictyocaulus filaria, Dictyocaulus viviparus, Dictyocaulus eckerti, Protostrongylus rufescens, Protostrongylus raillietti, Muellerius capillaris, and Cystocaulus ocreatus have been recorded from different ruminant hosts in Iran. Thirty-three studies conducted on small ruminant (sheep and goat) lungworms reported prevalences of lungworm infection of 11.6%, 45.81% and 66.29% using abattoir meat inspection, Baermann technique and fecal flotation, respectively. Eight studies conducted on large ruminants (cattle and water buffalo) reported prevalences of infection of 14.83%, 13.98% and 5% using abattoir meat inspection, the Baermann technique and fecal flotation, respectively. The prevalence of infection in wild ruminants was variable across examined species; 38% in urial, 37% in wild goats, 5% in goitered gazelles and 67% in red deer, in addition to a single case report in roe deer. There are few contemporary studies assessing the efficacy of currently available broad-spectrum anthelmintic compounds against lungworms in Iran. The high prevalence of multiple lungworm species in Iran, combined with a lack of information about drug efficacy, supports the need to improve the understanding of these important nematode parasites and inform the development of sustainable control strategies. The aim of this review and meta-analysis is to provide a baseline for future conventional parasitology and next generation molecular epidemiological studies of lungworm infection in pastoral ruminants in Iran

B Lymphocyte Memory: Role of Stromal Cell Complement and FcγRIIB Receptors

To dissect the influence of CD21/CD35 and FcγRIIB in antigen retention and humoral memory, we used an adoptive transfer model in which antigen-primed B and T lymphocytes were given to sublethally irradiated wild-type mice or mice deficient in CD21/CD35 (Cr2−/−) or FcγRIIB receptors (FcγRIIB−/−). Cr2−/− chimeras showed impaired memory as characterized by a decrease in antibody titer, reduced frequency of antibody secreting cells, an absence of affinity maturation, and significantly reduced recall response. The impaired memory in Cr2−/− chimeras corresponded with the reduced frequency of antigen-specific memory B cells. Interestingly, FcγRIIB−/− chimeras showed a differential phenotype with impaired splenic but normal bone marrow responses. These data suggest that CD21/CD35 on stroma, including follicular dendritic cells, is critical to the maintenance of long-term B lymphocyte memory

Assessment of knowledge, attitudes and practices relating to parasitic diseases and anthelmintic resistance among livestock farmers in Hamedan, Iran

Iranian studies have shown a high prevalence of broad spectrum anthelmintic resistance (AR) in gastrointestinal helminths of ruminants. However, there is a lack of information about levels of knowledge, attitudes and practices among livestock farmers in Iran regarding the concept of parasite control and AR. This study aimed to evaluate the knowledge, attitudes and practices of livestock farmers of Hamedan, Iran, regarding parasitic diseases and AR by interviewing 150 farmers using a structured questionnaire. Most of farmers had some knowledge of the clinical signs associated with helminth parasitism, but more than half were unaware of the existence of zoonotic parasites. More than half of the participants had never heard about AR, but were interested to learn about it through their veterinarians. Those who were aware of the problem considered non-prescribed anthelmintic drugs to play a role in its emergence, while several of the participants believed that ‘more expensive’ and ‘foreign-branded’ drugs worked best. Almost all of the farmers reported that they frequently consulted with a veterinarian about anthelmintic treatments, but very few adhered to recognised principles of responsible and sustainable drug use. About half of the participating farmers treated their sheepdogs for helminth parasites, despite the common practice of regularly feeding likely infected livestock offal. Education had a significantly positive association with farmers’ knowledge, attitudes and best practice scores, while knowledge was significantly associated with both attitudes and practices. Based on these results, we recommend that regular country-wide classes should be held to educate farmers on the evidence-based principles of sustainable helminth control and prevention of zoonotic helminth disease

The Effect of Structural Phase Changes on Fermi Level Shifts and Optoelectronic Properties of Lead-Free CsSnI3 Perovskites

The work carried out first-principles calculations within the framework of density functional theory to study the structural stability of the CsSnI3 compound and the influence of phase transitions on their electronic and optical properties. Using the GGA and SCAN functionals, the relaxed structures of the CsSnI3 phases were obtained and their geometric characteristics were assessed. Using the Phonopy code based on VASP, calculations of phonon and thermodynamic properties were performed, and the temperatures of phase transitions of CsSnI3 were determined. Electronic properties and Fermi level shifts as a result of phase transformations of CsSnI3 were assessed using the HSE06 functional and machine learning prediction. The values of the complex dielectric constant and the refractive index of all phases of the CsSnI3 were determined.Comment: 16 pages, 11 figures, 4 table

Long-term effectiveness of a lifestyle intervention on the prevention of type 2 diabetes in a middle-income country

This study aims to assess the effects of a community-based lifestyle intervention program on the incidence of type 2 diabetes (T2D). For this purpose, three communities in Tehran were chosen; one community received a face-to-face educational session embedded in a long-term community-wide lifestyle intervention aimed at supporting lifestyle changes. We followed up 9,204 participants (control: 5,739, intervention: 3,465) triennially from 1999 to 2015 (Waves 1–5). After a median follow-up of 3.5 years (wave 2), the risk of T2D was 30% lower in the intervention community as compared with two control communities by (Hazard-ratio: 0.70 [95% CI 0.53; 0.91]); however, the difference was not statistically significant in the following waves. After a median follow-up of 11.9 years (wave 5), there was a non-significant 6% reduction in the incidence of T2D in the intervention group as compared to the control group (Hazard-ratio: 0.94 [0.81, 1.08]). Moreover, after 11.9 years of follow-up, the intervention significantly improved the diet quality measured by the Dietary Approaches to Stop Hypertension concordance (DASH) score. Mean difference in DASH score in the intervention group versus control group was 0.2 [95% CI 0.1; 0.3]. In conclusion, the intervention prevented T2D by 30% in the short-term (3.5 years) but not long-term; however, effects on improvement of the diet maintained in the long-term.Registration: This study is registered at IRCT, a WHO primary registry (https://irct.ir). The registration date 39 is 2008-10-29 and the IRCT registration number is IRCT138705301058N1

Vector-borne pathogens in dogs of different regions of Iran and Pakistan

Canine vector-borne diseases (CVBDs) are highly prevalent in tropical and subtropical countries, mainly due to favorable climate conditions and reduced adoption of preventive measures. This study aimed to provide a comprehensive overview on the prevalence of CVBDs in Iran and Pakistan where limited data are available. Blood samples were collected from 403 dogs from six provinces in Iran and Pakistan to assess the presence of pathogen DNA (i.e., Anaplasma spp., Coxiella burnetii, Ehrlichia spp., Rickettsia spp., Babesia spp., Hepatozoon spp., filarioids, and Leishmania spp.). Sera were also screened by an immunofluorescence antibody test for the detection of antibodies against Leishmania infantum. In total, 46.9% of dogs scored positive to Hepatozoon canis being the most frequently detected (41.4%), followed by Anaplasma platys (6.4%), Ehrlichia canis (3.4%), Rickettsia spp. (2.2%), Babesia vogeli (1.0%), and L. infantum (0.3%). A seroprevalence of 9.6% to anti-L. infantum IgG was also recorded. Data reported herein demonstrate that dogs from Iran and Pakistan are at a high risk of CVBDs, particularly of canine hepatozoonosis. Effective control strategies are advocated for minimizing the risk of infection in animals and humans, also in consideration of the zoonotic potential of some pathogens detected