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Pulmonary hypertension (PH) adds a substantial disease burden, including higher mortality, when associated with interstitial lung disease (ILD), a severe, chronic, progressive condition. Yet little is known of the lived experiences, perspectives, priorities, and viewpoints of patients and carers living with PH‐ILD. The Voice of the Patient meeting at the center of this qualitative research study aims to provide these difficult‐to‐obtain insights from a European perspective for the first time. The multistakeholder approach brought together four PH‐ILD patients, three primary caregivers, two patient associations, clinical experts, sponsor representatives, and a facilitator. Of the six major themes identified in the thematic analysis, symptoms, and physical limitations were the most impactful. Shortness of breath was the most bothersome symptom affecting patients daily. Further symptoms included fatigue, cough, dizziness, syncope, edema, and palpitations. Physical limitations focused on reduced mobility, impacting patients' ability to perform daily tasks, hobbies, sports, and to enjoy travel. Existing antifibrotic and pulmonary arterial hypertension‐targeted treatments were perceived as beneficial. However, despite advances in treatment, severe disease burdens and high unmet medical needs persist from the perspectives of patients. Most meaningful to patients' daily wellbeing was supplemental oxygen, enabling greater mobility. Patients and carers reported difficulties and barriers in navigating the healthcare system and obtaining adequate information to reduce their considerable uncertainties, documenting the substantial challenges that rare and complex conditions such as PH‐ILD pose for routine clinical practice beyond PH expert centers and indicating an urgent need for high‐quality patient‐ and clinician‐directed information to support patient‐centered care. [ABSTRACT FROM AUTHOR]

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID‐19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID‐19 patients. Phase‐2, open‐label, randomized trial with a pick‐the‐winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID‐19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard‐care, baricitinib (4 mg qd, 7 days) plus standard‐care, or standard‐care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day‐by‐day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all‐cause mortality, and safety. One hundred and sixty‐five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96−2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94−2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID‐19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial. [ABSTRACT FROM AUTHOR]

In this work we present the Cartesian grid discontinuous Galerkin (cgDG) finite element method, a novel numerical technique that combines the high accuracy and efficiency of a high‐order discontinuous Galerkin discretization with the simplicity and hierarchical structure of a geometry‐independent Cartesian mesh. The elements that intersect the boundary of the physical domain require special treatment in order to minimize their effect on the performance of the algorithm. We considered the exact representation of the geometry for the boundary of the domain avoiding any nonphysical artifacts. We also define a stabilization procedure that eliminates the step size restriction of the time marching scheme due to extreme cut patterns. The unstable degrees of freedom are eliminated and the supporting regions of their shape functions are reassigned to neighboring elements. A subdomain matching algorithm and an a posterior enrichment strategy are presented. Combining these techniques we obtain a final spatial discretization that preserves stability and accuracy of the standard body‐fitted discretization. The method is validated through a series of numerical tests and it is successfully applied to the solution of problems of interest in the context of electromagnetic scattering with increasing complexity. [ABSTRACT FROM AUTHOR]

Background & Aims: Public health measures introduced to limit transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which causes coronavirus disease 2019 (COVID‐19), also disrupted various healthcare services in many regions worldwide, including British Columbia (BC), Canada. We assessed the impact of these measures, first introduced in BC in March 2020, on hepatitis C (HCV) testing and first‐time HCV‐positive diagnoses within the province. Methods: De‐identified HCV testing data for BC residents were obtained from the provincial Public Health Laboratory. Weekly changes in anti‐HCV, HCV RNA and genotype testing episodes and first‐time HCV‐positive (anti‐HCV/RNA/genotype) diagnoses from January 2018 to December 2020 were assessed and associations were determined using segmented regression models examining rates before vs after calendar week 12 of 2020, when measures were introduced. Results: Average weekly HCV testing and first‐time HCV‐positive diagnosis rates fell immediately following the imposition of public health measures by 62.3 per 100 000 population and 2.9 episodes per 1 000 000 population, respectively (P <.0001 for both), and recovered in subsequent weeks to near pre‐March 2020 levels. Average weekly anti‐HCV positivity rates decreased steadily pre‐restrictions and this trend remained unchanged afterwards. Conclusions: Reductions in HCV testing and first‐time HCV‐positive diagnosis rates, key drivers of progression along the HCV care cascade, occurred following the introduction of COVID‐19‐related public health measures. Further assessment will be required to better understand the full impact of these service disruptions on the HCV care cascade and to inform strategies for the re‐engagement of people who may have been lost to care because of these measures. [ABSTRACT FROM AUTHOR]

The characterization of vascular geometry is a fundamental step towards the correct interpretation of coronary artery disease. In this work, we report a comprehensive comparison of the geometry featured by coronary vessels as obtained from coronary computed tomography angiography (CCTA) and the combination of intravascular ultrasound (IVUS) with bi‐plane angiography (AX) modalities. We analyzed 34 vessels from 28 patients with coronary disease, which were deferred to CCTA and IVUS procedures. We discuss agreement and discrepancies between several geometric indexes extracted from vascular geometries. Such an analysis allows us to understand to which extent the coronary vascular geometry can be reliable in the interpretation of geometric risk factors, and as a surrogate to characterize coronary artery disease. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatitis C virus (HCV) reinfection among high‐risk groups threatens HCV elimination goals. We assessed HCV reinfection rates among men who have sex with men (MSM) in British Columbia (BC), Canada. Methods: We used data from the BC Hepatitis Testers Cohort, which includes nearly 1.7 million individuals tested for HCV or HIV in BC. MSM who had either achieved sustained virologic response (SVR) after successful HCV treatment, or spontaneous clearance (SC) and had ≥1 subsequent HCV RNA measurement, were followed from the date of SVR or SC until the earliest of reinfection, death, or last HCV RNA measurement. Predictors of reinfection were identified by Cox proportional modelling. The earliest study start date was 6 November 1997 and latest end date was 13 April 2018. Results: Of 1349 HCV‐positive MSM who met the inclusion criteria, 493 had SC while 856 achieved SVR. 349 (25.65%) had HIV coinfection. We identified 98 reinfections during 5203 person‐years (PYs) yielding a reinfection rate of 1.88/100PYs. The reinfection rate among SC (2.74/100PYs) was more than twice that of those with SVR (1.03/100 PYs). Problematic alcohol use (aHR 1.73, 95% CI 1.003‐2.92), injection drug use (aHR 2.60, 95% CI 1.57‐4.29) and HIV coinfection (aHR 2.04, 95% CI 1.29‐3.23) were associated with increased risk of HCV reinfection. Mental health counselling history (aHR 0.24, 95% CI 0.13‐0.46) was associated with reduced HCV reinfection risk. Conclusions: There is the need to engage MSM in harm reduction and prevention services following treatment to reduce reinfection risk. [ABSTRACT FROM AUTHOR]

BACKGROUND Cheese whey is a byproduct of the dairy industry, which is characterized by its high organic matter content, so its valorization by anaerobic digestion (AD) requires a pretreatment or a dilution that allows high values of degradability. However, this increases the cost and duration of whey treatment. In this paper, a study on the viability of anaerobic treatment of a type of crude whey is presented. For it, the effect of pH, substrate–inoculum ratio (S:I) and its interaction during mesophilic AD of raw cheese whey were evaluated. The interactions of the parameters were analyzed by response surface analysis. RESULTS: The results showed that in the mesophilic temperature range, the pH most suitable for AD of whey is slightly alkaline (pH = 8). Production and methane yield were improved, increasing the proportion of raw whey, which means that it is possible to operate with high organic loading rate, maintaining adequate operation conditions (pH = 8, T = 40 °C). The best performance of the digester reached 7.1 LCH4 Lwhey−1, and a specific methanogenic activity of 1.15 gCOD gTVSi−1 day−1. CONCLUSION: It is possible to use raw cheese whey to produce methane. The alkaline pH and high S:I ratio improved the methane yield and promote methanogenic activity. Intermediate compounds (volatile fatty acids, NH3 and/or H2S) accumulated during the AD operation, which could have influenced the reactor performance; hence, further study is advisable to elucidate their effect on the global process. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Background: Focal dermal hypoplasia (FDH) is rare X‐linked dominant disease characterized by atrophy and linear pigmentation of the skin, split hand/foot deformities and ocular anomalies. FDH is caused by mutations of the Porcupine (PORCN) gene, which encodes an enzyme that catalyzes the palmitoylation of Wnt ligands required for their secretion. High resolution melting analysis (HRM) is a technique that allows rapid, labor‐efficient, low‐cost detection of genomic variants. In the present study, we report the successful implementation of HRM in the molecular diagnosis of FDH. Methods: Polymerase chain reaction and HRM assays were designed and optimized for each of the coding exons of the PORCN gene, processing genomic DNA samples form a non‐affected control and a patient complying with the FDH diagnostic criteria. The causal mutation was characterized by Sanger sequencing from an amplicon showing a HRM trace suggesting heterozygous variation and was validated using an amplification‐refractory mutation system (ARMS) assay. Results: The melting profiles suggested the presence of a variant in the patient within exon 1. Sanger sequencing revealed a previously unknown C to T transition replacing a glutamine codon for a premature stop codon at position 28, which was validated using ARMS. Conclusions: Next‐generation sequencing facilitates the molecular diagnosis of monogenic disorders; however, its cost–benefit ratio is not optimal when a single, small or medium size causal gene is already identified and the clinical diagnostic presumption is strong. Under those conditions, as it is the case for FDH, HRM represents a cost‐ and labor‐effective approach. [ABSTRACT FROM AUTHOR]

Summary: The superconvergent patch recovery technique with constraints (SPR‐C) consists in improving the accuracy of the recovered stresses obtained with the original SPR technique by considering known information about the exact solution, like the internal equilibrium equation, the compatibility equation or the Neumann boundary conditions, during the recovery process. In this paper the SPR‐C is extended to consider the equilibrium around the contact area when solving contact problems with the Cartesian grid Finite Element Method. In the proposed method, the Finite Element stress fields of both bodies in contact are considered during the recovery process and the equilibrium is enforced by means of the continuity of tractions along the contact surface. [ABSTRACT FROM AUTHOR]

Neurocysticercosis is a parasitic brain disease caused by the larval form (Cysticercus cellulosae) of Taenia solium and is the leading cause of preventable epilepsy worldwide. However, the pathophysiology and relation to the wide range of clinical features remains poorly understood. Axonal swelling is emerging as an important early pathological finding in multiple neurodegenerative diseases and as a cause of brain injury, but has not been well described in neurocysticercosis. Histological analysis was performed on human, rat and porcine NCC brain specimens to identify axonal pathology. Rat infection was successfully carried out via two routes of inoculation: direct intracranial injection and oral feeding. Extensive axonal swellings, in the form of spheroids, were observed in both humans and rats and to a lesser extent in pigs with NCC. Spheroids demonstrated increased immunoreactivity to amyloid precursor protein and neurofilament indicating probable impairment of axonal transport. These novel findings demonstrate that spheroids are present in NCC which is conserved across species. Not only is this an important contribution toward understanding the pathogenesis of NCC, but it also provides a model to analyze the association of spheroids with specific clinical features and to investigate the reversibility of spheroid formation with antihelminthic treatment. [ABSTRACT FROM AUTHOR]

Objective Using a large-scale population-based study, we aimed to assess prevalence and patterns of presentation of neurocysticercosis ( NCC) and its relationship with epilepsy in community-dwellers aged ≥20 years living in Atahualpa (rural Ecuador). Methods In a three-phase epidemiological study, individuals with suspected seizures were identified during a door-to-door survey and an interview (phase I). Then, neurologists evaluated suspected cases and randomly selected negative persons to estimate epilepsy prevalence (phase II). In phase III, all participants were offered noncontrast computed tomography ( CT) for identifying NCC cases. The independent association between NCC (exposure) and epilepsy (outcome) was assessed by the use of multivariate logistic regression models adjusted for age, sex, level of education, and alcohol intake. CT findings were subsequently compared to archived brain magnetic resonance imaging in a sizable subgroup of participants. Results Of 1,604 villagers aged ≥20 years, 1,462 (91%) were enrolled. Forty-one persons with epilepsy ( PWE) were identified, for a crude prevalence of epilepsy of 28 per 1,000 population (95% confidence interval [CI] = 20.7-38.2). A head CT was performed in 1,228 (84%) of 1,462 participants, including 39 of 41 PWE. CT showed lesions consistent with calcified parenchymal brain cysticerci in 118 (9.6%) cases (95% CI = 8.1-11.4%). No patient had other forms of NCC. Nine of 39 PWE, as opposed to 109 of 1,189 participants without epilepsy, had NCC (23.1% vs. 9.2%, p = 0.004). This difference persisted in the adjusted logistic regression model (odds ratio = 3.04, 95% CI = 1.35-6.81, p = 0.007). Significance This large CT-based study demonstrates that PWE had three times the odds of having NCC than those without epilepsy, providing robust epidemiological evidence favoring the relationship between NCC and epilepsy. [ABSTRACT FROM AUTHOR]

[Re(CO)3([9]aneS3)][BAr′4] ( 1), prepared by reaction of ReBr(CO)5, 1,4,7-trithiacyclononane ([9]aneS3) and NaBAr′4, forms stable, soluble supramolecular adducts with chloride ( 2), bromide, methanosulfonate ( 3) and fluoride ( 4) anions. These new species were characterized by IR, NMR spectroscopy and, for 2 and 3, also by X-ray diffraction. The results of the solid state structure determinations indicate the formation of CH⋅⋅⋅X hydrogen bonds between the anion (X) and the exo-CH groups of the [9]aneS3 ligand, in accord with the relatively large shifts found by 1H NMR spectroscopy in dichloromethane solution for those hydrogens. The stability of the chloride adduct contrasts with the lability of the [9]aneS3 ligand in allyldicarbonyl molybdenum complexes recently studied by us. With fluoride, in dichloromethane solution, a second, minor neutral dimeric species 5 is formed in addition to 4. In 4, the deprotonation of a CH group of the [9]aneS3 ligand, accompanied by CS bond cleavage and dimerization, afforded 5, featuring bridging thiolates. Compounds [Mo(η3-methallyl)(CO)2(TpyN)][BAr′4] ( 6) and [Mo(η3-methallyl)(CO)2(TpyCH)][BAr′4] ( 7) were synthesized by the reactions of [MoCl(η3-methallyl)(CO)2(NCMe)2], NaBAr′4 and tris(2-pyridyl)amine (TpyN) or tris(2-pyridyl)methane (TpyCH) respectively, and characterized by IR and 1H and 13C NMR spectroscopy in solution, and by X-ray diffraction in the solid state. Compound 6 undergoes facile substitution of one of the 2-pyridyl groups by chloride, bromide, and methanosulfonate anions. Stable supramolecular adducts were formed between 7 and chloride, bromide, iodide, nitrate, and perrhenate anions. The solid state structures of these adducts ( 12- 16) were determined by X-ray diffraction. Binding constants in dichloromethane were calculated from 1H NMR titration data for all the new supramolecular adducts. The signal of the bridgehead CH group is the one that undergoes a more pronounced downfield shift when tetrabutylammonium chloride was added to 7, whereas smaller shifts were found for the 2-pyridyl C(3)H groups. In agreement, both types of CH groups form hydrogen bonds to the anions in the solid state structures. [ABSTRACT FROM AUTHOR]

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