Using a panel of U.S. public firms, we present the first evidence highlighting the relation between green technology innovation and cost of equity capital. Consistent with our prediction, we find that greater green technology innovation is associated with lower cost of equity capital. Our results are statistically significant and economically important. Our findings are robust to a battery of sensitivity checks, including use of multiple estimation methods, alternative proxies of green innovation, various measures of cost of equity capital, and potential truncation problem.
Biobanking of live microbiota is becoming indispensable for mechanistic and clinical investigations of drug-microbiome interactions and fecal microbiota transplantation. However, there is a lack of methods to rapidly and systematically evaluate whether the biobanked microbiota maintains their cultivability and functional activity. In this study, we use a rapid ex vivo microbiome assay and metaproteomics to evaluate the cultivability and the functional responses of biobanked microbiota to treatment with a prebiotic (fructo-oligosaccharide, FOS). Our results indicate that the microbiota cultivability and their functional responses to FOS treatment were well maintained by freezing in a deoxygenated glycerol buffer at -80°C for 12 months. We also demonstrate that the fecal microbiota is functionally stable for 48 hours on ice in a deoxygenated glycerol buffer, allowing off-site fecal sample collection and shipping to laboratory for live microbiota biobanking. This study provides a method for rapid evaluation of the cultivability of biobanked live microbiota. Our results show minimal detrimental influences of long-term freezing in deoxygenated glycerol buffer on the cultivability of fecal microbiota.
Muscular dystrophies are a group of rare and severe inherited disorders mainly affecting the muscle tissue. Duchene Muscular Dystrophy, Myotonic Dystrophy types 1 and 2, Limb Girdle Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy are some of the members of this family of disorders. In addition to the current diagnostic tools, there is an increasing interest for the development of novel non-invasive biomarkers for the diagnosis and monitoring of these diseases. miRNAs are small RNA molecules characterized by high stability in blood thus making them ideal biomarker candidates for various diseases. In this study, we present the first genome-wide next-generation small RNA sequencing in serum samples of five different types of muscular dystrophy patients and healthy individuals. We identified many small RNAs including miRNAs, lncRNAs, tRNAs, snoRNAs and snRNAs, that differentially discriminate the muscular dystrophy patients from the healthy individuals. Further analysis of the identified miRNAs showed that some miRNAs can distinguish the muscular dystrophy patients from controls and other miRNAs are specific to the type of muscular dystrophy. Bioinformatics analysis of the target genes for the most significant miRNAs and the biological role of these genes revealed different pathways that the dysregulated miRNAs are involved in each type of muscular dystrophy investigated. In conclusion, this study shows unique signatures of small RNAs circulating in five types of muscular dystrophy patients and provides a useful resource for future studies for the development of miRNA biomarkers in muscular dystrophies and for their involvement in the pathogenesis of the disorders.
It is expected that diseases are likely to spread to newer areas, and high-income countries may experience some illnesses that may have been restricted to low or middle-income countries. In addition, following the Intergovernmental Panel on Climate Change, the present study noted that climate change is likely to have many effects on the spatial and temporal distribution of malaria in many Sub-Saharan African countries. This study examines climate change effects on the geographical distribution of malaria occurrence and how extreme climatic events may perhaps be determining factors in the range of vectors for human diseases in SSA in the nearest future. Here, the study appraisals the symbiotic connection of (1) malaria transmission and association with the changes in temperature, rainfall, and humidity as well as their extremes in SSA and (2) the relationship between climate and malaria with the role of climate change in determining upsurge in malaria and meningitis occurrences in the SSA. The study concludes that major drivers of malaria occurrence are climatic elements such as precipitation and temperature. Therefore, we call for a better early Warning System on a proposed roadmap solution for Sub-Saharan Africa.
Background and objective: Triple therapy with an inhaled corticosteroid (ICS), a long-acting β2-agonist bronchodilator (LABA) and a long-acting muscarinic antagonist (LAMA) is recommended as step-up therapy for chronic obstructive pulmonary disease (COPD) patients who continue to have persistent symptoms and increased risk of exacerbation despite treatment with dual therapy. We sought to evaluate different treatment pathways through which COPD patients were escalated to triple therapy. Methods: We used population health databases from Ontario, Canada to identify individuals aged 66 or older with COPD who started triple therapy between 2014 and 2017. Median time from diagnosis to triple therapy was estimated using the Kaplan-Meier method. We classified treatment pathways based on treatments received prior to triple therapy and evaluated whether pathways differed by exacerbation history, blood eosinophil counts or time period. Results: Among 4108 COPD patients initiating triple therapy, only 41.2% had a COPD exacerbation in the year prior. The three most common pathways were triple therapy as initial treatment (32.5%), LAMA to triple therapy (29.8%), and ICS + LABA to triple therapy (15.4%). Median time from diagnosis to triple therapy was 362 days (95% confidence interval:331-393 days) overall, but 14 days (95% CI 12-17 days) in the triple therapy as initial treatment pathway. This pathway was least likely to contain patients with frequent or severe exacerbations (22.0% vs. 31.5%, p < 0.001) or with blood eosinophil counts ≥300 cells/µL (18.9% vs. 22.0%, p < 0.001). Conclusion: Real-world prescription of triple therapy often does not follow COPD guidelines in terms of disease severity and prior treatments attempted.
Background Careful development of interventions using principles of co-production is now recognized as an important step for clinical trial development, but practical guidance on how to do this in practice is lacking. This paper aims (1) provide practical guidance for researchers to co-produce interventions ready for clinical trial by describing the 4-stage process we followed, the challenges experienced and practical tips for researchers wanting to co-produce an intervention for a clinical trial; (2) describe, as an exemplar, the development of our intervention package. Method We used an Integrated Knowledge Translation (IKT) approach to co-produce a telehealth-delivered exercise program for people with stroke. The 4-stage process comprised of (1) a start-up planning phase with the co-production team. (2) Content development with knowledge user informants. (3) Design of an intervention protocol. (4) Protocol refinement. Results and reflections The four stages of intervention development involved an 11-member co-production team and 32 knowledge user informants. Challenges faced included balancing conflicting demands of different knowledge user informant groups, achieving shared power and collaborative decision making, and optimising knowledge user input. Components incorporated into the telehealth-delivered exercise program through working with knowledge user informants included: increased training for intervention therapists; increased options to tailor the intervention to participant’s needs and preferences; and re-naming of the program. Key practical tips include ways to minimise the power differential between researchers and consumers, and ensure adequate preparation of the co-production team. Conclusion Careful planning and a structured process can facilitate co-production of complex interventions ready for clinical trial. Graphical Abstract
This paper aims to explore the ways which expertise is covertly racialized in the contemporary humanitarian aid sector. While there are considerable discussions on the expat-local divide among aid professionals, such dichotomization is still inherently nationality-based, which may be an over-simplified explanation of the group dimensions within aid organizations. This study seeks to uncover that professional categorizations of “expatriate” and “local” are not race-neutral and, instead, colorblind. Organizations within the contemporary humanitarian aid apparatus have come to appeal to what Michael Omi and Howard Winant would characterize as a new racial discourse—one that does not require explicit references to race in order to be perpetuated, as racial subordination has been reconfigured to rely on implicit references to race woven within the everyday social fabrics of the humanitarian profession. The research suggests that embedded under the contemporary professional structure of the liberal humanitarian space is a covert power hierarchy fueled by perceptions of expertise and competency along racial lines—particularly around one’s whiteness.
Background Kuwait had its first COVID-19 in late February, and until October 6, 2020 it recorded 108,268 cases and 632 deaths. Despite implementing one of the strictest control measures-including a three-week complete lockdown, there was no sign of a declining epidemic curve. The objective of the current analyses is to determine, hypothetically, the optimal timing and duration of a full lockdown in Kuwait that would result in controlling new infections and lead to a substantial reduction in case hospitalizations. Methods The analysis was conducted using a stochastic Continuous-Time Markov Chain (CTMC), eight state model that depicts the disease transmission and spread of SARS-CoV 2. Transmission of infection occurs between individuals through social contacts at home, in schools, at work, and during other communal activities. Results The model shows that a lockdown 10 days before the epidemic peak for 90 days is optimal but a more realistic duration of 45 days can achieve about a 45% reduction in both new infections and case hospitalizations. Conclusions In the view of the forthcoming waves of the COVID19 pandemic anticipated in Kuwait using a correctly-timed and sufficiently long lockdown represents a workable management strategy that encompasses the most stringent form of social distancing with the ability to significantly reduce transmissions and hospitalizations.
Background: Dental personnel are at risk of developing occupational contact dermatitis. Objectives: The aims of the study were to determine prevalence of occupational contact dermatitis in dental personnel referred for patch testing and to characterize relevant allergens and sources. Methods: The study used a retrospective, cross-sectional analysis of the North American Contact Dermatitis Group (NACDG) data, 2001-2018. Results: Of 41,109 patients, 585 (1.4%) were dental personnel. Dental personnel were significantly more likely than nondental personnel to be female (75.7% vs 67.4%, P < 0.0001), have occupationally related dermatitis (35.7% vs 11.5%, P < 0.0001), and/or have primary hand involvement (48.6% vs 22.5%, P < 0.0001). More than one quarter of dental personnel (62/585, 27.7%) had 1 or more occupationally related allergic patch test reaction(s). There were 249 occupationally related reactions to NACDG screening allergens, most commonly glutaraldehyde (18.1%), thiuram mix (16.1%), and carba mix (14.1%). The most common sources of NACDG screening allergens were gloves (30.7%), dental materials (26.6%), and sterilizing solutions (13.1%). Seventy-three dental personnel (12.5%) had 1 or more positive patch test reactions to occupationally related allergen(s)/substances not on the screening series. Occupationally related irritant contact dermatitis was identified in 22.2% (n = 130) of dental personnel, most commonly to nonskin soaps/detergents/disinfectants (32.0%). Conclusions: Occupational contact dermatitis is common in dental personnel referred for patch testing. Comprehensive testing beyond screening series is important in these patients.
In simulation-based education, there is growing interest in the effects of emotions on learning from simulation sessions. The perception that emotions have an important impact on performance and learning is supported by the literature. Emotions are pervasive: at any given moment, individuals are in one emotional state or another. Emotions are also powerful: they guide ongoing cognitive processes in order to direct attention, memory and judgment towards addressing the stimulus that triggers the emotion. This occurs in a predictable way. The purpose of this paper is to present a narrative overview of the research on emotions, cognitive processes and learning, in order to inform the simulation community of the potential role of emotions during simulation-based education.
Background Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants. Results We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes. Conclusions Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS.
The relatively poor settling characteristics of particles produced in moving bed biofilm reactor (MBBR) outline the importance of developing a fundamental understanding of the characterization and settleability of MBBR-produced solids. The influence of carrier geometric properties and different levels of biofilm thickness on biofilm characteristics, solids production, particle size distribution (PSD), and particle settling velocity distribution (PSVD) is evaluated in this study. The analytical ViCAs method is applied to the MBBR effluent to assess the distribution of particle settling velocities. This method is combined with microscopy imaging to relate particle size distribution to settling velocity. Three conventionally loaded MBBR systems are studied at a similar loading rate of 6.0 g/m²•day and with different carrier types. The AnoxK™ K5 carrier, a commonly used carrier, is compared to so-called thickness-restraint carriers, AnoxK™ Z-carriers that are newly designed carriers to limit the biofilm thickness. Moreover, two levels of biofilm thickness, 200 μm and 400 μm, are studied using AnoxK™ Z-200 and Z-400 carriers. Statistical analysis confirms that K5 carriers demonstrated a significantly different biofilm mass, thickness, and density, in addition to distinct trends in PSD and PSVD in comparison with Z-carriers. However, in comparison of thickness-restraint carriers, Z-200 carrier results did not vary significantly compared to the Z-400 carrier. The K5 carriers showed the lowest production of suspended solids (0.7 ± 0.3 g-TSS/day), thickest biofilm (281.1 ± 8.7 μm) and lowest biofilm density (65.0 ± 1.5 kg/m³). The K5 effluent solids also showed enhanced settling behaviour, consisting of larger particles with faster settling velocities.
Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following the first and second COVID-19 vaccine doses, and again 3 months following the second dose, in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525–935) cells/mm ³ , though nadir CD4+ T-cell counts ranged as low as <10 cells/mm ³ . After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with lower anti-RBD antibody concentrations and ACE2 displacement activity after one vaccine dose. Following two doses however, HIV was not significantly associated with the magnitude of any humoral response after multivariable adjustment. Rather, older age, a higher burden of chronic health conditions, and dual ChAdOx1 vaccination were associated with lower responses after two vaccine doses. No significant correlation was observed between recent or nadir CD4+ T-cell counts and responses to two vaccine doses in PLWH. These results indicate that PLWH with well-controlled viral loads and CD4+ T-cell counts in a healthy range generally mount strong initial humoral responses to dual COVID-19 vaccination. Factors including age, co-morbidities, vaccine brand, response durability and the rise of new SARS-CoV-2 variants will influence when PLWH will benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment or who have low CD4+ T-cell counts are needed, as are longer-term assessments of response durability.
Background The Canadian government has committed to developing a national strategy for drugs for rare diseases starting in 2022. Considering this announcement, we conducted a comparative analysis to examine patient access to therapies for rare disease in Canada relative to Europe and the U.S. Methods Given its similarity to the Canadian health care system, we used Europe as the reference point to analyze all of the therapies with an orphan drug designation approved by the European Medicine Agency (EMA) from 1 January 2015 to 31 March 2020. We then contrasted access to these drugs in Canada (Health Canada) and the U.S. (Food and Drug Administration, FDA). We focused on: (1) the number of therapies for rare diseases entering the Canadian market; (2) the percentage of these therapies that are publicly available to Canadians; and (3) the timelines for patients to access these therapies in Canada. Results Sixty-three approved therapies with an orphan drug designation from the EMA were identified. Fifty-three (84%) of these drugs had also been submitted to the FDA for approval, and 41 (65%) were submitted to Health Canada for approval. In Europe, Germany, Denmark, and the U.K. had the highest percentage of publicly reimbursed orphan drugs (84%, 70%, 68%, respectively). In comparison, Ontario (32%), Quebec (25%), and Alberta (25%) had the highest percentage of drugs reimbursed among the Canadian provinces. The shortest median duration (in months) from EMA approval to jurisdictional decision on reimbursement was in Austria (3.2), followed by Germany (4.1), and Finland (6.0). In Canada, the shortest median duration (in months) from regulatory approval to reimbursement was in British Columbia (17.3), Quebec (19.6) and Manitoba (19.6), while the longest duration was in P.E.I (38.5), followed by Nova Scotia (25.9), and Newfoundland (25.1). Conclusions Our comparative analysis found that relative to the EU Canadians had less frequent and timely access to therapies for rare diseases. This highlights the need for a rare disease strategy in Canada that allows for clear identification and transparent tracking of the pathway for rare disease drugs, and ultimately optimizes the number of patients with access to these therapies.
Many individuals living with severe mental illness, such as schizophrenia, present cognitive deficits and reasoning biases negatively impacting clinical and functional trajectories. Remote cognitive assessment presents many opportunities for advancing research and treatment but has yet to be widely used in psychiatric populations. We conducted a scoping review of remote cognitive assessment in severe mental illness to provide an overview of available measures and guide best practices. Overall, 34 studies ( n = 20,813 clinical participants) were reviewed and remote measures, psychometrics, facilitators, barriers, and future directions were synthesized using a logic model. We identified 82 measures assessing cognition in severe mental illness across 11 cognitive domains and four device platforms. Remote measures were generally comparable to traditional versions, though psychometric properties were infrequently reported. Facilitators included standardized procedures and wider recruitment, whereas barriers included imprecise measure adaptations, technology inaccessibility, low patient engagement, and poor digital literacy. Our review identified several remote cognitive measures in psychiatry across all cognitive domains. However, there is a need for more rigorous validation of these measures and consideration of potentially influential factors, such as sex and gender. We provide recommendations for conducting remote cognitive assessment in psychiatry and fostering high-quality research using digital technologies.
Background and objectives Safety and effectiveness concerns may preclude physicians from recommending vaccination in mild/moderate inborn errors of immunity (IEI). This study describes attitudes and practices regarding vaccination among physicians who care for patients with mild/moderate B cell or mild/moderate combined immunodeficiencies (CID) and vaccination completeness among patients diagnosed with IEIs. Methods Canadian physicians caring for children with IEI were surveyed about attitudes and practices regarding vaccination in mild/moderate IEI. Following informed consent, immunization records of pediatric patients with IEI evaluated before 7 years of age were reviewed. Vaccine completeness was defined at age 2 years as 4 doses of diphtheria-tetanus-pertussis (DTaP), 3 doses pneumococcal conjugate (PCV), and 1 dose measles-mumps-rubella (MMR) vaccines. At 7 years 5 doses of DTP and 2 doses MMR were required. Results Forty-five physicians from 8 provinces completed the survey. Most recommended inactivated vaccines for B cell deficiency: (84% (38/45) and CID (73% (33/45). Fewer recommended live attenuated vaccines (B cell: 53% (24/45), CID 31% (14/45)). Of 96 patients with IEI recruited across 7 centers, vaccination completeness at age 2 was 25/43 (58%) for predominantly antibody, 3/13 (23%) for CID, 7/35 (20%) for CID with syndromic features, and 4/4 (100%) for innate/phagocyte defects. Completeness at age 7 was 15%, 17%, 5%, and 33%, respectively. Conclusion Most physicians surveyed recommended inactivated vaccines in children with mild to moderate IEI. Vaccine completeness for all IEI was low, particularly at age 7. Further studies should address the reasons for low vaccine uptake among children with IEI and whether those with mild-moderate IEI, where vaccination is recommended, eventually receive all indicated vaccines.
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