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ABSTRACTIntroductionStudies in patients with immune-mediated inflammatory diseases (IMIDs) have inconsistently suggested that anti-TNFα therapy may be associated with excessive weight gain.Areas coveredWe performed a nested case/non-case analysis to investigate the anti-TNF-α inhibitor-associated body-changes in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. The risk was expressed as a measure of disproportionality using the reporting odds ratio (ROR) while adjusting for sex, drugs known to cause weight gain and reporter type. We also performed a time-to-onset (TTO) analysis of body weight-related events.ResultsInfliximab was the most commonly involved TNF-α inhibitor in body weight-related changes, reaching an aROR of 1.42 (95%CI:1. 26; 1.59). An increased risk was especially found in patients affected by rheumatic disorders, both in the adult and pediatric population. The median TTO after the start of anti- TNFα therapy was about 6–7 months for both children and adults.ConclusionsGiven the potential effect of these agents on the excess weight gain in IMIDs patients, continuous attention for this side effect with appropriate counseling regarding lifestyle modifications are warranted, especially in those at high risk for obesity.

The International Bear News has announced the registration information for the IBA 28th Conference in Edmonton, Alberta, Canada in 2024. Early registration discounts have closed, but there are still spots available. The conference offers various benefits, including receptions, breakfasts, coffee breaks, and special sessions on indigenous perspectives. Registration rates vary for IBA members and non-members, with discounts available for members. Additional banquet tickets can be purchased for guests. The conference provides an opportunity to form new relationships and explore unique sites in the Edmonton area. [Extracted from the article]

Chinese hamster ovary (CHO) cells are a mammalian cell line used in the production of therapeutic proteins. Host cell proteins (HCPs) are process-related impurities that are derived from the host cell expression system. During biopharmaceutical drug development, removal of HCPs is required. Enzyme-linked immunosorbent assay (ELISA) is a common technique to quantitate HCPs, but is a labor-intensive process that takes up to 7 h. Ella®is an automated instrument that utilizes microfluidics and glass nanoreactors to quantitate HCPs in 75 min using similar ELISA reagents. The antibodies and antigens are captured on three distinct glass nanoreactors, resulting in sensitive reproducible data. Our results indicate that Ella quantitates CHO HCPs with precision, accuracy, sensitivity and trends comparable with our traditional CHO HCP ELISA.

AbstractPurpose:It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off values for CEA and CA19-9 are disputable. This study aimed to assess the value of CEA and CA19-9 serum levels at diagnosis of pancreatic ductal adenocarcinoma (PDAC) as predictors for the advanced stage of PDAC in patients discussed at pancreatic multidisciplinary team (MDT) meetings.Methods:Patients with suspected PDAC discussed at MDT meetings from 2013 to 2017 were reviewed, in order to determine optimal cut-off values of both CEA and CA19-9.Results:In total, 375 patients were included. Optimal cut-off values for predicting advanced PDAC were 7.0 ng/ml for CEA and 305.0 U/ml for CA19-9, resulting in positive predictive values of 83.3%, 73.6%, and 91.4% for CEA, CA19-9 and combined, respectively. Both tumour markers were independent predictors of advanced PDAC, demonstrated by an odds ratio of 4.21 (95% CI:1.85–9.56; p = 0.001) for CEA and 2.58 for CA19-9 (95% CI:1.30–5.14; p = 0.007).Conclusions:CEA appears to be a more robust predictor of advanced PDAC than CA19-9. Implementing CEA and CA19-9 serum levels during MDT meetings as an additional tool for establishing tumour resectability is worthwhile for tailored diagnostics.

The 28th International Association for Bear Research and Management Conference will be held in Edmonton, Alberta, Canada in September 2024. The conference will feature scientific papers, a special session on Indigenous perspectives, and opportunities for networking and collaboration. The call for abstracts is open until March 1, 2024, and travel grant applications are also being accepted until the same date. Attendees are encouraged to stay at the preferred hotels to support the conference and receive discounted rates. Registration rates vary depending on membership status and the date of registration. [Extracted from the article]

To explore ethics education needs in Canadian Neonatal Perinatal Medicine (NPM) training programs.

Grizzly bear (Ursus arctos) conflicts with humans, including livestock depredation on public land grazing allotments, have increased during the last several decades within the Greater Yellowstone Ecosystem (GYE) in the western United States as the grizzly bear population has grown in number and occupied range. Minimizing conflicts and improving conservation efficacy requires information on the relationships between livestock depredations, allotment management, grizzly bear habitat conditions, and their interactions. We used generalized linear mixed models to evaluate spatio‐temporal relationships between grizzly bear depredation of livestock and the characteristics of 316 United States Department of Agriculture Forest Service and National Park Service grazing allotments in the GYE during 1992–2014. We evaluated relationships at 2 spatial extents, representing daily and annual grizzly bear activity areas. During the study period, more grazing allotments became occupied by grizzly bears and most livestock depredations were associated with these areas of population expansion. Number of livestock (β = 1.15 ± 0.19 [SE]) and grizzly bear density index (β = 1.13 ± 0.10) had the greatest effects on the number of livestock depredation events relative to other allotment attributes. Estimated number of depredation events increased by approximately 20% when cow‐calf pairs increased by 100 pairs and grizzly bear density index increased by 1 bear/196 km2(the average annual home‐range size of a female grizzly bear in the GYE). Additionally, grazing allotment size was positively related to the number of depredation events (β = 0.56 ± 0.16), whereas the presence of bull cattle or horses was associated with an approximately 50% reduction in depredations (β = −0.71 ± 0.37). Livestock depredation events were greater for allotments with lower road density (β = −0.89 ± 0.28), less rugged terrain (β = −0.57 ± 0.25), higher vegetative primary productivity (β = 0.33 ± 0.16), and more whitebark pine coverage (β = 0.30 ± 0.15). Relationships between depredations and grizzly bear habitat conditions varied across spatial extents. As the grizzly bear population continues to expand, natural resource managers and livestock producers could focus efforts on allotments with a higher density of grizzly bears, fewer roads, and quality grizzly bear habitat, including higher vegetative productivity, when developing cooperative management plans and preventative measures to reduce the likelihood of depredation. The perspectives gained from our analysis provide context for long‐term, landscape‐level planning to accommodate livestock production on public lands while meeting conservation goals for grizzly bears. © 2018 The Wildlife Society. United States Department of Agriculture Forest Service and National Park Service grazing allotment characteristics, including indices of human presence and the number of livestock and grizzly bears, were associated with annual grizzly bear depredations on livestock during 1992–2014 in the Greater Yellowstone Ecosystem, USA. Managers can consider these relationships for long‐term, landscape‐level planning and conservation, and to focus future public land grizzly bear‐livestock conflict studies.

Assessment and stabilization of the newborn are expected competencies of trainees graduating from Canadian paediatrics residency training programs. There is limited evidence regarding the optimal approach to training, and whether such competencies are actually achieved by graduates. A national, cross-sectional survey was developed to explore paediatrics residents' self-reported experiences in performing neonatal procedures and resuscitation skills. Survey questions were constructed based on the review of the Royal College of Physicians and Surgeons of Canada objectives of training in paediatrics to include activities necessary in the assessment and stabilization of the newborn. The survey was distributed to residents across Canada. A total of 138 residents from 15 Canadian paediatrics residency training programs completed the survey. A minority of residents (17%) reported independently performing resuscitative skills (positive pressure ventilation, intubation and umbilical line insertion). Of all the different neonatal procedural skills, only lumbar puncture was reported as an activity that residents on average performed independently by senior years of training. Our study showed a direct relationship between the number of completed blocks of Neonatal Intensive Care Unit (NICU) and self-reported experiences in providing NICU resuscitation skills and procedures. We found an inverse relationship between the exposure to cross-cover calls and such experiences. Our study showed that a minority of paediatrics residents self-report evidence of competency in performing neonatal procedures and resuscitation skills. As residency programs are transitioning toward competence-based education, it is important to gain more insights with respect to strengths, deficiencies and opportunities for paediatrics residency training in terms of NICU experiences.

Background Parental bereavement after the death of an infant in a neonatal intensive care unit (NICU) is a complex and nuanced experience. Support from healthcare practitioners can have a significant impact on bereavement experiences in the short- and long-term. Although several studies exist exploring parental perceptions of their experience of loss and bereavement, there has not been a recent review of beneficial practices and common themes in the current literature.Objective This review synthesizes empirical research to identify considerations that ought to guide the caregiving practices of healthcare professionals to support parental bereavement.Settings/subjects Data was collected from studies identified in MEDLINE, Embase, and CINAHL. The search was limited to English-language studies describing parental bereavement in the NICU population from January 1990 to November 2021.Results Of 583 studies initially identified, 47 studies of varying geographic locations were included in this review. Various themes surrounding healthcare support in parental bereavement were identified including ensuring the opportunity for parents to spend time caring for their child, understanding their perception of infant suffering, recognizing the impact of communication experiences with healthcare providers, and offering access to alternative means of support, all of which have been described as suboptimal. Parents generally want the opportunity to say goodbye to their infant in a private and safe space, be supported through their decision-making and be offered bereavement follow-up after loss.Conclusion This review identifies methods of support in parental bereavement based on first-hand parental experiences and routine implementation of these strategies may be beneficial in supporting parents through their bereavement after the loss of a baby in the NICU.

COVID-19 vaccines have been widely used to control the SARS-CoV-2 pandemic. In individuals receiving replication-incompetent, adenovirus vector–based COVID-19 vaccines (eg, ChAdOx1 nCoV-19 [AstraZeneca] or Ad26.COV2.S [Johnson & Johnson/Janssen] vaccines), a very rare but serious adverse reaction has been reported and described as vaccine-induced immune thrombotic thrombocytopenia (VITT). The exact mechanism of VITT following Ad26.COV2.S vaccination is under investigation. Antibodies directed against human platelet factor 4 (PF4) are considered critical in the pathogenesis of VITT, suggesting similarities with heparin-induced thrombocytopenia. It has been postulated that components of these vaccines mimic the role of heparin by binding to PF4, triggering production of these anti-PF4 antibodies.

Paediatric training programs are committed to graduating paediatricians able to function independently in professional practice. The focus of this study was to gain understanding of a training program's strengths and deficiencies, while also exploring new methods to aid in transitioning trainees into practice.

More than 1·8 million new cases of HIV-1 infection were diagnosed worldwide in 2016. No licensed prophylactic HIV-1 vaccine exists. A major limitation to date has been the lack of direct comparability between clinical trials and preclinical studies. We aimed to evaluate mosaic adenovirus serotype 26 (Ad26)-based HIV-1 vaccine candidates in parallel studies in humans and rhesus monkeys to define the optimal vaccine regimen to advance into clinical efficacy trials.

The heavily glycosylated native-like envelope (Env) trimer of HIV-1 is expected to have low immunogenicity, whereas misfolded forms are often highly immunogenic. High-quality correctly folded Envs may therefore be critical for developing a vaccine that induces broadly neutralizing antibodies. Moreover, the high variability of Env may require immunizations with multiple Envs. Here, we report a universal strategy that provides for correctly folded Env trimers of high quality and yield through a repair-and-stabilize approach. In the repair stage, we utilized a consensus strategy that substituted rare strain-specific residues with more prevalent ones. The stabilization stage involved structure-based design and experimental assessment confirmed by crystallographic feedback. Regions important for the refolding of Env were targeted for stabilization. Notably, the α9-helix and an intersubunit β sheet proved to be critical for trimer stability. Our approach provides a means to produce prefusion-closed Env trimers from diverse HIV-1 strains, a substantial advance for vaccine development.