Congenital heart disease (CHD) is an indication which spans multiple specialties across various genetic counseling practices. This practice resource aims to provide guidance on key considerations ...when approaching counseling for this particular indication while recognizing the rapidly changing landscape of knowledge within this domain. This resource was developed with consensus from a diverse group of certified genetic counselors utilizing literature relevant for CHD genetic counseling practice and is aimed at supporting genetic counselors who encounter this indication in their practice both pre‐ and postnatally.
Directly-funded home care (DF) provides government funds to people who need assistance with the activities of daily living, allowing them to arrange their own services. As programs expand globally, ...many allow DF clients to hire home care agencies to organize their services rather than finding their own workers. In Canada, half of the DF home care programs allow users to purchase agency services. The goal of this research is to describe the role of agency providers in DF home care in Canada and consider potential equity implications for service access from the perspectives of clients and families.
Framed with intersectionality, the study included online focus groups with families and clients (n = 56) in the two Canadian provinces of Alberta and Manitoba between June 2021-April 2022. All transcripts underwent qualitative thematic analysis using open and axial coding techniques. Each transcript was analyzed by two of three possible independent coders using Dedoose qualitative analysis software.
The article presents five thematic findings. First, the focus groups document high rates of satisfaction with the care regardless of whether the client uses agency providers. Second, agency providers mediate some of the administrative barriers and emotional strain of using DF home care, and this is especially important for family caregivers who are working or have additional care responsibilities. Third, there are out-of-pocket expenses reported by most participants, with agency clients describing administrative fees despite lower pay for the frontline care workers. Fourth, agencies are not generally effective for linguistic and/or cultural matching between workers and families. Finally, we find that DF care programs cannot compensate for a limited informal support network.
Clients and families often intentionally choose DF home care after negative experiences with other public service options, yet the results suggest that in some Canadian contexts, DF home care is a privilege only afforded to some. Given the growing inequalities that exist in Canadian society, all public home care options must be open to all who need it, irrespective of ability to pay, degree of social support, or competence in the English language.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Licensed premises face particular challenges to operating safely within COVID-19 restrictions. Following a U.K. national lockdown from March 20, 2020, we studied business practices and behaviors in ...licensed premises to inform COVID-19 policies. To our knowledge, no previous study worldwide has examined these issues.
Before premises reopened in Scotland, we conducted in-depth telephone interviews (May-June 2020) with participants from hospitality trade associations, licensed premises, or in related roles (n = 18). Interviews focused on anticipated business practices and challenges relevant to minimizing COVID-19 transmission. Following reopening (July-August 2020), we conducted observations of relevant practices and behaviors in 29 bars purposively sampled for diversity, using a structured schedule. Interviews and observation reports were analyzed thematically.
Interviewees generally sought clarity, flexibility, and balance in government guidance on reopening, and they cited commercial and practical challenges to doing so safely. Alcohol consumption was perceived as an additional but potentially manageable challenge. Most observed premises had made physical and operational modifications; however, practices were variable. Observed incidents of concern included close physical interaction between customers and with staff, frequently featuring alcohol intoxication and rarely effectively stopped by staff.
Despite the efforts of bar operators and guidance from government, potentially significant risks of COVID-19 transmission persisted in a substantial minority of observed bars, especially when customers were intoxicated.
This article empirically examines the extent to which the co-occurrence of the maltreatment of companion animals and intimate partner violence (IPV) previously documented in samples of women ...accessing services from domestic violence shelters extends to a nationally representative sample of the general Canadian population, with a specific focus on emotional and financial abuse. Using data from the intimate partner victimization module of the 2014 Canadian General Social Survey (n = 17,950), the authors find that reporting one’s intimate partner threatened or abused companion animals in the home increased the probability that one had experienced at least one form of emotional abuse or financial abuse by 38.6% (p ≤ .001) and 7.5% (p ≤ .001), respectively, net of several key control variables. Moreover, the findings indicate that those who identify as women are significantly more likely to report their partner emotionally or financially abused them and threatened or mistreated their pet(s); the connection between animal maltreatment and IPV is particularly pronounced for emotional IPV when compared with other forms of IPV; challenge the commonplace conceptualization of animal abuse as a form of property abuse; and suggest a need for a more nuanced understanding of IPV perpetrators vis-à-vis animal maltreatment. This is the first study to use nationally representative data to assess the co-occurrence of animal abuse and IPV, and as such, it makes significant contributions to the interdisciplinary literature on animal abuse and IPV.
Neurospora crassa has served as a model organism for studying circadian pathways and more recently has gained attention in the biofuel industry due to its enhanced capacity for cellulase production. ...However, in order to optimize N. crassa for biotechnological applications, metabolic pathways during growth under different environmental conditions must be addressed. Reverse-transcription quantitative PCR (RT-qPCR) is a technique that provides a high-throughput platform from which to measure the expression of a large set of genes over time. The selection of a suitable reference gene is critical for gene expression studies using relative quantification, as this strategy is based on normalization of target gene expression to a reference gene whose expression is stable under the experimental conditions. This study evaluated twelve candidate reference genes for use with N. crassa when grown in continuous culture bioreactors under different light and temperature conditions. Based on combined stability values from NormFinder and Best Keeper software packages, the following are the most appropriate reference genes under conditions of: (1) light/dark cycling: btl, asl, and vma1; (2) all-dark growth: btl, tbp, vma1, and vma2; (3) temperature flux: btl, vma1, act, and asl; (4) all conditions combined: vma1, vma2, tbp, and btl. Since N. crassa exists as different cell types (uni- or multi-nucleated), expression changes in a subset of the candidate genes was further assessed using absolute quantification. A strong negative correlation was found to exist between ratio and threshold cycle (CT) values, demonstrating that CT changes serve as a reliable reflection of transcript, and not gene copy number, fluctuations. The results of this study identified genes that are appropriate for use as reference genes in RT-qPCR studies with N. crassa and demonstrated that even with the presence of different cell types, relative quantification is an acceptable method for measuring gene expression changes during growth in bioreactors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUNDInitial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. ...Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.METHODSWe prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data.RESULTSTwenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C.CONCLUSIONPediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.FUNDINGFinancial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex's Lemonade Stand Foundation for Childhood Cancer; Children's Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.
Autism spectrum disorder (ASD).
2018.
The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates ASD prevalence and monitors timing of ASD ...identification among children aged 4 and 8 years. This report focuses on children aged 4 years in 2018, who were born in 2014 and had a parent or guardian who lived in the surveillance area in one of 11 sites (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin) at any time during 2018. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement (diagnosis) in an evaluation, 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code. Suspected ASD also was tracked among children aged 4 years. Children who did not meet the case definition for ASD were classified as having suspected ASD if their records contained a qualified professional's statement indicating a suspicion of ASD.
For 2018, the overall ASD prevalence was 17.0 per 1,000 (one in 59) children aged 4 years. Prevalence varied from 9.1 per 1,000 in Utah to 41.6 per 1,000 in California. At every site, prevalence was higher among boys than girls, with an overall male-to-female prevalence ratio of 3.4. Prevalence of ASD among children aged 4 years was lower among non-Hispanic White (White) children (12.9 per 1,000) than among non-Hispanic Black (Black) children (16.6 per 1,000), Hispanic children (21.1 per 1,000), and Asian/Pacific Islander (A/PI) children (22.7 per 1,000). Among children aged 4 years with ASD and information on intellectual ability, 52% met the surveillance case definition of co-occurring intellectual disability (intelligence quotient ≤70 or an examiner's statement of intellectual disability documented in an evaluation). Of children aged 4 years with ASD, 72% had a first evaluation at age ≤36 months. Stratified by census-tract-level median household income (MHI) tertile, a lower percentage of children with ASD and intellectual disability was evaluated by age 36 months in the low MHI tertile (72%) than in the high MHI tertile (84%). Cumulative incidence of ASD diagnosis or eligibility received by age 48 months was 1.5 times as high among children aged 4 years (13.6 per 1,000 children born in 2014) as among those aged 8 years (8.9 per 1,000 children born in 2010). Across MHI tertiles, higher cumulative incidence of ASD diagnosis or eligibility received by age 48 months was associated with lower MHI. Suspected ASD prevalence was 2.6 per 1,000 children aged 4 years, meaning for every six children with ASD, one child had suspected ASD. The combined prevalence of ASD and suspected ASD (19.7 per 1,000 children aged 4 years) was lower than ASD prevalence among children aged 8 years (23.0 per 1,000 children aged 8 years).
Groups with historically lower prevalence of ASD (non-White and lower MHI) had higher prevalence and cumulative incidence of ASD among children aged 4 years in 2018, suggesting progress in identification among these groups. However, a lower percentage of children with ASD and intellectual disability in the low MHI tertile were evaluated by age 36 months than in the high MHI group, indicating disparity in timely evaluation. Children aged 4 years had a higher cumulative incidence of diagnosis or eligibility by age 48 months compared with children aged 8 years, indicating improvement in early identification of ASD. The overall prevalence for children aged 4 years was less than children aged 8 years, even when prevalence of children suspected of having ASD by age 4 years is included. This finding suggests that many children identified after age 4 years do not have suspected ASD documented by age 48 months.
Children born in 2014 were more likely to be identified with ASD by age 48 months than children born in 2010, indicating increased early identification. However, ASD identification among children aged 4 years varied by site, suggesting opportunities to examine developmental screening and diagnostic practices that promote earlier identification. Children aged 4 years also were more likely to have co-occurring intellectual disability than children aged 8 years, suggesting that improvement in the early identification and evaluation of developmental concerns outside of cognitive impairments is still needed. Improving early identification of ASD could lead to earlier receipt of evidence-based interventions and potentially improve developmental outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The proteasome was validated as an oncology target following the clinical success of VELCADE (bortezomib) for injection for the treatment of multiple myeloma and recurring mantle cell lymphoma. ...Consequently, several groups are pursuing the development of additional small-molecule proteasome inhibitors for both hematologic and solid tumor indications. Here, we describe MLN9708, a selective, orally bioavailable, second-generation proteasome inhibitor that is in phase I clinical development. MLN9708 has a shorter proteasome dissociation half-life and improved pharmacokinetics, pharmacodynamics, and antitumor activity compared with bortezomib. MLN9708 has a larger blood volume distribution at steady state, and analysis of 20S proteasome inhibition and markers of the unfolded protein response confirmed that MLN9708 has greater pharmacodynamic effects in tissues than bortezomib. MLN9708 showed activity in both solid tumor and hematologic preclinical xenograft models, and we found a correlation between greater pharmacodynamic responses and improved antitumor activity. Moreover, antitumor activity was shown via multiple dosing routes, including oral gavage. Taken together, these data support the clinical development of MLN9708 for both hematologic and solid tumor indications.
Type-I Diabetes (T1D) is caused by defective immunotolerance mechanisms enabling autoreactive T cells to escape regulation in lymphoid organs and destroy insulin-producing β-cells in the pancreas, ...leading to insulin dependence. Strategies to promote β-cell tolerance could arrest T1D. We previously showed that secretion of secondary lymphoid chemokine CCL21 by CCL21 transgenic β-cells induced tolerance and protected non-obese diabetic (NOD) mice from T1D. T1D protection was associated with formation of lymph node-like stromal networks containing tolerogenic fibroblastic reticular cells (FRCs). Here, we developed a polyethylene glycol (PEG) hydrogel platform with hydrolytically degradable PEG-diester dithiol crosslinkers to provide controlled and sustained delivery of CCL21 and β-cell antigens for at least 28 days in vitro and recapitulate properties associated with the tolerogenic environment of CCL21 transgenic β-cells in our previous studies. CCL21 and MHC-II restricted antigens were tethered to gels via simple click-chemistry while MHC-I restricted antigens were loaded in PEG-based polymeric nanovesicles and incorporated in the gel networks. CCL21 and antigen release kinetics depended on the PEG gel tethering strategy and the linkers. Importantly, in vitro functionality, chemotaxis, and activation of antigen-specific T cells were preserved. Implantation of CCL21 and β-cell antigen gels under the kidney capsule of pre-diabetic NOD mice led to enrichment of adoptively transferred antigen-specific T cells, formation of gp38 + FRC-like stromal cell networks, and increased regulation of specific T cells with reduced accumulation within pancreatic islets. Thus, our platform for sustained release of β-cell antigens and CCL21 immunomodulatory molecule could enable the development of antigen-specific tolerance therapies for T1D.
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•Different PEG-DD linkers can form hydrogels with fast (PEG-DD1) or slow (PEG-DD2) degradation and molecule release profiles.•Tethering CCL21 on PEG-DD linkers controls and prolongs its release while maintaining its functionality as a chemoattractant.•Beta cell peptides tethered on PEG-DD or loaded in nanovesicles have controlled release and maintain their functionality.•CCL21+BDC2.5 gels in NOD mice promote FRC-like networks and antigen-specific T cell enrichment in the implant site.•CCL21+BDC2.5 gels lead to a decrease of antigen-specific T cells and reduced infiltration in pancreatic islets.
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