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1.
J Hum Nutr Diet ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39290064

RESUMO

BACKGROUND: 2-(2-Nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) treatment of alkaptonuria (AKU) leads to increased blood tyrosine levels, causing skin issues and potentially sight-threatening corneal keratopathy. Adherence to dietary management of NTBC-induced tyrosinemia, a low-protein diet with or without protein substitutes, can be difficult for patients. This 28-day interventional study evaluated a low tyrosine casein glycomacropeptide (cGMP) protein substitute (TYR sphere)®, a 20 g protein equivalent, cGMP-based protein substitute, in terms of adherence, palatability, usability, comparison to amino acid (AA)-based protein substitutes, gastrointestinal tolerance and metabolic control in adults with NTBC-induced tyrosinaemia. METHODS: Four adults (mean 61.1 years, range 53.3-69.3 years) with AKU and NTBC-induced tyrosinaemia were recruited from the United Kingdom National Alkaptonuria Centre (NAC). The cGMP protein substitute was prescribed based on individual nutritional requirements, replacing ≥1 AA-based protein substitute. Participants recorded product-related data in study diaries, using five-point Likert scales and daily and weekly logs. To determine metabolic control, prestudy blood tyrosine levels were compared to weekly blood spot tests during the study. RESULTS: Median cGMP protein substitute adherence was 98%. Most participants rated palatability and usability positively, and preferred cGMP protein substitute to AA-based products. There were no notable gastrointestinal changes, and metabolic control was maintained. CONCLUSIONS: cGMP protein substitute is a palatable and well-tolerated option in the dietary management of AKU patients with NTBC-induced tyrosinaemia.

2.
Animals (Basel) ; 14(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891598

RESUMO

This Special Issue of Animals was launched to promote the discussion of how animal welfare can be best addressed in zoos and aquariums while accommodating conservation needs, as well as how further improvements can be made in a similar vein to how medical and scientific research has advanced human health and welfare [...].

3.
Drug Alcohol Depend ; 260: 111344, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38838479

RESUMO

BACKGROUND: Inadequate income is associated with higher likelihood of experiencing a substance use disorder (SUD). This study tests whether the earned income tax credit (EITC), which issues supplemental income for workers with children in the U.S., is associated with lower rates of SUD and fatal overdose. METHODS: We examined the effects of state-level refundable EITC presence and generosity (i.e., state EITC rate as a % of federal rate) on SUD-related outcomes (SUD prevalence and intentional and unintentional fatal overdose) using a difference-in-difference methodology, with both two-way fixed-effects models and event study plots. Several sensitivity analyses were conducted to assess the robustness of findings. Five data sources were used to create a combined state-level longitudinal dataset. RESULTS: We did not find significant effects of refundable EITC presence or generosity on unintentional or intentional fatal overdose or SUD prevalence in two-way models. Event study models detected a very slight upward shift in SUD prevalence following refundable EITC implementation (not seen in sensitivity analyses) and no significant effects of EITC implementation on any of the fatal overdose outcomes. CONCLUSIONS: Evidence regarding income support programs is being highly sought by policy makers as income support programs have become increasingly popular policy levers since the start of the COVID-19 pandemic. Our study indicates EITC policies likely have no impact on SUD or overdose, however, other income support programs without family restrictions are important to investigate further.


Assuntos
Overdose de Drogas , Imposto de Renda , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/economia , Overdose de Drogas/epidemiologia , Overdose de Drogas/mortalidade , Overdose de Drogas/economia , Estados Unidos/epidemiologia , Masculino , Feminino , Adulto , Renda , Prevalência
4.
Animals (Basel) ; 14(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38539994

RESUMO

Creative or novel behaviors in bottlenose dolphins (Tursiops truncatus) can be indicators of flexible thinking and problem solving. Over 50 years ago, two rough-tooth dolphins demonstrated creative novel behaviors acquired through reinforcement training in human care. Since this novel training, a variety of species have been trained to respond to this conceptual cue. The current study assessed the creativity of 12 bottlenose dolphins (5 females, 7 males) housed at the Roatan Institute for Marine Sciences (RIMS) in Roatan, Honduras. Individual differences were found across four constructs measured for creativity: fluency, flexibility, elaboration, and originality. Variability in performance occurred across test sessions. Animals with less experience with this task performed fewer "innovative" behaviors as compared to more experienced animals. Despite errors, dolphins continued to attempt the task during test sessions, suggesting the concept of "innovate" was intrinsically rewarding and cognitively engaging. This task may be utilized across species to promote the comparative study of innovative or creative behavior as well as to promote cognitive welfare.

5.
Phys Rev B ; 108(12)2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37841515

RESUMO

This work reports the experimental demonstration of single-slit diffraction exhibited by electrons propagating in encapsulated graphene with an effective de Broglie wavelength corresponding to their attributes as massless Dirac fermions. Nanometer-scale device designs were implemented to fabricate a single-slit followed by five detector paths. Predictive calculations were also utilized to readily understand the observations reported. These calculations required the modeling of wave propagation in ideal case scenarios of the reported device designs to more accurately describe the observed single-slit phenomenon. This experiment was performed at room temperature and 190 K, where data from the latter highlighted the exaggerated asymmetry between electrons and holes, recently ascribed to slightly different Fermi velocities near the K point. This observation and device concept may be used for building diffraction switches with versatile applicability.

6.
Learn Behav ; 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670175

RESUMO

Mother dolphins shift their signature whistles to higher frequencies and have larger bandwidths when calling to their dependent calves during separations involving stranded health assessments compared with separations when the calf is absent. While this shift may reflect a version of "child-directed communication," more research is needed to understand the parameters and function of this phenomenon.

7.
Zoo Biol ; 42(6): 730-743, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37283079

RESUMO

Belugas (Delphinapterus leucas) engage in many forms of play (e.g., object, water, locomotor), but no play is quite as curious as the unusual form of cooperative social play involving mouth-to-mouth interactions. These playful interactions are characterized by two belugas approaching each other head-to-head and interlocking their jaws, clasping one another, as if they were shaking hands. Observed in belugas both in the wild and in managed care, it is seemingly an important type of social play that offers a unique way of socializing with conspecifics. To describe this unusual behavior, a group of belugas in managed care was observed from 2007 to 2019. Although adults participated in mouth-to-mouth interactions, most were initiated and received by young belugas. Both males and females engaged in mouth-to-mouth interactions and did so at similar frequencies. Individual differences in how many mouth-to-mouth interactions were initiated among calves were also observed. Due to the unique, cooperative nature of mouth-to-mouth interactions, which require both social and motor skills, it is hypothesized that these interactions may be used to test social and motor competency.


Assuntos
Beluga , Masculino , Feminino , Animais , Bovinos , Animais de Zoológico , Boca , Programas de Assistência Gerenciada
8.
ACS Nano ; 17(11): 9694-9747, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37219929

RESUMO

Two-dimensional (2D) material research is rapidly evolving to broaden the spectrum of emergent 2D systems. Here, we review recent advances in the theory, synthesis, characterization, device, and quantum physics of 2D materials and their heterostructures. First, we shed insight into modeling of defects and intercalants, focusing on their formation pathways and strategic functionalities. We also review machine learning for synthesis and sensing applications of 2D materials. In addition, we highlight important development in the synthesis, processing, and characterization of various 2D materials (e.g., MXnenes, magnetic compounds, epitaxial layers, low-symmetry crystals, etc.) and discuss oxidation and strain gradient engineering in 2D materials. Next, we discuss the optical and phonon properties of 2D materials controlled by material inhomogeneity and give examples of multidimensional imaging and biosensing equipped with machine learning analysis based on 2D platforms. We then provide updates on mix-dimensional heterostructures using 2D building blocks for next-generation logic/memory devices and the quantum anomalous Hall devices of high-quality magnetic topological insulators, followed by advances in small twist-angle homojunctions and their exciting quantum transport. Finally, we provide the perspectives and future work on several topics mentioned in this review.

9.
PLoS One ; 18(5): e0282075, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37224091

RESUMO

Animal documentary films such as Blackfish, considered nonfiction accounts of reality, nonetheless use rhetorical devices to engage viewers and shape their emotional experience for maximum effect. Such devices can also influence attitudes and alter behavior. In animal documentaries, anthropomorphic impressions of the animals by audiences are key. Using general population samples in the US, three online experiments assessed the influence of background music and narrative setting on how viewers emotionally appraised the emotional state of a killer whale (Orcinus orca) and subsequently donated to causes affiliated with killer whales. While happy music led to perceptions of a happy whale, sad music led to perceptions of a sad whale. mediation analyses showed that these perceptions indirectly influence donation behavior, via beliefs about the killer whale's welfare and wellbeing. Analyses also indicated that the highest donation amounts towards killer whales were elicited from footage depicting a killer whale in the wild, with sad background music. These findings highlight the potential power that animal and nature documentaries have over viewers, which, when combined with human tendencies toward anthropomorphism, can have significant influence on conservation attitudes and behavior.


Assuntos
Música , Orca , Animais , Humanos , Julgamento , Emoções , Felicidade
10.
Soc Sci Med ; 322: 115817, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36905725

RESUMO

BACKGROUND: To date, research evaluating the association between minimum wage and health has been heterogenous and varies based on the specific subpopulation or health outcomes under evaluation while associations across racial, ethnic, and gender identities have been understudied. METHODS: A triple difference-in-differences strategy using modified Poisson regression was used to evaluate the associations between minimum wage and obesity, hypertension, fair or poor general health, and moderate psychological distress in 25-64-year-old adults with a high school education/GED or less. Data from the 1999-2017 Panel Study of Income Dynamics was linked to state policies and characteristics to estimate the risk ratio (RR) associated with a $1 increase in current and 2-year lagged state minimum wages overall and by race, ethnicity, and gender (non-Hispanic or non-Latino (NH) White men, NH White women, Black, indigenous, or people of color (BIPOC) men, and BIPOC women) adjusting for individual and state-level confounding. RESULTS: No associations between minimum wage and health were observed overall. Among NH White men 2-year lagged minimum wage was associated with reduced risk of obesity (RR = 0.82, 95% CI = 0.67, 0.99). Among NH White women, current minimum wage was associated lower risk of moderate psychological distress (RR = 0.73, 95% CI = 0.54, 1.00) while 2-year lagged minimum wage was associated with higher obesity risk (RR = 1.35, 95% CI = 1.12, 1.64) and lower risk of moderate psychological distress (RR = 0.75, 95% CI = 0.56, 1.00). Among BIPOC women, current minimum wage was associated with higher risk of fair or poor health (RR = 1.19, 95% CI = 1.02, 1.40). No associations were observed among BIPOC men. CONCLUSION: While no associations were observed overall, heterogeneous associations between minimum wage, obesity, and psychological distress by racial, ethnic, and gender strata warrant further study and have implications for health equity research.


Assuntos
Renda , Obesidade , Masculino , Adulto , Humanos , Feminino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Fatores Sexuais , Escolaridade , Obesidade/epidemiologia , Salários e Benefícios
11.
Anim Cogn ; 26(2): 667-686, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36333497

RESUMO

The investigation of individual responses to unexpected stimuli or outcomes provides insights into basic cognitive processes, such as mental representations, emotional states of surprise, and detections of anomalies. Three experiments using a violation of expectation paradigm were conducted with 12 belugas and 17 bottlenose dolphins in managed care to test two classes of stimuli (humans and objects) in manipulated sequences of familiar and unfamiliar humans (Study 1, trainers and strangers), familiar and unfamiliar objects (Study 2, typical enrichment devices and new objects), and finally objects and humans (Study 3). Gaze durations were assessed for each condition in a given study during free-swim contexts. The results supported previous findings that visual stimuli, regardless of class, were stimulating and intriguing for both belugas and bottlenose dolphins. Belugas were more likely to gaze longer at human and object stimuli and tended to gaze longer at unexpected experiences than control or expected experiences. Bottlenose dolphins showed similar trends except when objects were involved. Individual variability was present for both species with some individuals showing stronger patterns of responses for expected experiences than others. After 2 years of intermittent experiments, belugas and bottlenose dolphins in managed care maintained their curiosity about visual stimuli, for which they received no primary reinforcement. Investigating responses to unexpected stimuli with animals in managed care may provide insight into how these animals respond to biologically relevant conditions, such as boat presence, predators, and unfamiliar conspecifics.


Assuntos
Golfinho Nariz-de-Garrafa , Humanos , Animais , Golfinho Nariz-de-Garrafa/psicologia , Motivação , Emoções , Reforço Psicológico
12.
JAMA Netw Open ; 5(11): e2242864, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36399341

RESUMO

Importance: Childhood poverty is associated with poor health and behavioral outcomes. The Earned Income Tax Credit (EITC), first implemented in 1975, is the largest cash transfer program for working families with low income in the US. Objective: To assess whether cumulative EITC payments received during childhood are associated with the risk of criminal conviction during adolescence. Design, Setting, and Participants: In this cohort study, the analytic sample consisted of US children enrolled in the 1979 National Longitudinal Study of Youth. The children were born between 1979 and 1998 and were interviewed as adolescents (age 15-19 years) between 1994 and 2016. Data analyses were performed from May 2021 to September 2022. Exposure: Cumulative simulated EITC received by the individual's family from birth through age 14 years. Main Outcomes and Measures: The main outcome was dichotomous, self-reported conviction for a crime during adolescence (age 14-18 years). A cumulative, simulated measure of mean EITC benefits received by a child's family from birth through age 14 years was derived from federal, state, and family-size differences in EITC eligibility and payments during the study period to capture EITC benefit variation due to differences in policy parameters but not endogenous factors such as changes in household income. Logistic regression models with fixed effects for state and year and robust SEs clustered by mother estimated relative risk of adolescent conviction. Models were adjusted for state-, mother-, and child-level covariates. Results: The analytical sample consisted of 5492 adolescents born between 1979 and 1998; 2762 (50.3%) were male, 1648 (30.0%) were Black, 1125 (20.5%) were Hispanic, and 2719 (49.5%) were not Black or Hispanic. Each additional $1000 of EITC received during childhood was associated with an 11% lower risk of self-reported criminal conviction during adolescence (adjusted odds ratio, 0.89; 95% CI, 0.84-0.95). Adjusted risk differences were larger among boys (-14.2 self-reported convictions per 1000 population [95% CI, -22.0 to -6.3 per 1000 population]) than among girls (-6.2 per 1000 population [95% CI, -10.7 to -1.6 per 1000 population]). Conclusions and Relevance: The findings suggest that income support from the EITC may be associated with reduced youth involvement with the criminal justice system in the US. Cost-benefit analyses of the EITC should consider these longer-term and indirect outcomes.


Assuntos
Criminosos , Imposto de Renda , Humanos , Adolescente , Feminino , Masculino , Adulto Jovem , Adulto , Estudos Longitudinais , Estudos de Coortes , Mães
13.
Anim Cogn ; 25(5): 1091-1108, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36125643

RESUMO

Thinking flexibly is a skill that enables animals to adapt to changing environments, which enhances survival. Killer whales, Orcinus orca, as the ocean apex predator display a number of complex cognitive abilities, especially flexible thinking or creativity when it comes to foraging. In human care, smaller dolphins and other marine mammals have been trained to think creatively while under stimulus control. The results of these previous studies have demonstrated that bottlenose dolphins, Tursiops truncatus, can create original behaviors in response to an innovative cue. We trained and tested a total of nine killer whales from two different facilities on the innovate concept, using the same methodology. The killer whales ranged in age from 5 to 29 yrs with 4 females and 5 males. The results indicate that the killer whales demonstrated high fluency, originality, some elaboration, and flexibility in their behaviors. Individual variability was observed with younger animals demonstrating more variable behaviors as compared to the older animals. Males seemed to display less complex and lower energy behaviors as compared to females, but this impression may be driven by the age or size of the animal. These results support existing evidence that killer whales are dynamic in their thinking and behavior.


Assuntos
Golfinho Nariz-de-Garrafa , Orca , Feminino , Masculino , Humanos , Animais , Orca/psicologia
14.
Prev Sci ; 23(8): 1370-1378, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35917082

RESUMO

Family- and neighborhood-level poverty are associated with youth violence. Economic policies may address this risk factor by reducing parental stress and increasing opportunities. The federal Earned Income Tax Credit (EITC) is the largest cash transfer program in the US providing support to low-income working families. Many states have additional EITCs that vary in structure and generosity. To estimate the association between state EITC and youth violence, we conducted a repeated cross-sectional analysis using the variation in state EITC generosity over time by state and self-reported data in the Youth Risk Behavior Surveillance System (YRBSS) from 2005 to 2019. We estimated the association for all youth and then stratified by sex and race and ethnicity. A 10-percentage point greater state EITC was significantly associated with 3.8% lower prevalence of physical fighting among youth, overall (PR: 0.96; 95% CI 0.94-0.99), and for male students, 149 fewer (95% CI: -243, -55) students per 10,000 experiencing physical fighting. A 10-percentage point greater state EITC was significantly associated with 118 fewer (95% CI: -184, -52) White students per 10,000 experiencing physical fighting in the past 12 months while reductions among Black students (75 fewer; 95% CI: -176, 26) and Hispanic/Latino students (14 fewer; 95% CI: -93, 65) were not statistically significant. State EITC generosity was not significantly associated with measures of violence at school. Economic policies that increase financial security and provide financial resources may reduce the burden of youth violence; further attention to their differential benefits among specific population subgroups is warranted.


Assuntos
Imposto de Renda , Renda , Masculino , Adolescente , Humanos , Estudos Transversais , Assunção de Riscos , Violência/prevenção & controle
15.
Behav Processes ; 201: 104718, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35914616

RESUMO

The majority of cetacean research suggests a right side/left cerebral hemisphere bias for processing visuospatial information and a left side/right cerebral hemisphere bias for processing social information. Beluga (Delphinapterus leucas) socio-sexual behavior involves motor skills coordination and is also hypothesized to serve a social function. The present study assessed whether 14 belugas in managed care displayed side bias in their lateral socio-sexual presentation behavior. No species-level bias was found, the majority of individuals did not display a side bias, and side use was not dependent on sex of the recipient, although some influence of swim direction was found. Only males had a statistically significant but small left side preference. Furthermore, there was a linear correlation with the left side being used increasingly more over Years 1-6 of life. This study suggests that belugas do not display consistent laterality of socio-sexual presentation behavior, which is in contrast to the laterality of mother-calf positions for belugas and the high levels of laterality that are reported for some behaviors of other cetacean species. Thus, it seems that beluga socio-sexual presentation behavior is flexible and may serve both motor skills practice and social functions, which likely involve both cerebral hemispheres as a cognitively engaging behavior.


Assuntos
Beluga , Animais , Feminino , Lateralidade Funcional , Gelatina , Humanos , Masculino , Comportamento Sexual , Natação
16.
Prev Med ; 165(Pt A): 107133, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35803348

RESUMO

Firearm violence is a major threat to global public health and safety. Several individual, family, peer, community, and societal risk and protective factors determine or modify the risk of firearm violence. Specifically, there is a strong relationship between poverty, income inequality, and firearm violence; as such, interventions that influence upstream determinants of health by providing income support may hold much promise in affecting multiple domains of risk that are on the causal pathway to firearm violence. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we conducted a scoping review to examine the current state of evidence on the relationship between income support policies and risk of firearm violence. We searched 8 databases related to health and social sciences from inception through March 30, 2022, and placed no time, language, setting, or other publication restrictions on our search, as long as the study was quantitative or mixed-methods and addressed firearm violence specifically, rather than violence more broadly, as an outcome in relation to income support policies. We found 4 studies; of those, 3 were conducted in the United States and 1 in Brazil. All 4 found associations of policy-relevant magnitude between income support policies and reductions in risk of inter-personal firearm violence. We propose future opportunities to enhance the substantive scope and methodologic rigor of this field of research and inform policy and practice for greater impact.


Assuntos
Armas de Fogo , Ferimentos por Arma de Fogo , Humanos , Renda , Políticas , Estados Unidos , Violência/prevenção & controle
17.
Behav Processes ; 200: 104695, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35779700

RESUMO

While the ontogeny of beluga (Delphinapterus leucas) socio-sexual behavior has been documented in animals between 37- and 108-months-old, the first 36 months of life are yet to be examined. This study investigated how socio-sexual behaviors emerge over the first three years of life in a group of belugas in managed care. The emergence of socio-sexual behaviors was relatively consistent among immature animals. More complex behaviors, like s-posture presentations, developed in a piecemeal fashion (i.e., simple components of the behavior sequence emerged before complex components). The presence of an adult male significantly predicted if immature belugas would initiate and participate in socio-sexual behavior. However, partner preferences changed with age. In the first year of life, belugas engaged in sexual behavior with their mother most frequently but preferred to play with older males if given a choice. By the third year of life, belugas engaged in socio-sexual behavior most frequently with other immature animals. These findings enhance our understanding of how belugas develop sexually and socially and have implications for social housing practices of immature belugas.


Assuntos
Beluga , Animais , Bovinos , Feminino , Gelatina , Humanos , Masculino , Mães
18.
Pediatrics ; 150(1)2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35662354

RESUMO

OBJECTIVES: Poverty and low income are associated with increased risk for child maltreatment. The Earned Income Tax Credit (EITC) and Child Tax Credit (CTC) are among the largest antipoverty programs in the United States. We estimated associations between income transfer payments via the EITC and CTC and child maltreatment reports in the period shortly after families receive payments from these programs. METHODS: We linked weekly EITC and CTC refund data from the Internal Revenue Service to state-specific child maltreatment report data from 48 states and the District of Columbia during the 2015 through 2018 tax seasons (January - April). We leveraged the natural experiment of a legislated change in the timing of EITC and CTC transfer payments to low-income families and quasi-experimental methods to estimate the association between EITC and CTC payments and child maltreatment reports. RESULTS: EITC and CTC payments were associated with lower state-level rates of child maltreatment reports. For each additional $1000 in per-child EITC and CTC tax refunds, state-level rates of reported child maltreatment declined in the week of and 4 weeks following refund payments by an overall estimated 5.0% (95% confidence interval = 2.3%-7.7%). CONCLUSIONS: Federal income assistance programs are associated with immediate reductions in child maltreatment reporting. These results are particularly relevant at this time, as expansions to such programs continue to be discussed at the state and federal levels.


Assuntos
Maus-Tratos Infantis , Imposto de Renda , Criança , Humanos , Renda , Pobreza , Impostos , Estados Unidos/epidemiologia
19.
Vaccine ; 40(9): 1271-1281, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35125219

RESUMO

BACKGROUND: New influenza vaccines are needed to increase vaccine efficacy. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational low viscosity, free-flowing, water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets. METHODS: A phase 1, double-blind, safety and immunogenicity, HA dose escalation, randomized clinical trial was conducted. MAS-1 adjuvant with 1, 3, 5 or 9 µg per HA derived from licensed seasonal trivalent high dose inactivated influenza vaccine (IIV, Fluzone HD 60 µg per HA) in a 0.3 mL dose were compared to standard dose IIV (Fluzone SD, 15 µg per HA). Safety was measured by reactogenicity, adverse events, and clinical laboratory tests. Serum hemagglutination inhibition (HAI) antibody titers were measured for immunogenicity. RESULTS: Seventy-two subjects, aged 18-47 years, received one dose of either 0.3 mL adjuvanted vaccine or SD IIV intramuscularly. Common injection site and systemic reactions post-vaccination were mild tenderness, induration, pain, headache, myalgia, malaise and fatigue. All reactions resolved within 14 days post-vaccination. Safety laboratory measures were not different between groups. Geometric mean antibody titers, geometric mean fold increases in antibody titer, seroconversion rates and seroprotection rates against vaccine strains were in general higher and of longer duration (day 85 and 169 visits) with MAS-1-adjuvanted IIV at all doses of HA compared with SD IIV. Adjuvanted vaccine induced higher antibody responses against a limited number of non-study vaccine influenza B and A/H3N2 viruses including ones from subsequent years. CONCLUSION: MAS-1 adjuvant in a 0.3 mL dose volume provided HA dose-sparing effects without safety concerns and induced higher HAI antibody and seroconversion responses through at least 6 months, demonstrating potential to provide greater vaccine efficacy throughout an influenza season in younger adults. In summary, MAS-1 may provide enhanced, more durable and broader protective immunity compared with non-adjuvanted SD IIV. Clinical Trial Registry: ClinicalTrials.gov # NCT02500680.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Adjuvantes Imunológicos , Adolescente , Adulto , Anticorpos Antivirais , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/prevenção & controle , Pessoa de Meia-Idade , Estações do Ano , Vacinas de Produtos Inativados/efeitos adversos , Água , Adulto Jovem
20.
Vaccine ; 40(10): 1472-1482, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35125224

RESUMO

BACKGROUND: Increased influenza vaccine efficacy is needed in the elderly at high-risk for morbidity and mortality due to influenza infection. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets. METHODS: A phase 1, randomized, double-blind, safety and immunogenicity, adjuvant dose escalation trial was conducted in persons aged 65 years and older. MAS-1 adjuvant dose volumes at 0.3 mL or 0.5 mL containing 9 µg per HA derived from licensed seasonal trivalent influenza vaccine (IIV, Fluzone HD 60 µg per HA, Sanofi Pasteur) were compared to high dose (HD) IIV (Fluzone HD). Safety was measured by reactogenicity, adverse events, and safety laboratory measures. Immunogenicity was assessed by serum hemagglutination inhibition (HAI) antibody titers. RESULTS: Forty-five subjects, aged 65-83 years, were randomly assigned to receive 9 µg per HA in 0.3 mL MAS-1 (15 subjects) or HD IIV (15 subjects) followed by groups randomly assigned to receive 9 µg per HA in 0.5 mL MAS-1 (10 subjects) or HD IIV (5 subjects). Injection site tenderness, induration, and pain, and headache, myalgia, malaise and fatigue were common, resolving before day 14 post-vaccination. Clinically significant late-onset injection site reactions occurred in four of ten subjects at the 0.5 mL adjuvant dose. Safety laboratory measures were within acceptable limits. MAS-1-adjuvanted IIV enhanced mean antibody titers, mean-fold increases in antibody titer, and seroconversion rates against vaccine strains for at least 168 days post-vaccination and enhanced cross-reactive antibodies against some non-study vaccine influenza viruses. CONCLUSION: MAS-1 adjuvant provided HA dose-sparing without safety concerns at the 0.3 mL dose, but the 0.5 mL dose caused late injection site reactions. MAS-1-adjuvanted IIV induced higher HAI antibody responses with prolonged durability including against historical strains, thereby providing greater potential vaccine efficacy in the elderly throughout an influenza season. Clinical Trial Registry: ClinicalTrials.gov # NCT02500680.


Assuntos
Vacinas contra Influenza , Influenza Humana , Adjuvantes Imunológicos , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais , Formação de Anticorpos , Testes de Inibição da Hemaglutinação , Hemaglutininas , Humanos , Estações do Ano , Água
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