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The Flavor and Extract Manufacturers Association has published the 24th safety and usage data on 236 new generally recognized as safe (GRAS) flavoring ingredients. A substance must be evaluated by experts to qualify for GRAS status. The organization's substance screening processes are also discussed. A brief history of the publication is also supplied.

Eucalyptus globulus is the main eucalypt species grown in Australian plantations. The focus on seedling deployment systems, coupled with exploitation of large, open-pollinated base populations for breeding purposes over the last two decades, has required a detailed understanding of the reproductive biology of this species. We review our research on the reproductive biology of E. globulus, with a focus on its breeding system and advances made in seed production systems. While most improved seed is still obtained from open-pollinated seedling or grafted seed orchards, the development of the one-stop/single-visit pollination procedure has revolutionised the breeding and deployment of this species. The reduced costs of controlled pollination has meant full pedigree-control can now be maintained in large advanced-generation breeding populations and E. globulus is one of the few eucalypt species where large-scale production of manually pollinated seed for family forestry is being undertaken. [ABSTRACT FROM AUTHOR]

Hospitalization outcomes are examined in a three year random assignment controlled study of two capitated Integrated Service Agencies (ISAs) in California. Study participants were a cross-section of severely mentally ill clients. Using the flexibility of capitated funding, the urban ISA reduced inpatient length of stay and days, but not admissions. Elements of the capitated ISA model worked together to produce clinically appropriate and less costly use of inpatient services. At the rural ISA, admissions were reduced substantially during the first two years of the demonstration but not costs. [ABSTRACT FROM AUTHOR]

Employment outcomes are examined in a three year controlled study of two Integrated Service Agencies (ISAs) for a cross-section of severely mentally ill clients. At each site significantly more ISA members than comparison clients obtained some paid employment. At the urban site the difference was dramatic: 73 vs 15 percent worked during the study period, and 29 percent of the ISA clients worked competitively. The significant but still limited ISA results argue for increased employment opportunities for all seriously mentally ill clients. [ABSTRACT FROM AUTHOR]

Abstract Background Representatives of Cetacea have the greatest absolute brain size among animals, and the largest relative brain size aside from humans. Despite this, genes implicated in the evolution of large brain size in primates have yet to be surveyed in cetaceans. Results We sequenced ~1240 basepairs of the brain development gene microcephalin (MCPH1) in 38 cetacean species. Alignments of these data and a published complete sequence from Tursiops truncatus with primate MCPH1 were utilized in phylogenetic analyses and to estimate ω (rate of nonsynonymous substitution/rate of synonymous substitution) using site and branch models of molecular evolution. We also tested the hypothesis that selection on MCPH1 was correlated with brain size in cetaceans using a continuous regression analysis that accounted for phylogenetic history. Our analyses revealed widespread signals of adaptive evolution in the MCPH1 of Cetacea and in other subclades of Mammalia, however, there was not a significant positive association between ω and brain size within Cetacea. Conclusion In conjunction with a recent study of Primates, we find no evidence to support an association between MCPH1 evolution and the evolution of brain size in highly encephalized mammalian species. Our finding of significant positive selection in MCPH1 may be linked to other functions of the gene.

Abstract Background Cetacea (dolphins, porpoises, and whales) is a clade of aquatic species that includes the most massive, deepest diving, and largest brained mammals. Understanding the temporal pattern of diversification in the group as well as the evolution of cetacean anatomy and behavior requires a robust and well-resolved phylogenetic hypothesis. Although a large body of molecular data has accumulated over the past 20 years, DNA sequences of cetaceans have not been directly integrated with the rich, cetacean fossil record to reconcile discrepancies among molecular and morphological characters. Results We combined new nuclear DNA sequences, including segments of six genes (~2800 basepairs) from the functionally extinct Yangtze River dolphin, with an expanded morphological matrix and published genomic data. Diverse analyses of these data resolved the relationships of 74 taxa that represent all extant families and 11 extinct families of Cetacea. The resulting supermatrix (61,155 characters) and its sub-partitions were analyzed using parsimony methods. Bayesian and maximum likelihood (ML) searches were conducted on the molecular partition, and a molecular scaffold obtained from these searches was used to constrain a parsimony search of the morphological partition. Based on analysis of the supermatrix and model-based analyses of the molecular partition, we found overwhelming support for 15 extant clades. When extinct taxa are included, we recovered trees that are significantly correlated with the fossil record. These trees were used to reconstruct the timing of cetacean diversification and the evolution of characters shared by "river dolphins," a non-monophyletic set of species according to all of our phylogenetic analyses. Conclusions The parsimony analysis of the supermatrix and the analysis of morphology constrained to fit the ML/Bayesian molecular tree yielded broadly congruent phylogenetic hypotheses. In trees from both analyses, all Oligocene taxa included in our study fell outside crown Mysticeti and crown Odontoceti, suggesting that these two clades radiated in the late Oligocene or later, contra some recent molecular clock studies. Our trees also imply that many character states shared by river dolphins evolved in their oceanic ancestors, contradicting the hypothesis that these characters are convergent adaptations to fluvial habitats.

Background: In 2017, the San Francisco Cancer Initiative (SF CAN) established the Colorectal Cancer (CRC) Screening Program to provide technical assistance and financial support to improve CRC screening processes, and outcomes in a consortium of community health centers (CHCs) serving low-income communities in San Francisco. The purpose of this study was twofold: to evaluate the perceived influence of the support provided by the CRC Screening Program's Task Force on CRC screening processes and outcomes in these settings and to identify facilitators and barriers to SF CAN-supported CRC screening activities before and after the onset of the COVID-19 pandemic., Methods: Semi-structured key informant interviews were conducted with consortium leaders, medical directors, quality improvement team members, and clinic screening champions. Interviews were audio-recorded, professionally transcribed, and analyzed for themes. The Consolidated Framework for Implementation Research (CFIR) was used to develop the interview questions and organize the analysis., Results: Twenty-two participants were interviewed. The most commonly cited facilitators of improved screening processes included the expertise, funding, screening resources, regular follow-up, and sustained engagement with clinic leaders provided by the task force. The most salient barriers identified were patient characteristics, such as housing instability; staffing challenges, such as being understaffed and experiencing high staff turnover; and clinic-level challenges, such as lack of ability to implement and sustain formalized patient navigation strategies, and changes in clinic priorities due to the COVID-19 pandemic and other competing health care priorities., Conclusions: Implementing CRC screening programs in a consortium of CHCs is inherently challenging. Technical assistance from the Task Force was viewed positively and helped to mitigate challenges both before and during the pandemic. Future research should explore opportunities to increase the robustness of technical assistance offered by groups such as SF CAN to support cancer screening activities in CHCs serving low-income communities., (© 2023. The Author(s).)

The large interspecific variation in marine mammal skull and dental morphology reflects ecological specialisations to foraging and communication. At the intraspecific level, the drivers of skull shape variation are less well understood, having implications for identifying putative local foraging adaptations and delineating populations and subspecies for taxonomy, systematics, management and conservation. Here, we assess the range-wide intraspecific variation in 71 grey seal skulls by 3D surface scanning, collection of cranial landmarks and geometric morphometric analysis. We find that skull shape differs slightly between populations in the Northwest Atlantic, Northeast Atlantic and Baltic Sea. However, there was a large shape overlap between populations and variation was substantially larger among animals within populations than between. We hypothesize that this pattern of intraspecific variation in grey seal skull shape results from balancing selection or phenotypic plasticity allowing for a remarkably generalist foraging behaviour. Moreover, the large overlap in skull shape between populations implies that the separate subspecies status of Atlantic and Baltic Sea grey seals is questionable from a morphological point of view., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Context: The COVID-19 pandemic continues to be a major socioeconomic disruptor in the U.S. and around the globe. The only intervention that has a far-reaching impact is the adoption of an efficient large-scale vaccination campaign with the highly effective COVID-19 vaccines. While the success of this strategy is predicated on the presence of adequate healthcare systems capacity, it also hinges on the trust and acceptance of the public. Vaccine hesitancy, which varies by the geosocial context, is considered a top obstacle. Objective: The Overton Brooks VA embarked on a survey to explore the demographic patterns and reasons for COVID-19 vaccination hesitancy among cancer patients. Study Design: phone survey. Setting: five Hematology-Oncology clinics across the ArkLATX. Population: random sample of 240 veterans with cancer. Intervention: Veterans were asked whether they are interested in getting vaccinated and to state the reason if they declined. They were asked to categorize the reason as relating to safety, efficacy, inadequate Information, aversion to any vaccine, not wanting to be the first, or other/explain. Outcome Measures: 1. Descriptive statistics of those who want and those who decline the vaccine. 2. Determine the impact of demographic factors on COVID19 vaccine hesitancy. Results: The median age was 71 years. The participants were 92% males and 40% Black vs 59% White. Seventy nine percent wanted to get vaccinated. Among the veterans that declined (21%), the reasons were due to concerns about safety (33%), not wanting to be the first (33%), anti-vaxxer stance (14%), and inadequate information (8%). No one cited concerns about efficacy as a reason. Other reasons (12%) included seeing no reason for the vaccination, citing severe reactions to prior vaccines, and voicing mistrust of the government. There were no statistical differences between veterans that approved or declined the vaccine with respect to demographic characteristics. Conclusions: This survey indicates that the majority of ArkLATX veterans with cancer are willing to be vaccinated against COVID-19. The major reasons behind vaccine hesitancy seem to be information problems consisting of questions about safety, inadequate information, and seeing no reason for the vaccine. Such barriers can be potentially circumvented by providing the appropriate information and counseling., Competing Interests: Authors report none., (© 2021 Annals of Family Medicine, Inc.)

The diversity of the dolphin family was established during a short window of time. We investigated delphinid skull shape evolution, mapping shapes on an up-to-date nuclear phylogeny. In this model, the common ancestor was similar to Lagenorhynchus albirostris . Initial diversification occurred in three directions: toward specialized raptorial feeders of small prey with longer, narrower beaks, e.g., Delphinus ; toward wider skulls with downward-oriented rostra and reduced temporal fossae, exemplified by suction feeders, e.g., Globicephala; and toward shorter and wider skulls/rostra and enlarged temporal fossae, e.g., Orcinus . Skull shape diversity was established early, the greatest later developments being adaptation of Steno to raptorial feeding on large prey and the convergence of Pseudorca toward Orcinus , related to handling large prey. Delphinid skull shapes are related to feeding mode and prey size, whereas adaptation to habitat is not marked. Over a short period, delphinid skulls have evolved a diversity eclipsing other extant odontocete clades., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)

Phylogeographic inference has provided extensive insight into the relative roles of geographical isolation and ecological processes during evolutionary radiations. However, the importance of cross-lineage admixture in facilitating adaptive radiations is increasingly being recognised, and suggested as a main cause of phylogenetic uncertainty. In this study, we used a double digest RADseq protocol to provide a high resolution (~4 Million bp) nuclear phylogeny of the Delphininae. Phylogenetic resolution of this group has been especially intractable, likely because it has experienced a recent species radiation. We carried out cross-lineage reticulation analyses, and tested for several sources of potential bias in determining phylogenies from genome sampling data. We assessed the divergence time and historical demography of T. truncatus and T. aduncus by sequencing the T. aduncus genome and comparing it with the T. truncatus reference genome. Our results suggest monophyly for the genus Tursiops, with the recently proposed T. australis species falling within the T. aduncus lineage. We also show the presence of extensive cross-lineage gene flow between pelagic and European coastal ecotypes of T. truncatus, as well as in the early stages of diversification between spotted (Stenella frontalis; Stenella attenuata), spinner (Stenella longirostris), striped (Stenella coeruleoalba), common (Delphinus delphis), and Fraser's (Lagenodelphis hosei) dolphins. Our study suggests that cross-lineage gene flow in this group has been more extensive and complex than previously thought. In the context of biogeography and local habitat dependence, these results improve our understanding of the evolutionary processes determining the history of this lineage., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavoring ingredients. This publication is the first in a series and summarizes the evaluation of 54 Citrus-derived NFCs using the procedure outlined in Smith et al. (2005) and updated in Cohen et al. (2018) to evaluate the safety of naturally-occurring mixtures for their intended use as flavoring ingredients. The procedure relies on a complete chemical characterization of each NFC intended for commerce and organization of each NFC's chemical constituents into well-defined congeneric groups. The safety of the NFC is evaluated using the well-established and conservative threshold of toxicological concern (TTC) concept in addition to data on absorption, metabolism and toxicology of members of the congeneric groups and the NFC under evaluation. As a result of the application of the procedure, 54 natural flavor complexes derived from botanicals of the Citrus genus were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavoring ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The human brain and human cognitive abilities are strikingly different from those of other great apes despite relatively modest genome sequence divergence. However, little is presently known about the interspecies divergence in gene structure and transcription that might contribute to these phenotypic differences. To date, most comparative studies of gene structure in the brain have examined humans, chimpanzees, and macaque monkeys. To add to this body of knowledge, we analyze here the brain transcriptome of the western lowland gorilla (Gorilla gorilla gorilla), an African great ape species that is phylogenetically closely related to humans, but with a brain that is approximately one-third the size. Manual transcriptome curation from a sample of the planum temporale region of the neocortex revealed 12 protein-coding genes and one noncoding-RNA gene with exons in the gorilla unmatched by public transcriptome data from the orthologous human loci. These interspecies gene structure differences accounted for a total of 134 amino acids in proteins found in the gorilla that were absent from protein products of the orthologous human genes. Proteins varying in structure between human and gorilla were involved in immunity and energy metabolism, suggesting their relevance to phenotypic differences. This gorilla neocortical transcriptome comprises an empirical, not homology- or prediction-driven, resource for orthologous gene comparisons between human and gorilla. These findings provide a unique repository of the sequences and structures of thousands of genes transcribed in the gorilla brain, pointing to candidate genes that may contribute to the traits distinguishing humans from other closely related great apes., (© 2015 Wiley Periodicals, Inc.)

This publication is the thirteenth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Since then, the number of flavoring substances has grown to more than 2600 substances. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of aliphatic and aromatic terpene hydrocarbons as flavoring ingredients are evaluated. The group of aliphatic and aromatic terpene hydrocarbons was reaffirmed as GRAS (GRASr) based, in part, on their self-limiting properties as flavoring substances in food; their rapid absorption, metabolic detoxication, and excretion in humans and other animals; their low level of flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic and chronic studies and the lack of significant genotoxic potential., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The dermal hand transfer of three fragrance materials (cinnamic aldehyde, d-limonene and eugenol) from scented candles was determined in 10 subjects (i.e., 20 hands) after grasping scented candles for 5 consecutive 20s exposures/grasps. The fragrance materials from each subject's hands were recovered by isopropyl alcohol wipes and subsequent extractions. Removal efficiencies for both cinnamic aldehyde and eugenol placed directly on the hands were not concentration dependent and ranged from 103% to 106%. The removal efficiency of d-limonene showed an inverse relation with 74.3% removed at the low concentration of 50 microg and 63.8% removed at the high concentration of 500 microg. The residue/transfer of d-limonene from the candles to the hands was below the limit of detection of 50 microg. The residue/transfer of cinnamic aldehyde and eugenol to each subject's hands was consistent between subjects as well as between each exposure/grasp. The total mean residues of cinnamic aldehyde and eugenol transferred per grasp from the candles to the hands were 0.255 microg/cm(2) and 0.279 microg/cm(2), respectively.

This publication is the 11th in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. The list of GRAS substances has now grown to more than 2100 substances. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. In this monograph, a detailed interpretation is presented on the renal carcinogenic potential of the aromatic secondary alcohol alpha-methylbenzyl alcohol, aromatic ketone benzophenone, and corresponding alcohol benzhydrol. The relevance of these effects to the flavor use of these substances is also discussed. The group of aromatic substituted secondary alcohols, ketones, and related esters was reaffirmed as GRAS (GRASr) based, in part, on their rapid absorption, metabolic detoxication, and excretion in humans and other animals; their low level of flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic and chronic studies and the lack of significant genotoxic and mutagenic potential.

Hospitalization outcomes are examined in a three year random assignment controlled study of two capitated Integrated Service Agencies (ISAs) in California. Study participants were a cross-section of severely mentally ill clients. Using the flexibility of capitated funding, the urban ISA reduced inpatient length of stay and days, but not admissions. Elements of the capitated ISA model worked together to produce clinically appropriate and less costly use of inpatient services. At the rural ISA, admissions were reduced substantially during the first two years of the demonstration but not costs.

This article explores the cost implications of the capitated integrated service agency (ISA) model for persons with severe and persistent mental illness. Two demonstration sites in California were chosen for a randomized comparison between an ISA model and usual care under the existing county service system. Each ISA demonstration program assumed fiscal and service responsibility for approximately 100 clients. Cost information was collected during a 3-year study period. The capitated ISAs reduced the previously skewed distribution of resources to clients and reduced family economic burden (in one site). However, they did not reduce law enforcement, health, and other nontreatment public costs. Although capitated funding enabled programmatic effectiveness and the shifting of services toward rehabilitation, it did not itself ensure such results.

Objective: In a three-year controlled study, two California integrated service agency demonstration programs that combined structural and program reforms were tested to see if they produced improved outcomes for a cross-section of clients with severe and persistent mental illness., Methods: Clients at an urban site and a rural site were randomly assigned to an integrated service agency program or to a comparison group who received the usual services. Data on client outcomes, were drawn from databases and client and family interviews., Results: Compared with the comparison groups, clients served by the integrated service agencies had less hospital care, greater workforce participation, fewer group and institutional housing arrangements, less use of conservatorship, greater social support, more leisure activity, less family burden, and greater client and family satisfaction. Clients in the urban demonstration program, but not those in the rural program, did better than the comparison group on measures of financial stability, personal well-being, and friendship. At the urban site, 72.6 percent of clients participated in the work force during the three-year study period, compared with 14.6 percent of the clients in the comparison group. No differences were found at either site in rates of arrest and conviction and in self-reported ratings of self-esteem, symptoms, medication compliance, homelessness, and criminal victimization. The capitated costs for demonstration clients were much higher than the costs for services used by comparison clients., Conclusions: Three-year outcomes for a cross-section of clients with severe mental illness in the integrated service agencies were broadly favorable, but costs of services for those clients were high relative to costs for clients receiving the current standard of care.

Objective: Client outcomes for the first year of a three-year study were measured in two integrated service agencies (ISAs) for severely mentally ill persons to test the effectiveness of a model combining financing reform (consolidated funding and capitation) with an assertive continuous treatment team approach., Methods: Clients referred to pilot ISAs at an urban and a rural site in California were randomly assigned to the ISA programs or to comparison groups receiving usual services. Objective data from clients' records as well as subjective information from interviews were compared., Results: At both sites, demonstration clients' participation in the work force was significantly higher than that of the comparison groups. At the urban ISA, clients' participation in the work force rose from a baseline rate of 11 percent to 36 percent. Both ISAs decreased use of hospital care, particularly the rural ISA, which reduced admissions from a baseline rate of 40 percent to 21 percent in the study year. Both ISAs retained clients in treatment with significantly more success than did comparison programs, and urban ISA clients reported participating in more leisure and social activities than did clients in the comparison group. No differences were found at either site in rates of long-term hospitalization, arrest, or conviction or in measures of self-esteem, symptomatology, substance use, homelessness, or quality of life., Conclusions: After 12 months of a 36-month program, demonstration clients spent less time in hospitals, were more likely to have worked for pay, and were more likely to have remained in treatment.