IPS Supported Employment for Transition Age Youth: Helping Youth with Serious Mental Health Conditions to Access Jobs, Education and Careers

This manual describes IPS supported employment and education services for adolescents and young adults (IPS-Y). IPS stands for Individual Placement and Support and indicates a type of supported employment program that is evidence-based for people who have mental illnesses. Growing evidence indicates that IPS may be an effective approach for other populations and age groups as well. IPS practitioners in Maryland and other states helped us learn more about serving youth as a part of developing this manual. Young workers and students also described what helped them and what may benefit other youth. We appreciate their assistance in developing this manual

Biodiesel Exhaust: The Need for Health Effects Research

BACKGROUND: Biodiesel is a diesel fuel alternative that has shown potential of becoming a commercially accepted part of the United States’ energy infrastructure. In November 2004, the signing of the Jobs Creation Bill HR 4520 marked an important turning point for the future production of biodiesel in the United States because it offers a federal excise tax credit. By the end of 2005, industry production was 75 million gallons, a 300% increase in 1 year. Current industry capacity, however, stands at just over 300 million gallons/year, and current expansion and new plant construction could double the industry’s capacity within a few years. Biodiesel exhaust emission has been extensively characterized under field and laboratory conditions, but there have been limited cytotoxicity and mutagenicity studies on the effects of biodiesel exhaust in biologic systems. OBJECTIVES: We reviewed pertinent medical literature and addressed recommendations on testing specific research needs in the field of biodiesel toxicity. DISCUSSION: Employment of biodiesel fuel is favorably viewed, and there are suggestions that its exhaust emissions are less likely to present any risk to human health relative to petroleum diesel emissions. CONCLUSION: The speculative nature of a reduction in health effects based on chemical composition of biodiesel exhaust needs to be followed up with investigations in biologic systems

The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

<p>Abstract</p> <p>Background</p> <p>Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate ³H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.</p> <p>Methods</p> <p>Melanoma cells were gamma- and/or UV-irradiated. ³H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression.</p> <p>Results</p> <p>UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100.</p> <p>Conclusion</p> <p>These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.</p

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Protocol for a home-based self-delivered prehabilitation intervention to proactively reduce fall risk in older adults: a pilot randomized controlled trial of transcranial direct current stimulation and motor imagery

Abstract Background Several changes occur in the central nervous system with increasing age that contribute toward declines in mobility. Neurorehabilitation has proven effective in improving motor function though achieving sustained behavioral and neuroplastic adaptations is more challenging. While effective, rehabilitation usually follows adverse health outcomes, such as injurious falls. This reactive intervention approach may be less beneficial than prevention interventions. Therefore, we propose the development of a prehabilitation intervention approach to address mobility problems before they lead to adverse health outcomes. This protocol article describes a pilot study to examine the feasibility and acceptability of a home-based, self-delivered prehabilitation intervention that combines motor imagery (mentally rehearsing motor actions without physical movement) and neuromodulation (transcranial direct current stimulation, tDCS; to the frontal lobes). A secondary objective is to examine preliminary evidence of improved mobility following the intervention. Methods This pilot study has a double-blind randomized controlled design. Thirty-four participants aged 70–95 who self-report having experienced a fall within the prior 12 months or have a fear of falling will be recruited. Participants will be randomly assigned to either an active or sham tDCS group for the combined tDCS and motor imagery intervention. The intervention will include six 40-min sessions delivered every other day. Participants will simultaneously practice the motor imagery tasks while receiving tDCS. Those individuals assigned to the active group will receive 20 min of 2.0-mA direct current to frontal lobes, while those in the sham group will receive 30 s of stimulation to the frontal lobes. The motor imagery practice includes six instructional videos presenting different mobility tasks related to activities of daily living. Prior to and following the intervention, participants will undergo laboratory-based mobility and cognitive assessments, questionnaires, and free-living activity monitoring. Discussion Previous studies report that home-based, self-delivered tDCS is safe and feasible for various populations, including neurotypical older adults. Additionally, research indicates that motor imagery practice can augment motor learning and performance. By assessing the feasibility (specifically, screening rate (per month), recruitment rate (per month), randomization (screen eligible who enroll), retention rate, and compliance (percent of completed intervention sessions)) and acceptability of the home-based motor imagery and tDCS intervention, this study aims to provide preliminary data for planning larger studies. Trial registration This study is registered on ClinicalTrials.gov (NCT05583578). Registered October 13, 2022. https://www.clinicaltrials.gov/study/NCT0558357

The course of eating disorders involving bingeing and purging among adolescent girls: prevalence, stability, and transitions

To quantify eating disorder (ED) stability and diagnostic transition among a community-based sample of adolescents and young adult females in the United States