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Entry of antigen-specific T cells into human tumors is critical for immunotherapy, but the underlying mechanisms are poorly understood. Here, we combined high-dimensional spatial analyses with in vitro and in vivo modeling to study the mechanisms underlying immune infiltration in human multiple myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS). Clustered tumor growth was a feature of MM but not MGUS biopsies, and this growth pattern was reproduced in humanized mouse models. MM biopsies exhibited intralesional as well as spatial heterogeneity, with coexistence of T cell-rich and T cell-sparse regions and the presence of areas of T cell exclusion. In vitro studies demonstrated that T cell entry into MM clusters was regulated by agonistic signals and CD2-CD58 interactions. Upon adoptive transfer, antigen-specific T cells localized to the tumor site but required in situ DC-mediated antigen presentation for tumor entry. C-type lectin domain family 9 member A-positive (CLEC9A+) DCs appeared to mark portals of entry for gradients of T cell infiltration in MM biopsies, and their proximity to T cell factor 1-positive (TCF1+) T cells correlated with disease state and risk status. These data illustrate a role for tumor-associated DCs and in situ activation in promoting the infiltration of antigen-specific T cells in MM and provide insights into spatial alterations in tumor/immune cells with malignant evolution.

Several immediate and distal social environmental factors work directly and indirectly with one another to contribute to multiple forms of peer victimization. Bullying is the most prevalent form of peer victimization during adolescence; however, peer victimization typically takes the form of indirect aggression during young adulthood. Therefore, we examined how perceptions of school and neighborhood income inequality worked through perceptions of school climate, neighborhood violence, and neighborhood distrust to predict retrospective adolescent bullying victimization and current young adulthood indirect peer victimization. In a cross-sectional sample of 460 young adults (Mage = 20.2, SDage = 2.18; 59.6% women; 40.4% men; 51.6% White), path analyses revealed that higher school income inequality indirectly predicted higher levels of bullying and indirect peer victimization through lower school climate. Higher neighborhood income inequality also indirectly predicted higher levels indirect peer victimization through higher neighborhood violence. Our findings highlight the importance of targeting adverse environmental risk factors to prevent and intervene in multiple forms of peer victimization across development.

Despite advances in genome sequencing, many individuals with rare genetic disorders remain undiagnosed. Transcriptional profiling via RNA-seq can reveal functional impacts of DNA variants and improve diagnosis. We assessed blood-derived RNA-seq in the largely undiagnosed SickKids Genome Clinic cohort ( n  = 134), which has been subjected to multiple analyses benchmarking the utility of genome sequencing. Our RNA-centric analysis identifies gene expression outliers, aberrant splicing, and allele-specific expression. In one-third of diagnosed individuals (20/61), RNA-seq reinforced DNA-based findings. In 2/61 cases, RNA-seq revised diagnoses ( EPG5 to LZTR1 in an individual with a Noonan syndrome-like disorder) and discovered an additional relevant gene ( CEP120 in addition to SON in an individual with ZTTK syndrome). Additionally, ~7% (5/73) of undiagnosed cases had at least one plausible candidate gene identified. This study highlights both the benefits and limitations of whole-blood RNA profiling in refining genetic diagnoses and uncovering novel disease mechanisms.

Rather than relying solely on projected outcomes derived from previous literature and statistics, this study sought to understand the experiences of young adults between the ages of 18 and 36 that were exposed to adverse childhood experiences (ACEs) in order to gain an understanding of their perceived connection of childhood household dysfunction (CHD), a type of ACEs, and their educational attainment. The research question was, How do millennials perceive their dysfunctional households to be connected to their educational attainment? The research methodology for this study was qualitative and the design was generic qualitative. I aimed to collect responses to open-ended questions, identify themes, and thoroughly examine the phenomena being studied while being fundamentally interpretive without preconceptions of the results. The population utilized in this study included 10 millennials from diverse backgrounds between the ages of 18 and 36. Thematic analysis was used to analyze the collected data. The findings in this research study suggested the need for school professionals to be educated on the proper ways to implement strategies that could help individuals exposed to CHD advance academically on a similar level or higher than their peers who lack exposure to childhood adversities by using up-to-date training materials. Also, recommended future research associated with these findings is to address the socioeconomic disparities that create academic and social deficits for youth exposed to CHD.

[...] in 2007, thefts of 150-pound cylinders of chlorine gas occurred in California and Texas, prompting the Department of Homeland Security to alert local bomb squads and chemical plants across the U.S. The good news is that at least 220 chemical facilities have voluntarily converted to safer chemical processes since 2001 that eliminated risks to millions of people.

Introduction Cabotegravir plus rilpivirine (CAB + RPV) is the first complete long‐acting (LA) regimen recommended for maintaining HIV‐1 virological suppression. Cabotegravir And Rilpivirine Implementation Study in European Locations (CARISEL) is an implementation–effectiveness study examining the implementation of CAB+RPV LA administered every 2 months (Q2M) in European HIV centres. We present staff study participant (SSP) perspectives on the administration of CAB+RPV LA over 12 months. Methods Eighteen clinics were randomized to one of two implementation support packages: standard arm (Arm‐S) or enhanced arm (Arm‐E). Arm‐S included video injection training and provider/patient toolkits. Additionally, Arm‐E included skilled wrap‐around team meetings, face‐to‐face injection training and continuous quality improvement (CQI) calls. SSPs completed surveys on the acceptability, appropriateness and feasibility of CAB+RPV LA as an intervention and its implementation into their clinics, as well as barriers and facilitators to implementation. All surveys were completed at Month (M)1 (baseline), M5 and M12; data collection was completed by February 2022. Qualitative data were obtained from semi‐structured interviews at M1, M5 and M12. The primary objective was assessed via formal statistical comparisons between study arms of the Acceptability of Implementation Measure, Implementation Appropriateness Measure and Feasibility of Implementation Measure surveys (1–5 Likert scale ranging from 1 = “completely disagree” to 5 = “completely agree”). Equivalent measures anchored to CAB+RPV LA as a therapy were also assessed. Results Seventy SSPs completed surveys and interviews at M1, 68 at M5 and 62 at M12. Mean acceptability/appropriateness/feasibility scores were ≥3.8 (out of 5) at M12 for implementation‐ and intervention‐based measures. An analysis of covariance showed no significant differences between study arms for these outcomes. Although barriers were noted, most SSPs were not overly concerned that these would impact implementation; concern about these anticipated barriers also decreased over time. At M12, 90.3% (n = 56/62) of SSPs held a positive opinion about CAB+RPV LA implementation. Qualitative interviews and CQI calls highlighted three top practices that supported implementation: implementation planning; education about CAB+RPV LA clinical efficacy; and education around administering injections and managing pain/discomfort after injections. Conclusions CARISEL demonstrated that CAB+RPV LA dosed Q2M was successfully implemented across a range of European locations, with SSPs finding implementation highly acceptable, appropriate and feasible. ClinicalTrials.gov number NCT04399551

Automation continues to play a greater role in agricultural production with commercial systems now available for machine vision identification of weeds and other pests, autonomous weed control, and robotic harvesters for fruits and vegetables. The growing availability of autonomous machines in agriculture indicates that there are opportunities to increase automation in cotton production. This article considers how current and future advances in automation has, could, or will impact cotton production practices. The results are organized to follow the cotton production process from land preparation to planting to within season management through harvesting and ginning. For each step, current and potential opportunities to automate processes are discussed. Specific examples include advances in automated weed control and progress made in the use of robotic systems for cotton harvesting.

AbstractObjectiveTo describe the incidence of, risk factors for, and impact of vaccines on primary SARS-CoV-2 infection during the second wave of the covid-19 pandemic in susceptible hospital healthcare workers in England.DesignMulticentre prospective cohort study.SettingNational Health Service secondary care health organisations (trusts) in England between 1 September 2020 and 30 April 2021.ParticipantsClinical, support, and administrative staff enrolled in the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study with no evidence of previous infection. Vaccination status was obtained from national covid-19 vaccination registries and self-reported.Main outcome measureSARS-CoV-2 infection confirmed by polymerase chain reaction. Mixed effects logistic regression was conducted to determine demographic and occupational risk factors for infection, and an individual based mathematical model was used to predict how large the burden could have been if vaccines had not been available from 8 December 2020 .ResultsDuring England’s second wave, 12.9% (2353/18 284) of susceptible SIREN participants became infected with SARS-CoV-2. Infections peaked in late December 2020 and decreased from January 2021, concurrent with the cohort’s rapid vaccination coverage and a national lockdown. In multivariable analysis, factors increasing the likelihood of infection in the second wave were being under 25 years old (20.3% (132/651); adjusted odds ratio 1.35, 95% confidence interval 1.07 to 1.69), living in a large household (15.8% (282/1781); 1.54, 1.23 to 1.94, for participants from households of five or more people), having frequent exposure to patients with covid-19 (19.2% (723/3762); 1.79, 1.56 to 2.06, for participants with exposure every shift), working in an emergency department or inpatient ward setting (20.8% (386/1855); 1.76, 1.45 to 2.14), and being a healthcare assistant (18.1% (267/1479); 1.43, 1.16 to 1.77). Time to first vaccination emerged as being strongly associated with infection (P<0.001), with each additional day multiplying a participant’s adjusted odds ratio by 1.02. Mathematical model simulations indicated that an additional 9.9% of all patient facing hospital healthcare workers would have been infected were it not for the rapid vaccination coverage.ConclusionsThe rapid covid-19 vaccine rollout from December 2020 averted infection in a large proportion of hospital healthcare workers in England: without vaccines, second wave infections could have been 69% higher. With booster vaccinations being needed for adequate protection from the omicron variant, and perhaps the need for further boosters for future variants, ensuring equitable delivery to healthcare workers is essential. The findings also highlight occupational risk factors that persisted in healthcare workers despite vaccine rollout; a greater understanding of the transmission dynamics responsible for these is needed to help to optimise the infection prevention and control policies that protect healthcare workers from infection and therefore to support staffing levels and maintain healthcare provision.Trial registrationISRCTN registry ISRCTN11041050.

The current body of research suggests that attention-deficit/hyperactivity disorder (ADHD) negatively affects multiple aspects of social functioning; however, limited research exists that differentiates between individuals with different presentations of ADHD. There is particularly limited research with adolescents, given their specific ADHD presentation, according to the criteria in most recent version of the criteria in the Diagnostic and Statistical Manual of Mental Health, Fifth Edition (DSM-V) by the American Psychological Association (APA) in 2013, that expanded the diagnosis to adolescence and adulthood. The present study examined three domains of social functioning: Social skills, adaptability, and leadership between adolescents with attention-deficit/hyperactivity disorder - Inattentive presentation (ADHD-I) and attention-deficit/hyperactivity disorder - Combined presentation (ADHD-C). Proper treatment modalities based on the specific ADHD presentation could then be identified. Statistical analyses were performed with BASC-2 and BASC-3 parent report and teacher report scores obtained from archival data from 2006 - 2018 with adolescents between the ages of 10 and 17. Hypotheses stated that there would be a statistically significant difference between adolescents with ADHD-I and ADHD-C on the measures of social functioning of adaptability, leadership, and social skills; and that adolescents with ADHD-C would score statistically significantly lower. Small sample size was a limitation. Results were not conclusive across all three measures to support the hypotheses; however significant differences were found between parent report scores and teacher report scores for the individual measures of adaptability and leadership.