From High School to the Future

For Chicago Public School (CPS) graduates, grades are a more important predictor of college enrollment and graduation than college entrance test scores, according to a study from the Consortium on Chicago School Research at the University of Chicago. This study also found substantial differences across colleges in graduation rates among highly qualified CPS graduates, suggesting that the colleges students attend matters a great deal. The study paints a discouraging picture of college success for CPS graduates. Despite the fact that nearly 80% of seniors state they expect to graduate from a four-year college, only about one-third enroll in a 4-year college within a year of high school graduation, and only 35% of those who enroll received a bachelor's degree within 6 years. The study found that boys are less likely to enter and graduate from college than girls with similar abilities. Also, CPS Latino graduates attend college below both national and Illinois averages for Latino high school graduates

Efficient human-machine control with asymmetric marginal reliability input devices

Input devices such as motor-imagery brain-computer interfaces (BCIs) are often unreliable. In theory, channel coding can be used in the human-machine loop to robustly encapsulate intention through noisy input devices but standard feedforward error correction codes cannot be practically applied. We present a practical and general probabilistic user interface for binary input devices with very high noise levels. Our approach allows any level of robustness to be achieved, regardless of noise level, where reliable feedback such as a visual display is available. In particular, we show efficient zooming interfaces based on feedback channel codes for two-class binary problems with noise levels characteristic of modalities such as motor-imagery based BCI, with accuracy <75%. We outline general principles based on separating channel, line and source coding in human-machine loop design. We develop a novel selection mechanism which can achieve arbitrarily reliable selection with a noisy two-state button. We show automatic online adaptation to changing channel statistics, and operation without precise calibration of error rates. A range of visualisations are used to construct user interfaces which implicitly code for these channels in a way that it is transparent to users. We validate our approach with a set of Monte Carlo simulations, and empirical results from a human-in-the-loop experiment showing the approach operates effectively at 50-70% of the theoretical optimum across a range of channel conditions

Is There a Difference in Staging and Treatment of Head and Neck Squamous Cell Tumors Between Tertiary Care and Community‐Based Institutions?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145574/1/lio2178.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145574/2/lio2178_am.pd

Recommendations for the surveillance of education and employment outcomes in survivors of childhood, adolescent, and young adult cancer: A report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Educational achievement and employment outcomes are critical indicators of quality of life in survivors of childhood, adolescent, and young adult (CAYA) cancer. This review is aimed at providing an evidence-based clinical practice guideline (CPG) with internationally harmonized recommendations for the surveillance of education and employment outcomes in survivors of CAYA cancer diagnosed before the age of 30 years. The CPG was developed by a multidisciplinary panel under the umbrella of the International Late Effects of Childhood Cancer Guideline Harmonization Group. After evaluating concordances and discordances of 4 existing CPGs, the authors performed a systematic literature search through February 2021. They screened articles for eligibility, assessed quality, and extracted and summarized the data from included articles. The authors formulated recommendations based on the evidence and clinical judgment. There were 3930 articles identified, and 83 of them, originating from 17 countries, were included. On a group level, survivors were more likely to have lower educational achievement and more likely to be unemployed than comparisons. Key risk factors for poor outcomes included receiving a primary diagnosis of a central nervous system tumor and experiencing late effects. The authors recommend that health care providers be aware of the risk of educational and employment problems, implement regular surveillance, and refer survivors to specialists if problems are identified. In conclusion, this review presents a harmonized CPG that aims to facilitate evidence-based care, positively influence education and employment outcomes, and ultimately minimize the burden of disease and treatment-related late adverse effects for survivors of CAYA cancers. LAY SUMMARY: A multidisciplinary panel has developed guidelines for the surveillance of education and employment outcomes among survivors of childhood, adolescent, and young adult cancer. On the basis of evidence showing that survivors are at risk for lower educational achievement and unemployment, it is recommended that all survivors receive regular screening for educational and employment outcomes

Fanconi-BRCA pathway mutations in childhood T-cell acute lymphoblastic leukemia

BRCA2 (also known as FANCD1) is a core component of the Fanconi pathway and suppresses transformation of immature T-cells in mice. However, the contribution of Fanconi-BRCA pathway deficiency to human T-cell acute lymphoblastic leukemia (T-ALL) remains undefined. We identified point mutations in 9 (23%) of 40 human T-ALL cases analyzed, with variant allele fractions consistent with heterozygous mutations early in tumor evolution. Two of these mutations were present in remission bone marrow specimens, suggesting germline alterations. BRCA2 was the most commonly mutated gene. The identified Fanconi-BRCA mutations encode hypomorphic or null alleles, as evidenced by their inability to fully rescue Fanconi-deficient cells from chromosome breakage, cytotoxicity and/or G2/M arrest upon treatment with DNA cross-linking agents. Disabling the tumor suppressor activity of the Fanconi-BRCA pathway is generally thought to require biallelic gene mutations. However, all mutations identified were monoallelic, and most cases appeared to retain expression of the wild-type allele. Using isogenic T-ALL cells, we found that BRCA2 haploinsufficiency induces selective hypersensitivity to ATR inhibition, in vitro and in vivo. These findings implicate Fanconi-BRCA pathway haploinsufficiency in the molecular pathogenesis of T-ALL, and provide a therapeutic rationale for inhibition of ATR or other druggable effectors of homologous recombination

Associations with age and glomerular filtration rate in a referred population with chronic kidney disease: Methods and baseline data from a UK multicentre cohort study (NURTuRE-CKD)

BACKGROUND: Chronic kidney disease (CKD) is common but heterogenous and is associated with multiple adverse outcomes. The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort was established to investigate risk factors for clinically important outcomes in persons with CKD referred to secondary care. METHODS: Eligible participants with CKD stages G3-4 or stages G1-2 plus albuminuria > 30 mg/mmol were enrolled from 16 nephrology centres in England, Scotland and Wales from 2017 to 2019. Baseline assessment included demographic data, routine laboratory data and research samples. Clinical outcomes are being collected over 15 years by the UK Renal Registry using established data linkage. Baseline data are presented with subgroup analysis by age, sex and estimated GFR (eGFR). RESULTS: 2996 participants were enrolled. Median (interquartile range) age was 66 (54 to 74) years, 58.5% were male, eGFR 33.8 (24.0 to 46.6) ml/min/1.73m2 and UACR 209 (33 to 926) mg/g. 1883 participants (69.1%) were in high-risk CKD categories. Primary renal diagnosis was CKD of unknown cause in 32.3%, glomerular disease in 23.4% and diabetic kidney disease in 11.5%. Older participants and those with lower eGFR had higher systolic blood pressure and were less likely to be treated with renin-angiotensin system inhibitors (RASi) but were more likely to receive a statin. Female participants were less likely to receive a RASi or statin. CONCLUSIONS: NURTuRE-CKD is a prospective cohort of persons who are at relatively high risk of adverse outcomes. Long-term follow-up and a large biorepository create opportunities for research to improve risk prediction and investigate underlying mechanisms to inform new treatment development

Nano-biomimetic drug delivery vehicles: potential approaches for COVID-19 treatment

The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a “Trojan horse” for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed

Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors : a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium

Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.Peer reviewe

Novel Nitro-PAH Formation from Heterogeneous Reactions of PAHs with NO₂, NO₃/N₂O₅, and OH Radicals: Prediction, Laboratory Studies and Mutagenicity

The heterogeneous reactions of benzo[a]pyrene-d₁₂ (BaP-d₁₂), benzo[k]fluoranthene-d₁₂ (BkF-d₁₂), benzo[ghi]perylene-d₁₂ (BghiP-d₁₂), dibenzo[a,i]pyrene-d₁₄ (DaiP-d₁₄), and dibenzo[a,l]pyrene (DalP) with NO₂, NO₃/N₂O₅, and OH radicals were investigated at room temperature and atmospheric pressure in an indoor Teflon chamber and novel mono NO₂-DaiP, and mono NO₂-DalP products were identified. Quartz fiber filters (QFF) were used as a reaction surface and the filter extracts were analyzed by GC/MS for nitrated-PAHs (NPAHs) and tested in the Salmonella mutagenicity assay, using Salmonella typhimurium strain TA98 (with and without metabolic activation). In parallel to the laboratory experiments, a theoretical study was conducted to rationalize the formation of NPAH isomers based on the thermodynamic stability of OH-PAH intermediates, formed from OH-radical-initiated reactions. NO₂ and NO₃/N₂O₅ were effective oxidizing agents in transforming PAHs to NPAHs, with BaP-d₁₂ being the most readily nitrated. Reaction of BaP-d₁₂, BkF-d₁₂ and BghiP-d₁₂ with NO₂ and NO₃/N₂O₅ resulted in the formation of more than one mono-nitro isomer product, while the reaction of DaiP-d₁₄ and DalP resulted in the formation of only one mono-nitro isomer product. The direct-acting mutagenicity increased the most after NO₃/N₂O₅ exposure, particularly for BkF-d₁₂ in which di-NO₂-BkF-d₁₀ isomers were measured. The deuterium isotope effect study suggested that substitution of deuterium for hydrogen lowered both the direct and indirect acting mutagenicity of NPAHs and may result in an underestimation of the mutagenicity of the novel NPAHs identified in this study.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society and can be found at: http://pubs.acs.org/journal/esthag

Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non-small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically-engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways leading to epigenetic transformation independent from canonical growth factor pathway activation. As such, tumors feature a transcriptional program distinct from KRAS- and EGFR-mutant mouse lung cancers, but shared with human lung adenocarcinomas exhibiting high EZH2 expression. To target EZH2-dependent cancers, we developed a novel and potent EZH2 inhibitor JQEZ5 that promoted the regression of EZH2-driven tumors in vivo, confirming oncogenic addiction to EZH2 in established tumors and providing the rationale for epigenetic therapy in a subset of lung cancer