The Right to Counsel in Illinois: Evaluation of Adult Criminal Trial-Level Indigent Defense Services

This study shows there are two overarching reasons why the State of Illinois is defaulting on its constitutional right to counsel obligations. First, the state requires counties and courts to provide and predominantly fund indigent defense systems in a way that bakes in governmental interference with the right to counsel. Second, as one of only seven states with no state-level mechanism to oversee any aspect of trial-level right to counsel services, Illinois lacks information about every aspect of the varied indigent defense systems implemented by the county governments and courts in their efforts to fulfill the Sixth Amendment right to counsel responsibilities that the state has delegated to them. There is a path forward, and it is important for Illinois to get this right

Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

Effect of Smartphone Use on Sleep in Undergraduate Medical Students: A Cross-Sectional Study

Smartphone use, particularly at night, has been shown to provoke various circadian sleep–wake rhythm disorders such as insomnia and excessive daytime tiredness. This relationship has been mainly scrutinized among patient groups with higher rates of smartphone usage, particularly adolescents and children. However, it remains obscure how smartphone usage impacts sleep parameters in adults, especially undergraduate college students. This study sought to (1) investigate the association between smartphone use (actual screen time) and four sleep parameters: Pittsburgh sleep quality score (PSQI), self-reported screen time, bedtime, and rise time; (2) compare the seven PSQI components between good and poor sleep quality subjects. In total, 264 undergraduate medical students (aged 17 to 25 years) were recruited from the Government Doon Medical College, Dehradun, India. All participants completed a sleep questionnaire, which was electronically shared via a WhatsApp invitation link. Hierarchical and multinomial regression analyses were performed in relation to (1) and (2). The average PSQI score was 5.03 ± 0.86, with approximately one in two respondents (48.3%) having a poor sleep index. Smartphone use significantly predicted respondents’ PSQI score (β = 0.142, p = 0.040, R2 = 0.027), perceived screen time (β = 0.113, p = 0.043, R2 = 343), bedtime (β = 0.106, p = 0.042, R2 = 045), and rise time (β = 0.174, p = 0.015, R2 = 0.028). When comparing poor-quality sleep (PSQI ≥ 5) to good-quality sleep (PSQI 0.05), five PSQI components declined significantly: subjective sleep quality (β = −0.096, p < 0.001); sleep latency (β = −0.034, p < 0.001); sleep duration (β = −0.038, p < 0.001); sleep disturbances (β = 1.234, p < 0.001); and sleep dysfunction (β = −0.077, p < 0.001). Consequently, public health policymakers should take this evidence into account when developing guidelines around smartphone use—i.e., the when, where, and how much smartphone use—to promote improved sleep behaviour and reduce the rate of sleep–wake rhythm disorders

Comprehensive Biostatistical Analysis of CpG Island Methylator Phenotype in Colorectal Cancer Using a Large Population-Based Sample

The CpG island methylator phenotype (CIMP) is a distinct phenotype associated with microsatellite instability (MSI) and BRAF mutation in colon cancer. Recent investigations have selected 5 promoters (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1) as surrogate markers for CIMP-high. However, no study has comprehensively evaluated an expanded set of methylation markers (including these 5 markers) using a large number of tumors, or deciphered the complex clinical and molecular associations with CIMP-high determined by the validated marker panel. METHOLODOLOGY/PRINCIPAL FINDINGS: DNA methylation at 16 CpG islands [the above 5 plus CDKN2A (p16), CHFR, CRABP1, HIC1, IGFBP3, MGMT, MINT1, MINT31, MLH1, p14 (CDKN2A/ARF) and WRN] was quantified in 904 colorectal cancers by real-time PCR (MethyLight). In unsupervised hierarchical clustering analysis, the 5 markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1), CDKN2A, CRABP1, MINT31, MLH1, p14 and WRN were generally clustered with each other and with MSI and BRAF mutation. KRAS mutation was not clustered with any methylation marker, suggesting its association with a random methylation pattern in CIMP-low tumors. Utilizing the validated CIMP marker panel (including the 5 markers), multivariate logistic regression demonstrated that CIMP-high was independently associated with older age, proximal location, poor differentiation, MSI-high, BRAF mutation, and inversely with LINE-1 hypomethylation and beta-catenin (CTNNB1) activation. Mucinous feature, signet ring cells, and p53-negativity were associated with CIMP-high in only univariate analysis. In stratified analyses, the relations of CIMP-high with poor differentiation, KRAS mutation and LINE-1 hypomethylation significantly differed according to MSI status.Our study provides valuable data for standardization of the use of CIMP-high-specific methylation markers. CIMP-high is independently associated with clinical and key molecular features in colorectal cancer. Our data also suggest that KRAS mutation is related with a random CpG island methylation pattern which may lead to CIMP-low tumors

Ocular surface squamous neoplasia masquerading as pseudoepitheliomatous hyperplasia in chronic vernal keratoconjunctivitis

We report a rare case of ocular surface squamous neoplasia (OSSN) masquerading as pseudoepitheliomatous hyperplasia in chronic vernal keratoconjunctivitis (VKC). A 24-year-old man presented with a history of bilateral VKC since childhood with a superior limbal mass in the right eye. There was a history of use of intermittent corticosteroids in the past. He underwent impression cytology followed by excision biopsy with wide margins (no touch technique), cryotherapy and amniotic membrane transplantation. Histopathological analysis confirmed the diagnosis of OSSN with mild to moderate dysplasia. This case highlights the importance of strong clinical suspicion and detailed cytological and histopathological examination for early detection and management of OSSN

Impact and Diagnostic Gaps of Comprehensive Genomic Profiling in Real-World Clinical Practice

Purpose: next-generation sequencing based comprehensive genomic profiling (CGP) is becoming common practice. Although numerous studies have shown its feasibility to identify actionable genomic alterations in most patients, its clinical impact as part of routine management across all cancers in the community remains unknown. Methods: we conducted a retrospective study of all patients that underwent CGP as part of routine cancer management from January 2013 to June 2017 at an academic community-based NCI-designated cancer center. CGP was done in addition to established first tier reflex molecular testing as per national guidelines (e.g., EGFR/ALK for non-small cell lung cancer (NSCLC) and extended-RAS for colorectal cancer). Results: 349 tests were sent for CGP from 333 patients and 95% had at least one actionable genomic alteration reported. According to the reported results, 23.2% had a Food and Drug Administration (FDA) approved therapy available, 61.3% had an off-label therapy available and 77.9% were potentially eligible for a clinical trial. Treatment recommendations were also reviewed within the OncoKB database and 47% of them were not clinically validated therapies. The CGP results led to treatment change in only 35 patients (10%), most commonly in NSCLC. Nineteen of these patients (54% of those treated and 5% of total) had documented clinical benefit with targeted therapy. Conclusion: we demonstrate that routine use of CGP in the community across all cancer types detects potentially actionable genomic alterations in a majority of patients, however has modest clinical impact enriched in the NSCLC subset