The Effects of Strategy Instruction with a CDO Procedure in General Education Settings

The purpose of this study was to evaluate a revision strategy for middle school students in a three general education classrooms. Three teachers and 23 sixth-graders in an elementary school in an urban school district in the Northeast participated in this study. Classroom teachers were trained in the revision strategy and provided instruction to their respective students. Although all students received instruction, data was collected on four pairs of students from each class (2 high-achieving, 2 average achieving, 2 low achieving, and 2 students with learning disabilities). This study examined the effects of a Compare-Diagnose-Operate (CDO) procedure (using the acronym FIX) embedded within a self-regulation strategy (SRSD) to allow students the opportunity to internalize the elements of revising. The strategy emphasized the need for students to (a) examine their draft, focusing specifically on the essential elements or parts of an essay, (b) identify problems in their essay between what they wanted to write versus what was actually written, and (c) act on, or execute necessary changes to the draft in response to specific problems they had identified. Improvement in students' writing and revising skills was based on number of meaningful changes, quality of changes between first and second drafts, and holistic quality of the students' revised essays. The effects of teaching the revising strategy were assessed using a multiple-probe design with multiple probes at baseline. The results of this study showed that all students regardless of achievement level benefited from instruction. Students showed significant gains in the number of meaningful changes made from baseline to postinstruction. In addition, holistic quality ratings doubled for students across all achievement levels. The findings emphasize the importance of providing strategy instruction in the classroom and the need for future research in this area

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Incidence and Trends of High Tibial Osteotomy and Unicompartmental Knee Arthroplasty Over the Past Decade: A Lost Art

Background: After failed nonoperative treatment, unicompartmental osteoarthritis can be treated surgically by either unicompartmental knee arthroplasty (UKA) or high tibial osteotomy (HTO). The purpose of this retrospective study is to analyze utilization and demographic trends of UKA and HTO relative to total knee arthroplasty (TKA) over the past decade. Methods: A retrospective review was conducted using the PearlDiver database. Patients that received a UKA or HTO were identified. Trend analyses of surgical procedure utilization were performed with the Mann-Kendall trend test. Demographic data and the rates of various comorbidities were also queried. Results: A total of 103,465 UKAs, 2183 HTOs, and 1,413,425 TKAs, between 2010 and 2021 quarter 1, were analyzed. Trend analyses revealed that relative to TKA utilization, UKA utilization significantly increased (P < .001) while HTO utilization significantly decreased (P < .001). The compound annual growth rate of UKA utilization relative to TKA was +5.16% from 2010 to 2017 but was −10.61% from 2018 to 2021, while that of HTO relative to TKA was −9.69% from 2010 to 2021. Demographic analyses demonstrated the UKA cohort (63.1) was significantly older than the HTO cohort (46.5) (P < .001). Additionally, there were significantly more female patients who underwent UKA than HTO (P < .001). Conclusions: The present study demonstrated that relative to TKA, UKA utilization increased from 2010 to 2017, with a subsequent decrease afterward, whereas HTO utilization decreased since 2010. Demographic differences exist between the 2 operations, with HTOs more commonly performed in younger male patients, and UKAs in older female patients. Level of Evidence: Level III

Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection

Many human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generations and is sufficiently common to be considered a polymorphism. We hypothesized that this deletion might affect spermatogenesis because it removes almost half of the Y chromosome's AZFc region, a gene-rich segment that is critical for sperm production(1,2). An association study established that this deletion, called gr/gr, is a significant risk factor for spermatogenic failure. The gr/gr deletion has far lower penetrance with respect to spermatogenic failure than previously characterized Y-chromosomal deletions; it is often transmitted from father to son. By studying the distribution of gr/gr-deleted chromosomes across the branches of the Y chromosome's genealogical tree, we determined that this deletion arose independently at least 14 times in human history. We suggest that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate new gr/gr deletion

Gypsum addition to soils contaminated by red mud: Implications for aluminium, arsenic, molybdenum and vanadium solubility

Red mud is highly alkaline (pH 13), saline and can contain elevated concentrations of several potentially toxic elements (e.g. Al, As, Mo and V). Release of up to 1 million m of bauxite residue (red mud) suspension from the Ajka repository, western Hungary, caused large-scale contamination of downstream rivers and floodplains. There is now concern about the potential leaching of toxic metal(loid)s from the red mud as some have enhanced solubility at high pH. This study investigated the impact of red mud addition to three different Hungarian soils with respect to trace element solubility and soil geochemistry. The effectiveness of gypsum amendment for the rehabilitation of red mud-contaminated soils was also examined. Red mud addition to soils caused a pH increase, proportional to red mud addition, of up to 4 pH units (e.g. pH 7 → 11). Increasing red mud addition also led to significant increases in salinity, dissolved organic carbon and aqueous trace element concentrations. However, the response was highly soil specific and one of the soils tested buffered pH to around pH 8.5 even with the highest red mud loading tested (33 % w/w); experiments using this soil also had much lower aqueous Al, As and V concentrations. Gypsum addition to soil/red mud mixtures, even at relatively low concentrations (1 % w/w), was sufficient to buffer experimental pH to 7.5-8.5. This effect was attributed to the reaction of Ca supplied by the gypsum with OH and carbonate from the red mud to precipitate calcite. The lowered pH enhanced trace element sorption and largely inhibited the release of Al, As and V. Mo concentrations, however, were largely unaffected by gypsum induced pH buffering due to the greater solubility of Mo (as molybdate) at circumneutral pH. Gypsum addition also leads to significantly higher porewater salinities, and column experiments demonstrated that this increase in total dissolved solids persisted even after 25 pore volume replacements. Gypsum addition could therefore provide a cheaper alternative to recovery (dig and dump) for the treatment of red mud-affected soils. The observed inhibition of trace metal release within red mud-affected soils was relatively insensitive to either the percentage of red mud or gypsum present, making the treatment easy to apply. However, there is risk that over-application of gypsum could lead to detrimental long-term increases in soil salinity