Search

Not available.

Research indicates healthy family relationships can reduce recidivism. More effort has been placed towards providing family life programming in prisons to promote healthy individual and relational functioning, yet only a handful of studies have evaluated and provided insight on relationship education (RE) for incarcerated adults. This study contributes to this emerging effort and examines changes following participation in a RE program, using a sample of 461 incarcerated men and women. Findings indicate significant improvements in anxiety and depressive symptoms and conflict resolution skills. Additional tests of moderation of change by gender, relationship status, and child age revealed a greater change in individual functioning for those in a relationship compared to those who were not. Indications are that RE programs hold promise for contributing to better individual well-being and healthy relationships during incarceration and the potential for reducing recidivism incidence after re-entry.

‘Mutations in the chromatin remodeler ASXL1 (ASXL1MT) are associated with poor clinical outcome, however, their impact on chromatin dynamics remains unexplored. Here the authors use a multi-omics approach for chronic myelomonocytic leukemia (CMML) and investigate the transcriptome and chromatin landscape of ASXL1MT CMML.

Abstract The current World Health Organization (WHO) classification of myeloid malignancies includes myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) as a distinct entity. Previous literature on predictors of survival was based on the provisional category of refractory anemia with ring sideroblast and thrombocytosis (RARS-T), which was not subject to MDS/MPN-RS-T exclusionary criteria such as PB blast% ≥1, BM blast% ≥5 or cytogenetic abnormalities such as t(3;3)(q21.2;q26.2), inv(3)(q21.23q26.2) or isolated del(5q). We examined overall (OS) and leukemia-free (LFS) survival and its predictors, among 158 patients with WHO-defined MDS/MPN-RS-T. In univariate analysis, age ≥70 years (P = 0.006), hemoglobin (Hb) ≤10 g/dL (P = 0.03) and abnormal karyotype (excluding -Y, P = 0.008) were associated with shortened OS, which was otherwise not affected by either ASXL1 (P = 0.7), SF3B1 (P = 0.4) or JAK2 V617F (P = 0.7) mutations; in multivariable analysis, Hb ≤ 10 g/dL (P = 0.03) and abnormal karyotype (P = 0.001) remained significant, and thus allowed the development of an operational survival model with low (0 risk factors, median OS 10.5 years), intermediate (1 risk factor, median OS 4.8 years) and high risk (2 risk factors, median OS 1.4 years) categories (P = 0.0009). Comparison of MDS/MPN-RS-T (n = 158) and MDS/MPN-U with BM RS ≥ 15% (MDS/MPN-U-RS; n = 25) did not reveal significant differences in frequency of thrombosis, OS, or LFS, although SF3B1 mutation frequency was higher in the former (93% versus 59%; P = 0.0005). These data suggest limited survival impact for molecular abnormalities and the morphological distinction between MDS/MPN-RS-T and MDS/MPN-U-RS.

Partial hospitalization programming (PHP) is a treatment option available for individuals with eating disorders (ED) who have made insufficient progress in outpatient settings or are behaviorally or medically unstable. Research demonstrates that this level of care yields efficacy for the majority of patients. However, not all patients achieve recovery in PHP and later admit to a higher level of care (HLOC) including residential treatment or inpatient hospitalization. Although PHP is an increasingly common treatment choice for ED, research concerning outcome predictors in outpatient, stepped levels of care remains limited. Thus, the current study sought to identify the predictors of patients first admitted to PHP that later enter residential or inpatient treatment. Participants were 788 patients (after exclusions) enrolled in adolescent or adult partial hospitalization programs in a specialized ED clinic. When compared to patients who maintained treatment in PHP, a significantly greater proportion of patients who discharged to a HLOC had previously received ED residential treatment. Moreover, patients who discharged to a HLOC were diagnosed with a comorbid anxiety disorder and reported greater anxious and depressive symptomatology. A logistic regression model predicting discharge from PHP to a HLOC was significant, and lower body mass index (BMI) was a significant predictor of necessitating a HLOC. Supplemental programming in partial hospitalization settings might benefit individuals with previous ED residential treatment experience, higher levels of anxiety and depression, and lower BMIs. Specialized intervention for these cases is both practically and economically advantageous, as it might reduce the risk of rehospitalization and at-risk patients needing to step up to a HLOC.

The ability to properly identify species present in a landscape is foundational to ecology and essential for natural resource management and conservation. However, many species are often unaccounted for due to ineffective direct capture and visual surveys, especially in aquatic environments. Environmental DNA metabarcoding is an approach that overcomes low detection probabilities and should consequently enhance estimates of biodiversity and its proxy, species richness. Here, we synthesize 37 studies in natural aquatic systems to compare species richness estimates for bony fish between eDNA metabarcoding and conventional methods, such as nets, visual census, and electrofishing. In freshwater systems with fewer than 100 species, we found eDNA metabarcoding detected more species than conventional methods. Using multiple genetic markers further increased species richness estimates with eDNA metabarcoding. For more diverse freshwater systems and across marine systems, eDNA metabarcoding reported similar values of species richness to conventional methods; however, more studies are needed in these environments to better evaluate relative performance. In systems with greater biodiversity, eDNA metabarcoding will require more populated reference databases, increased sampling effort, and multi-marker assays to ensure robust species richness estimates to further validate the approach. eDNA metabarcoding is reliable and provides a path for broader biodiversity assessments that can outperform conventional methods for estimating species richness.

Abstract: Among 248 consecutive patients with blast phase myeloproliferative neoplasm (MPN-BP), DNA collected at the time of blast transformation was available in 75 patients (median age, 66 years; 64% men). MPN-BP followed primary myelofibrosis in 39 patients, essential thrombocythemia in 20 patients, and polycythemia vera in 16 patients. A myeloid neoplasm–relevant 33-gene panel was used for next-generation sequencing. Driver mutation distribution was JAK2 57%, CALR 20%, MPL 9%, and triple-negative 13%. Sixty-four patients (85%) harbored other mutations/variants, including 37% with ≥3 mutations; most frequent were ASXL1 47%, TET2 19%, RUNX1 17%, TP53 16%, EZH2 15%, and SRSF2 13%; relative mutual exclusivity was expressed by TP53, EZH2, LNK, RUNX1, SRSF2, and NRAS/KRAS mutations. Paired chronic-blast phase sample analysis was possible in 19 patients and revealed more frequent blast phase acquisition of ASXL1, EZH2, LNK, TET2, TP53, and PTPN11 mutations/variants. In multivariable analysis, RUNX1 and PTPN11 mutations/variants were associated with shorter survival duration; respective hazard ratios (HRs) (95% confidence interval [CI]) were 2.1 (95% CI, 1.1-3.8) and 3.0 (95% CI, 1.1-6.6). An all-inclusive multivariable analysis confirmed the prognostic relevance of RUNX1 mutations (HR, 1.9; 95% CI, 1.5-5.5) and also showed additional contribution from a treatment strategy that includes transplant or induction of complete or near-complete remission (HR, 0.3; 95% CI, 0.2-0.5). The current study points to specific mutations that might bear pathogenetic relevance for leukemic transformation in MPN and also suggest an adverse survival effect of RUNX1 mutations.

Abstract: A myeloid neoplasm–relevant 27-gene panel was used for next-generation sequencing of bone marrow or whole blood DNA in 182 patients with primary myelofibrosis (PMF). DNA sequence variants/mutations other than JAK2/CALR/MPL were detected in 147 patients (81%), with the most frequent being ASXL1 (36%), TET2 (18%), SRSF2 (18%), and U2AF1 (16%); furthermore, 35%, 26%, 10%, and 9% of the patients harbored 1, 2, 3, or 4 or more such variants/mutations, respectively. Adverse variants/mutations were identified by age-adjusted multivariable analysis of impact on overall survival or leukemia-free survival and included ASXL1, SRSF2, CBL, KIT, RUNX1, SH2B3, and CEBPA; their combined prevalence was 56%. Adverse variants/mutations were associated with inferior overall survival (median, 3.6 vs 8.5 years; P < .001) and leukemia-free survival (7-year risk, 25% vs 4%; P < .001), and the effect on survival was independent of both the Dynamic International Prognostic Scoring System Plus and JAK2/CALR/MPL mutational status, with respective hazard ratios of 2.0 (95% confidence interval [CI], 1.3-3.1) and 2.9 (95% CI, 1.9-4.4). Additional prognostic information was obtained by considering the number of adverse variants/mutations; median survivals in patients with zero (n = 80), 1 or 2 (n = 93), or 3 or more (n = 9) adverse variants/mutations were 8.5, 4, and 0.7 years, respectively (P < .001). Additional data were obtained on pattern of mutation co-segregation and phenotypic correlation, including significant associations between U2AF1 and JAK2 mutations (P = .04) and U2AF1 mutations and anemia (P = .003) and thrombocytopenia (P = .006). We conclude that DNA variants/mutations other than JAK2/CALR/MPL are prevalent in PMF and are qualitatively and quantitatively relevant in predicting overall and leukemia-free survival.

Abstract: Polycythemia vera (PV) is characterized by JAK2 and essential thrombocythemia (ET) by JAK2, calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) mutations; we describe the occurrence and prognostic relevance of DNA sequence variants/mutations other than JAK2/CALR/MPL. A myeloid neoplasm–relevant 27-gene panel was used for next-generation sequencing of bone marrow or whole blood DNA and conventional tools were used for analysis. “Adverse variants/mutations” were identified by age-adjusted multivariable analysis of impact on overall, leukemia-free, or myelofibrosis-free survival. Fifty-three percent of 133 Mayo Clinic patients with PV and 53% of 183 with ET harbored 1 or more sequence variants/mutations other than JAK2/CALR/MPL; the most frequent were TET2 and ASXL1. “Adverse variants/mutations” in PV included ASXL1, SRSF2, and IDH2 and in ET SH2B3, SF3B1, U2AF1, TP53, IDH2, and EZH2; combined prevalence was 15% and 15%, respectively. Adverse variants/mutations were associated with inferior survival in both PV (median, 7.7 vs 16.9 years) and ET (median, 9 vs 22 years) and the effect was independent of conventional prognostic models with respective hazard ratio (95% confidence interval) of 2.8 (1.5-5.1) and 2.6 (1.4-4.8); these observations were validated in 215 Italian patients with PV and 174 with ET. In both Mayo Clinic and Italian cohorts, leukemic or fibrotic progression was also predicted by adverse variants/mutations. Number of mutations did not provide additional prognostic information. We conclude that targeted deep sequencing in PV and ET allows for genetic risk stratification that is independent of clinically derived prognostic models.

In a retrospective analysis of 205 patients (median age 62 years) with primary myelofibrosis and known JAK2V617F mutational status, 13.2% experienced a vaso-occlusive event at or prior to their diagnosis. After a median follow up of 31 months, post-diagnosis thrombosis occurred in 22 patients (10.7%), including 9 (4.4%) and 16 (7.8%) patients with a total of 9 arterial and 24 venous events, respectively. The majority (71%) of the venous events were temporally associated with other exogenous risk factors for thrombosis such as surgery, line placement or hormonal therapy. On multivariable analysis that included age, JAK2V617F mutation status and leukocyte count as covariates, history of thrombosis was the only predictive variable in general (P=0.04) or when arterial (P=0.007) and venous (P=0.02) thromboses were analyzed separately. The current study demonstrates a higher prevalence of venous, as opposed to arterial, events in PMF, post-diagnosis, and clarifies their nature as being mostly provoked.

Partial hospitalization programming (PHP) is a treatment option available for individuals with eating disorders (ED) who have made insufficient progress in outpatient settings or are behaviorally or medically unstable. Research demonstrates that this level of care yields efficacy for the majority of patients. However, not all patients achieve recovery in PHP and later admit to a higher level of care (HLOC) including residential treatment or inpatient hospitalization. Although PHP is an increasingly common treatment choice for ED, research concerning outcome predictors in outpatient, stepped levels of care remains limited. Thus, the current study sought to identify the predictors of patients first admitted to PHP that later enter residential or inpatient treatment. Participants were 788 patients (after exclusions) enrolled in adolescent or adult partial hospitalization programs in a specialized ED clinic. When compared to patients who maintained treatment in PHP, a significantly greater proportion of patients who discharged to a HLOC had previously received ED residential treatment. Moreover, patients who discharged to a HLOC were diagnosed with a comorbid anxiety disorder and reported greater anxious and depressive symptomatology. A logistic regression model predicting discharge from PHP to a HLOC was significant, and lower body mass index (BMI) was a significant predictor of necessitating a HLOC. Supplemental programming in partial hospitalization settings might benefit individuals with previous ED residential treatment experience, higher levels of anxiety and depression, and lower BMIs. Specialized intervention for these cases is both practically and economically advantageous, as it might reduce the risk of rehospitalization and at-risk patients needing to step up to a HLOC.

Objective To retrospectively identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) among male patients with bone marrow vacuolization using a clinically applicable, targeted-screening approach. Methods Bone marrow reports from 1 May 2014 through 18 February 2022 were reviewed for documentation of cytoplasmic vacuolization. Patients with acute leukaemia, lymphoma, metastatic solid tumour, amyloidosis or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome were excluded, as were those without clinical records available for direct chart review. Cases were rated for suspicion of VEXAS syndrome using a 5-point scale based on the presence of laboratory findings, clinical features and treatment response. Patients with available DNA material and moderate (three patients) or high (four to five patients) suspicion were tested for somatic UBA1 variants associated with VEXAS syndrome. Results A total of 315 reports from 292 unique patients included documentation of vacuolization. Following exclusion criteria, 64 patients underwent direct medical chart review to assess likelihood of VEXAS syndrome, for which 21 patients met moderate to high suspicion. Available DNA was present in eight patients, seven (87.5%) of whom had a pathogenic somatic UBA1 variant consistent with VEXAS syndrome. The distribution of cytoplasmic vacuolization in the bone marrow biopsy reports among patients with VEXAS syndrome were erythroid and myeloid precursors (6/7), erythroid precursors only (1/7) and myeloid precursors only (0/7). Conclusion In this study, the utilization of a clinically applicable targeted-screening approach to test bone marrow specimens (with vacuolization) for the presence of previously undiagnosed VEXAS syndrome resulted in a positive detection rate of 87.5%. [ABSTRACT FROM AUTHOR]