Predicting patterns of service utilization within children\u27s mental health agencies

Background: Some children with mental health (MH) problems have been found to receive ongoing care, either continuously or episodically. We sought to replicate patterns of MH service use over extended time periods, and test predictors of these patterns. Methods: Latent class analyses were applied to 4 years of visit data from five MH agencies and nearly 6000 children, 4-to 13-years-old at their first visit. Results: Five patterns of service use were identified, replicating previous findings. Overall, 14% of cases had two or more episodes of care and 23% were involved for more than 2 years. Most children (53%) were seen for just a few visits within a few months. Two patterns represented cases with two or more episodes of care spanning multiple years. In the two remaining patterns, children tended to have just one episode of care, but the number of sessions and length of involvement varied. Using discriminant function analyses, we were able to predict with just over 50% accuracy children\u27s pattern of service use. Severe externalizing behaviors, high impairment, and high family burden predicted service use patterns with long durations of involvement and frequent visits. Conclusions: Optimal treatment approaches for children seen for repeated episodes of care or for care lasting multiple years need to be developed. Children with the highest level of need (severe pathology, impairment, and burden) are probably best served by providing high intensity services at the start of care

Taxonomic surrogacy in biodiversity assessments, and the meaning of Linnaean ranks

Copyright © 2006 The Natural History MuseumThe majority of biodiversity assessments use species as the base unit. Recently, a series of studies have suggested replacing numbers of species with higher ranked taxa (genera, families, etc.); a method known as taxonomic surrogacy that has an important potential to save time and resources in assesments of biological diversity. We examine the relationships between taxa and ranks, and suggest that species/higher taxon exchanges are founded on misconceptions about the properties of Linnaean classification. Rank allocations in current classifications constitute a heterogeneous mixture of various historical and contemporary views. Even if all taxa were monophyletic, those referred to the same rank would simply denote separate clades without further equivalence. We conclude that they are no more comparable than any other, non-nested taxa, such as, for example, the genus Rattus and the phylum Arthropoda, and that taxonomic surrogacy lacks justification. These problems are also illustrated with data of polychaetous annelid worms from a broad-scale study of benthic biodiversity and species distributions in the Irish Sea. A recent consensus phylogeny for polychaetes is used to provide three different family-level classifications of polychaetes. We use families as a surrogate for species, and present Shannon–Wiener diversity indices for the different sites and the three different classifications, showing how the diversity measures rely on subjective rank allocations.Y. Bertrand, F. Pleijel and G. W. Rous

Outcomes following Microvascular Mandibular Reconstruction in Pediatric Patients and Young Adults

Background: The etiology and treatment of complex mandibular defects in children differ markedly from those of adults, although treatment with free bone flaps is historical in both groups. While adult outcomes and complication rates are well known, few pediatric data exist, especially for patients with congenital deficiencies. This study reports early and late outcomes from a cohort of young, primarily syndromic patients undergoing microvascular mandibular reconstruction. Methods: This is a retrospective case series of patients who underwent microvascular mandibular reconstruction between 1995 and 2016. Results: Thirteen patients received a total of 13 fibula transfers and 1 medial femoral condyle transfer. Most patients carried a congenital diagnosis (77%), and the average age during surgery was 11.7 ± 5.7 years. The median (interquartile range) [IQR] length of follow-up was 6.3 (5.7) years. There was a 100% flap survival rate, although 86% of all patients experienced at least one complication. Half of all procedures resulted in an early complication. Nine patients (69%) developed late complications, of which temporal mandibular joint ankylosis was the most common (n = 5; 38%). Conclusions: This study is one of few detailing outcomes following mandibular reconstruction by free flap transfer in pediatric patients. These patients were primarily syndromic with appreciable complication rates higher than in other adult and pediatric studies. Some complications are manageable or self-resolving, but others lead to functional problems that may require late operative interventions to correct. Microsurgical treatment should be reserved for children with large, complex mandibular defects when other options are unavailable or have been exhausted

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pathological response and tumour bed histopathological features correlate with survival following neoadjuvant immunotherapy in stage III melanoma

Background: Guidelines for pathological evaluation of neoadjuvant specimens and pathological response categories have been developed by the International Neoadjuvant Melanoma Consortium (INMC). As part of the Optimal Neo-adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN-neo) clinical trial of neoadjuvant combination anti-programmed cell death protein 1/anti-cytotoxic T-Iymphocyte-associated protein 4 immunotherapy for stage III melanoma, we sought to determine interobserver reproducibility of INMC histopathological assessment principles, identify specific tumour bed histopathological features of immunotherapeutic response that correlated with recurrence and relapse-free survival (RFS) and evaluate proposed INMC pathological response categories for predicting recurrence and RFS.Patients and methods: Clinicopathological characteristics of lymph node dissection specimens of 83 patients enrolled in the OpACIN-neo clinical trial were evaluated. Two methods of assessing histological features of immunotherapeutic response were evaluated: the previously described immune-related pathologic response (irPR) score and our novel immunotherapeutic response score (ITRS). For a subset of cases (n = 29), cellular composition of the tumour bed was analysed by flow cytometry.Results: There was strong interobserver reproducibility in assessment of pathological response (kappa = 0.879) and percentage residual viable melanoma (intraclass correlation coefficient = 0.965). The immunotherapeutic response subtype with high fibrosis had the strongest association with lack of recurrence (P = 0.008) and prolonged RFS (P = 0.019). Amongst patients with criteria for pathological non-response (pNR, >50% viable tumour), all who recurred had >= 70% viable melanoma. Higher ITRS and irPR scores correlated with lack of recurrence in the entire cohort (P = 0.002 and P = 70% viable melanoma and incorporating additional criteria of <10% fibrosis subtype of response may identify those at highest risk of recurrence, but requires validation.Analysis and support of clinical decision makin

Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma

Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN () and phase 2 OpACIN-neo () studies(1,2). While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n = 7/9 patients) in the OpACIN study had relapsed. In OpACIN-neo (n = 86), the 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (P < 0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-gamma score) were associated with pathologic response and low risk of relapse; pRR was 100% in patients with high IFN-gamma score/high TMB; patients with high IFN-gamma score/low TMB or low IFN-gamma score/high TMB had pRRs of 91% and 88%; while patients with low IFN-gamma score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-gamma score. Our findings provide a strong rationale for a randomized phase 3 study comparing neoadjuvant ipilimumab plus nivolumab versus standard adjuvant therapy with antibodies against the programmed cell death protein-1 (anti-PD-1) in macroscopic stage III melanoma

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness