Attachment disorders diagnosed by community practitioners:a replication and extension

Background: While considered a rare diagnosis, reactive attachment disorder (RAD) is simultaneously the subject of considerable debate. A recent report suggested that RAD is overdiagnosed in community settings and that conduct problems may be used to make a diagnosis of RAD (Woolgar & Baldock, Child and Adolescent Mental Health, 20, 2015, 34–40). This study seeks to replicate and extend these findings. Method: Clinical assessment data from 100 consecutive admissions of maltreated foster and adopted children (ages 3–17) to a specialty treatment clinic in the United States were reviewed. Measures included semi-structured interviews of RAD and disinhibited social engagement disorder (DSED) symptoms and caregiver-report questionnaires of emotional problems, conduct problems, and the quality of the parent–child relationship. Results: Of the 100 cases reviewed, 39 presented with a diagnostic history of RAD, DSED, or ‘attachment disorder’. Of these cases, three were diagnosed in-clinic with DSED; no cases met diagnostic criteria for RAD according to DSM-5 criteria. However, analyses found that those diagnosed with RAD by community-based clinicians were significantly more likely to display conduct problems and to be adopted (as opposed to in foster care). Conclusions: These findings confirm those of Woolgar and Baldock (Child and Adolescent Mental Health, 20, 2015, 34–40). It appears that the diagnostic criteria of RAD are commonly being inaccurately applied in general community-based practice. Clarification of diagnostic criteria for RAD in recent revisions of diagnostic taxonomies, the accumulation of empirical data on RAD, and improved instrumentation are either poorly disseminated or inadequately implemented in community-based practice settings

Dynamic Changes in High-Sensitivity Cardiac Troponin I in Response to Anthracycline-Based Chemotherapy

Aims: Treatment advances have improved cancer-related outcomes and shifted interest towards minimising long-term iatrogenic complications, particularly chemotherapy-related cardiotoxicity. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of plasma troponin and enable early detection of cardiomyocyte injury prior to the development of myocardial dysfunction. The profile of hs-cTnI in response to anthracycline-based treatment has not previously been described. Materials and methods: This was a multicentre prospective observational cohort study. Female patients with newly diagnosed invasive breast cancer scheduled to receive anthracycline-based (epirubicin) chemotherapy were recruited. Blood sampling was carried out before and 24 h after each cycle. Hs-cTnI concentrations were measured using the Abbott ARCHITECTSTAT assay. Results: We recruited 78 women with a median (interquartile range) age of 52 (49–61) years. The median baseline troponin concentration was 1 (1–4) ng/l and the median cumulative epirubicin dose was 394 (300–405) mg/m2. Following an initial 33% fall 24 h after anthracycline dosing (P < 0.001), hs-cTnI concentrations increased by a median of 50% (P < 0.001) with each successive treatment cycle. In total, 45 patients had troponin measured immediately before the sixth treatment cycle, 21 (46.6%) of whom had hs-cTnI concentrations ≥16 ng/l, indicating myocardial injury. Plasma hs-cTnI concentrations before the second treatment cycle were a strong predictor of subsequent myocardial injury. Conclusions: Cardiotoxicity arising from anthracycline therapy is detectable in the earliest stages of breast cancer treatment and is cumulative with each treatment cycle. This injury is most reliably determined from blood sampling carried out before rather than after each treatment cycle

Angle-resolved photoemission in doped charge-transfer Mott insulators

A theory of angle-resolved photoemission (ARPES) in doped cuprates and other charge-transfer Mott insulators is developed taking into account the realistic (LDA+U) band structure, (bi)polaron formation due to the strong electron-phonon interaction, and a random field potential. In most of these materials the first band to be doped is the oxygen band inside the Mott-Hubbard gap. We derive the coherent part of the ARPES spectra with the oxygen hole spectral function calculated in the non-crossing (ladder) approximation and with the exact spectral function of a one-dimensional hole in a random potential. Some unusual features of ARPES including the polarisation dependence and spectral shape in YBa2Cu3O7 and YBa2Cu4O8 are described without any Fermi-surface, large or small. The theory is compatible with the doping dependence of kinetic and thermodynamic properties of cuprates as well as with the d-wave symmetry of the superconducting order parameter.Comment: 8 pages (RevTeX), 10 figures, submitted to Phys. Rev.

Electronic correlation in the infrared optical properties of the quasi two dimensional κ\kappa-type BEDT-TTF dimer system

The polarized optical reflectance spectra of the quasi two dimensional organic correlated electron system $\kappa$-(BEDT-TTF)$_{2}$Cu[N(CN)$_{2}$]$Y$, $Y =$ Br and Cl are measured in the infrared region. The former shows the superconductivity at $T_{\rm c} \simeq$ 11.6 K and the latter does the antiferromagnetic insulator transition at $T_{\rm N} \simeq$ 28 K. Both the specific molecular vibration mode $\nu_{3}(a_{g})$ of the BEDT-TTF molecule and the optical conductivity hump in the mid-infrared region change correlatively at $T^{*} \simeq$ 38 K of $\kappa$-(BEDT-TTF)$_{2}$Cu[N(CN)$_{2}$]Br, although no indication of $T^{*}$ but the insulating behaviour below $T_{\rm ins} \simeq$ 50-60 K are found in $\kappa$-(BEDT-TTF)$_{2}$Cu[N(CN)$_{2}$]Cl. The results suggest that the electron-molecular vibration coupling on the $\nu_{3}(a_{g})$ mode becomes weak due to the enhancement of the itinerant nature of the carriers on the dimer of the BEDT-TTF molecules below $T^{*}$, while it does strong below $T_{\rm ins}$ because of the localized carriers on the dimer. These changes are in agreement with the reduction and the enhancement of the mid-infrared conductivity hump below $T^{*}$ and $T_{\rm ins}$, respectively, which originates from the transitions between the upper and lower Mott-Hubbard bands. The present observations demonstrate that two different metallic states of $\kappa$-(BEDT-TTF)$_{2}$Cu[N(CN)$_{2}$]Br are regarded as {\it a correlated good metal} below $T^{*}$ including the superconducting state and {\it a half filling bad metal} above $T^{*}$. In contrast the insulating state of $\kappa$-(BEDT-TTF)$_{2}$Cu[N(CN)$_{2}$]Cl below $T_{\rm ins}$ is the Mott insulator.Comment: 8 pages, 7 figure

Quantifying stratospheric biases and identifying their potential sources in subseasonal forecast systems

The stratosphere can be a source of predictability for surface weather on timescales of several weeks to months. However, the potential predictive skill gained from stratospheric variability can be limited by biases in the representation of stratospheric processes and the coupling of the stratosphere with surface climate in forecast systems. This study provides a first systematic identification of model biases in the stratosphere across a wide range of subseasonal forecast systems. It is found that many of the forecast systems considered exhibit warm global-mean temperature biases from the lower to middle stratosphere, too strong/cold wintertime polar vortices, and too cold extratropical upper-troposphere/lowerstratosphere regions. Furthermore, tropical stratospheric anomalies associated with the Quasi-Biennial Oscillation tend to decay toward each system¿s climatology with lead time. In the Northern Hemisphere (NH), most systems do not capture the seasonal cycle of extreme-vortex-event probabilities, with an underestimation of sudden stratospheric warming events and an overestimation of strong vortex events in January. In the Southern Hemisphere (SH), springtime interannual variability in the polar vortex is generally underestimated, but the timing of the final breakdown of the polar vortex often happens too early in many of the prediction systems. These stratospheric biases tend to be considerably worse in systems with lower model lid heights. In both hemispheres, most systems with low-top atmospheric models also consistently underestimate the upward wave driving that affects the strength of the stratospheric polar vortex. We expect that the biases identified here will help guide model development for subseasonal-to-seasonal forecast systems and further our understanding of the role of the stratosphere in predictive skill in the troposphere.This work uses S2S Project data. S2S is a joint initiative of the World Weather Research Programme (WWRP) and the World Climate Research Programme (WCRP). This work was initiated by the Stratospheric Network for the Assessment of Predictability (SNAP), a joint activity of SPARC (WCRP) and the S2S Project (WWRP–WCRP). The work of Rachel W.-Y. Wu is funded through ETH grant ETH-05 19-1. Support from the Swiss National Science Foundation through projects PP00P2_170523 and PP00P2_198896 to Daniela I. V. Domeisen is gratefully acknowledged. Chaim I. Garfinkel and Chen Schwartz are supported by the ISF–NSFC joint research program (grant no. 3259/19). The work of Marisol Osman was supported by UBACyT20020170100428BA and PICT-2018-03046 projects. The work of Alvaro de la Cámara is funded by the Spanish Ministry of Science and Innovation through project PID2019-109107GB-I00. Blanca Ayarzagüena and Natalia Calvo acknowledge the support of the Spanish Ministry of Science and Innovation through the JeDiS (RTI2018-096402-B-I00) project. Froila M. Palmeiro and Javier García-Serrano have been partially supported by the Spanish ATLANTE project (PID2019-110234RB-C21) and Ramón y Cajal program (RYC-2016-21181), respectively. Neil P. Hindley and Corwin J. Wright are supported by UK Natural Environment Research Council (NERC), grant number NE/S00985X/1. Corwin J. Wright is also supported by a Royal Society University Research Fellowship UF160545. Seok-Woo Son and Hera Kim are supported by the Basic Science Research Program through the National Research Foundation of Korea (2017R1E1A1A01074889). This material is based upon work supported by the US Department of Energy, Office of Science, Office of Biological and Environmental Research (BER), Regional and Global Model Analysis (RGMA) component of the Earth and Environmental System Modeling program under award no. DE-SC0022070 and National Science Foundation (NSF) IA 1947282. This work was also supported by the National Center for Atmospheric Research (NCAR), which is a major facility sponsored by the NSF under cooperative agreement no. 1852977. Pu Lin is supported by award NA18OAR4320123 from the National Oceanic and Atmospheric Administration (NOAA), U.S. Department of Commerce. Zachary D. Lawrence was partially supported under NOAA award NA20NWS4680051; Zachary D. Lawrence and Judith Perlwitz also acknowledge support from US federally appropriated funds

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

Mutation of a single residue, β-glutamate-20, alters protein–lipid interactions of light harvesting complex II

It is well established that assembly of the peripheral antenna complex, LH2, is required for proper photosynthetic membrane biogenesis in the purple bacterium Rhodobacter sphaeroides. The underlying interactions are, as yet, not understood. Here we examined the relationship between the morphology of the photosynthetic membrane and the lipid–protein interactions at the LH2–lipid interface. The non-bilayer lipid, phosphatidylethanolamine, is shown to be highly enriched in the boundary lipid phase of LH2. Sequence alignments indicate a putative lipid binding site, which includes β-glutamate-20 and the adjacent carotenoid end group. Replacement of β-glutamate-20 with alanine results in significant reduction of phosphatidylethanolamine and concomitant raise in phosphatidylcholine in the boundary lipid phase of LH2 without altering the lipid composition of the bulk phase. The morphology of the LH2 housing membrane is, however, unaffected by the amino acid replacement. In contrast, simultaneous modification of glutamate-20 and exchange of the carotenoid sphaeroidenone with neurosporene results in significant enlargement of the vesicular membrane invaginations. These findings suggest that the LH2 complex, specifically β-glutamate-20 and the carotenoids' polar head group, contribute to the shaping of the photosynthetic membrane by specific interactions with surrounding lipid molecules

Genome-wide association and Meta-analysis of age at onset in Parkinson Disease

Background and Objectives Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD; these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. Methods A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC). Results The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (p < 5 × 10−8). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance (p < 0.025): (rs34311866: β(SE)COURAGE = 0.477(0.203), pCOURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (Ntotal = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361: β(SE)COURAGE+IPDGC = 0.720(0.122), pCOURAGE+IPDGC = 3.13 × 10−9) and a novel BST1 locus (rs4698412: β(SE)COURAGE+IPDGC = −0.526(0.096), pCOURAGE+IPDGC = 4.41 × 10−8). Discussion Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of BST1 as a novel AAO PD locus. These findings open a new direction for the development of treatments to delay the onset of PD

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies