True Continuum Research Articles

Developmental ecology in embryos of an estuarine pupfish endemic of the Yucatan peninsula: Survival out of water, metabolic depression, and asynchronous hatching.

Theory predicts that drought-resistant embryos with extended incubations are evolutionarily favored in environments with high mortality of larvae but safe for eggs. Here, we experimentally test, under common garden conditions, the effect of three incubation temperatures and media on embryonic developmental length, extended incubation out of the water, survival, metabolic rate, and hatching dynamics in the estuarine pupfish Garmanella pulchra. We also described the morphological changes of embryonic cortical structures related to air exposure. We found that embryos incubated out of water in low and medium temperatures present an extended incubation period beyond their hatching capability with a deep metabolic depression. Also, these embryos exhibited a hatching asynchrony not related to water availability. Embryos incubated at high temperatures did not show extended incubation, with decreased probability of survival out of water. Our morphological observations of the embryonic cortical structures reveal that the perivitelline space and hair-like filaments buffer the deleterious drought effects. Our results reveal that G. pulchra possesses life-history traits typical of two separate phenomena: delay hatching and diapause; supporting a true continuum between them, rather than a dichotomy. The evolution of these traits may respond to aerial exposure during low tides in the estuaries of Yucatán they inhabit.

Reimagining Initial Certification as a Process That Begins During Residency to Support Continuous Development Across Training and Practice.

In the United States, initial board certification remains focused on a high-stakes knowledge examination after completion of training. A more contemporary view supports a program of assessment that includes multiple types and sources of data with an emphasis on direct workplace observation to get the best picture of an individual's performance. In this article, the authors reimagine initial certification as a continuous assessment for learning that begins in residency, focuses on both knowledge acquisition and its application, and interdigitates intentionally with the first cycle of maintenance of certification to advance learning and smooth the transition from training to practice. A more expanded view of competence, as a 3-layered construct (canonical, contextual, and personalized), supports this proposal. Canonical competence (context-independent knowledge)-best assessed through examinations of knowledge-is most heavily weighted and assessed during medical school but remains critical throughout one's career. Contextual competence (context-dependent knowledge) is best assessed in the workplace and is key during residency and fellowship as trainees navigate a myriad of clinical work environments. Personalized competence, representing the totality of one's unique areas of expertise, is best demonstrated during the practice years when deliberate practice experience supports the growth of personalized expertise and discoveries that advance the field. Shifting initial board certification from relying on an anxiety-provoking, high-stakes, often single moment in time standardized examination to a nuanced approach that is part of an individual trainee's program of assessment offers a more just and robust decision about readiness for unsupervised practice. Such a model would also sow the seeds of meaningful individualization of learning needs that begins in training, continues through practice, and lays the foundation for improving the quality of care for patients within a given practice as well as shifting the current contiguous phases of training and practice into a true continuum.

Photoionization from the Ground and Excited Vibrational States of and Its Deuterated Isotopologues

Photoionization cross sections and rate coefficients have been calculated for all bound vibrational levels of the 1sσ g state of , HD+, and . The Born–Oppenheimer approximation is employed in our calculation of vibrationally resolved photoionization cross sections. Vibrationally resolved and local thermal equilibrium photoionization rate coefficients are presented for photon temperatures less than 50,000 K and are found to be several orders of magnitude larger than previous results in the literature. Analytic fits for the vibrationally resolved and local thermal equilibrium photoionization rate coefficients are provided. Near-threshold oscillations in the vibrationally resolved photoionization are observed. A benchmark set of photoionization cross sections are presented. Fixed-nuclei photoionization cross sections are calculated using two-center true continuum wave functions and are verified by comparison with previous calculations and are found to be in excellent agreement in all cases. Data files for our set of benchmark cross sections, rate coefficients, and fitting parameters for , HD+, and are available on Zenodo under an open-source Creative Commons Attribution license at doi:10.5281/zenodo.8304061.

Cellular automaton for spinor gravity in four dimensions

Certain fermionic quantum field theories are equivalent to probabilistic cellular automata, with fermionic occupation numbers associated to bits. We construct an automaton that represents a discrete model of spinor gravity in four dimensions. Local Lorentz symmetry is exact on the discrete level and diffeomorphism symmetry emerges in the naive continuum limit. Our setting could serve as a model for quantum gravity if diffeomorphism symmetry is realized in the true continuum limit and suitable collective fields for vierbein and metric acquire non-vanishing expectation values. The discussion of this interesting specific model reveals may key qualitative features of the continuum limit for probabilistic cellular automata. This limit obtains for a very large number of cells if the probabilistic information is sufficiently smooth. It is associated to coarse graining. The automaton property that every bit configuration is updated at every discrete time step to precisely one new bit configuration does no longer hold on the coarse grained level. A coarse grained configuration of occupation numbers can evolve into many different configurations with certain probabilities. This characteristic feature of quantum field theories can come along with the emergence of continuous space-time symmetries.

"Dismantling Fixed Time, Variable Outcome Education: Abandoning 'Ready or Not, Here they Come' is Overdue".

Two decades after competency-based medical education appeared in the lexicon of medical educators, the community continues to struggle with realizing its full potential. The implementation of the time variable, fixed outcome component has languished based on complexity compounded by resistance to change. Learners continue to transition from medical school to residency, and then practice, primarily based on time rather than having achieved the ability to meet the needs of the patient populations they will serve. Only those few who demonstrate glaring deficiencies do not graduate. The authors urge the medical education community to move from the current fixed time path of medical education toward the implementation of a true continuum of time variable, fixed outcome education, training, and deliberate practice. The latter is defined by purposeful learning, coaching, feedback, and repetition on the path to achieving and maintaining expertise. The opportunities afforded by such a time-variable, fixed outcome approach include: 1) development of a career long growth mindset, 2) ability to address evolving population health needs and careers within the context of one's practice, and 3) continual improvement of care quality and outcomes for patients on the journey towards expertise for providers.

Targeted Mutational Profiling Reveals Clonal Relationships in Metachronous Occurrence of Classic Hodgkin and Mediastinal Large B-Cell Lymphomas.

Classic Hodgkin lymphoma (CHL) patients may infrequently present with a prior or recurrent disease with discordant histology resembling non-Hodgkin lymphomas. These include primary mediastinal large B-cell lymphoma (PMBL), diffuse large B-cell lymphoma (DLBCL), or mediastinal gray-zone lymphoma (MGZL). Such patients are often refractory to standard therapy and their diagnosis is hampered by significant morphologic and immunophenotypic overlap and insufficient molecular data. Among 509 CHL patients seen at an academic medical center, 6 patients had a prior or subsequent diagnosis different from CHL. Paired tissue samples were evaluated by targeted mutational analysis using a 164-gene panel. Our findings show multiple shared variants indicative of a clonal relationship between the CHL and the PMBL, DLBCL, or MGZL diagnoses. Most frequent mutated genes included TNFAIP3 (4 of 6, 66.7%), STAT6 (3 or 6, 50%), ARID1A (3 of 6, 50%), and XPO1 (3 of 5, 60%). Three patients showed the same oncogenic variant within the XPO1 gene (E571K), and mutations in TNFAIP3 and B2M were observed in 2 of the 5 patients with shared variants. In addition, differences in the mutation profile between the lymphoma pairs were also observed, which could represent clonal evolution. Mutational profiling could be of benefit in patients with recurrent/refractory disease with discordant histology, where the clonal relationship could be helpful to inform and guide therapeutic decisions. These findings provide further evidence of a true biological continuum surrounding CHL, PMBL, DLBCL, and MGZL and shed light on underlying genetic events and their clinical impact.

The education passport: connecting programmatic assessment across learning and practice.

Competency-based medical education (CBME) shifts us from static assessment of learning to developmental assessment for learning. However, implementation challenges associated with CBME remain a major hurdle, especially after training and into practice. The full benefit of developmental assessment for learning over time requires collaboration, cooperation, and trust among learners, regulators, and the public that transcends each individual phase. The authors introduce the concept of an “Education Passport” that provides evidence of readiness to travel across the boundaries between undergraduate medical education, graduate medical education, and the expanse of practice.The Education Passport uses programmatic assessment, a process of collecting numerous low stakes assessments from multiple sources over time, judging these data using criterion-referencing, and enhancing this with coaching and competency committees to understand, process, and accelerate growth without end. Information in the Passport is housed on a cloud-based server controlled by the student/physician over the course of training and practice. These data are mapped to various educational frameworks such Entrustable Professional Activities or milestones for ease of longitudinal performance tracking. At each stage of education and practice the student/physician grants Passport access to all entities that can provide data on performance. Database managers use learning analytics to connect and display information over time that are then used by the student/physician, their assigned or chosen coaches, and review committees to maintain or improve performance. Global information is also collected and analyzed to improve the entire system of learning and care.Developing a true continuum that embraces performance and growth will be a long-term adaptive challenge across many organizations and jurisdictions and will require coordination from regulatory and national agencies. An Education Passport could also serve as an organizing tool and will require research and high-value communication strategies to maximize public trust in the work.

Rôle de la génétique et de l’épigénétique dans l’obésité de l’enfant et de l’adolescent

Obesity is a complex, multifactorial disease due to a dysfunction of the hypothalamic control of weight and food intake. The contribution of genetics is constant, but its impact is variable depending on the situations ranging from rare genetic obesities (around 5% of cases) to more frequently polygenic obesity (or common obesity) (95% of cases). Other factors as pre- and post-natal, societal or psychological determinants always interact closely with these genetic factors explaining the high variability of the phenotype and the complex pathophysiology. A true continuum exists between all these situations through the involvement of more or less rare genetic variants located in genes encoding key proteins in the central regulation of food intake. Rare forms of obesity are characterized by their common phenotype including a very early-onset severe obesity (BMI Z score greater than+3 SD early before the age of 3 years) with resistance to medical treatment, and major eating disorders characterized by difficulties in voluntary control of food intake. Central endocrine abnormalities such as hypogonadotropic hypogonadism or GH deficiency for example, and metabolic abnormalities due to abnormal adipose tissue distribution are also associated with variable degrees (Alström syndrome for example). Neuropsychological abnormalities are also present such as neurodevelopmental disorders (intellectual disability with variable intensity and/or adaptive development disorders which are part of many syndromes such as in Prader-Wili Syndrome; autism spectrum disorders (in SH2B1 or MYT1L deficiency for example), cognitive disorders with difficulties in emotional regulation (eg: Bardet-Biedl Syndrome or specific rare variants located on genes of the melanocortin pathway), behavioral or psychiatric disorders, sleep disorders and major hypothalamic dysfunctions (eg: Prader-Willi Syndrome, Smith Magenis syndrome). This better understanding of the mechanisms has made it possible to better precise the associated phenotypes and, recently, to lead to therapeutic innovations targeting these key genes. This evolution helps to quickly envisage the development of a real personalized medicine in early onset obesity using the combination of drug treatments targeted according to the identified genetic anomaly and/or a multidisciplinary global approach targeting the patient's phenotype or even the bariatric surgery in specific situations.

Mixed variational principle and finite element formulation for couple stress elastostatics

Skew-symmetric couple stress theory may permit the exploration of solids and fluids at the finest scales for which continuum mechanics applies. This theory is founded upon a true continuum representation. As a result, for solids, the rotation equals one half the curl of the displacement field. In addition, the couple-stress tensor reduces to skew-symmetric form and can be written as a polar couple-stress vector, which is energy conjugate to the mean-curvature polar vector field. The resulting theory is fully self-consistent and parsimonious, requiring only a single extra material parameter, a length scale, for the linear elastic isotropic and cubic single crystal cases. Previous finite element formulations for this theory have required either Lagrange multipliers or penalty parameters to enforce rotation-displacement compatibility, while maintaining C0 continuity. Here, we introduce a novel mixed C0 variational principle written in terms of displacement and couple-stress polar vectors that avoids any extraneous contributions to the energy functional. This stationary principle, in turn, provides the basis for a robust finite element method, which is developed in this paper for planar quasistatic size-dependent response of linear elastic isotropic media, and then generalized to consider a cubic single crystal example. The finite element implementation uses standard linear three-node triangles for the displacements and tangential edge elements on the triangles to represent the divergence-free couple-stresses. The formulation, however, is quite comprehensive in nature and thus can be extended to examine a broad range of problems, such as those associated with the dynamic response of non-centrosymmetric anisotropic bodies in three-dimensions.

Envisioning a True Continuum of Competency-Based Medical Education, Training, and Practice.

The existing structure of physician education has developed in siloed stages, with consecutive degrees and certifications and progressively longer training programs. As further fragmentation of health care and training systems will not improve the quality of care and education, the authors argue that a new vision of education, training, and practice as a continuum is needed.They advocate for a model of competency-based medical education that merges with competency-based medical practice. In this system, education and training will result in individual, dynamic portfolios of valid entrustable professional activities (EPAs) for which physicians are certified. Physicians can maintain and renew that entrustment as long as the EPAs remain within their scope of practice. Entrustment occurs initially during training but is then granted for new activities as physicians' careers evolve.This model accounts for the need to keep pace with changes in population health needs and expectations of competence over time. It de-emphasizes the divides between the stages of training and views the continuum from undergraduate medical education until retirement as a whole. Key obligations of self-regulating medical professionals include both the reception and the provision of supervision from and for others, respectively. Learning must be embedded in practice to address expectations regarding new knowledge and skills as they evolve with scientific and technological advances.Entrusting physicians to deliver effective and safe care, based on their performance of the requisite EPAs without supervision, should ensure that they provide high-value, quality care to patients.

Bombardment history of asteroid 4 Vesta recorded by brecciated eucrites: Large impact event clusters at 4.50 Ga and discreet bombardment until 3.47 Ga

Abstract The thermal/impact histories of sixteen eucrite meteorites were investigated: three monomict eucrites (NWA 999, A-87272,87, and Stannern), five polymict eucrites (NWA 1000, NWA 1666, NWA 5601, Y-980066,100, and Y-980255,100), three quench-textured, eucrite melt rocks (Y-981646,21, Y-981651,105, and MIL 0766214), one eucrite dominantly comprised of quench-textured clasts (QUE 99005,11), three unclassified eucrite breccias (LAP 031316,9, LAR 06870,5, QUE 99799,4) and one unbrecciated eucrite (EET 92004,17), included here due to its shock features. We have measured fifteen high-precision new 40 Ar/ 39 Ar plateau ages on plagioclase and matrix for ten of these meteorites with a tight cluster of nine ages obtained from three different polymict breccias. These ages range from 4534 ± 56 Ma to 4491 ± 16 Ma resulting in a concordant age population ( P = 0.16). The fact that such a cluster of ages is recorded in unrelated breccias which are made of a priori unrelated components, leads us to propose that those ages recorded a single heating event on a large scale, and is interpreted here as a high-energy impact event, early in the history of Vesta at 4500 ± 4 Ma. We propose that the debris was ejected and isolated from subsequent large impacts in a secondary rubble pile asteroid where the energy of the outgoing shock wave from an impact is significantly reduced as it compacts the target material ( Holsapple et al., 2002 , and references therein) . The other analyses define a spread of five plateau ages ranging from 3851± 21 Ma to 3469 ± 35 Ma, over ∼380 Ma. An additional apparent plateau age of 4288 ± 38 Ma, but with a diffusion profile of cumulative 39 Ar release, along with published U-Pb apatite age of ∼4.14 Ga, suggests that the data might either define a true continuum (normal background bombardment) from 4.5 Ga to 3.47 Ga or cluster between ∼3.85 Ga and ∼3.47 Ga (excavation of a fresh surface at 3.85 Ga continuously bombarded until 3.47 Ga). Both scenarios are compatible with a final ejection age of 3.47 Ga when a major impact liberates the bulk of the brecciated meteorites into another secondary rubble pile asteroid, where the brecciated eucrites stayed relatively well protected from subsequent major impacts. Based on these results and recent crater counting measurements, we propose that the excavation and bulk ejection were caused by the Rheasilvia (ca. 3.47 Ga) basin-forming impact. Diffusion models on plagioclase crystals with different Ar age spectrum signatures, from a single breccia (NWA1666; 4501 ± 7 Ma), suggest that either: (1) the formation of the breccia is very young, or (2) different plagioclase crystals have different diffusion characteristics, and/or (3) the porosity caused heterogeneous temperatures during an impact heating event, particularly likely if the 4.5 Ga brecciated eucrites were stored in a rubble pile asteroid. Many or possibly most large asteroids being re-accumulated rubble piles with potential large porosity ( Holsapple et al., 2002 ). Scenarios (2) and (3) preclude the usage of multi-grain aliquots to decipher the time-temperature history of most impact breccia using 40 Ar/ 39 Ar thermochronology.

Identifying structures in the continuum: Application to Be16

The population and decay of two-nucleon resonances offer exciting new opportunities to explore dripline phenomena. The understanding of these systems requires a solid description of the three-body (core+N+N) continuum. The identification of a state with resonant character from the background of non-resonant continuum states in the same energy range poses a theoretical challenge. It is the purpose of this work to establish a robust theoretical framework to identify and characterize three-body resonances in a discrete basis. A resonance operator is proposed, which describes the sensitivity to changes in the potential. Resonances are then identified from the lowest eigenstates of the resonance operator. The operator is diagonalized in a basis of Hamiltonian pseudostates, built within the hyperspherical harmonics formalism using the analytical THO basis. The energy and width of the resonance are determined from its time dependence. The method is applied to 16Be in a 14Be+n+n model. An effective core+n potential, fitted to the available information on the subsystem 15Be, is employed. The 0+ ground state resonance of 16Be presents a strong dineutron configuration, which favors the picture of a correlated two-neutron emission. Fitting the three body interaction to the experimental two-neutron separation energy |S2n|=1.35(10) MeV, the computed width is Gamma(0+)=0.16 MeV. From the same Hamiltonian, a 2+ resonance is also predicted with E_r(2+)=2.42 MeV and Gamma(2+)=0.40 MeV. The dineutron configuration and the computed 0+ width are consistent with previous R-matrix calculations for the true three-body continuum. The extracted values of the resonance energy and width converge with the size of the pseudostate basis and are robust under changes in the basis parameters. This supports the reliability of the method in describing the properties of unbound core+N+N systems in a discrete basis.

Making the Learning Continuum a Reality: The Critical Role of a Graduate Medical Education-Continuing Medical Education Partnership.

A true continuum of learning in physician education, envisioned as the seamless integration of undergraduate, graduate, and continuing medical education that results in lifelong learning, has yet to be realized. Rapid clinical change, evolving systems of health care, and a shift to competency-based training make the continuum and lifelong learning even more critical. Because they function independently, the efforts of Graduate Medical Education (GME) and Continuing Medical Education (CME) have fallen short of the integrated ideal. The complementary threads of accreditation requirements, expertise, resources, and scholarly activities provide an opportunity for GME and CME to operate in a more integrated and coordinated fashion. Our local GME-CME partnership model demonstrates that these complimentary threads can be tied together to effectively facilitate lifelong learning and promote an integrated learning continuum.

High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence

Historically, mRNA measurements have been tested on several commercially available platforms, but none have gained broad acceptance for assessment of HER2. An mRNA measurement, as a continuous value, has the potential for use in adjudication of the equivocal category. Here we use a real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay in a closed, single-use cartridge, automated system. Multiple cores (1 mm in diameter) were retrospectively collected from 80 formalin-fixed paraffin-embedded (FFPE) tissue blocks with invasive breast cancer seen by Yale Pathology Labs between 1998 and 2011. Tissue cores were processed with a FFPE lysis kit to create lysates that were tested with the automated RT-qPCR assay. Results for IHC and FISH were extracted from the pathology reports and quantitative immunofluorescence (QIF) for each case was measured as previously described. Quality control testing showed that the GX platform RT-qPCR shows no case to case cross contamination on material from routine histology practices. Concordance between RT-qPCR and IHC/FISH was 91.25% (sensitivity=0.87; specificity=0.94; PPV=0.89; NPV=0.92) using a pre-defined delta Ct cut-off (dCt≥−1) for HER2. Concordance (OPA) between RT-qPCR and QIF was 94% (sensitivity=0.90; specificity=0.96; PPV=0.93; NPV=0.94) using dCt≥−1 and a previously defined cut-point for positivity by QIF. In conclusion, the closed system RT-qPCR assay shows >90% concordance with the ASCO/CAP HER2 IHC/FISH scoring. Additionally, the RT-qPCR assay is highly concordant (94%) with the continuous variable HER2 QIF assay, and may better reflect the true continuum of HER2 receptor status in invasive breast cancer. These initial results suggest that fast, closed system molecular assays may have future value for the adjudication of the ASCO/CAP HER2 equivocal category or possibly routine usage in time constrained or low resource settings.

Power1D: a Python toolbox for numerical power estimates in experiments involving one-dimensional continua

The unit of experimental measurement in a variety of scientific applications is the one-dimensional (1D) continuum: a dependent variable whose value is measured repeatedly, often at regular intervals, in time or space. A variety of software packages exist for computing continuum-level descriptive statistics and also for conducting continuum-level hypothesis testing, but very few offer power computing capabilities, where ‘power’ is the probability that an experiment will detect a true continuum signal given experimental noise. Moreover, no software package yet exists for arbitrary continuum-level signal/noise modeling. This paper describes a package called power1d which implements (a) two analytical 1D power solutions based on random field theory (RFT) and (b) a high-level framework for computational power analysis using arbitrary continuum-level signal/noise modeling. First power1d’s two RFT-based analytical solutions are numerically validated using its random continuum generators. Second arbitrary signal/noise modeling is demonstrated to show how power1d can be used for flexible modeling well beyond the assumptions of RFT-based analytical solutions. Its computational demands are non-excessive, requiring on the order of only 30 s to execute on standard desktop computers, but with approximate solutions available much more rapidly. Its broad signal/noise modeling capabilities along with relatively rapid computations imply that power1d may be a useful tool for guiding experimentation involving multiple measurements of similar 1D continua, and in particular to ensure that an adequate number of measurements is made to detect assumed continuum signals.

Abstract P1-03-07: High concordance of a closed system, near point of care, RT-qPCR breast cancer assay for HER2 (ERBB2) mRNA compared to both IHC/FISH and quantitative immunofluorescence

Abstract Background Reliable assessment of HER2 receptor status in breast cancer by either IHC or FISH does not unequivocally define receptor expression, due to their semi-quantitative nature, and as many as 10-15% of cases fall into the ASCO/CAP “equivocal” category. Historically, RNA measurements by PCR, including using several commercially available platforms, have been tested, but have not gained broad acceptance for assessment of HER2. However, RNA measurement, as a continuous value, has potential for use for adjudication of the equivocal category. In the current study, we used a real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay (GeneXpert® Breast Cancer Stratifier RUO Assay, Cepheid, Sunnyvale, CA, USA) for ERBB2 (HER2) mRNA on the GeneXpert® (GX) platform (Cepheid), which utilizes a closed-system, single-use cartridge, automated system. The RT-qPCR results from GX were then compared with results from clinical HER2 IHC/FISH assays following ASCO/CAP 2013 HER2 testing guidelines (Wolff et al JCO 2013) and quantitative immunofluorescence (QIF). Methods Multiple cores (1mm in diameter) were retrospectively collected from 80 formalin-fixed paraffin-embedded (FFPE) tissue blocks with invasive breast cancer seen by Yale Pathology Labs between 1998 and 2011. Tissue cores were processed as lysates for testing at Yale in the automated GX assay. Briefly, gene-specific reverse transcription was performed, followed by RT-qPCR (TaqMan) and ERBB2 mRNA results were expressed as the difference in cycle threshold values (delta Ct) between the endogenous control transcript (CYFIP1) and the ERBB2 mRNA transcript. Results from IHC and FISH were extracted from the pathology reports for the Yale CLIA lab and QIF for each case was measured as previously described (Carvajal et al, JNCI 2015). Results Quality control testing showed that the GX platform shows no case to case cross contamination on material from routine histology practices. Concordance between RT-qPCR and IHC/FISH was 91.25% (sensitivity = 0.87; specificity = 0.94; PPV = 0.89; NPV = 0.92) using a pre-defined delta Ct cut-off (dCt ≥ -1) for HER2 (+) based on prior concordance studies with HER2 IHC/FISH. Concordance between RT-qPCR and QIF was 99% (sensitivity = 0.97; specificity = 1.0; PPV = 1.0; NPV = 0.98) using dCt ≥ -1 and the pre-defined cut-point for positivity by QIF. Conclusions The GX closed system RT-qPCR assay shows greater than 90% concordance with the ASCO/CAP 2013 HER2 IHC/FISH scoring. Additionally, the GX RT-qPCR assay is highly concordant (99%) with the continuous variable HER2 QIF assay, and may better reflect the true continuum of HER2 receptor status in invasive breast cancer. These initial results suggest that rapid, closed system molecular assays may have future value for the adjudication of the ASCO/CAP HER2 equivocal category. This pilot study did not include ASCO/CAP 2013 “equivocal” cases, but that effort is underway. Citation Format: Wasserman B, Carvajal-Hausdorf D, Ho K, Wong W, Wu N, Chu VC, Lai EW, Weidler JM, Bates M, Neumenister V, Rimm DL. High concordance of a closed system, near point of care, RT-qPCR breast cancer assay for HER2 (ERBB2) mRNA compared to both IHC/FISH and quantitative immunofluorescence [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-03-07.

Cooper pairs in the Borromean nuclei 6He and 11Li using continuum single particle level density

A Borromean nucleus is a bound three-body system which is pairwise unbound because none of the two-body subsystem interactions are strong enough to bind them in pairs. As a consequence, the single-particle spectrum of a neutron in the core of a Borromean nucleus is purely continuum, similarly to the spectrum of a free neutron, but two valence neutrons are bound up in such a core. Most of the usual approaches do not use the true continuum to solve the three-body problem but use a discrete basis, like for example, wave functions in a finite box. In this paper the proper continuum is used to solve the pairing Hamiltonian in the continuum spectrum of energy by using the single particle level density devoid of the free gas. It is shown that the density defined in this way modulates the pairing in the continuum. The partial-wave occupation probabilities for the Borromean nuclei 6He and 11Li are calculated as a function of the pairing strength. While at the threshold strength the (s1/2)2 and (p3/2)2 configurations are equally important in 6He, the (s1/2)2 configuration is the main one in 11Li. For very small strength the (s1/2)2 configuration becomes the dominant in both Borromean nuclei. At the physical strength, the calculated wave function amplitudes show a good agreement with other methods and experimental data which indicates that this simple model grasps the essence of the pairing in the continuum.

Dimensional and discrete variations on the psychosis continuum in a Dutch crowd-sourcing population sample

BackgroundMild psychotic experiences are common in the general population. Although transient and benign in most cases, these experiences are predictive of later mental health problems for a significant minority. The goal of the present study was to perform examinations of the dimensional and discrete variations in individuals’ reporting of subclinical positive and negative psychotic experiences in a unique Dutch internet-based sample from the general population. MethodsPositive and negative subclinical psychotic experiences were measured with the Community Assessment of Psychic Experiences in 2870 individuals. First, the prevalence of these experiences and their associations with demographics, affect, psychopathology and quality of life were investigated. Next, latent class analysis was used to identify data-driven subgroups with different symptom patterns, which were subsequently compared on aforementioned variables. ResultsSubclinical psychotic experiences were commonly reported. Both positive and negative psychotic experiences were associated with younger age, more negative affect, anxiety and depression as well as less positive affect and poorer quality of life. Seven latent classes (‘Low psychotic experiences’, ‘Lethargic’, ‘Blunted’, ‘Distressed’, ‘Paranormal’, ‘Distressed/grandiose’ and ‘Distressed/positive psychotic experiences’) were identified that demonstrated both dimensional differences in the number/severity of psychotic experiences and discrete differences in the patterns of reported experiences. ConclusionSubclinical psychotic experiences show both dimensional severity variations and discrete symptom-pattern variations across individuals. To understand and capture all interindividual variations in subclinical psychotic experiences, their number, nature and context (co-occurrence patterns) should be considered at the same time. Only some psychotic experiences may lay on a true psychopathological psychosis continuum.

Near-infrared spectroscopy of M dwarfs. III. Carbon and oxygen abundances in late M dwarfs, including the dusty rapid rotator 2MASSI J1835379+325954

Abstract Carbon and oxygen abundances of eight late M dwarfs are determined based on the near-infrared spectra of medium resolution (R = λ/Δ λ ≈ 20000). In late M dwarfs, dust forms in their photospheres for Teff below about 2600 K, and this case applies to the M8.5 dwarf 2MASSI J1835379+325954 (hereafter 2MASS 1835+32) whose Teff is 2275 K. The other seven objects with Teff above 2600 K are analyzed with dust-free models. For the case of 2MASS 1835+32 analyzed with the dusty model, the surface temperature is higher by about 600 K due to the blanketing effect of the dust grains, mainly composed of iron grains, and the carbon and oxygen abundances are higher by 0.25 and 0.15 dex, respectively, compared to the analysis by the dust-free model. Once dust forms in the photosphere, the dust works as a kind of thermostat and the temperatures of the surface layers remain nearly the same as the condensation temperatures of the dust grains. For this reason, the temperatures of the surface layers of dusty dwarfs are relatively insensitive to the fundamental parameters, including Teff. In addition, it appears that 2MASS 1835+32 is a rapid rotator, for which its equivalent widths (EWs) are thought to remain unchanged by the rotational broadening. This is, however, true only when the true continuum is well defined. Otherwise, the pseudo-continuum level depends on the rotational velocity and hence the EWs as well. For this reason, the derived abundances depend on the rotational velocity assumed: for the values of Vrotsin i = 37.6 and 44.0 km s−1 available in the literature, the derived carbon and oxygen abundances differ by 0.23 and 0.14 dex, respectively, and we find that the higher value provides a better account of the observed spectrum. The resulting carbon and oxygen abundances in the eight late M dwarfs show no systematic difference from our results for the early and middle M dwarfs, and confirm the higher AO/AC ratio at the lower metallicity. In late M dwarfs, CO and H2O remain as excellent abundance indicators of carbon and oxygen, respectively, except for additional uncertainty due to complexity associated with dust formation in the latest M dwarfs.

La place du pédiatre dans le suivi de ces grossesses, la consultation anténatale – de la grande prématurité à l’appréhension du risque psychosocial

At the time of networked care organizations, especially during the existence of vulnerabilities identified such as the existence of maternal or parental psychiatric disorders more broadly, the pediatrician is part of the actors of pregnancy care, anticipation of birth and postnatal support. The antenatal consultation at pediatric-obstetric true continuum from pregnancy to neurodevelopmental and psychological follow-up of the child, we discuss the various places of the pediatrician, as well as some interdisciplinary working tools. Just as there may be a referent obstetrician monitoring these particular pregnancies, a referring pediatrician may enter the scene early, at his side, in anticipation of the child’s arrival and all possible futures.