The quest for sustained multiple morbidity reduction in very low-birth-weight infants: the Antifragility project.

OBJECTIVE: Can a comprehensive, explicitly directive evidence-based guideline for all therapies that might affect the major morbidities of very low-birth-weight (VLBW) infants help a neonatal intensive care unit (NICU) further improve generally favorable morbidity rates? Can Antifragility principles of provider adaptive growth from stressors, enhanced infant risk assessment and adherence to effective therapies minimize unproven treatments and reduce all morbidities? STUDY DESIGN: Prospectively planned observational trial in VLBW infants: control group born October 2011 to September 2013 and study group October 2013 to September 2015. Multi-disciplinary evidence-based review assigned all NICU treatments into one of four distinct categories: (1) always employ this therapy for VLBW infants, (2) never use this therapy, (3) employ this questionable therapy thoughtfully, only in certain circumstances and (4) this therapy has insufficient evidence of efficacy and safety. Extensive staff education emphasized evidence-based potentially better practice (PBP) selection with compliance checks, appreciation of intertwined co-morbidities and prioritizing infant risk reduction strategies. RESULTS: Control included 221 infants, mean (s.d.) age 29 (2.6) weeks, birth weight 1129 (257) g and Study included 197 infants, 29 (2.7) weeks, 1093 (292) g. One hundred and four distinct therapies were placed into categories 1 to 4, with 32 specific compliance checks. Overall mean compliance with the process checks during the second era was 70%, high: 100% (exclusive breast milk use), low: 24% (correct pulse oximetry alarm settings). Morbidity and mortality rates did not significantly change during the second era. CONCLUSIONS: In our NICU with favorable morbidity rates, an expanded effort using a comprehensive therapy guideline for VLBW infants did not further improve outcomes. We need deeper understanding of continuous quality improvement (CQI) fundamentals, therapy compliance, co-morbidity relationships and enhanced sensitivity of risk assessment. Our innovative Antifragility PBP guideline could be useful to other NICUs seeking improvement in VLBW infant morbidities, as we offer a reasoned and concise template of a broad array of therapies categorized efficiently for transparency and review, designed to enhance responsible CQI decision-making

Ribosomal Incorporation of Aromatic Oligoamides as Peptide Sidechain Appendages

Derivatives of 4‐aminomethyl‐l ‐phenylalanine with aromatic oligoamide foldamers as sidechain appendages were successfully charged on tRNA by means of flexizymes. Their subsequent incorporation both at the C‐terminus of, and within, peptide sequences by the ribosome, was demonstrated. These results expand the registry of chemical structures tolerated by the ribosome to sidechains significantly larger and more structurally defined than previously demonstrated

A person-centered perspective on working with people who have experienced psychological trauma and helping them move forward to posttraumatic growth

Over the past decade posttraumatic growth (PTG) has become a major topic for theory, research and practice in mainstream trauma psychology. The aim of this paper is to discuss the implications of PTG for the person-centered approach. It is argued that PTG provides a new non-medical language for understanding psychological trauma that is consistent with the person-centered approach. Person-centered personality theory provides an explanation for how PTG arises and leads to new testable predictions for research into how person-centered therapy may be able to facilitate PTG

The position of authenticity within extant models of personality.

The aim of the current study was to explore where authenticity, derived from the humanistic tradition of psychology, was positioned within a number of extant models of personality. Exploratory and Confirmatory Factor Analysis of data from four samples (total N = 1286) suggested that authenticity can be considered as loading on the Honesty–Humility factor of personality. These findings are discussed in terms of the wider theoretical overlaps between Honesty–Humility and psychological functioning as emphasised by the humanistic tradition of psychology

Dementia assessment and management in primary care settings: a survey of current provider practices in the United States.

BACKGROUND:Primary care providers (PCPs) are typically the first to screen and evaluate patients for neurocognitive disorders (NCDs), including mild cognitive impairment and dementia. However, data on PCP attitudes and evaluation and management practices are sparse. Our objective was to quantify perspectives and behaviors of PCPs and neurologists with respect to NCD evaluation and management. METHODS:A cross-sectional survey with 150 PCPs and 50 neurologists in the United States who evaluated more than 10 patients over age 55 per month. The 51-item survey assessed clinical practice characteristics, and confidence, perceived barriers, and typical practices when diagnosing and managing patients with NCDs. RESULTS:PCPs and neurologists reported similar confidence and approaches to general medical care and laboratory testing. Though over half of PCPs performed cognitive screening or referred patients for cognitive testing in over 50% of their patients, only 20% reported high confidence in interpreting results of cognitive tests. PCPs were more likely to order CT scans than MRIs, and only 14% of PCPs reported high confidence interpreting brain imaging findings, compared to 70% of specialists. Only 21% of PCPs were highly confident that they correctly recognized when a patient had an NCD, and only 13% were highly confident in making a specific NCD diagnosis (compared to 72 and 44% for neurologists, both p < 0.001). A quarter of all providers identified lack of familiarity with diagnostic criteria for NCD syndromes as a barrier to clinical practice. CONCLUSIONS:This study demonstrates how PCPs approach diagnosis and management of patients with NCDs, and identified areas for improvement in regards to cognitive testing and neuroimaging. This study also identified all providers' lack of familiarity with published diagnostic criteria for NCD syndromes. These findings may inform the development of new policies and interventions to help providers improve the efficacy of their decision processes and deliver better quality care to patients with NCDs

Quantifying the UV-continuum slopes of galaxies to z ˜ 10 using deep Hubble+Spitzer/IRAC observations

Measurements of the UV-continuum slopes β provide valuable information on the physical properties of galaxies forming in the early universe, probing the dust reddening, age, metal content, and even the escape fraction. While constraints on these slopes generally become more challenging at higher redshifts as the UV-continuum shifts out of the Hubble Space Telescope bands (particularly at z > 7), such a characterization actually becomes abruptly easier for galaxies in the redshift window z = 9.5-10.5 due to the Spitzer/Infrared Array Camera 3.6 μm-band probing the rest-UV continuum and the long wavelength baseline between this Spitzer band and the Hubble Hf160w band. Higher S/N constraints on β are possible at z ˜ 10 than at z = 8. Here, we take advantage of this opportunity and five recently discovered bright z = 9.5-10.5 galaxies to present the first measurements of the mean β for a multi-object sample of galaxy candidates at z ˜ 10. We find the measured βobs's of these candidates are -2.1 ± 0.3 ± 0.2 (random and systematic), only slightly bluer than the measured β's (βobs ≈ -1.7) at 3.5 < z < 7.5 for galaxies of similar luminosities. Small increases in the stellar ages, metallicities, and dust content of the galaxy population from z ˜ 10 to z ˜ 7 could easily explain the apparent evolution in β

Unconditional positive self-regard, intrinsic aspirations and authenticity: pathways to psychological well-being

Unconditional positive self-regard (UPSR) is regarded by humanistic psychologists as an important determinant of well-being. However, until recently it has received little empirical attention. The current study aims to examine the association between unconditional positive self-regard and several key constructs consistent with the ideas of well-being within contemporary positive psychology. Study 1 is a confirmatory factor analysis of the UPSR scale. The statistically significant best fit for the data was a related two-factor model. Study 2 used the two-factors of the UPSR scale to explore the association with intrinsic aspirations. The study showed positive self-regard was statistically significantly positively correlated with the intrinsic aspirations total scale and with each of the separate scores for IA-importance and IA-chance. Unconditionality of regard was statistically significantly negatively correlated with IA-importance but was not statistically significantly correlated to either the IA-total or IA-chance scores. Study 3 considers the association between UPSR, intrinsic aspirations and authenticity. Unconditionality of regard was statistically significantly positively correlated with the authenticity scale score. Only IA-chance scores showed a statistically significant and positive correlation with authenticity. The remaining correlations between intrinsic aspirations and authenticity were not statistically significant. Results call for further empirical attention to UPSR within positive psychology research

Plasmodium falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion

The most lethal form of malaria in humans is caused by Plasmodium falciparum. These parasites invade erythrocytes, a complex process involving multiple ligand-receptor interactions. The parasite makes initial contact with the erythrocyte followed by dramatic deformations linked to the function of the Erythrocyte binding antigen family and P. falciparum reticulocyte binding-like families. We show EBA-175 mediates substantial changes in the deformability of erythrocytes by binding to glycophorin A and activating a phosphorylation cascade that includes erythrocyte cytoskeletal proteins resulting in changes in the viscoelastic properties of the host cell. TRPM7 kinase inhibitors FTY720 and waixenicin A block the changes in the deformability of erythrocytes and inhibit merozoite invasion by directly inhibiting the phosphorylation cascade. Therefore, binding of P. falciparum parasites to the erythrocyte directly activate a signaling pathway through a phosphorylation cascade and this alters the viscoelastic properties of the host membrane conditioning it for successful invasion

Interplay between partner and ligand facilitates the folding and binding of an intrinsically disordered protein.

Protein-protein interactions are at the heart of regulatory and signaling processes in the cell. In many interactions, one or both proteins are disordered before association. However, this disorder in the unbound state does not prevent many of these proteins folding to a well-defined, ordered structure in the bound state. Here we examine a typical system, where a small disordered protein (PUMA, p53 upregulated modulator of apoptosis) folds to an α-helix when bound to a groove on the surface of a folded protein (MCL-1, induced myeloid leukemia cell differentiation protein). We follow the association of these proteins using rapid-mixing stopped flow, and examine how the kinetic behavior is perturbed by denaturant and carefully chosen mutations. We demonstrate the utility of methods developed for the study of monomeric protein folding, including β-Tanford values, Leffler α, Φ-value analysis, and coarse-grained simulations, and propose a self-consistent mechanism for binding. Folding of the disordered protein before binding does not appear to be required and few, if any, specific interactions are required to commit to association. The majority of PUMA folding occurs after the transition state, in the presence of MCL-1. We also examine the role of the side chains of folded MCL-1 that make up the binding groove and find that many favor equilibrium binding but, surprisingly, inhibit the association process.This is the final version. It was first published online by PNAS via http://dx.doi.org/10.1073/pnas.140912211

A theory on reports of constructive (real) and illusory posttraumatic growth

It has been suggested that self-reported posttraumatic growth could sometimes be considered as a way for people to protect themselves from the distress of trauma. In this case, reports of posttraumatic growth could be illusory. We suggest a theory on self-reported constructive (real) posttraumatic growth and illusory posttraumatic growth by using Rogers’s (1959) theory and the work by Vaillant (1995). Through this theoretical framework we attempt to explain when reports of posttraumatic growth are likely to be constructive and real and when such reports are likely to represent aspects of illusions. We will also consider the implications for research practice