Laying the foundation of the effective-one-body waveform models SEOBNRv5: improved accuracy and efficiency for spinning non-precessing binary black holes

We present SEOBNRv5HM, a more accurate and faster inspiral-merger-ringdown gravitational waveform model for quasi-circular, spinning, nonprecessing binary black holes within the effective-one-body (EOB) formalism. Compared to its predecessor, SEOBNRv4HM, the waveform model i) incorporates recent high-order post- Newtonian results in the inspiral, with improved resummations, ii) includes the gravitational modes (l, |m|) = (3, 2), (4, 3), in addition to the (2, 2), (3, 3), (2, 1), (4, 4), (5, 5) modes already implemented in SEOBNRv4HM, iii) is calibrated to larger mass-ratios and spins using a catalog of 442 numerical-relativity (NR) simulations and 13 additional waveforms from black-hole perturbation theory, iv) incorporates information from second-order gravitational self-force (2GSF) in the nonspinning modes and radiation-reaction force. Computing the unfaithfulness against NR simulations, we find that for the dominant (2, 2) mode the maximum unfaithfulness in the total mass range $10-300 M_{\odot}$ is below $10^{-3}$ for 90% of the cases (38% for SEOBNRv4HM). When including all modes up to l = 5 we find 98% (49%) of the cases with unfaithfulness below $10^{-2} (10^{-3})$, while these numbers reduce to 88% (5%) when using SEOBNRv4HM. Furthermore, the model shows improved agreement with NR in other dynamical quantities (e.g., the angular momentum flux and binding energy), providing a powerful check of its physical robustness. We implemented the waveform model in a high-performance Python package (pySEOBNR), which leads to evaluation times faster than SEOBNRv4HM by a factor 10 to 50, depending on the configuration, and provides the flexibility to easily include spin-precession and eccentric effects, thus making it the starting point for a new generation of EOBNR waveform models (SEOBNRv5) to be employed for upcoming observing runs of the LIGO-Virgo-KAGRA detectors

Tackling health inequalities: moving theory to action

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Sequential Immunization Strategies to Elicit HIV-1 bNAbs in Animal Models With a Polyclonal B Cell Repertoire

Background: Immunization regimens that can elicit broadly neutralizing antibodies (bNAbs) in humans would be an effective vaccine against HIV-1. Our previous work showed that an immunization strategy involving a sequence of Env-based germline targeting immunogens that were gradually engineered to resemble the native Env protein, successfully elicited bNAb-like antibodies in a knock-in mouse carrying the inferred germline PGT121/10-1074 antibody. Despite this achievement, immunization protocols that elicit bNAbs in systems with a polyclonal B cell repertoire have not been reported to date. The low frequencies of germline bNAb precursors in polyclonal systems hinder their activation by immunization which therefore requires high affinity immunogens. In addition, competition between different epitope-specific B cells in polyclonal germinal centers may frustrate bNAb development. Methods: Based on our previous results in knock-in mice, we have aimed to optimize sequential immunization strategies to elicit bNAbs in animal models with polyclonal B cell repertoires. Results: The results of immunization experiments in several animal models will be presented

Sequential Immunization Strategies to Elicit HIV-1 bNAbs in Animal Models With a Polyclonal B Cell Repertoire

Background: Immunization regimens that can elicit broadly neutralizing antibodies (bNAbs) in humans would be an effective vaccine against HIV-1. Our previous work showed that an immunization strategy involving a sequence of Env-based germline targeting immunogens that were gradually engineered to resemble the native Env protein, successfully elicited bNAb-like antibodies in a knock-in mouse carrying the inferred germline PGT121/10-1074 antibody. Despite this achievement, immunization protocols that elicit bNAbs in systems with a polyclonal B cell repertoire have not been reported to date. The low frequencies of germline bNAb precursors in polyclonal systems hinder their activation by immunization which therefore requires high affinity immunogens. In addition, competition between different epitope-specific B cells in polyclonal germinal centers may frustrate bNAb development. Methods: Based on our previous results in knock-in mice, we have aimed to optimize sequential immunization strategies to elicit bNAbs in animal models with polyclonal B cell repertoires. Results: The results of immunization experiments in several animal models will be presented

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Polygenic signal for symptom dimensions and cognitive performance in patients with chronic schizophrenia

Genetic etiology of psychopathology symptoms and cognitive performance in schizophrenia is supported by candidate gene and polygenic risk score (PRS) association studies. Such associations are reported to be dependent on several factors - sample characteristics, illness phase, illness severity etc. We aimed to examine if schizophrenia PRS predicted psychopathology symptoms and cognitive performance in patients with chronic schizophrenia. We also examined if schizophrenia associated autosomal loci were associated with specific symptoms or cognitive domains. Case-only analysis using data from the Clinical Antipsychotics Trials of Intervention Effectiveness-Schizophrenia trials (n = 730). PRS was constructed using Psychiatric Genomics Consortium (PGC) leave one out genome wide association analysis as the discovery data set. For candidate region analysis, we selected 105-schizophrenia associated autosomal loci from the PGC study. We found a significant effect of PRS on positive symptoms at p-threshold (PT) of 0.5 (R2 = 0.007, p = 0.029, empirical p = 0.029) and negative symptoms at PT of 1e-07 (R2 = 0.005, p = 0.047, empirical p = 0.048). For models that additionally controlled for neurocognition, best fit PRS predicted positive (p-threshold 0.01, R2 = 0.007, p = 0.013, empirical p = 0.167) and negative symptoms (p-threshold 0.1, R2 = 0.012, p = 0.004, empirical p = 0.329). No associations were seen for overall neurocognitive and social cognitive performance tests. Post-hoc analyses revealed that PRS predicted working memory and vigilance performance but did not survive correction. No candidate regions that survived multiple testing corrections were associated with either symptoms or cognitive performance. Our findings point to potentially distinct pathogenic mechanisms for schizophrenia symptoms

Forgiveness and chronic low back pain: A preliminary study examining the relationship of forgiveness to pain, anger, and psychological distress

Clinical observations suggest that many patients with chronic pain have difficulty forgiving persons they perceive as having unjustly offended them in some way. By using a sample of 61 patients with chronic low back pain, this study sought to determine the reliability and variability of forgiveness assessments in patients and to examine the relationship of forgiveness to pain, anger, and psychological distress. Standardized measures were used to assess patients’ current levels of forgiveness, forgiveness self-efficacy, pain, anger, and psychological distress. Results showed that forgiveness-related constructs can be reliably assessed in patients with persistent pain, and that patients vary considerably along dimensions of forgiveness. Furthermore, correlational analyses showed that patients who had higher scores on forgiveness-related variables reported lower levels of pain, anger, and psychological distress. Additional analyses indicated that state anger largely mediated the association between forgiveness and psychological distress, as well as some of the associations between forgiveness and pain. These findings indicate that forgiveness can be reliably assessed in patients with persistent pain, and that a relationship appears to exist between forgiveness and important aspects of living with persistent pain.<br/

Fear of movement in children and adolescents undergoing major surgery : a psychometric evaluation of the Tampa Scale for Kinesiophobia

Background The objective of this study was to evaluate the psychometric properties of the 17-item Tampa Scale for Kinesiophobia (TSK) in youth. Methods Participants were 264 children and adolescents (58.7% female, Mage = 14.1 years, SDage = 2.51) scheduled for major surgery who were assessed before surgery, while in hospital postoperatively, and at 6 and 12 months after surgery. Exploratory factor analyses (EFA) were conducted to determine the factor structure of pre-operative TSK scores. Reliability, and convergent, discriminant, and predictive validity were examined. Results EFA on the 17-item TSK revealed a two-factor model distinguishing the 13 positively scored items from the 4 reverse scored items, but the fit was poor. A second EFA was conducted on the 13 positively scored items (TSK-13) revealing a three-factor model: Fear of injury, bodily vulnerability, and activity avoidance. The TSK-13 showed adequate internal consistency (Ω = 0.82) and weak convergent validity. The TSK-13 was not correlated with postoperative, in-hospital physical activity (actigraphy; r (179) = −0.10, p = 0.18) and showed adequate discriminant validity, that is correlations less than 0.70, with measures of depression (r (225) = 0.41, p < 0.001) and general anxiety (r (224)=0.35, p < 0.001). Predictive validity for pain-related disability at 12 months (r (70) = 0.34, p < 0.001) was adequate. Conclusions The original TSK-17 does not appear to be a meaningful measure of kinesiophobia in youth after surgery possibly because of the syntactic structure of the reverse scored items. In contrast, a modified TSK-13, comprised of only the positively scored items, revealed a 3-factor structure that is reliable and demonstrates adequate convergent, discriminant, and predictive validity. Significance Kinesiophobia is an important construct to evaluate in the transition from acute to chronic pain among children and adolescents. The 17 item Tampa Scale for Kinesiophobia (TSK) does not show adequate validity or reliability in youth undergoing major surgery, however, the psychometric properties of a 13-item modified scale (TSK-13) are promising