The second finale of Beethoven's string quartet Opus 130: a study of the composing score and autograph manuscript

Scholars and performers have long wondered when and why Beethoven composed an alternative ending to his string quartet, Opus 130. The original, the Grosse Fuge, was an immense and heavy multi-sectioned fugal finale; the second was a much shorter and lighter hybrid sonata-rondo form finale. The second finale was the last substantial piece Beethoven composed and is reminiscent of earlier dance-like 2/4 Allegro finales composed by Beethoven, likely influenced by Haydn. This style is seemingly incongruous with our current understanding of Beethoven’s late style, centered around foreign harmonies and forms, with expansive thematic material. While research on this topic has been extensive, including studies in biography, source material, reception history, and harmonic and formal analysis, it has not led to a fully adequate understanding of this second finale. My study aims to provide a fresh understanding of this movement through the examination and evaluation of the later stages of its composition. The major sections of revision found in the composing score, Berlin, Deutsche Staatsbibliothek, MS Autograph 19c, and the autograph fair copy, Berlin, Deutsche Staatsbibliothek, MS Grasnick 10, are closely studied here for the first time. In order to highlight important steps in the creative process, I have selected four heavily revised areas from each of the sonata-form sections of this movement as shown in both manuscripts. My interpretation of these revisions is based on comparison to parallel sections in both manuscripts and the final version, as shown in transcriptions of these passages from the sketches along with accompanying images of the original pages. For each of these sections, I attempt to suggest the order in which Beethoven made his revisions, and I discuss their formal, thematic and harmonic implications. As a whole, these revisions reveal Beethoven’s concern for economical treatment of thematic material, especially motives from theme 1a, and a concern for playing upon the harmonic and formal expectations of his audience. The voicing of theme 2a in the exposition and recapitulation, and the voicing and texture of theme 1a in the development, the false and authentic recapitulations and the coda are analyzed in terms of momentum, sectional balance, texture, and dramatic tension. I suggest that further study of these sketches and related primary source material might help to revise our notion of Beethoven’s late style

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Feasibility of neonatal dried blood spot retrieval amid evolving state policies (2009-2010): a Children's Oncology Group study

Dried blood spots (DBS) are collected uniformly from US newborns to test for metabolic and other disorders. Because evidence exists for prenatal origins of some diseases, DBS may provide unique prenatal exposure records. Some states retain residual DBS and permit their use in aetiological studies. The primary study aim was to assess the feasibility of obtaining residual DBS from state newborn screening programmes for paediatric and adolescent cancer patients nationwide with parental/subject consent/assent. Families of leukaemia and lymphoma patients aged ≤21 years diagnosed from 1998 to 2007 at randomly selected Children's Oncology Group institutions across the US were questioned (n = 947). Parents/guardians and patients aged ≥18 years were asked to release DBS to investigators in spring 2009. DBS were then requested from states. Overall, 299 families (32%) released DBS. Consenting/assenting patients were born in 39 US states and 46 DBS were obtained from five states; 124 DBS were unobtainable because patients were born prior to dates of state retention. State policies are rapidly evolving and there is ongoing discussion regarding DBS storage and secondary research uses. Currently, population-based DBS studies can be conducted in a limited number of states; fortunately, many have large populations to provide reasonably sized paediatric subject groups

The Influence of Obesity-Related Single Nucleotide Polymorphisms on BMI Across the Life Course: The PAGE Study

Evidence is limited as to whether heritable risk of obesity varies throughout adulthood. Among >34,000 European Americans, aged 18–100 years, from multiple U.S. studies in the Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we examined evidence for heterogeneity in the associations of five established obesity risk variants (near FTO, GNPDA2, MTCH2, TMEM18, and NEGR1) with BMI across four distinct epochs of adulthood: 1) young adulthood (ages 18–25 years), adulthood (ages 26–49 years), middle-age adulthood (ages 50–69 years), and older adulthood (ages ≥70 years); or 2) by menopausal status in women and stratification by age 50 years in men. Summary-effect estimates from each meta-analysis were compared for heterogeneity across the life epochs. We found heterogeneity in the association of the FTO (rs8050136) variant with BMI across the four adulthood epochs (P = 0.0006), with larger effects in young adults relative to older adults (β [SE] = 1.17 [0.45] vs. 0.09 [0.09] kg/m2, respectively, per A allele) and smaller intermediate effects. We found no evidence for heterogeneity in the association of GNPDA2, MTCH2, TMEM18, and NEGR1 with BMI across adulthood. Genetic predisposition to obesity may have greater effects on body weight in young compared with older adulthood for FTO, suggesting changes by age, generation, or secular trends. Future research should compare and contrast our findings with results using longitudinal data

Acute pain pathways:protocol for a prospective cohort study

INTRODUCTION: Opioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses. METHODS AND ANALYSIS: This multicentre prospective observational study will recruit 1550 opioid-naïve participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments and dental clinics. Participants will be followed for 6 months with the aid of a patient-centred health data aggregating platform that consolidates data from study questionnaires, electronic health record data on healthcare services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients’ patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centred outcomes including resolution of pain, satisfaction with care and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids. ETHICS AND DISSEMINATION: This study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community and the public. TRIAL REGISTRATION NUMBER: NCT04509115

An Unusual Pulse Shape Change Event in PSR J1713+0747 Observed with the Green Bank Telescope and CHIME

The millisecond pulsar J1713+0747 underwent a sudden and significant pulse shape change between 2021 April 16 and 17 (MJDs 59320 and 59321). Subsequently, the pulse shape gradually recovered over the course of several months. We report the results of continued multifrequency radio observations of the pulsar made using the Canadian Hydrogen Intensity Mapping Experiment and the 100 m Green Bank Telescope in a 3 yr period encompassing the shape change event, between 2020 February and 2023 February. As of 2023 February, the pulse shape had returned to a state similar to that seen before the event, but with measurable changes remaining. The amplitude of the shape change and the accompanying time-of-arrival residuals display a strong nonmonotonic dependence on radio frequency, demonstrating that the event is neither a glitch (the effects of which should be independent of radio frequency, ν) nor a change in dispersion measure alone (which would produce a delay proportional to ν−2). However, it does bear some resemblance to the two previous "chromatic timing events" observed in J1713+0747, as well as to a similar event observed in PSR J1643−1224 in 2015

An unusual pulse shape change event in PSR J1713+0747 observed with the Green Bank Telescope and CHIME

The millisecond pulsar J1713+0747 underwent a sudden and significant pulse shape change between April 16 and 17, 2021 (MJDs 59320 and 59321). Subsequently, the pulse shape gradually recovered over the course of several months. We report the results of continued multi-frequency radio observations of the pulsar made using the Canadian Hydrogen Intensity Mapping Experiment (CHIME) and the 100-meter Green Bank Telescope (GBT) in a three-year period encompassing the shape change event, between February 2020 and February 2023. As of February 2023, the pulse shape had returned to a state similar to that seen before the event, but with measurable changes remaining. The amplitude of the shape change and the accompanying TOA residuals display a strong non-monotonic dependence on radio frequency, demonstrating that the event is neither a glitch (the effects of which should be independent of radio frequency, $\nu$) nor a change in dispersion measure (DM) alone (which would produce a delay proportional to $\nu^{-2}$). However, it does bear some resemblance to the two previous "chromatic timing events" observed in J1713+0747 (Demorest et al. 2013; Lam et al. 2016), as well as to a similar event observed in PSR J1643-1224 in 2015 (Shannon et al. 2016).Comment: 19 pages, 8 figures. Submitted to ApJ. Data available at https://doi.org/10.5281/zenodo.723645

The impact of decision aids to enhance shared decision making for diabetes (the DAD study): protocol of a cluster randomized trial

Background. Shared decision making contributes to high quality healthcare by promoting a patientcentered approach. Patient involvement in selecting the components of a diabetes medication program that best match the patient's values and preferences may also enhance medication adherence and improve outcomes. Decision aids are tools designed to involve patients in shared decision making, but their adoption in practice has been limited. In this study, we propose to obtain a preliminary estimate of the impact of patient decision aids vs. usual care on measures of patient involvement in decision making, diabetes care processes, medication adherence, glycemic and cardiovascular risk factor control, and resource utilization. In addition, we propose to identify, describe, and explain factors that promote or inhibit the routine embedding of decision aids in practice. Methods. We will be conducting a mixed-methods study comprised of a cluster-randomized, practical, multicentered trial enrolling clinicians and their patients (n = 240) with type 2 diabetes from rural and suburban primary care practices (n = 8), with an embedded qualitative study to examine factors that influence the incorporation of decision aids into routine practice. The intervention will consist of the use of a decision aid (Statin Choice and Aspirin Choice, or Diabetes Medication Choice) during the clinical encounter. The qualitative study will include analysis of video recordings of clinical encounters and in-depth, semi-structured interviews with participating patients, clinicians, and clinic support staff, in both trial arms. Discussion. Upon completion of this trial, we will have new knowledge about the effectiveness of diabetes decision aids in these practices. We will also better understand the factors that promote or inhibit the successful implementation and normalization of medication choice decision aids in the care of chronic patients in primary care practices